Category: 3. Business

  • Ricoh recognized as a Prime Seat Company in the 2025 Nikkei SDGs Management Grand Prix | Global

    Ricoh recognized as a Prime Seat Company in the 2025 Nikkei SDGs Management Grand Prix | Global

    Ricoh is a leading provider of integrated digital services and print and imaging solutions designed to support digital transformation of workplaces, workspaces and optimize business performance.

    Headquartered in Tokyo, Ricoh’s global operation reaches customers in approximately 200 countries and regions, supported by cultivated knowledge, technologies, and organizational capabilities nurtured over its 85-year history. In the financial year ended March 2025, Ricoh Group had worldwide sales of 2,527 billion yen (approx. 16.8 billion USD).

    It is Ricoh’s mission and vision to empower individuals to find Fulfillment through Work by understanding and transforming how people work so we can unleash their potential and creativity to realize a sustainable future.

    For further information, please visit

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    © 2025 RICOH COMPANY, LTD. All rights reserved. All referenced product names are the trademarks of their respective companies.

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  • Hou, K. et al. Microbiota in health and diseases. Signal Transduct. Target. Ther. 7, 135 (2022).

    Google Scholar 

  • Aguilar-Lopez, M., Dinsmoor, A. M., Ho, T. T. B. & Donovan, S. M. A systematic review of the factors influencing microbial colonization of the preterm infant gut. Gut Microbes 13, 1–33 (2021).

    Google Scholar 

  • DeVeaux, A., Ryou, J., Dantas, G., Warner, B. B. & Tarr, P. I. Microbiome-targeting therapies in the neonatal intensive care unit: safety and efficacy. Gut Microbes 15, 2221758 (2023).

    Google Scholar 

  • Staude, B. et al. The microbiome and preterm birth: a change in paradigm with profound implications for pathophysiologic concepts and novel therapeutic strategies. Biomed. Res. Int. 2018, 7218187 (2018).

    Google Scholar 

  • Bårdsen, T. et al. Impaired lung function in extremely preterm-born adults in their fourth decade of life. Am. J. Respir. Crit. Care Med. 208, 493–495 (2023).

    Google Scholar 

  • Islam, J. Y., Keller, R. L., Aschner, J. L., Hartert, T. V. & Moore, P. E. Understanding the short- and long-term respiratory outcomes of prematurity and bronchopulmonary dysplasia. Am. J. Respir. Crit. Care Med. 192, 134–156 (2015).

    Google Scholar 

  • Bårdsen, T. et al. Tracking of lung function from 10 to 35 years after being born extremely preterm or with extremely low birth weight. Thorax 77, 790–798 (2022).

    Google Scholar 

  • Lee, D. M. X., Tan, A. K. S., Ng, Y. P. M. & Amin, Z. Quality of life of patients and caregivers affected by bronchopulmonary dysplasia: a systematic review. Qual. Life Res. 32, 1859–1869 (2023).

    Google Scholar 

  • Horbar, J. D. et al. Trends in mortality and morbidities for infants born 24 to 28 weeks in the US: 1997–2021. Pediatrics 153, e2023064153 (2024).

    Google Scholar 

  • Holzfurtner, L. et al. When inflammation meets lung development-an update on the pathogenesis of bronchopulmonary dysplasia. Mol. Cell Pediatr. 9, 7 (2022).

    Google Scholar 

  • Pammi, M. et al. Airway microbiome and development of bronchopulmonary dysplasia in preterm infants: a systematic review. J.Pediatr. 204, 126-133.e2 (2019).

    Google Scholar 

  • Young, K. C., Del Moral, T., Claure, N., Vanbuskirk, S. & Bancalari, E. The association between early tracheal colonization and bronchopulmonary dysplasia. J. Perinatol. 25, 403–407 (2005).

    Google Scholar 

  • Mourani, P. M., Harris, J. K., Sontag, M. K., Robertson, C. E. & Abman, S. H. Molecular identification of bacteria in tracheal aspirate fluid from mechanically ventilated preterm infants. PloS one 6, e25959 (2011).

    Google Scholar 

  • Ehrhardt, H. et al. Mode of delivery and incidence of bronchopulmonary dysplasia: results from the population-based EPICE cohort. Neonatology 119, 464–473 (2022).

    Google Scholar 

  • Staude, B. et al. Microbial signatures in amniotic fluid at preterm birth and association with bronchopulmonary dysplasia. Respir. Res. 24, 248 (2023).

    Google Scholar 

  • Lauer, T. et al. Bacterial Colonization within the First Six Weeks of Life and Pulmonary Outcome in Preterm Infants <1000 g. J. Clin. Med. 9, 2240 (2020).

    Google Scholar 

  • Rofael, S. A. D. et al. Airway microbiome in adult survivors of extremely preterm birth: the EPICure study. The European respiratory journal 53 (2019).

  • Dolma, K. et al. Effects of hyperoxia on alveolar and pulmonary vascular development in germ-free mice. Am. J. Physiol. Lung Cell.Mol. physiol. 318, L421–L428 (2020).

    Google Scholar 

  • Dong, Y. et al. Insights into the black box of intra-amniotic infection and its impact on the premature lung: from clinical and preclinical perspectives. Int. J. Mol. Sci. 23, 9792 (2022).

    Google Scholar 

  • Shrestha, A. K. et al. Consequences of early postnatal lipopolysaccharide exposure on developing lungs in mice. Am. J. physiol. Lung cell. Mol. Physiol. 316, L229–L244 (2019).

    Google Scholar 

  • Shrestha, A. K. et al. Interactive and independent effects of early lipopolysaccharide and hyperoxia exposure on developing murine lungs. Am. J. physiol. Lung cell. Mol. Physiol. 319(L981), L996 (2020).

    Google Scholar 

  • Huang, J. et al. Human milk as a protective factor for bronchopulmonary dysplasia: a systematic review and meta-analysis. Arch. Dis. Child Fetal Neonatal. Ed. 104, F128–F136 (2019).

    Google Scholar 

  • Köstlin-Gille, N. et al. Early initiation of antibiotic therapy and short-term outcomes in preterm infants: a single-centre retrospective cohort analysis. Arch. Dis. Child. Fetal Neonatal Ed. 108(623), 630 (2023).

    Google Scholar 

  • Romijn, M. et al. Prediction models for bronchopulmonary dysplasia in preterm infants: a systematic review and meta-analysis. J. Pediatr. 258, 113370 (2023).

    Google Scholar 

  • Christoph J et al. Risikocharakterisierung Intensivmedizinisch Behandelter Früh- Und Neugeborener Und Daten Zur Ist-Situation in Deutschen Neonatologischen Intensivpflegestationen 2013 – Fachliche Erläuterungen Zu Folgender Empfehlung: Praktische Umsetzung Sowie Krankenhaushygienische Und Infektionspräventive Konsequenzen Des Mikrobiellen Kolonisationsscreenings Bei Intensivmedizinisch Behandelten Früh- Und Neugeborenen Ergänzende Empfehlung Der Kommission Für Krankenhaushygiene Und Infektionsprävention (KRINKO) Beim Robert Koch-Institut, Berlin Zur Implementierung Der Empfehlungen Zur Prävention Nosokomialer Infektionen Bei Neonatologischen Intensivpflegepatienten Mit Einem Geburtsgewicht Unter 1.500 g Aus Dem Jahr 2007 Und 2012. 42 (Epidemiologisches Bulletin des Robert Koch-Instituts, Berlin, 2013).

  • Parm, U. et al. Risk factors associated with gut and nasopharyngeal colonization by common gram-negative species and yeasts in neonatal intensive care units patients. Early Hum. Dev. 87, 391–399 (2011).

    Google Scholar 

  • Sgro, M. et al. Early-onset neonatal sepsis: rate and organism pattern between 2003 and 2008. J. Perinatol. : Off. J. California Perinat. Assoc. 31, 794–798 (2011).

    Google Scholar 

  • Kaufman, D. & Fairchild, K. D. Clinical microbiology of bacterial and fungal sepsis in very-low-birth-weight infants. Clin. Microbiol. Rev. 17, 638–80 (2004).

    Google Scholar 

  • Joubert, I. A., Otto, M., Strunk, T. & Currie, A. J. Look who’s talking: host and pathogen drivers of staphylococcus epidermidis virulence in neonatal sepsis. Int. J. Mol. Sci. 23, 860 (2022).

    Google Scholar 

  • Davis, E. C. et al. Gut microbiome and breast-feeding: Implications for early immune development. J.Allergy Clin. Immunol. 150, 523–534 (2022).

    Google Scholar 

  • Thiess, T. et al. Correlation of early nutritional supply and development of bronchopulmonary dysplasia in preterm infants <1,000 g. Front. Pediatr. 9, 741365 (2021).

    Google Scholar 

  • Voigt, M., Schneider, K. T. M. & Jährig, K. Analyse des Geburtengutes des Jahrgangs 1992 der Bundesrepublik Deutschland [Analysis of a 1992 birth sample in Germany. 1: New percentile values of the body weight of newborn infants]. Geburtshilfe Frauenheilkd 56, 550–558 (1996).

  • Jobe, A. H. & Bancalari, E. Bronchopulmonary dysplasia. Am. J. Respir. Crit. Care Med. 163, 1723–1729 (2001).

    Google Scholar 

  • Fawke, J. et al. Lung function and respiratory symptoms at 11 years in children born extremely preterm: the EPICure study. Am. J. Respire. Crit. Care Med. 182, 237–245 (2010).

    Google Scholar 

  • Walter, S. D., Feinstein, A. R. & Wells, C. K. Coding ordinal independent variables in multiple regression analyses. Am. J. Epidemiol. 125, 319–323 (1987).

    Google Scholar 

  • Wood, S. N. Generalized Additive Models: An Introduction with R, Second Edition. (Chapman and Hall/CRC, New York). https://doi.org/10.1201/9781315370279. (2017)

  • Gertheiss, J., Scheipl, F., Lauer, T. & Ehrhardt, H. Statistical inference for ordinal predictors in generalized additive models with application to bronchopulmonary dysplasia. BMC Res. Notes 15, 112 (2022).

    Google Scholar 

  • Hothorn, T., Hornik, K. & Zeileis, A. Unbiased recursive partitioning: a conditional inference framework. J. Comput. Graphical Stat. 15, 651–674 (2006).

    Google Scholar 

  • Strobl, C., Boulesteix, A.-L., Kneib, T., Augustin, T. & Zeileis, A. Conditional variable importance for random forests. BMC Bioinform. 9, 307 (2008).

    Google Scholar 

  • R Core Team. R: A Language and Environment for Statistical Computing. (2023).

  • Rückle, X. et al. Different probiotic strains alter human cord blood monocyte responses. Pediatr. Res. 94, 103–111 (2023).

    Google Scholar 

  • Samara, J. et al. Supplementation with a probiotic mixture accelerates gut microbiome maturation and reduces intestinal inflammation in extremely preterm infants. Cell Host Microbe 30, 696-711.e5 (2022).

    Google Scholar 

  • Elazab, N. et al. Probiotic administration in early life, atopy, and asthma: a meta-analysis of clinical trials. Pediatrics 132, e666-76 (2013).

    Google Scholar 

  • Collins, J. J. P. et al. Repeated intrauterine exposures to inflammatory stimuli attenuated transforming growth factor-\textgreekb signaling in the ovine fetal lung. Neonatology 104, 49–55 (2013).

    Google Scholar 

  • Azizia, M., Lloyd, J., Allen, M., Klein, N. & Peebles, D. Immune status in very preterm neonates. Pediatrics 129, e967-74 (2012).

    Google Scholar 

  • Schmidt, B., Roberts, R., Millar, D. & Kirpalani, H. Evidence-based neonatal drug therapy for prevention of bronchopulmonary dysplasia in very-low-birth-weight infants. Neonatology 93, 284–287 (2008).

    Google Scholar 

  • Brewer, M. R. et al. Determinants of the lung microbiome in intubated premature infants at risk for bronchopulmonary dysplasia. J. Maternal-fetal Neonatal Med.:Official J. Euro. Assoc. Perinat. Med. Federation Asia Oceania Perinat. Soc. Int. Soc. Perinat. Obstetricians 34, 3220–3226 (2021).

    Google Scholar 

  • Strobel, N. A., Adams, C., McAullay, D. R. & Edmond, K. M. 2022 Mother’s own milk compared with formula milk for feeding preterm or low birth weight infants: systematic review and meta-analysis. Pediatrics 150,= (2022).

  • Vatne, A. et al. Early empirical antibiotics and adverse clinical outcomes in infants born very preterm: a population-based cohort. J. Pediatr. 253, 107-114.e5 (2023).

    Google Scholar 

  • Batta, V. K., Rao, S. C. & Patole, S. K. Bifidobacterium infantis as a probiotic in preterm infants: a systematic review and meta-analysis. Pediatr. Res. 94, 1887–1905 (2023).

    Google Scholar 

  • Villamor-Martínez, E. et al. Probiotic supplementation in preterm infants does not affect the risk of bronchopulmonary dysplasia: a meta-analysis of randomized controlled trials. Nutrients 9, 1197 (2017).

    Google Scholar 

  • Beck, L. C. et al. Strain-specific impacts of probiotics are a significant driver of gut microbiome development in very preterm infants. Nat. Microbiol. 7, 1525–1535 (2022).

    Google Scholar 

  • Wang, Y. et al. Probiotics, prebiotics, lactoferrin, and combination products for prevention of mortality and morbidity in preterm infants: a systematic review and network meta-analysis. JAMA Pediatr. 177, 1158–1167 (2023).

    Google Scholar 

  • Martí, M. et al. Effects of Lactobacillus reuteri supplementation on the gut microbiota in extremely preterm infants in a randomized placebo-controlled trial. Cell Rep. Med. 2, 100206 (2021).

    Google Scholar 

  • Hoshiyar, A. ordPens: an R package for selection, smoothing and principal components analysis for ordinal variables. J. Open Source Softw. 6, 3828 (2021).

    Google Scholar 

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  • Rapid growth of US tax-minimising ETFs draws scrutiny

    Rapid growth of US tax-minimising ETFs draws scrutiny

    Billions of dollars are flowing into US exchange traded funds designed primarily as tax-minimising vehicles, in a move that is drawing criticism from politicians and which some in the industry believe could attract the attention of tax authorities.

    A number of fund firms have been creating ETFs that either lower the interest or dividend income that can be taxed, or alternatively reduce capital gains tax on investors’ pre-existing stock portfolios.

    The latter type is proving the most contentious. Known as section 351 or ETF swap funds, they are designed specifically to help investors with large portfolios who would face a significant tax bill if they sold holdings that had risen in value. At least seven such funds managing $2.2bn have launched this year, with four more currently being seeded.

    “Everybody is looking at this creatively, which is great, but it then also makes you wonder sometimes how far is too far,” said Brittany Christensen, head of business development at Tidal Financial Group, which manages $50bn of assets and has several 351 funds among its near-300 ETFs.

    Some US politicians are already opposing these funds. In June, Ron Wyden, the top Democrat on the Senate finance committee, put forward legislation that would prevent tax-free transfers of appreciated securities to 351 funds.

    Jeffrey Colon, professor of law at Fordham University School of Law, said that, unless Congress acts, tax paid by publicly traded investment vehicles would “inevitably” decline.

    “The Wyden proposal is a necessary and appropriate first step in reining in the newest tax abuse of ETFs,” he said. “The growing popularity of ETFs and recent launches of ETF swap funds requires a new urgency.”

    “The government is clearly aware of these issues, but so far has not indicated any inclination to attack them. The investment company lobby is very powerful,” he added.

    ETFs have always been more tax efficient than more traditional mutual funds in the US, due to a quirk in the tax system. Whereas mutual funds often trigger a capital gains tax event when they sell profitable positions, ETFs can usually avoid doing so by trading “in kind” with market makers, so that no cash changes hands.

    Three decades on from the birth of ETFs, though, some issuers are looking to turbocharge this tax efficiency. The less contentious funds minimise coupon or dividend income — subject to income tax — by switching holdings shortly before payments fall due.

    In August Washington DC-based F/m Investments launched the F/m Compoundr High Yield Bond ETF and F/m Compoundr US Aggregate Bond ETF. The two funds invest in bond ETFs but then rotate into other ETFs just before each underlying fund’s ex-dividend date, “converting monthly interest income into unrealised capital gains”, according to the firm. This strategy also minimises withholding taxes for non-US investors.

    Roundhill Investments and LionShares have launched similar funds that invest in equity funds.

    While the extent to which investors will take advantage of these tax loopholes remains to be seen, some funds are already delivering savings.

    The Alpha Architect 1-3 Month Box ETF, known as BOXX, which invests in options to mimic an ultra-short duration bond portfolio, has had net flows of $8.6bn since launch and now holds $9bn of assets, implying it has made a total return of $400mn. Assuming investors would have paid the highest rate of interest income tax but instead pay the long-term capital gains tax rate of 20 per cent, this would translate into a tax saving of $68mn, according to Financial Times calculations.

    “This is a significant trend because taxes are often top of mind for investors and ETFs have found ways to manage tax exposures,” said Bryan Armour, director of passive strategies research in North America at Morningstar.

    Section 351 funds — named after a previously little-used section in the US Internal Revenue Code — are seen by some as upping the ante still further. Contributing their pre-existing shareholdings allows wealthy investors to convert them into shares in an ETF, without triggering a capital gain.

    Tidal’s Christensen said the Internal Revenue Service might have some concerns over people contributing stock they received as part of an employee share plan. That is particularly the case if they are slicing this stock up into several 351 conversions in order to ensure they contribute a diversified portfolio, which is required under US tax rules, to each ETF.

    “At what point does the IRS start to look into this and say we are giving this to people who have had a compensation equity plan?” she said. “This is a new use case for section 351. It makes you wonder if it started to raise some red flags.”

    Fund firm Exchange Traded Concepts has conducted a number of such launches, with “several billion dollars more” in the pipeline, according to chief executive Garrett Stevens.

    He added that several have been for family offices “that have their own assets, but they are going ‘why wouldn’t we do what we do inside the more tax-advantaged tax wrapper?’”

    Stevens said similar arrangements already exist for holders of real estate and annuity contracts, allowing them to rotate positions without incurring tax.

    “It’s not unique. It’s an IRS rule,” he said. “It’s all legal, we are not skirting any regulations. There are probably a lot of unintended consequences in tax legislation.”

    But Elisabeth Kashner, director of global fund analytics at FactSet, said this strategy, coupled with other aspects of tax law used by the wealthy, “is certainly not honouring the intention of the tax code. It’s not playing by the consensus of how we run this country.”

    She added: “From a tax fairness point of view the investor has brilliantly avoided taxes and has had access to a good portion of his or her assets, and everyone else in the country has been deprived of that money for the Treasury.” 

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  • Targeting tumor metabolic flexibility enhances radiotherapeutic efficacy via mitochondrial complex I Inhibition in an intracranial S180 sarcoma mouse model

  • Hanahan, D. & Weinberg, R. A. Hallmarks of cancer: the next generation. Cell 144 (5), 646–674 (2011).

    Google Scholar 

  • Vander Heiden, M. G., Cantley, L. C. & Thompson, C. B. Understanding the Warburg effect: the metabolic requirements of cell proliferation. Science (New York) 324 (5930), 1029–1033 (2009).

    Google Scholar 

  • Warburg, O. On the Origin of Cancer Cells Vol. 123, p. 309–314 (Science, 1956). 3191.

  • Koppenol, W. H., Bounds, P. L. & Dang, C. V. Otto warburg’s contributions to current concepts of cancer metabolism. Nat. Rev. Cancer. 11 (5), 325–337 (2011).

    Google Scholar 

  • Jose, C., Bellance, N. & Rossignol, R. Choosing between Glycolysis and oxidative phosphorylation: a tumor’s dilemma? Biochim. Biophys. Acta. 1807 (6), 552–561 (2011).

    Google Scholar 

  • Bonnet, S. et al. A mitochondria-K + channel axis is suppressed in cancer and its normalization promotes apoptosis and inhibits cancer growth. Cancer Cell. 11 (1), 37–51 (2007).

    Google Scholar 

  • Greene, J., Segaran, A. & Lord, S. Targeting OXPHOS and the electron transport chain in cancer; molecular and therapeutic implications. Sem. Cancer Biol. 86 (Pt 2), 851–859 (2022).

    Google Scholar 

  • Ward, P. S. & Thompson, C. B. Metabolic reprogramming: a cancer hallmark even Warburg did not anticipate. Cancer Cell. 21 (3), 297–308 (2012).

    Google Scholar 

  • Pavlova, N. N. & Thompson, C. B. The Emerg. Hallm. Cancer Metabolism Cell. Metabolism, 23(1): 27–47. (2016).

    Google Scholar 

  • Dang, C. V. MYC on the path to cancer. Cell 149 (1), 22–35 (2012).

    Google Scholar 

  • Zong, W. X., Rabinowitz, J. D. & White, E. Mitochondria Cancer Mol. Cell., 61(5): 667–676. (2016).

    Google Scholar 

  • Sancho, P. et al. MYC/PGC-1α balance determines the metabolic phenotype and plasticity of pancreatic cancer stem cells. Cell Metabol. 22 (4), 590–605 (2015).

    Google Scholar 

  • Vlashi, E. & Pajonk, F. Cancer stem cells, cancer cell plasticity and radiation therapy. Sem. Cancer Biol. 31, 28–35 (2015).

    Google Scholar 

  • Fendt, S. M., Frezza, C. & Erez, A. Targeting metabolic plasticity and flexibility dynamics for cancer therapy. Cancer Discov. 10 (12), 1797–1807 (2020).

    Google Scholar 

  • Kreuzaler, P. et al. Adapt and conquer: metabolic flexibility in cancer growth, invasion and evasion. Mol. Metabolism, 33. 83-101 (2020). doi:10.1016/j.molmet.2019.08.021

  • Bailleul, J. & Vlashi, E. Glioblastomas: Hijacking Metabolism To Build a Flexible Shield for Therapy Resistance Vol. 39, p. 957–979 (Antioxidants & Redox Signaling, 2023). 13–15.

  • Obre, E. & Rossignol, R. Emerging concepts in bioenergetics and cancer research: metabolic flexibility, coupling, symbiosis, switch, oxidative tumors, metabolic remodeling, signaling and bioenergetic therapy. Int. J. Biochem. Cell Biol. 59, 167–181 (2015).

    Google Scholar 

  • Yang, B. & Shi, J. Chemistry of Advanced Nanomedicines in Cancer Cell Metabolism Regulation. Adv. Sci. (Weinheim Baden-Wurttemberg Germany). 7 (18), p2001388 (2020).

    Google Scholar 

  • Luo, Z. et al. Targeting cancer metabolic pathways for improving chemotherapy and immunotherapy. Cancer Lett. 575, 216396 (2023).

    Google Scholar 

  • Weinberg, S. E. & Chandel, N. S. Targeting mitochondria metabolism for cancer therapy. Nat. Chem. Biol. 11, 9-15 (2015). doi:10.1038/nchembio.1712

  • Sabharwal, S. S. & Schumacker, P. T. Mitochondrial ROS in cancer: initiators, amplifiers or an achilles’ heel? Nat. Rev. Cancer. 14 (11), 709–721 (2014).

    Google Scholar 

  • Brown, J. M. & Wilson, W. R. Exploiting tumour hypoxia in cancer treatment. Nat. Rev. Cancer. 4 (6), 437–447 (2004).

    Google Scholar 

  • Minchinton, A. I. & Tannock, I. F. Drug penetration in solid tumours. Nat. Rev. Cancer. 6 (8), 583–592 (2006).

    Google Scholar 

  • Vlashi, E. et al. Metabolic state of glioma stem cells and nontumorigenic cells. Proc. Natl. Acad. Sci. U.S.A. 108 (38), 16062–16067 (2011).

    Google Scholar 

  • Batlle, E. & Clevers, H. Cancer stem cells revisited. Nat. Med. 23 (10), 1124–1134 (2017).

    Google Scholar 

  • Janiszewska, M. et al. Imp2 controls oxidative phosphorylation and is crucial for preserving glioblastoma cancer stem cells. Genes Dev. 26 (17), 1926–1944 (2012).

    Google Scholar 

  • Viale, A. et al. Oncogene ablation-resistant pancreatic cancer cells depend on mitochondrial function. Nature 514 (7524), 628–632 (2014).

    Google Scholar 

  • Molina, J. R. et al. An inhibitor of oxidative phosphorylation exploits cancer vulnerability. Nat. Med. 24 (7), 1036–1046 (2018).

    Google Scholar 

  • Baran, N. et al. Inhibition of mitochondrial complex I reverses NOTCH1-driven metabolic reprogramming in T-cell acute lymphoblastic leukemia. Nat. Commun. 13 (1), 2801 (2022).

    Google Scholar 

  • Zhou, Y. et al. Recent advances of mitochondrial complex I inhibitors for cancer therapy: current status and future perspectives. Eur. J. Med. Chem. 251, 115219 (2023).

    Google Scholar 

  • Al Assi, A. et al. A novel inhibitor of the mitochondrial respiratory complex I with uncoupling properties exerts potent antitumor activity. Cell Death Dis. 15 (5), 311 (2024).

    Google Scholar 

  • Basit, F. et al. Mitochondrial complex I Inhibition triggers a mitophagy-dependent ROS increase leading to necroptosis and ferroptosis in melanoma cells. Cell Death Dis. 8 (3), e2716 (2017).

    Google Scholar 

  • Yap, T. A. et al. Complex I inhibitor of oxidative phosphorylation in advanced solid tumors and acute myeloid leukemia: phase I trials. Nat. Med. 29 (1), 115–126 (2023).

    Google Scholar 

  • Tufail, M., Jiang, C. H. & Li, N. Altered metabolism in cancer: insights into energy pathways and therapeutic targets. Mol. Cancer. 23 (1), 203 (2024).

    Google Scholar 

  • Gao, X. et al. Inhibition of Mitochondria NADH-Ubiquinone Oxidoreductase (complex I) Sensitizes the Radioresistant Glioma U87MG Cells To Radiation Vol. 129, p. 110460 (Biomedicine & Pharmacotherapy = Biomedecine & Pharmacotherapie, 2020).

  • Hess-Stumpp, H. J. C. R. Abstract LB-244: BAY 87-2243, an inhibitor of HIF-1α-induced gene activation, showed promising anti-tumor efficacy in combination with anti-angiogenic therapy and irradiation in preclinical tumor models. Cancer Res. 72 (8_Supplement), LB-244-LB-244 (2012).

    Google Scholar 

  • Ashton, T. M. et al. Oxidative phosphorylation as an emerging target in cancer therapy. Clin. Cancer Research: Official J. Am. Association Cancer Res. 24 (11), 2482–2490 (2018).

    Google Scholar 

  • Liu, Z. et al.Synergistic Antitumor Effect of Combined Radiotherapy and Engineered Salmonella typhimurium in an Intracranial Sarcoma Mouse Model. Vaccines 11 (7), (2023).

  • Tran, T. A. T. et al. Natural killer cell therapy potentially enhances the antitumor effects of bevacizumab plus Irinotecan in a glioblastoma mouse model. Front. Immunol. 13, 1009484 (2022).

    Google Scholar 

  • Smilowitz, H. M. et al. Increasing radiation dose improves immunotherapy outcome and prolongation of tumor dormancy in a subgroup of mice treated for advanced intracerebral melanoma. Cancer Immunol. Immunotherapy: CII. 65 (2), 127–139 (2016).

    Google Scholar 

  • Lan, X. Y. et al. Unlocking the potential of Ultra-High dose fractionated radiation for effective treatment of glioblastoma in mice. J. Cancer. 15 (13), 4060–4071 (2024).

    Google Scholar 

  • Zarghami, N. et al. Half brain irradiation in a murine model of breast cancer brain metastasis: magnetic resonance imaging and histological assessments of dose-response. Radiation Oncol. (London England). 13 (1), 104 (2018).

    Google Scholar 

  • Zanoni, M. et al. Irradiation causes senescence, ATP release, and P2X7 receptor isoform switch in glioblastoma. Cell Death Dis. 13 (1), 80 (2022).

    Google Scholar 

  • Jin, L. et al. The ROS/AKT/S6K axis induces corneal epithelial dysfunctions under LED blue light exposure. Ecotoxicol. Environ. Saf. 287, 117345 (2024).

    Google Scholar 

  • Jiang, J. et al. Catechin Promotes Endoplasmic Reticulum stress-mediated Gastric Cancer Cell Apoptosis Via NOX4-induced Reactive Oxygen Species (Molecular and Cellular Biochemistry, 2024).

  • DeBerardinis, R. J. et al. The biology of cancer: metabolic reprogramming fuels cell growth and proliferation. Cell Metabol. 7 (1), 11–20 (2008).

    Google Scholar 

  • Zong, Y. et al. Mitochondrial dysfunction: mechanisms and advances in therapy. Signal. Transduct. Target. Therapy. 9 (1), 124 (2024).

    Google Scholar 

  • Raimondi, V., Ciccarese, F. & Ciminale, V. Oncogenic pathways and the electron transport chain: a DangeROS liaison. Br. J. Cancer. 122 (2), 168–181 (2020).

    Google Scholar 

  • Perillo, B. et al. ROS in cancer therapy: the bright side of the Moon. Exp. Mol. Med. 52 (2), 192–203 (2020).

    Google Scholar 

  • Dosunmu-Ogunbi, A. M. et al. Decoding the role of SOD2 in sickle cell disease. Blood Adv. 3 (17), 2679–2687 (2019).

    Google Scholar 

  • Bastin, J. et al. Downregulation of mitochondrial complex I induces ROS production in colorectal cancer subtypes that differently controls migration. J. Translational Med. 21 (1), 522 (2023).

    Google Scholar 

  • Hubackova, S. et al. Mitochondria-driven elimination of cancer and senescent cells. Biol. Chem. 400 (2), 141–148 (2019).

    Google Scholar 

  • Martínez-Reyes, I. & Chandel, N. S. Mitochondrial TCA cycle metabolites control physiology and disease. Nat. Commun. 11 (1), 102 (2020).

    Google Scholar 

  • Martell, E. et al. Metabolism-based targeting of MYC via MPC-SOD2 axis-mediated oxidation promotes cellular differentiation in group 3 Medulloblastoma. Nat. Commun. 14 (1), 2502 (2023).

    Google Scholar 

  • Zhang, Z. et al. Redox signaling in drug-tolerant persister cells as an emerging therapeutic target. EBioMedicine 89, 104483 (2023).

    Google Scholar 

  • Ivashkevich, A. et al. Use of the γ-H2AX assay to monitor DNA damage and repair in translational cancer research. Cancer Lett. 327 (1–2), 123–133 (2012).

    Google Scholar 

  • Guo, C. et al. Oxidative stress, mitochondrial damage and neurodegenerative diseases. Neural Regeneration Res. 8 (21), 2003–2014 (2013).

    Google Scholar 

  • Borodkina, A. et al. Interaction between ROS dependent DNA damage, mitochondria and p38 MAPK underlies senescence of human adult stem cells. Aging 6 (6), 481–495 (2014).

    Google Scholar 

  • Stiff, T. et al. ATM and DNA-PK function redundantly to phosphorylate H2AX after exposure to ionizing radiation. Cancer Res. 64 (7), 2390–2396 (2004).

    Google Scholar 

  • Alarifi, S. et al. Regulation of apoptosis through bcl-2/bax proteins expression and DNA damage by nano-sized gadolinium oxide. Int. J. Nanomed. 12, 4541–4551 (2017).

    Google Scholar 

  • Kalkavan, H. & Green, D. R. MOMP, cell suicide as a BCL-2 family business. Cell Death Differ. 25 (1), 46–55 (2018).

    Google Scholar 

  • Chipuk, J. E. & Green, D. R. How do BCL-2 proteins induce mitochondrial outer membrane permeabilization? Trends Cell Biol. 18 (4), 157–164 (2008).

    Google Scholar 

  • Wang, C. & Youle, R. J. The role of mitochondria in apoptosis*. Annu. Rev. Genet., 43. 95-118 (2009). doi:10.1146/annurev-genet-102108-134850

  • Vyas, S., Zaganjor, E. & Haigis, M. C. Mitochondria Cancer Cell., 166(3): 555–566. (2016).

    Google Scholar 

  • Porter, A. G. & Jänicke, R. U. Emerging roles of caspase-3 in apoptosis. Cell Death Differ., 6, 99-104 (1999). doi:10.1038/sj.cdd.4400476

  • Ferreira, K. S. et al. Caspase-3 feeds back on caspase-8, bid and XIAP in type I Fas signaling in primary mouse hepatocytes. Apoptosis: Int. J. Program. Cell. Death. 17 (5), 503–515 (2012).

    Google Scholar 

  • Diepart, C. et al. Arsenic trioxide treatment decreases the oxygen consumption rate of tumor cells and radiosensitizes solid tumors. Cancer Res. 72 (2), 482–490 (2012).

    Google Scholar 

  • Park, Y. Y. et al. ATP Depletion during Mitotic Arrest Induces Mitotic Slippage and APC/CCdh1-dependent Cyclin B1 Degradation Vol. 50 (Experimental & Molecular Medicine, 2018). 4.

  • Hoeijmakers, J. H. J. DNA damage, aging, and cancer. N. Engl. J. Med. 361 (15), 1475–1485 (2009).

    Google Scholar 

  • Sancar, A. et al. Molecular mechanisms of mammalian DNA repair and the DNA damage checkpoints. Annu. Rev. Biochem. 73, 39–85 (2004).

    Google Scholar 

  • McCann, E., O’Sullivan, J. & Marcone, S. Targeting cancer-cell mitochondria and metabolism to improve radiotherapy response. Translational Oncol. 14 (1), 100905 (2021).

    Google Scholar 

  • Engeland, K. Cell cycle regulation: p53-p21-RB signaling. Cell Death Differ. 29 (5), 946–960 (2022).

    Google Scholar 

  • Zheng, X. X. et al. Mitochondria in cancer stem cells: Achilles heel or hard armor. Trends Cell Biol. 33 (8), 708–727 (2023).

    Google Scholar 

  • Fan, M. et al. Cancer stem cell fate determination: mito-nuclear communication. Cell. Communication Signaling: CCS. 21 (1), 159 (2023).

    Google Scholar 

  • Fleury, C., Mignotte, B. & Vayssière, J. L. Mitochondrial reactive oxygen species in cell death signaling. Biochimie 84 (2–3), 131–141 (2002).

    Google Scholar 

  • Stine, Z. E. et al. Targeting cancer metabolism in the era of precision oncology. Nat. Rev. Drug Discov. 21 (2), 141–162 (2022).

    Google Scholar 

  • Xu, Y. et al. Why all the fuss about oxidative phosphorylation (OXPHOS)? J. Med. Chem. 63 (23), 14276–14307 (2020).

    Google Scholar 

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  • Japan’s Two-Year Bond Sale Demand Weaker Than 12-Month Average – Bloomberg.com

    1. Japan’s Two-Year Bond Sale Demand Weaker Than 12-Month Average  Bloomberg.com
    2. Japanese government bonds edge lower ahead of 40-year debt auction  Business Recorder
    3. Benchmark JGB yields rise on issuance shuffle; 2-year notes stable before auction  TradingView
    4. Japan’s 40-Year Bond Sale Demand Slightly Higher Than Average  Bloomberg.com
    5. JGB Yields Higher After Strong Tokyo Inflation Data  The Wall Street Journal

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  • Here’s what new debt-to-income home loan caps mean for banks and borrowers

    Here’s what new debt-to-income home loan caps mean for banks and borrowers

    For the first time ever, the Australian banking regulator has announced it will impose new debt-to-income limits on housing loans made by banks.

    Such limits are a common tool used by regulators in other nations – including the United Kingdom, Ireland, New Zealand and Canada – to cool housing market lending. The aim is to prevent meltdowns like we saw in the global financial crisis in 2008.

    Here’s what’s changing – and what it could mean for prospective home buyers and the housing market as a whole.

    What’s been announced

    When you apply to take out a loan at a bank, one of their key considerations is how much income you earn each year, compared to the size of the loan.

    Having a high debt-to-income ratio – earning relatively less compared to the amount borrowed – is considered riskier.

    Until now, there there have been no debt-to-income limits on banks, though other controls such as the serviceability buffer, help curb high-risk lending.




    Read more:
    How do banks assess you for a home loan? And how do you work out what you can afford?


    From February 1 2026, the Australian Prudential and Regulatory Authority (APRA) will make banks and other lenders limit the share of new home loans with a high debt-to-income ratio – above or equal to six times before-tax income – to 20% of their new mortgage lending.

    For a prospective borrower on the average taxable income of about A$75,000, this ratio would theoretically allow for a loan of up to $450,000.

    The limit will apply separately to owner-occupier and investment home loans, meaning those loans won’t be grouped together as a single pool to calculate the 20% limit for each bank. The limits exclude bridging loans for owner-occupiers and loans for the construction of new homes.

    Figures cited by APRA show Australia’s new ratio is roughly on par with a similar limit in New Zealand (six to seven times income) but notably higher than that of similar policies in Ireland (3.5 to four times income) and Canada (4.5 times income).

    The new debt-to-income limits will be a first for Australia.
    Bianca De Marchi/AAP

    How will it work?

    Banks will need to monitor the new home loans they issue to ensure no more than 20% of loans have a high debt-to-income ratio. This will be measured quarterly.

    While the debt-to-income limit is new, APRA has intervened previously with other limits. For example, in 2017, it imposed limits on the percentage of new interest-only mortgages banks could write (though these limits were lifted at the beginning of 2019).

    What does this mean for getting a loan?

    It’s important to note the rules won’t stop banks issuing loans with a debt-to-income ratio above six. It will just restrict the amount of these they can issue.

    But the new regulations raise a fair question – if you’re applying for a “high-risk” home loan, will getting one now depend on how many other high risks home loans your bank has handed out?

    Well, sort of. The limits will only affect borrowers with a high debt-to-income ratio if the bank they are applying to is near or has hit their limit in a given quarter.

    APRA expects some banks to hit such limits within the near future without intervention.

    This would make such banks more selective in choosing which loans to approve. It’s possible some could even increase their mortgage rates to deter such loans.

    There will be no effect on low debt-to-income borrowers’ ability to obtain a mortgage. Keep in mind existing borrowers are unaffected unless they choose to refinance.

    What other effects could there be?

    There was no significant reaction to the announcement in the price of Australian bank stocks, suggesting market pundits don’t see the limits hitting bank profitability.

    However, studies in other countries, such as the United States and the Netherlands, show debt-to-income and other such limits are effective at curbing risky loans and reducing household stress.

    But it can have some unintended side effects. In one Norwegian study, modelling showed debt-to-income limits reduce household debt and housing prices, but also prevent those on low incomes from moving as they are unable to borrow.

    This lack of mobility then creates an inequality in the access of better opportunities.

    A related study, examining the housing market in Israel, found such limits force some borrowers to buy in cheaper areas with higher commuting costs which are more socio-disadvantaged.

    APRA’s balancing act

    APRA has used these limits as a new tool to stop risky loans being made. While the current limits won’t affect lending in a big way, the regulator is signalling to borrowers and lenders that they are concerned about risky borrowing and may continue to take action.

    As shown elsewhere, more restrictive actions can have the desired effect of reducing risky loans, and therefore curbing housing market crashes.

    But such limits can also worsen inequalities, particularly for those already financially constrained. And they could have indirect impacts on prospective first-home buyers looking to take advantage of Labor’s expanded 5% deposit scheme – which by design, allows people to take out larger loans than they otherwise would have been able.

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  • Petrobras cuts dividend, investment projections in new five-year business plan

    Petrobras cuts dividend, investment projections in new five-year business plan

    RIO DE JANEIRO, Nov 27 (Reuters) – Brazilian state-run oil firm Petrobras has lowered its dividend forecast and cut expected investments by almost 2% in a new five-year business plan announced Thursday, as it grapples with lower crude prices.

    Petrobras expects to dole out between $45 billion and $50 billion during the 2026-2030 period in ordinary dividends, a filing showed. In its previous five-year plan to 2029, released last year, the firm had expected to give shareholders up to $55 billion.

    Sign up here.

    There was no mention of extraordinary dividends in the new plan, while the previous one estimated up to $10 billion could be disbursed during the 2025-2029 period.

    The cut in investments to $109 billion comes as Petrobras faces lower Brent oil prices, that it now expects to hover around $63 a barrel for next year, below the $77 estimate it had set for 2026 in the previous plan.

    This marks the first drop in investments of the state-run firm under President Luiz Inacio Lula da Silva’s current administration.

    The last time investment was cut was the 2021-2025 plan, under former President Jair Bolsonaro’s administration, when Petrobras was undergoing a series of divestments.

    Reuters reported on Wednesday, citing sources, that Petrobras’ expected investments were set to drop to around $109 billion in the new plan.

    Since taking office, Lula has pushed the oil firm to invest more in order to boost the country’s economy. Next year, the leftist leader is set to seek a fourth, non-consecutive term as president.

    Despite lowering investments overall, Petrobras raised investments in exploration and production activities by about $1 billion to $78 billion for the period, while keeping refining, transportation and marketing investments at around $20 billion.

    Petrobras also said it expects to reach peak oil production within the period of 2.7 million barrels per day (bpd) in 2028.

    Peak total production within the plan’s timeframe would be 3.4 million barrels of oil and gas equivalent per day (boed) in 2028 and 2029, based on annual projections with a margin of variation of plus or minus 4%.

    Reporting by Fabio Teixeira and Rodrigo Viga Gaier in Rio de Janeiro; Editing by Natalia Siniawski and Kevin Buckland

    Our Standards: The Thomson Reuters Trust Principles., opens new tab

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  • Hyundai Motor Group Drives Next-Generation Battery Innovation with Future Mobility Battery Campus

    Daehyun Shin
    daehyun.shin@hyundai.com
    Global PR Strategy & Planning · Hyundai Motor Company

    Disclaimer: Hyundai Motor Group believes the information contained herein to be accurate at the time of release. However, the company may upload new or updated information if required and assumes that it is not liable for the accuracy of any information interpreted and used by the reader.

    About Hyundai Motor Group

    Hyundai Motor Group is a global enterprise that has created a value chain based on mobility, steel, and construction, as well as logistics, finance, IT, and service. With about 250,000 employees worldwide, the Group’s mobility brands include Hyundai, Kia, and Genesis. Armed with creative thinking, cooperative communication and the will to take on any challenges, we strive to create a better future for all.

    More information about Hyundai Motor and its products can be found at:

    http://www.hyundaimotorgroup.com or Newsroom: Media Hub by Hyundai , Kia Global Media Center (kianewscenter.com) , Genesis Global Newsroom


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  • Chinese yuan weakens to 7.0789 against USD Friday-Xinhua

    BEIJING, Nov. 28 (Xinhua) — The central parity rate of the Chinese currency renminbi, or the yuan, weakened 10 pips to 7.0789 against the U.S. dollar Friday, according to the China Foreign Exchange Trade System.

    In China’s spot foreign exchange market, the yuan is allowed to rise or fall by 2 percent from the central parity rate each trading day.

    The central parity rate of the yuan against the U.S. dollar is based on a weighted average of prices offered by market makers before the opening of the interbank market each business day.

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  • JFCR, NEC, and Taiho to Develop Cancer Vaccines Utilizing Whole-Genome Information: Press Releases

    JFCR, NEC, and Taiho to Develop Cancer Vaccines Utilizing Whole-Genome Information: Press Releases

    The Japanese Foundation for Cancer Research (JFCR), NEC Corporation (NEC), and Taiho Pharmaceutical Co., Ltd. (Taiho) have signed a three-party joint research (Joint Research) agreement aimed at developing new cancer vaccines through the utilization of whole-genome information.

    This Joint Research project will be carried out as part of the Japan Agency for Medical Research and Development (AMED)’s “Action Plan for Whole-Genome Analysis for Cancer and Rare/Intractable Diseases,” within the research initiative “Demonstration of the Clinical Utility of Cancer Whole-Genome Analysis and Research on Establishing Systems for Patient Benefit.”

    JFCR, NEC, and Taiho will design and develop shared neoantigen cancer vaccines that target newly identified cancer-specific antigens (neoantigens) shared among multiple patients with cancer. The initiative aims to demonstrate the therapeutic efficacy of vaccines for a wide range of cancer patients and to be quickly available.

    The Joint Research will utilize the unique research information, AI-based drug discovery technologies, and experimental materials held by the three parties. Specifically, JFCR’s high quality whole-genome information linked to clinical information*1 for various cancer types with high unmet medical needs*2, common cancer antigens across patients identified with NEC’s proprietary predictive AI technology, and immunological evaluations of the those cancer antigens conducted using Taiho’s proprietary evaluation models, will be used to narrow down highly reliable cancer antigens based on experimental data to design shared neoantigen cancer vaccine candidates suitable for clinical trials. This approach will identify novel cancer-specific antigens shared among multiple patients, including cryptic antigens which are derived from the dark genome*3, in addition to conventional neoantigens, advancing drug discovery research for shared neoantigen cancer vaccines.

    Cancer vaccines induce immune responses against cancer cells, which differ from conventional chemotherapeutic agents. They hold the potential to become innovative treatments for cancers where unmet medical needs remain. Particularly, there is current expectation for the use of cancer vaccines in preventing postoperative recurrence and early-stage settings*4. Through this Joint Research, the three parties aim to contribute to overcoming the significant social and medical challenges of cancer.

    Tetsuo Noda, M.D., Ph.D., Advisor, Atsushi Ohtsu, M.D., Ph.D., Research Director at JFCR, stated: “We are delighted to launch this new collaborative initiative with NEC and Taiho to develop novel cancer vaccines by leveraging whole-genome data, under the AMED research program based on the Action Plan for Whole-Genome Analysis 2022 (Ministry of Health, Labour and Welfare). Within this joint research, we will advance the development of shared neoantigen vaccines that integrate both conventional neoantigens and diverse cancer-restricted cryptic antigens derived from the dark genome, identified through AI-driven analysis and immunological validation. Through these efforts, we aspire to realize the next generation of cancer immunotherapy.”

    Motoo Nishihara, Executive Officer, Corporate EVP and CTO at NEC, commented: “We are honored to commence this pioneering collaborative research with JFCR and Taiho to create novel cancer vaccines utilizing whole-genome information. In this Joint Research promoted by AMED, we will combine NEC’s proprietary AI-based genome analysis technology with insights into dark genome and neoantigens. This will enable us to address diverse HLA types and achieve highly accurate cancer antigen prediction, which will contribute to creating a future where optimal medical care is delivered to a wider range of patients.”

    Takeshi Sagara, Executive Director, Clinical Development and Medical Affairs, Discovery & Preclinical Research at Taiho, stated: “We believe that future anticancer drug discovery focusing on research and development, not only for advanced cancer, but also for early-stage recurrent cancer, with an eye on the patient journey, will lead to long-term survival and ultimately the overcoming of cancer. We are very pleased to begin this new initiative together with JFCR and NEC toward creating novel cancer vaccines. Utilizing our proprietary patented evaluation models, we will play a key role in evaluating target cancer antigens and identifying clinical trial candidates continuing our challenge in tackling intractable cancers.”


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