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  • Land Rover Defender Octa goes stealth with Black Edition: Check pics

    Land Rover Defender Octa goes stealth with Black Edition: Check pics

    Land Rover Defender Octa Black Edition breaks cover.

    Earlier this year, Land Rover launched the Defender Octa in India at a starting price of Rs 2.59 crore, ex-showroom. Now, the SUV has received a new all-black version called the Octa Black Edition. Unveiled globally, this version gets several visual upgrades inside and out. Here’s a look at what’s new.

    Land Rover Defender Octa Black Edition: All you need to know

    The model is painted in Narvik Black and comes with over 30 blacked-out elements like the grille, exhaust tips, tow hooks, scuff plates, and even parts underneath the car. It will be available with an option to choose between 20- or 22-inch gloss black wheels with black brake calipers, that lend it a stealthier look.

    Defender Octa Black

    Moving inside, the cabin continues the blackout theme with Ebony Semi-Aniline Leather paired with Kvadrat fabric: a first for any Defender. The seats carry new perforation patterns, and the dashboard can be optioned with chopped carbon fibre. Standard features include a new 13.1-inch touchscreen, smoked taillamps, and revised LED signature graphics.

    Defender Octa Black

    Under the hood, the OCTA Black continues with a 4.4-litre twin-turbo mild-hybrid V8 that delivers 635 hp and 750 Nm, capable of sprinting from 0–100 kmph in just 3.8 seconds. It also retains features like the advanced 6D Dynamics suspension and OCTA Mode for high-speed off-roading.

    Defender’s most Towering version: India plans, electric Defender and more | TOI Auto

    Defender Octa Black

    Having already launched the Range Rover Sport SV Black Edition, Land Rover seems to be riding high on the stealth trend. We can expect the Defender OCTA Black to land in India later this year or early 2026.Stay tuned to TOI Auto for latest updates on the automotive sector and do follow us on our social media handles on Facebook, Instagram and X.


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  • Adolescent and Current Exercise Habits in Chronic Obstructive Pulmonar

    Adolescent and Current Exercise Habits in Chronic Obstructive Pulmonar

    Introduction

    Chronic obstructive pulmonary disease (COPD) is a major public health concern, as it remains one of the leading causes of death worldwide.1 Patients with COPD often experience reduced musculoskeletal mass due to chronic inflammation, malnutrition, and inactivity resulting from dyspnea.2,3 This musculoskeletal loss contributes to sarcopenia and osteoporosis, increasing fracture risk and further inactivity, which worsens prognosis.4,5 Exercise plays a vital role in maintaining healthy body composition.6 The Global Initiative for Chronic Obstructive Lung Disease (GOLD) 2025 report emphasizes the importance of pulmonary rehabilitation.7 However, its availability is limited due to high costs and a shortage of therapists.8 Encouraging patients with COPD to establish their exercise habits may promote physical activity (PA) and help reduce healthcare costs.

    Musculoskeletal mass reaches a peak in young adulthood and gradually declines with age.9 Higher levels of PA during youth are associated with increased lean mass, and maintaining PA in later life helps preserve it.6 However, to the best of our knowledge, no study has clarified the associations of adolescent versus current exercise habits on body composition in patients with COPD. Moreover, the association of adolescent exercise on current PA levels and pulmonary function in patients with COPD has not been thoroughly investigated.

    We hypothesized that adolescent and current exercise habits would independently contribute to an improved clinical profile of COPD. In the present study, we aimed to clarify the associations of adolescent and current exercise habits with body composition, PA, and pulmonary function. Furthermore, we determined whether disease severity influences these effects.

    Materials and Methods

    Participants

    Outpatients with COPD or pre-COPD at our university hospital between October 2021 and December 2023 were enrolled in this cross-sectional study, as part of exploratory research. Participants with a smoking history of more than 10 pack-years and no exacerbation of respiratory symptoms within 4 weeks prior to enrollment were included. The exclusion criteria included severe heart failure, progressive malignant diseases, or other chronic pulmonary diseases, except for stable asthma. COPD and pre-COPD were diagnosed according to the GOLD recommendations.7 In this study, Pre-COPD and GOLD 1 were defined as mild COPD (forced expiratory volume in 1 s [FEV1] % predicted ≥ 80%), and GOLD 2 to 4 were defined as moderate-to-severe COPD (FEV1 % predicted < 80%). This study was conducted in accordance with the ethical principles outlined in the Declaration of Helsinki. This study was approved by the Ethics Committee of Shiga University of Medical Science (registration number: R2021-026), and all participants provided written informed consent before participation.

    Exercise Habit Questionnaire

    Self-report questionnaires were used to ask the participants about their exercise habits at different stages of their lives (Figure S1). We defined exercise habit as engaging in any sport or exercise at least twice a week for a minimum of 30 min per session.10 Participants were categorized as “adolescent exercisers” if they had exercise habits between the ages of 16 and 22 years for at least 1 continuous year,11 and as “current exercisers” if they had maintained exercise habits for at least 1 year.

    PA Assessment

    PA was measured using a triaxial accelerometer (Active Style Pro HJA-750C; Omron Healthcare, Kyoto, Japan). The participants wore the device during the daytime, except while bathing, for 14 days. Rainy days were excluded, and the data were validated as previously described.12 The mean durations of PA based on metabolic equivalents (METs) and step counts were analyzed. The intensity of PA was defined as moderate to vigorous PA (moderate to vigorous physical activity [MVPA] ≥ 3.0 METs), light PA (1.6 to 2.9 METs), and sedentary behavior (1.0 to 1.5 METs), based on a previous report.13

    Body Composition Analysis

    Body composition was assessed using direct segmental multifrequency bioelectrical impedance analysis (BIA) (InBody S10; InBody Co., Ltd., Seoul, South Korea).6 Multifrequency measurements were performed for each body segment in the supine position. Fat-free mass index (FFMI) and fat mass index (FMI) were calculated by dividing the respective mass values by height squared. Phase angle (PhA), a raw BIA variable, reflects the relationship between reactance and resistance in the body as a conductor, and a smaller value indicates a worse cellular condition.14 The PhA at 50 kHz provides information about muscle quality.14,15

    Handgrip Strength Test

    Handgrip strength was measured twice per hand, and the maximum value was analyzed.

    6-minute Walk Test

    A 6-minute walk test was performed according to the guidelines.16

    Pulmonary Function Tests

    Pulmonary function tests were performed after the inhalation of 20 μg procaterol using a spirometer (FUDAC77; Fukuda Denshi, Tokyo, Japan), according to the ATS/ERS guidelines.17 Carbon monoxide diffusing capacity was measured using the single-breath washout technique. Predicted spirometry values were calculated according to the Japanese Respiratory Society guidelines.18

    Computed Tomography Imaging

    Chest computed tomography (CT) was performed in the supine position using a 320-detector row CT scanner (Aquilion ONE; Canon Medical Systems Corporation, Tochigi, Japan) with full inspiration. The 20 μg procaterol inhalation was given 1 hour before CT scan. Emphysematous lesions were assessed as the percentage of low attenuation volume (LAV%), which is defined as the percentage of lung volume exhibiting CT attenuation values below –950 Hounsfield units. Small airway lesions were assessed by plotting the square root of the wall area (√Aaw) of each visible bronchial segment against its internal perimeter, and estimating the √Aaw for a hypothetical airway with an internal perimeter of 10 mm using linear regression (√Aaw at Pi10). All parameters were quantified using the Apollo software version 1.2 (VIDA, Coralville, IA, USA), based on previous reports.19,20

    Statistical Analysis

    Statistical analyses were performed using JMP Pro 17 software (SAS Institute, Cary, NC, USA). Differences between exercisers and non-exercisers were evaluated using the Wilcoxon rank-sum and Fisher’s exact tests. The correlations between PA and body composition were assessed using Spearman’s rank correlation coefficients. Statistical significance was set at p < 0.05.

    Results

    A total of 86 participants (81 men and 5 women) were enrolled in this study. Seventy-two patients were diagnosed with COPD, and 36 patients were diagnosed with moderate-to-severe COPD (Table 1). As presented in Figure S2, there was no relationship between the presence or absence of adolescent exercise habits and current exercise habits. Adolescence and current exercise habits were not related to exercise habits in the 30s to 40s.

    Table 1 Patient Characteristics

    Association Between Adolescent Exercise Habits and Current Conditions

    The demographic and clinical characteristics of the participants were not significantly different between adolescent exercisers and non-exercisers (Table S1). Adolescent exercise habits did not influence step count, PA duration at any intensity, (Figure 1A–D), or body composition parameters (Figure 1E–H). When pulmonary function and CT imaging were determined, only vital capacity was significantly higher in adolescent exercisers than in non-exercisers (p = 0.038; Table 2).

    Table 2 Associations of Adolescent Exercise Habits with Pulmonary Functions and CT Imaging Biomarkers

    Figure 1 Associations of adolescent exercise habits with physical activity and body composition parameters. (A) Comparison of step counts per day. (B) Comparison of MVPA per day. (C) Comparison of light PA per day. (D) Comparison of sedentary behavior per day. (E) Comparison of fat-free mass index. (F) Comparison of bone mineral content. (G) Comparison of phase angle at 50 kHz. (H) Comparison of fat mass index.

    Abbreviations: MVPA, moderate to vigorous physical activity; PA, physical activity.

    Association Between Current Exercise Habits and Current Conditions

    Table S2 presents the demographic and clinical characteristics of current exercisers and non-exercisers. Current non-exercisers were more likely to be current smokers or female sex. They also showed a non-significant trend toward lower grip strength. Current exercisers were more physically active (p < 0.001; Figure 2A, and p < 0.001; Figure 2B) throughout the day. The duration of light PA tended to be longer in current exercisers than in non-exercisers, but this difference was not significant (p = 0.059; Figure 2C). Current exercisers spent less time engaging in sedentary behaviors (p = 0.021; Figure 2D). Body composition measures, including FFMI (p = 0.002; Figure 2E), bone mineral content (BMC, p = 0.009; Figure 2F), and PhA (p = 0.017; Figure 2G), were significantly higher in current exercisers than in non-exercisers, whereas the FMI (p = 0.52; Figure 2H) and body mass index (BMI; p = 0.42; Table S2) showed no significant differences. Multiple linear regression analysis, adjusted for age, sex, FEV1 % predicted, and both adolescent and current exercise habits, revealed that current exercise habits were independent factors affecting FFMI, BMC, and PhA (Table 3). The results remained consistent when an interaction term between adolescents and their current exercise habits was incorporated into the multivariate analysis (data not shown). Although CT imaging parameters were not related to current exercise habits, diffusing capacity was higher in current exercisers than in non-exercisers (p = 0.006; Table 4).

    Table 3 Factors Associated with Body Composition Parameters Based on the Multiple Linear Regression Test

    Table 4 Associations of Current Exercise Habits with Pulmonary Functions and CT Imaging Biomarkers

    Figure 2 Associations of current exercise habits with physical activity and body composition parameters. *is significant at the P < 0.05 level. (A) Comparison of step counts per day. (B) Comparison of MVPA per day. (C) Comparison of light PA per day. (D) Comparison of sedentary behavior per day. (E) Comparison of fat-free mass index. (F) Comparison of bone mineral content. (G) Comparison of phase angle at 50 kHz. (H) Comparison of fat mass index.

    Abbreviations: MVPA, moderate to vigorous physical activity; PA, physical activity.

    Associations Between MVPA per Day and Body Composition Parameters by COPD Severity

    As presented in Table 5 and Figure 3, MVPA per day was positively correlated with the FFMI and PhA, especially in moderate-to-severe COPD (rho = 0.51, p = 0.003; rho = 0.45, p = 0.011, respectively). In contrast, in mild COPD, MVPA per day was associated with the PhA and FMI (rho = 0.32, p = 0.024; rho = −0.29, p = 0.042, respectively).

    Table 5 Associations Between MVPA per Day and Body Composition Parameters by COPD Severity

    Figure 3 Correlations between MVPA per day and muscle quantity or quality indicators in moderate-to-severe COPD. (A) Correlation between MVPA per day and fat-free mass index. (B) Correlation between MVPA per day and phase angle at 50 kHz.

    Abbreviation: MVPA, moderate to vigorous physical activity.

    Discussion

    In patients with COPD, adolescent exercise habits showed no significant association with daily PA levels or body composition, although they were associated with increased lung volume. In contrast, current exercise habits were associated with prolonged engagement in higher PA, with a reduction in sedentary behavior, improved body composition, and enhanced diffusing capacity. In addition, the correlation between PA and musculoskeletal parameters varied with COPD severity and was more pronounced in patients with moderate-to-severe COPD than in those with mild COPD.

    Previous studies have suggested that in healthy older adults, youth sports participation is associated with elevated PA levels and improved body composition in later life.21,22 Contrary to our hypothesis, adolescent exercisers neither showed a tendency to maintain a high level of PA nor a better body composition in later life. Prolonged chronic inflammation, disease-related inactivity, particularly due to breathlessness, and COPD comorbidities may negate any long-term benefits of adolescent exercise.2,5 Although adolescent exercise habits did not significantly affect COPD features, a notable finding was a higher lung volume in adolescent exercisers than in non-exercisers. Our results align with those of earlier studies in healthy adults;23,24 however, to the best of our knowledge, our study is the first to describe this association in patients with COPD. Although the mechanisms underlying lung development through exercise are not fully understood, regular exercise during adolescence may be associated with lung development.23,24 As impaired lung development reportedly contributes to the future onset of obstructive lung diseases, early life exercise may play a beneficial role in preventing the development or progression of COPD.25

    In the present study, current exercisers were physically active regularly and did not exhibit sedentary behaviors such as prolonged periods of television viewing. Increased PA is associated with improved body composition in COPD.26,27 Consistently, our study demonstrated that current exercisers had significantly higher musculoskeletal measures than non-exercisers. Furthermore, these associations persisted even after adjusting for confounders, including adolescent exercise habits. It is possible that patients with well-controlled COPD are more likely to maintain exercise routines. However, regular exercise, even after the onset of COPD, may be more important than exercise during adolescence for achieving optimal body composition, leading to a good prognosis and indirectly contributing to reduced healthcare costs.4 Moreover, a low level of PA is associated with muscle wasting and reduced exercise performance.27 Although the difference in grip strength was not statistically significant—possibly due to the relatively small sample size—grip strength, a reported prognostic factor, tended to be higher in current exercisers.28,29

    Diffusing capacity was significantly higher in current exercisers, which is consistent with the findings of a previous observational study.30 However, there were no statistically significant differences in CT imaging factors. Individuals with a higher diffusing capacity may engage in higher levels of PA. However, regular exercise may promote pulmonary circulation at the capillary level and prevent a decrease in diffusing capacity,30 regardless of morphological changes. Further studies are required to investigate these causal relationships.

    In addition, we observed correlations between the duration of MVPA and musculoskeletal parameters in patients with moderate-to-severe COPD, consistent with a previous study.31 Patients with more severe COPD reportedly have lower musculoskeletal mass and experience faster muscle loss than those with mild disease.2,3,20 Notably, exercise-induced changes in the muscle are not impaired in patients with severe COPD, and exercise may have an even greater impact on body composition in this population.32 Our finding further suggests that maintaining daily PA levels is crucial for preventing musculoskeletal mass loss, particularly in patients with more severe COPD.

    This study had some limitations. This was a single-center study conducted in Japan with a relatively small sample size. As a cross-sectional study, it cannot establish causal relationships, and recall bias may have occurred. Moreover, nutritional supplementation, which may be related to body composition, was not evaluated. However, no participant reported anorexia at the time of examination. Further prospective studies are needed to confirm our findings and explore the mechanisms underlying these associations.

    Conclusion

    Exercise during adolescence may be associated with increased lung volume. However, even after the onset of COPD, regular exercise routines can help maintain PA, improve body composition, and diffusing capacity, particularly if the disease has progressed. The results of this study effectively underscore the importance of exercise habits in patients with COPD.

    Acknowledgments

    The authors would like to thank Yasutaka Horii, Yukie Miyatake, and Yoko Naito for their assistance throughout this study.

    Disclosure

    The authors report no conflicts of interest in this work.

    References

    1. GBD 2021 Causes of Death Collaborators. Global burden of 288 causes of death and life expectancy decomposition in 204 countries and territories and 811 subnational locations, 1990–2021: a systematic analysis for the global burden of disease study 2021. Lancet. 2024;403(10440):2100–2132. doi:10.1016/S0140-6736(24)00367-2

    2. Jin X, Yang Y, Chen G, et al. Correlation between body composition and disease severity in patients with chronic obstructive pulmonary disease. Front Med Lausanne. 2024;11:1304384. doi:10.3389/fmed.2024.1304384

    3. Watanabe K, Onoue A, Kubota K, et al. Association between airflow limitation severity and reduced bone mineral density in Japanese men. Int J Chron Obstruct Pulmon Dis. 2019;14:2355–2363. doi:10.2147/COPD.S213746

    4. Vestbo J, Prescott E, Almdal T, et al. Body mass, fat-free body mass, and prognosis in patients with chronic obstructive pulmonary disease from a random population sample: findings from the Copenhagen City heart study. Am J Respir Crit Care Med. 2006;173(1):79–83. doi:10.1164/rccm.200506-969OC

    5. Lehouck A, Boonen S, Decramer M, Janssens W. COPD, bone metabolism, and osteoporosis. Chest. 2011;139(3):648–657. doi:10.1378/chest.10-1427

    6. Cruz-Jentoft AJ, Bahat G, Bauer J, et al. Sarcopenia: revised European consensus on definition and diagnosis. Age Ageing. 2019;48(1):16–31. doi:10.1093/ageing/afy169

    7. Global strategy for the diagnosis, management, and prevention of obstructive pulmonary disease (2025 report) [homepage on the Internet]. Global Initiative for Chronic Obstructive Lung Disease; 2025. Available from: https://goldcopd.org/2025-gold-report/. Accessed June 25, 2025.

    8. Choi JY, Kim KU, Kim DK, et al. Pulmonary rehabilitation is associated with decreased exacerbation and mortality in patients with COPD: a Nationwide Korean study. Chest. 2024;165(2):313–322. doi:10.1016/j.chest.2023.09.026

    9. Sayer AA, Syddall H, Martin H, Patel H, Baylis D, Cooper C. The developmental origins of sarcopenia. J Nutr Health Aging. 2008;12(7):427–432. doi:10.1007/BF02982703

    10. Active guide Japanese official physical activity guidelines for health promotion. [homepage on the Internet]. Ministry of Health, Labour and Welfare. 2013. Available from: https://www.nibiohn.go.jp/eiken/programs/pdf/active2013-e.pdf. Accessed June 25, 2025.

    11. Conroy MB, Cook NR, Manson JE, Buring JE, Lee IM. Past physical activity, current physical activity, and risk of coronary heart disease. Med Sci Sports Exerc. 2005;37(8):1251–1256. doi:10.1249/01.mss.0000174882.60971.7f

    12. Miyamoto S, Minakata Y, Azuma Y, et al. Verification of a motion sensor for evaluating physical activity in COPD patients. Can Respir J. 2018;2018:8343705. doi:10.1155/2018/8343705

    13. Cavalheri V, Straker L, Gucciardi DF, Gardiner PA, Hill K . Changing physical activity and sedentary behaviour in people with COPD. Respirology. 2016;21(3):419–426. doi:10.1111/resp.12680

    14. Baumgartner RN, Chumlea WC, Roche AF. Bioelectric impedance phase angle and body composition. Am J Clin Nutr. 1988;48(1):16–23. doi:10.1093/ajcn/48.1.16

    15. Hamada R, Tanabe N, Oshima Y, et al. Phase angle measured by bioelectrical impedance analysis in patients with chronic obstructive pulmonary disease: associations with physical inactivity and frailty. Respir Med. 2024;233:107778. doi:10.1016/j.rmed.2024.107778

    16. Holland AE, Spruit MA, Troosters T, et al. An official European respiratory society/American thoracic society technical standard: field walking tests in chronic respiratory disease. Eur Respir J. 2014;44(6):1428–1446. doi:10.1183/09031936.00150314

    17. Miller MR, Hankinson J, Brusasco V, et al. Standardisation of spirometry. Eur Respir J. 2005;26(2):319–338. doi:10.1183/09031936.05.00034805

    18. Sasaki H, Nakamura M, Kida K, et al. Reference values for spirogram and blood gas analysis in Japanese adults. J Jpn Respir Soc. 2001;39:S1–S17.

    19. Nakano Y, Wong JC, de Jong PA, et al. The prediction of small airway dimensions using computed tomography. Am J Respir Crit Care Med. 2005;171(2):142–146. doi:10.1164/rccm.200407-874OC

    20. Yamazaki A, Kinose D, Kawashima S, et al. Predictors of longitudinal changes in body weight, muscle and fat in patients with and ever-smokers at risk of COPD. Respirology. 2023;28(9):851–859. doi:10.1111/resp.14537

    21. Teraž K, Kalc M, Šimunič B, et al. Participation in youth sports influences sarcopenia parameters in older adults. PeerJ. 2023;11:e16432. doi:10.7717/peerj.16432

    22. Tanaka T, Kawahara T, Aono H, et al. A comparison of sarcopenia prevalence between former Tokyo 1964 Olympic athletes and general community-dwelling older adults. J Cachexia, Sarcopenia Muscle. 2021;12(2):339–349. doi:10.1002/jcsm.12663

    23. Hancox RJ, Rasmussen F. Does physical fitness enhance lung function in children and young adults? Eur Respir J. 2018;51(2):1701374. doi:10.1183/13993003.01374-2017

    24. Twisk JW, Staal BJ, Brinkman MN, Kemper HC, van Mechelen W. Tracking of lung function parameters and the longitudinal relationship with lifestyle. Eur Respir J. 1998;12(3):627–634. doi:10.1183/09031936.98.12030627

    25. Hopkinson NS, Bush A, Allinson JP, Faner R, Zar HJ, Agustí A. Early life exposures and the development of COPD across the life course. Am J Respir Crit Care Med. 2024;210(5):572–580. doi:10.1164/rccm.202402-0432PP

    26. Liu WT, Kuo HP, Liao TH, et al. Low bone mineral density in COPD patients with osteoporosis is related to low daily physical activity and high COPD assessment test scores. Int J Chron Obstruct Pulmon Dis. 2015;10:1737–1744. doi:10.2147/COPD.S87110

    27. Furlanetto KC, Pinto IF, Sant’Anna T, Hernandes NA, Pitta F. Profile of patients with chronic obstructive pulmonary disease classified as physically active and inactive according to different thresholds of physical activity in daily life. Braz J Phys Ther. 2016;20(6):517–524. doi:10.1590/bjpt-rbf.2014.0185

    28. Leong DP, Teo KK, Rangarajan S, et al. Prognostic value of grip strength: findings from the Prospective Urban Rural Epidemiology (PURE) study. Lancet. 2015;386(9990):266–273. doi:10.1016/S0140-6736(14)62000-6

    29. Kyomoto Y, Asai K, Yamada K, et al. Handgrip strength measurement in patients with chronic obstructive pulmonary disease: possible predictor of exercise capacity. Respir Investig. 2019;57(5):499–505. doi:10.1016/j.resinv.2019.03.014

    30. Garcia-Aymerich J, Serra I, Gómez FP, et al. Physical activity and clinical and functional status in COPD. Chest. 2009;136(1):62–70. doi:10.1378/chest.08-2532

    31. Yoshimura K, Sato S, Muro S, et al. Interdependence of physical inactivity, loss of muscle mass and low dietary intake: extrapulmonary manifestations in older chronic obstructive pulmonary disease patients. Geriatr Gerontol Int. 2018;18(1):88–94. doi:10.1111/ggi.13146

    32. Mølmen KS, Hammarström D, Falch GS, et al. Chronic obstructive pulmonary disease does not impair responses to resistance training. J Transl Med. 2021;19(1):292. doi:10.1186/s12967-021-02969-1

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  • PDMA issues Glof warning in KP amid heavy rains – Pakistan

    PDMA issues Glof warning in KP amid heavy rains – Pakistan

    The Khyber Pakhtunkhwa Provincial Disaster Management Authority (PDMA) warned on Friday that the risk of glacial lake outburst flood (Glof) has increased in the glacial areas of the province due to heavy rains and flash floods.

    Glof refers to the sudden release of water and debris from a glacial lake, leading to the loss of lives, property and livelihoods in mountain communities. Over 7.1 million people in Gilgit Baltistan and KP are vulnerable, according to the Ministry of Climate Change.

    In an advisory issued today, the PDMA warned that continuous increase in temperature increases the possibility of melting of glaciers and flash floods.

    “The residents of Chitral, Dir, Swat and Kohistan have been instructed to remain alert about possible glacial outbursts. The district administration has been instructed to monitor sensitive areas, ensure timely warning and evacuation drills,” the disaster management agency said.

    The PDMA has advised residents to avoid unnecessary movement near rivers and canals and refrain from taking vehicles into fast-flowing water. It also instructed tourists to remain alert and take precautionary measures.

    The agency said evacuation sites have been set up in potentially affected areas and rescue services have been instructed to remain alert with required emergency equipment.

    The National Highway Authority (NHA), Frontier Works Organisation (FWO), and the Communication and Works Department (CWD) have been instructed to remain alert and take preventive measures for timely restoration of roads.

    The PDMA has instructed district administration to take emergency measures in case of any untoward incident. District authorities have launched awareness campaign to inform the general public about measures to prevent possible losses.

    “The PDMA’s Emergency Operation Centre is fully functional. The public should contact 1700 for further information,” it added.

    The advisory comes heavy rainfall and flash floods across the country that have killed 64 people and injured 117 in a week, according to the National Disaster Management Authority (NDMA).

    The highest toll was in Khyber Pakhtunkhwa with 23 dead, including 10 children, the authority said. Fourteen of the victims were swept away in a flash flood in the Swat Valley last week.

    The PDMA has already warned district administrations across the province about the possibility of flash floods, urban flooding and landslides due to a new spell of monsoon rains from July 5 to 11.

    In an advisory, the PDMA quoted the Pakistan Meteorological Department as revealing that moist currents are penetrating into most parts of the region and likely to intensify in the next couple of days.

    It also said that urban flooding was very likely to happen in low-lying areas of Mardan, Nowshera, Peshawar, Kohat and Dera Ismail Khan, while there’s a likelihood of riverine flooding in Chitral, Swat, Panjkora and Kabul rivers.

    The PDMA said authorities should keep monitoring rivers, streams, local and rainfed nullahs, ensure drainage systems are clear from obstacles to facilitate the efficient flow of water and minimise the risk of urban flooding.

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  • Probiotics improve ovarian damage in premature menopausal mice

    Probiotics improve ovarian damage in premature menopausal mice

    Can probiotics reverse early ovarian decline? A new study in mice suggests they might restore hormonal balance and microbial health after chemotherapy-induced damage.

    Study: Probiotics may improve vaginal microbiota, metabolic disorders and ovarian function-related markers by modulating gut microbiota in POI mice. Image credit: ALIOUI MA/Shutterstock.com

    A study conducted by Nanjing Medical University researchers revealed that probiotics can potentially improve ovarian functions and gut and vaginal microbiota compositions in mice with premature ovarian insufficiency, a condition characterized by early deterioration of ovarian function. The study was published in BMC Microbiology. 

    Background

    Premature ovarian insufficiency (POI) is a condition of premature menopause, causing deterioration of ovarian functions before the age of 40 years. The condition is characterized by abnormal menstruation and hormonal imbalance.

    Women with POI experience a range of short-term and long-term health complications, which collectively affect their mental health and overall quality of life. Apart from increasing the risk of osteoporosis, cardiovascular disease, and cognitive impairment, POI can potentially affect fertility.

    Existing evidence on the pathophysiology of POI indicates that the condition can lead to changes in gut and vaginal microbiota compositions, and that these changes are associated with hormonal imbalance observed in women with POI.

    Given the potential link between microbial composition and POI pathophysiology, researchers at the Nanjing Medical University, China, conducted this study in a chemotherapy-induced mouse model of POI to investigate the effect of probiotics on the composition of gut and vaginal microbiota, markers of ovarian function, and markers of lipid metabolism.

    Probiotics are a class of microorganisms that promote the growth of beneficial bacterial populations and suppress the growth of harmful bacteria. This leads to improvements in gut microbiota and a range of physiological processes in the host’s body. 

    The study

    The researchers generated a mouse model of POI by injecting cyclophosphamide, a chemotherapeutic drug that damages ovarian follicles. They randomly divided these mice into the POI and probiotic-treated POI groups and used healthy mice as controls.

    The mice in the treatment group received a mixture of 12 probiotics for 28 consecutive days, while the control and the POI group mice received normal saline for the same duration.

    Blood samples collected from the mice following treatment completion were analyzed for anti-Müllerian hormone (a crucial hormone for reproductive development) and sex hormone levels, the number of follicles, and serum levels of total cholesterol and triglycerides. The gut and vaginal microbiota compositions were analyzed using fecal and vaginal samples, respectively.

    Key findings

    The analysis of mice with POI revealed significantly lower levels of anti-Müllerian hormone and growing ovarian follicles and significantly higher levels of atretic follicles (degenerated ovarian follicles) than healthy mice. The POI mice also exhibited impairments in gut and vaginal microbiota.

    Regarding the effect of the study intervention, the study reported that 28-day probiotic treatment caused non-significant (P > 0.05) but trending improvements in ovarian function markers, including anti-Müllerian hormone and estradiol levels, in mice with POI. The treated mice also exhibited a slight increase in growing follicle numbers and a notable, though not statistically significant, decrease in degenerated follicle numbers compared to untreated mice with POI.

    The probiotic treatment caused a slight reduction in serum levels of total cholesterol and triglycerides, with a statistically significant decrease observed in triglycerides, indicating possible metabolic improvements in POI mice.

    Regarding microbial compositions, the study found that the probiotic treatment significantly altered the gut microbiota, leading to restoration of microbial compositions to levels that trended towards those of healthy mice.

    While alpha diversity measure of gut and vaginal microbiota did not differ significantly amoung groups (P > 0.05), beta diversity and microbial composition showed notable shifts with probiotic treatment.

    Probiotic treatment also increased the abundance of beneficial bacteria in the vagina, particularly Rodentibacter, with bacterial populations even exceeding those in the control group; however, the health implications of this increase require further study.

    Study significance

    The study highlights that probiotics may help mitigate ovarian dysfunction, improve lipid metabolism, and restore vaginal microbiota homeostasis in POI mice by modulating gut microbiota composition.

    Existing evidence regarding reproductive endocrine diseases suggests a link between gut and vaginal microbiota disruption, which in turn is associated with the progression and outcome of diverse reproductive endocrine disorders, including polycystic ovary syndrome and endometriosis. The gut microbiota plays a vital role in shaping various physiological functions, including immune, neurological, metabolic, and endocrine functions. Recent evidence indicates that both gut and vaginal microbiotas are involved in the regulation of sex hormones and female reproductive system.

    Scientific literature also documents that gut microbiota alterations can remotely affect vaginal immunity through the modulation of circulating immune cells. Gut microbiota-derived metabolites, such as short-chain fatty acids, can reach the vagina through circulation and modulate the vaginal microenvironment.

    Given the study findings, the researchers suggest that probiotics could offer a promising avenue for future therapeutic development. However, they emphasize that clinical trials in humans are needed to confirm these effects. The current results are based on a preclinical mouse model, and direct clinical application in women with POI is not yet supported by sufficient evidence.

    Probiotics may help alleviate clinical symptoms, such as atrophic vaginal inflammation and metabolic syndrome, and improve long-term quality of life in women living with POI.

    Future studies should focus on exploring specific mechanisms involved in probiotic-mediated regulation of microbial composition and improvement of ovarian functions to clinically establish the therapeutic potential of probiotics in patients with chemotherapy-induced ovarian insufficiency. The researchers noted that clinical studies in human populations are currently underway.

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  • Accelerating Industrial Digital Intelligence in South Africa at Huawei South Africa Connect 2025

    [Johannesburg, South Africa, July 3, 2025] Huawei held the Huawei South Africa Connect 2025 in Johannesburg, South Africa. Themed Accelerate Industrial Digital Intelligence for South Africa, this event attracted over 2,900 participants from the South African government, industry customers, and partners.

    South Africa has placed digital inclusion at the heart of its developmental agenda. At the event, Solly Malatsi, Hon. Minister of the Department of Communications and Digital Technologies noted that South Africa has developed four measurable Ministerial Priorities: Expanding Connectivity and Access to Devices, Building a Digitally Skilled Society, Unlocking the Productive Use of Technology, and Creating a Supportive Environment for Inclusion and Investment. These four priorities aim to build an innovative and high-performing digital ecosystem for all South Africans.

    Solly Malatsi, Hon. Minister of the Department of Communications and Digital Technologies, delivering a speech

    Will Meng, CEO of Huawei South Africa, stated in his welcome speech, that “Digital transformation is more than technology — It’s the engine of national progress. Our goal is clear: to accelerate South Africa’s journey to industrial digital intelligence, driving innovation, boosting productivity, and ensuring long-term competitiveness.”

    Will Meng, CEO of Huawei South Africa, delivering a welcome speech

    Cloud and AI are a key driving force for industry innovation and economic growth. Joy Huang, Vice President of Huawei Cloud, expressed that ” Huawei Cloud is dedicated to offering AI-native cloud services. By implementing the ‘Cloud for AI’ and ‘AI for Cloud’ strategies, we aim to expedite the intelligent transformation across industries in South Africa.” 

    Joy Huang, Vice President of Huawei Cloud, delivering a keynote speech

    Hong-Eng Koh, Global Chief Public Services Industry Scientist of Huawei, agreed; “From a technological angle, gone are the days of siloed implementations. We need a long-term architecture for the intelligent transformation journey, including unified networks and unified clouds.” Huawei has accumulated extensive digital transformation practices globally, which provide concrete and feasible pathways for intelligent upgrade. It aims to use its expertise to contribute to South Africa’s digital economic development.

    Gene Zhang, CEO of Huawei South Africa Enterprise Business, further introduced that Huawei, with its All Intelligence strategy and a deep understanding of industry scenarios, has released a reference architecture, 4 enablement models, and over 200 industry solutions to help various industries go digital and intelligent faster.

    Gene Zhang, CEO of Huawei South Africa Enterprise Business, delivering a keynote speech

    Digital and intelligent advancement relies on ecosystem building and cooperation with partners. Peter Zhang, Vice President of Global Partner, Commercial & Distribution, Enterprise Sales, Huawei, underscored in his speech, “Our strategy in the government and enterprise market is ‘Partners + Huawei’. Huawei attaches great importance to partner development and will constantly enhance investment and support for partners.”
    In South Africa, Huawei has collaborated with over 1,400 local companies to jointly address customers’ digital and intelligent transformation needs. 
    Additionally, leveraging over 3,000 courses covering 22 technical categories, Huawei aims to train over 50,000 ICT professionals in the region by 2028.

    At the event, Jonas Bogoshi, CEO of BCX, and customers from sectors like government, transportation, electric power, finance, and ISP, shared their success stories of digital and intelligent transformation.

    With a slogan of “In South Africa, for South Africa,” Huawei has been doing business in this country for 26 years. Huawei has consistently provided leading ICT infrastructure on top of talent development and technological innovation platforms to further the development of South Africa’s digital and intelligent economy. Moving forward, Huawei will continue to work closely with customers and partners, gain profound insights into industry scenarios and needs, provide customized solutions, and jointly build a thriving ecosystem.

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  • Pakistan PM, Azerbaijan president vow to boost trade and investment on ECO summit sidelines

    Pakistan PM, Azerbaijan president vow to boost trade and investment on ECO summit sidelines

    Pakistan to use $1.4 billion climate loan to expand green investment, fiscal space — IMF


    KARACHI: Pakistan will use a $1.4 billion loan from the International Monetary Fund’s climate resilience fund to expand fiscal space, embed climate planning into public investment decisions and unlock private-sector capital for green projects, the IMF said on Friday.


    The financing, approved by the IMF’s Executive Board in May under its Resilience and Sustainability Facility (RSF), is part of a broader reform program that aims to help Pakistan adapt to increasingly frequent and devastating climate shocks.


    Pakistan is the first country in the Middle East and Central Asia region to access the IMF’s Resilience and Sustainability Facility. The fund was launched in 2022 to help climate-vulnerable low- and middle-income countries make the structural changes needed to protect their economies and populations.


    “The RSF will help build climate resilience in Pakistan by creating fiscal space to address climate vulnerabilities, such as the need to improve climate-resilient adaptation infrastructure,” the IMF’s country office in Islamabad told Arab News in a written response.


    “It will also boost climate’s prominence in public investment management and budget processes,” the statement said, “helping Pakistan better identify and target projects needed to strengthen resilience to climate shocks.”


    A third pillar of the reforms, the IMF said, is improving the overall “enabling environment for green investment” so that banks and private firms could incorporate climate-related risk considerations into their risk management and investment activities.


    The RSF financing will be disbursed over a 28-month period and runs alongside Pakistan’s $7 billion Extended Fund Facility (EFF), whose first review was also approved in May, releasing roughly $1 billion in immediate support.


    CLIMATE-FINANCE GAP


    Pakistan, one of the world’s most climate-vulnerable countries, has long struggled to align its public finances with the scale of climate risk it faces. The 2022 floods alone affected over 33 million people and caused more than $30 billion in damages and economic losses.


    By reforming how climate priorities are reflected in budget planning and investment screening, the IMF says Pakistan will be better equipped to attract funding and respond to future disasters.


    The RSF does not fund individual infrastructure projects. Instead, it supports “policy and institutional reforms that make climate action more effective,” the statement explained.


    These include reforms in disaster coordination, water and irrigation infrastructure, and provincial implementation capacity.


    The IMF program supports better coordination between the federal and provincial governments on disaster risk financing, a chronic weakness in past emergency responses, and policy changes that would strengthen water and irrigation management, the lender added in the statement.


    “Policy reforms that directly target Pakistan’s water management and irrigation infrastructure would help make farmers more resilient to climate shocks,” it said, adding the focus would be on improving irrigation service standards, reliability, and water supply adequacy.


    The reforms also aim to reduce waterlogging, salinity, groundwater depletion, and growing water insecurity, issues that disproportionately impact poor rural communities.


    The IMF said its climate program in Pakistan takes a “whole-of-government” approach, with many reforms to be implemented at the provincial level.


    “Much of the focus is on improving coordination mechanisms between the federal government and the provinces.”

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  • Photo Gallery: TNA iMPACT! July 3, 2025 – TNA Wrestling

    1. Photo Gallery: TNA iMPACT! July 3, 2025  TNA Wrestling
    2. TNA iMPACT! Results: July 3, 2025  TNA Wrestling
    3. Masha Slamovich Defends The Knockouts Title On Tonight’s TNA IMPACT!  theringreport.com
    4. TNA iMPACT 7/3 Recap:Trick Williams Takes Out Joe Hendry And Mike Santana  Yardbarker
    5. International title match booked for next TNA Impact  F4W/WON

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  • Safety Profiles of Contezolid versus Linezolid in the Treatment of Rif

    Safety Profiles of Contezolid versus Linezolid in the Treatment of Rif

    Introduction

    Tuberculosis (TB) is a chronic respiratory infectious disease that seriously threatens human health and the quality of life. According to the Global Tuberculosis Report 2023, approximately 10 million new TB cases were reported worldwide, of which 748000 were in China, making China a country with high TB and rifampicin-resistant tuberculosis (RR-TB)/multidrug-resistant TB (MDR-TB) burden.1 Long-term treatment is usually required to manage TB patients, which makes them prone to treatment noncompliance and drug resistance. The introduction of new drugs, such as bedaquiline and delamanid, into clinical practice has contributed to the control of MDR-TB,2 but more innovative drugs are still required to further improve the management of MDR-TB.

    Linezolid is the first generation of oxazolidinone drug and is mainly used for gram-positive bacterial infections. Linezolid also has good efficacy in the treatment of MDR-TB.3 Therefore, both the WHO Consolidated Guidelines on Drug-resistant Tuberculosis Treatment and Chinese expert consensus on the all-oral treatment of drug-resistant pulmonary tuberculosis have adopted linezolid as a core drug for the treatment of drug-resistant TB since 2019.4,5 In particular, the Nix-TB study published in the New England Journal of Medicine in 2020 confirmed that the treatment success rate of the new drug regimen, including linezolid, pretomanid, and bedaquiline, reached 90% for the treatment of MDR-TB.6 However, a high percentage of patients had adverse events (AEs) related to linezolid in the Nix-TB trial. Myelosuppression (anemia, leukopenia, and thrombocytopenia) was reported in 49% of the patients, and peripheral neuropathy was reported in 81% of the patients receiving linezolid-containing anti-TB regimen; only 15% of the patients completed the 26-week course of linezolid without interruption or a reduction of 1200 mg/day,6 which severely limits the long-term use of linezolid. About 29% of patients discontinued linezolid due to adverse drug reactions in real-world settings. Linezolid-related myelosuppression frequently occurs within the first 2 months of treatment in most cases. Findings from programmatic experience in field conditions have also demonstrated similar results. A recent study conducted under programmatic conditions focused on a WHO-endorsed bedaquiline-containing all-oral regimen for MDR-TB treatment. Linezolid, serving as a key component of this regimen, was associated with adverse drug reactions in 42.45% of patients. Among these, 93.33% experienced peripheral neuropathy – an agonizing adverse reaction for people with MDR-TB in field conditions, often compromising their treatment outcomes.7 Therefore, there is an urgent need to develop safer drugs and regimens to address MDR-TB.

    Contezolid is a new generation of oxazolidinone antibiotics originally developed and approved in China.8 Contezolid has shown good in vitro activity against M. tuberculosis strains (MIC50/MIC90 = 0.5/1 mg/L).9,10 Additionally, the good antimicrobial activity is maintained and the safety profile is optimized for contezolid by improving its structure-activity relationship. Short-term treatment clinical trials also suggest a better safety profile than that observed with linezolid.11 However, safety information on clinical use of contezolid is still limited. We conducted a randomized, active-controlled trial of contezolid vs linezolid in combination with other anti-TB drugs for the treatment of drug-resistant TB to characterize the safety and tolerability of contezolid treatment for two months.

    Patients and Methods

    Study Design

    This study was designed as a randomized, active-controlled trial in patients with RR-TB who were treated at the Tuberculosis Department of Beijing Chest Hospital Affiliated to Capital Medical University from August 1, 2023, to March 31, 2024. The study protocol and informed consent form were reviewed and approved by the Institutional Review Board for Human Investigation of Beijing Chest Hospital of Capital Medical University (approval no. YJS-2021-022). This study was registered at https://www.chictr.org.cn (identifier: ChiCTR2300074234) on August 1, 2023. The study was conducted in accordance with the Declaration of Helsinki and Good Clinical Practice guidelines.

    Patients

    All participants voluntarily participated in this study. Enrolled patients were randomized using a randomization table based on block randomization after signing an informed consent form. The inclusion criteria included 18–65 (inclusive) years of age and diagnosis of RR-TB based on molecular biology methods, and admission to the hospital to receive initial anti-TB treatment or retreatment. The patient did not show fluoroquinolone resistance based on a line probe assay (LPA). An acid-fast bacteria (AFB) smear was positive (at least 1+) in sputum samples. Patients receiving treatment with other anti-TB drugs were willing to discontinue all anti-TB drugs and agreed to undergo a 7-day wash-out period. The patients were closely monitored to address the concerns regarding potential disease progression or worsening symptoms during the 7-day wash-out.

    Subjects were excluded if they met any of the following criteria: (1) A history of allergy to the study drug or any of its components, or an effective treatment plan was not available; (2) complicated with severe comorbidities such as respiratory failure, cardiac insufficiency, or liver and kidney dysfunction (serum creatinine level, ALT and/or AST levels higher than three times the upper limit of normal [ULN]); (3) significant electrocardiogram abnormalities (QT interval prolongation > 430 ms for males, or > 450 ms for females); (4) severe cardiovascular or cerebrovascular diseases; (5) pregnant or lactating women; (6) participation in any other clinical trial within three months before initiation of this study; and (7) positive for HIV antibody or AIDS patients.

    Anti-TB Regimens

    Patients were randomly assigned to receive linezolid or contezolid in combination with other background anti-TB drugs, such as linezolid-bedaquiline (pyrazinamide)-levofloxacin (moxifloxacin)-cycloserine-clofazimine or contezolid-bedaquiline (pyrazinamide)-levofloxacin (moxifloxacin)-cycloserine-clofazimine. Anti-TB drugs were purchased from the same manufacturer and provided in the same dosage form and strength. The specific dosage was linezolid 600 mg q12h, contezolid 800 mg q12h, bedaquiline 400 mg/d for 2 weeks, adjusted to 200 mg three times per week, moxifloxacin 400 mg/d, levofloxacin 600 mg/d, cycloserine 250 mg bid, and clofazimine 100 mg/d.

    Safety Assessment

    All patients were closely monitored during the treatment period for the occurrence and progression of AEs, including clinical symptoms, vital signs, electrocardiogram findings, and laboratory test abnormalities. Hematology tests, urinalysis, and biochemical assays, including liver and kidney function tests, were performed for all patients every two weeks. The clinical characteristics, severity, onset time, duration, management, and outcome of AEs were documented and drug relatedness was evaluated. The risk factors for AEs were also analyzed. The frequency of dose reduction or discontinuation owing to AEs was also evaluated.

    All AEs were coded and graded according to the Common Terminology Criteria for Adverse Events (CTCAE) version 5.0.12 Grade 1 AE was defined as mild, asymptomatic, or mild symptoms; clinical or diagnostic observations only; and intervention not required. Grade 2 AE was defined as moderate, minimal, local, or noninvasive intervention indicated and limiting age-appropriate instrumental activities of daily living. Grade 3 AE was defined as severe or medically significant but not immediately life-threatening, hospitalization or prolongation of hospitalization indicated, disabling, and limiting self-care activities of daily living. Grade 4 AE was defined as life-threatening consequences and urgent intervention was indicated. Grade 5 AE was defined as death related to AE.

    Anti-TB Efficacy Monitoring

    Anti-TB efficacy was analyzed in terms of microbiology diagnostic testing and imaging examinations. All patients underwent monthly sputum smear tests for AFB and sputum cultures for Mycobacterium tuberculosis. Chest CT scan was scheduled for all the patients at the end of the second month of treatment.

    Statistical Analysis

    Sample size calculation was based on superiority study design. The patients were randomly assigned to contezolid or linezolid group at a ratio of 1:1. Contezolid is expected to be safer than linezolid. The sample size was calculated using the following formula:

    Set α = 0.05, 1- β = 0.80,


    In our experience, the expected incidence of AEs was 2.5% in contezolid group and 49% in linezolid group, based on the safety profiles of such regimens. At least 10 evaluable cases were required in contezolid and linezolid groups to test the superiority of contezolid, assuming two-sided α = 0.05, β = 0.2, superiority threshold δ = 15%, and a 20% dropout rate.

    Statistical analyses were conducted using SPSS 24.0 software. Data are expressed as mean ± standard deviation (SD) and compared between groups using Student’s t test or Wilcoxon’s signed rank test. The incidence of AEs was compared between groups using Chi-square test or Mehta’s modification of Fisher’s exact test.

    Results

    Baseline Patient Characteristics

    A total of 35 smear-positive RR-TB patients were screened, and 29 patients were enrolled and randomized to receive treatment at Beijing Chest Hospital from August 1, 2023 to March 31, 2024. Of the 15 patients treated with contezolid, one patient was excluded from the analysis due to rifampicin-susceptible TB. One of the 14 patients in linezolid group was excluded from the analysis because of withdrawal of informed consent. Finally, 14 patients in contezolid group and 13 patients in linezolid group completed the study and were included in the safety analysis (Figure 1).

    Figure 1 Disposition of the patients in the study.

    Abbreviation: RR-TB, rifampicin-resistant tuberculosis.

    The median (range) age was 40.9 (26–65) years for the patients in contezolid group, and 36.7 (18–64) years for the patients in linezolid group. The baseline characteristics of the two groups of patients were comparable (Table 1).

    Table 1 Demographic and Clinical Characteristics of Rifampicin-Resistant Tuberculosis Patients Receiving Contezolid or Linezolid for Anti-TB Treatment

    AE Profiles of Contezolid Versus Linezolid

    Overall, the incidence of treatment-emergent AEs (TEAEs) was 14.3% (2/14) in contezolid-treated patients and 92.3% (12/13) in linezolid group (P < 0.05). The most common TEAEs were peripheral neuropathy, myelosuppression, and gastrointestinal reactions in linezolid group, but only gastrointestinal reactions in contezolid-treated patients (Table 2).

    Table 2 Treatment-Emergent Adverse Events of Contezolid and Linezolid During Anti-TB Treatment for 2 months

    Patients in contezolid group did not experience any AEs related to bone marrow suppression (anemia, neutropenia, or thrombocytopenia) during the 2-month treatment period. AEs related to bone marrow suppression (anemia) were observed in 4 patients in linezolid group (30.8%), all of which were Grade 2 or higher (hemoglobin levels reduced from 132 to 48 g/L, 112 to 86 g/L, 142 to 59 g/L, and 128 to 89 g/L, respectively). Specifically, 2 cases (15.3%) of Grade 2 anemia completely resolved after linezolid dose reduction to 600 mg/day. One case of Grade 3 anemia occurred in a patient after linezolid treatment for one month. The patient discontinued linezolid and received blood transfusion. The remaining one case of Grade 4 anemia (hemoglobin level reduced from 132 g/L to 48 g/L) developed two months after linezolid treatment. The patient was managed with blood transfusion and permanent discontinuation of linezolid.

    Peripheral neuropathy was not observed in any patient who received contezolid. Peripheral neuropathy (numbness and/or tingling in the limbs) was observed in 7 patients in the linezolid group (53.8%). Most of these cases (6/7) were Grade 2 AEs and the remaining one case was Grade 3. Two of these patients discontinued linezolid treatment due to concurrent Grade 4 and Grade 3 anemia, respectively. The peripheral neuropathy of these two patients was also resolved after discontinuation of linezolid. The peripheral neuropathy AE in three patients were not relieved, even after linezolid dose was reduced to 600 mg qd. Linezolid dose was reduced to 600 mg/day in one patient because of gastrointestinal reactions after treatment for 20 days. One month later, this patient experienced finger numbness. The symptoms did not resolve during treatment at this dose. One patient (7.7%) developed Grade 3 AE one and half months after linezolid treatment. The symptoms were partially resolved after permanent discontinuation of linezolid.

    Two patients (14.3%) in contezolid treatment group developed Grade 2 gastrointestinal AEs. All symptoms were resolved completely after the dose was reduced to 400 mg q12h. Three patients (23.1%) in linezolid group experienced Grade 2 gastrointestinal AEs. All symptoms were resolved completely after the linezolid dose was reduced to 600 mg/day.

    In summary, contezolid showed significantly lower incidence rates than linezolid for myelosuppression and peripheral neuropathy but not for gastrointestinal AEs. Furthermore, dose reduction or discontinuation owing to AEs was observed for linezolid in most patients (84.6%, 11/13).

    Sputum Smear Conversion After 2-month Treatment

    Both contezolid-containing and linezolid-containing anti-TB regimens showed good clinical efficacy. Overall, the sputum negative conversion rate was 92.9% (13/14) in contezolid group and 92.3% (12/13) in linezolid group. The imaging-confirmed lesion absorption rate was 85.7% (12/14) in contezolid group and 84.6% (11/13) in linezolid group. The clinical efficacy was similar between contezolid-containing and linezolid-containing regimens (Table 3).

    Table 3 Anti-Tuberculosis Effect of Contezolid-Containing Versus Linezolid-Containing Regimens for Rifampicin-Resistant Tuberculosis Patients

    Discussion

    Contezolid is an innovative drug of a new generation of oxazolidinone antibiotics. It is derived from structural modification of linezolid to form a non-coplanar structure between the B ring and the A and C rings, which makes the structure-activity relationship of contezolid more favorable in terms of safety and efficacy. Structural modification enables contezolid with enhanced binding to bacterial target and so reduced risk of drug resistance, leading to more efficient antimicrobial activity.13 The optimized structure of contezolid is associated with lower somatic and mitochondrial permeability, and thus, the normal function of mitochondria is not damaged, which may effectively reduce the side effects of bone marrow suppression. The National Medical Products Administration of China approved contezolid in 2021 for the treatment of infections caused by susceptible pathogens after pivotal Phase III clinical trials in China provided favorable and supporting data.14–17

    Shoen et al demonstrated that contezolid was similar to linezolid in the in vitro and in vivo anti-TB activities in mouse infection models against drug-sensitive and drug-resistant M. tuberculosis.9 However, the safety and efficacy of contezolid treatment for MDR-TB patients have not yet been evaluated in China at present time. The Nix-TB trial targeting MDR-TB has shown that most of the adverse reactions of linezolid occur after treatment for approximately 8 weeks.18 Therefore, linezolid was used as the control group in this study to monitor the occurrence of any AEs during the 2-month anti-TB treatment with contezolid- or linezolid-containing regimens.

    In this study, during the 2-month anti-TB treatment period, TEAE was reported in 12 of 13 subjects receiving linezolid treatment (92.3%). All AEs were considered to be related to linezolid treatment. Eleven of the 12 patients underwent dose reduction or discontinuation of linezolid owing to adverse drug reactions. Only one patient continued to complete 2-month treatment with linezolid at a dose of 600 mg q12h. Linezolid-related AEs included anemia, peripheral neuropathy, and gastrointestinal reactions. All AEs occurred 1–2 months after the initiation of linezolid treatment. In contrast, AE was reported in 14.3% (2/14) of the patients receiving contezolid. All AEs were gastrointestinal reactions, one case each of nausea and vomiting. Both AEs were related to contezolid and occurred within one month after the initiation of contezolid treatment. The symptoms were resolved after reducing the contezolid dose to 400 mg q12h. Contezolid was associated with a significantly lower incidence of bone marrow suppression and peripheral neuropathy AEs compared with linezolid. Our data support the good safety of contezolid in the treatment of patients with TB. These findings are consistent with those of previous reports on contezolid regimens for the treatment of TB patients.19–23

    The results of this study indicated that the sputum negative conversion rate (92.9%) after treatment with contezolid-containing regimens for two months was comparable to that in patients treated with linezolid-containing regimens (92.3%). Contezolid-containing anti-TB regimens and linezolid-containing regimens showed similar clinical efficacy in terms of sputum negative conversion rate and imaging-confirmed pulmonary lesion absorption rate.

    This study has some limitations, such as the small sample size, single-center design, relatively short treatment duration of anti-TB regimens, potential selection bias, and the effect of background anti-TB drugs. Especially, the dosage of linezolid used in this study (600 mg q12h) exceeds the current WHO recommended dose of 600 mg/day for MDR-TB treatment. Following the Nix-TB trial, the ZeNix trial demonstrated that reducing both the dose and duration of linezolid to 600 mg/day for 26 weeks was associated with statistically significant treatment success. The higher dose used in this study may have contributed to the elevated adverse drug reaction rate (92.3%) observed in the linezolid group.24,25 These limitations could impact the generalizability of the study conclusion. Therefore, adequate-designed multi-center clinical trials are needed to confirm the utility of contezolid versus linezolid for the long-term treatment of MDR-TB.

    Conclusion

    Preliminary data in this randomized controlled study further support that contezolid has a safer safety profile than linezolid in combination with other background anti-TB drugs for a 2-month treatment of patients with MDR-TB. Both drugs showed similar anti-TB efficacy. However, the long-term safety beyond the 2-month window is unclear yet. Contezolid is safer based on the body of evidence available even though small sample size in this study may weaken the robustness and generalizability of the conclusion. Adequate-designed multicenter long-term clinical trials are required to confirm our findings.

    Data Sharing Statement

    The original data have been included in this article. Further inquiries can be directed to the corresponding author.

    Ethics Approval and Consent to Participate

    This study was approved by the Ethics Committee of Beijing Chest Hospital of Capital Medical University (approval no. YJS-2021-022). Informed consent was obtained from all participants.

    Acknowledgments

    We would like to thank the sample bank of Beijing Chest Hospital, Capital Medical University, Beijing Tuberculosis, and Thoracic Tumor Research Institute for supporting this study.

    Funding

    This research was supported by Special “Sailing” Plan for Clinical Medical Development (Grant number: ZLRK202331) and the National Natural Science Foundation of China (Grant number: 8210002).

    Disclosure

    The authors declared no potential conflict of interest with respect to the research, authorship, and/or publication of this article.

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    2. Hafkin J, Hittel N, Martin A, Gupta R. Early outcomes in MDR-TB and XDR-TB patients treated with delamanid under compassionate use. Eur Respir J. 2017;50(1):1700311. doi:10.1183/13993003.00311-2017

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    12. U.S. Department of Health and Human Services. Common Terminology Criteria for Adverse Events (CTCAE). Version 5.0. Available from: https://ctep.cancer.gov/protocoldevelopment/electronic_applications/docs/ctcae_v5_quick_reference_5x7.pdf. Accessed June 1, 2023.

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    15. Zhao X, Huang H, Yuan H, Yuan Z, Zhang Y. A Phase III multicentre, randomized, double-blind trial to evaluate the efficacy and safety of oral contezolid versus linezolid in adults with complicated skin and soft tissue infections. J Antimicrob Chemother. 2022;77(6):1762–1769. doi:10.1093/jac/dkac073

    16. Wu J, Yang X, Wu J, et al. Dose adjustment not required for contezolid in patients with moderate hepatic impairment based on pharmacokinetic/pharmacodynamic analysis. Front Pharmacol. 2023;14:1135007. doi:10.3389/fphar.2023.1135007

    17. Wu J, Wu H, Wang Y, et al. Tolerability and pharmacokinetics of contezolid at therapeutic and supratherapeutic doses in healthy Chinese subjects, and assessment of contezolid dosing regimens based on pharmacokinetic/pharmacodynamic analysis. Clin Ther. 2019;41(6):1164–74.e4. doi:10.1016/j.clinthera.2019.04.025

    18. Solans BP, Imperial MZ, Olugbosi M, Savic RM. Analysis of dynamic efficacy endpoints of the Nix-TB Trial. Clin Infect Dis. 2023;76(11):1903–1910. doi:10.1093/cid/ciad051

    19. Wang J, Nie W, Ma L, et al. Clinical utility of contezolid-containing regimens in 25 cases of linezolid-intolerable tuberculosis patients. Infect Drug Resist. 2023;16:6237–6245. doi:10.2147/IDR.S425743

    20. Xu Z, Zhang J, Guan T, et al. Case report: successful treatment with contezolid in a patient with tuberculous meningitis who was intolerant to linezolid. Front Med. 2023;10:1224179. doi:10.3389/fmed.2023.1224179

    21. Li J, Yu Z, Jiang Y, Lao S, Li D. Rare tuberculosis in recipients of allogeneic hematopoietic stem cell transplantation successfully treated with contezolid-a typical case report and literature review. Front Cell Infect Microbiol. 2023;13:1258561. doi:10.3389/fcimb.2023.1258561

    22. Guo W, Hu M, Xu N, et al. Concentration of contezolid in cerebrospinal fluid and serum in a patient with tuberculous meningoencephalitis: a case report. Int J Antimicrob Agents. 2023;62(2):106875. doi:10.1016/j.ijantimicag.2023.106875

    23. Yang M, Zhan S, Fu L, Wang Y, Zhang P, Deng G. Prospects of contezolid (MRX-I) against multidrug-resistant tuberculosis and extensively drug-resistant tuberculosis. Drug Discov Ther. 2022;16(2):99–101. doi:10.5582/ddt.2022.01025

    24. Mishra G. Nix-TB and ZeNix trials: paving the way for shorter regimens for drug-resistant tuberculosis. Asian Pac J Trop Med. 2021;14(10):431–432. doi:10.4103/1995-7645.329004

    25. WHO Handbook on Tuberculosis. Module 4: treatment – Drug-Resistant Tuberculosis Treatment. Geneva: World Health Organization, 2020. Available from: https://www.who.int/publications/i/item/9789240069236. Accessed December 30, 2024.

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  • European Innovation Council (EIC) Pre-Accelerator Online Info Session

    European Innovation Council (EIC) Pre-Accelerator Online Info Session

    The European Innovation Council (EIC) is organising an online information session dedicated to EIC Pre-Accelerator on July 23, 2025.

    This online info session will present the EIC Pre-Accelerator call – a joint scheme between the European Innovation Council and the Widening participation and strengthening the European Research Area (WIDERA) programme funded under the WIDERA Work Programme 2025.

    The speakers will present an overview and key features of the scheme and will answer questions from the attendees.

    The event will be held in English and recorded. 

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  • Mecha BREAK launches globally, but faces player criticism · TechNode

    Mecha BREAK launches globally, but faces player criticism · TechNode

    Mecha BREAK, a sci-fi mecha shooter game developed by Chinese studio Seasun Games, launched globally on Wednesday across PC, PlayStation 5, and Xbox platforms. Touted as a beacon of hope for AAA-quality Chinese mecha games, the title saw a peak of over 130,000 concurrent players on Steam in the past two days.

    Despite (or perhaps because of) the hype, Mecha BREAK has received a tepid reception from players so far, holding a mixed rating on Steam with over 6,000 reviews and a modest 63% approval rate.

    Diverse mecha designs and gameplay modes

    Set in a near-future world ravaged by the carbon-silicon substance EIC, Mecha BREAK follows elite mech pilots fighting to save humanity from an escalating existential threat. The game features three core gameplay modes: 6v6 Edge Battlefield (strategy-focused team combat), 3v3 Ace Sequence (death-match), and PvPvE Marsh Mark (loot-and-extract survival mode).

    Mecha BREAK is free-to-play but offers in-game purchases for game skins, season passes, gears, extra bonuses, and other premium content. The current version offers 12 free mechs. They are divided into five roles: assault, melee, sniper, defense, and support. Each mech also falls into a weight class of light, medium, or heavy, which affects its movement speed, armor durability, and skill cooldowns.

    UI issues disrupt the experience

    Many players on Steam have criticized the user interface, describing it as cluttered, confusing, and poorly organized. Key functions are buried in deep menu layers, while overlapping prompts create an overwhelming experience, especially for first-time players.

    Poor color contrast and low icon recognizability, combined with interaction logic that ignores typical PC game conventions, have led some players to complain that the game “feels like a mobile UI ported directly to PC.” 

    Monetization discomfort and unsatisfying combat feedback

    Early Steam reviews have also voiced strong dissatisfaction with the game’s monetization approach, particularly the instant pop-up of a RMB 288 ($40) limited-time offer immediately after the tutorial. Some players argued that the early emphasis on spending detracts from the gameplay experience and breaks immersion.

    In an interview with TechNode, an online gamer known as Phantom Core criticized the game’s combat compared to titles such as Armored Core VI. He described the hit feedback as “plastic”, saying that the sound and visual effects are not properly matched and that the attack impacts are underwhelming. 

    Core gameplay balance faces questions

    The game’s 6v6 battlefield mode has drawn criticism for balance issues. Steam players report a clear disparity in mech performance, which makes fair competition difficult. Heavier defense-focused mechs offer disproportionately high firepower and survivability, whereas lighter units intended as assassins are under-powered and poorly tuned, Phantom Core said.

    The PvPvE (Player vs Player vs Environment) mode also brought complaints on Steam for resource imbalances. Players who invest more time or money can quickly power up their mechs via boss drops and lootable upgrades, while average players fall behind in progression. This system translates directly into PvP combat power gaps, leading to a “grind (or spend) more, win more” experience that widens the divide between veteran and new players, Phantom Core explained.

    Can Mecha BREAK defy the drop?

    Despite ongoing controversy around the title, the development team is expected to continue refining the gameplay and system mechanics in response to player feedback. Whether the game can break away from the common pattern of early hype followed by rapid decline and disappointment remains to be seen.

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