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  • Dynamic adaptation mutations and pathogenic characterization of a mouse-adapted seasonal human H3N2 influenza virus | Virology Journal

    Dynamic adaptation mutations and pathogenic characterization of a mouse-adapted seasonal human H3N2 influenza virus | Virology Journal

    Dynamic adaptation of A(H3N2) virus in mice

    To obtain an A(H3N2)-MA strain, we conducted successive lung-to-lung passages of the A(H3N2)-WT strain in C57BL/6J mice. The A(H3N2) viruses identified in 17 passages were designated as MA1–MA17, respectively (Fig. 1A). According to the changes in body weight, survival state, lung index (a ratio of the weight of the lung to the body weight of the mouse), and lung viral RNA loads of the infected mice, MA1, MA5, MA8, MA13, and MA17 were selected as key passages in the following analysis.

    Fig. 1

    Adaptation of human seasonal H3N2 influenza virus in mice. A Schematic diagram of the lung-to-lung passage experiment of A(H3N2) virus and pathogenicity test of the A(H3N2)-MA and A(H3N2)-WT strains in the mouse model. B Change in body weight, (C) survival rate, and (D) lung index of mice were monitored during key passages (MA1, MA5, MA8, MA13, and MA17). The dotted line in panel B represents 75% of the initial body weight. E Virus loads in the lungs of infected mice during key passages were detected by qRT-PCR. The dashed horizontal line indicates the lowest limit of detection. Each group includes three mice. Grey asterisks represent statistical significance between the infected group and the control group (intranasally inoculated with an equal volume of sterile PBS), while blue asterisks indicate significant differences between the MA1 group and other groups. Statistical significance among groups was analyzed using Kruskal–Wallis test with Dunn’s multiple comparisons (D, E). Error bars show the mean ± SD. *, P < 0.05; **, P < 0.01

    In the MA1, no body weight loss was observed in mice infected with the A(H3N2)-WT strain (Fig. 1B), and all mice survived during the observation period (Fig. 1C). The lung indexes of the infected mice showed no noticeable changes compared to the controls (Fig. 1D), and virus was detected in one of the three mice at 5 dpi. In the MA5, the infected mice have a decrease of approximately 5% in body weight at 7 dpi and later the body weight returned to a normal state. No mice died, but the lung indexes and lung virus RNA loads of the infected mice were higher than those of the control group (Fig. 1B–E).

    As the number of passages increased, the body weight losses of the infected mice increased compared with their initial body weights before virus infection. Specifically, from 5 to 7 dpi, the rates of body weight reduction were greater than 22% for MA8, 25% for MA13, and 25% for MA17 compared to their initial body weights (Fig. 1B). In addition, in the MA8 passage, the survival rate of the infected mice dropped to 33%, while all mice in the MA13 and MA17 passages died within 7 and 5 dpi, respectively (Fig. 1C). Additionally, the lung indexes of the infected mice gradually increased as passage increased. The lung indexes for mice from the MA13 and MA17 passages were significantly higher than that of the control group, respectively (Fig. 1D). Meanwhile, the lung virus RNA loads of mice from the MA5, MA8 and MA13 passages progressively increased. The mean virus RNA loads of MA17 was comparable with that of the MA13 passage, which were both significantly higher than that of MA1 (Fig. 1E). These results suggest that as the passage number increased, the A(H3N2) virus from the infected mice showed gradual enhancement in their virulence, replication ability, and adaptation to mice.

    Adaptation of A(H3N2) in mice involves dynamic mutations of the virus

    To reveal the molecular basis correlated to the adaptation of the A(H3N2) virus in mice, we analyzed AA mutations that occurred in the viruses from five key passages (MA1, MA5, MA8, MA13, and MA17). This analysis was based on the genomic data generated using NGS method. We identified fourteen mutations that are unique in the A(H3N2)-MA virus rather than the A(H3N2)-WT strain (Table 1). These AA mutations include twelve nonsynonymous mutations (PB2-S590R, PB1-I682V, PA-K615E, PA-X-F246S, HA-N91T, HA-N122D, HA-K207E, HA-I242T, HA-N246K, HA-M478I, NP-G384R, and M1-D232N) in PB2, PB1, PA, PA-X, HA, NP, and M1 genes, and two synonymous mutations (PA-G(GGG)462G(GGA) and PA-L(CTT)246L(CTC)) in PA gene.

    Table 1 Amino acid mutations occurred at different passages of A(H3N2) viruses

    Among these, four mutations are prone to occur during the mice infection. The HA-N246K (H3 numbering throughout), HA-M478I, NP-G384R, and M1-D232N mutations occurred in the MA1 passage, with a higher proportion of greater than 90%. In addition, six of the fourteen mutations (i.e., PB2-S590R, PB1-I682V, PA-K615E, PA-X-F246S,PA-G(GGG)462G(GGA), and PA-L246L) have a gradual accumulation progress during the passaging. The PB2-S590R, PA-K615E, and PA-G(GGG)462G(GGA) mutations occurred in the MA1 passage, with proportions of 1.47%, 1.27%, and 7.56%, respectively, and their proportions reached 97.73%, 98.57%, and 98.59% in the MA17 passage, respectively. The PB1-I682V, PA-X-F246S, and PA-L(CTT)246L(CTC) mutations were first found in the MA5, MA8, and MA8, respectively. Furthermore, three mutations on the HA genes occurred at the late stage of the virus adaptation, and the HA-N91T, HA-K207E, and HA-I242T mutations were first observed in the MA13 passage, with proportions of 11.6%, 11.16%, and 11.18%, respectively; and these mutations increased to approximately 70% in the MA17 passage. In addition, the HA-N122D had already occurred in the MA5 passage with a proportion of 97.75% but was not found in the MA1 passage.

    Moreover, eight mutations, PB2-S590R, PA-K615E, HA-N122D, HA-N246K, HA-M478I, NP-G384R, M1-D232N, and PA-G(GGG)462G(GGA) with the proportion greater than 95% were kept in the MA17 passage. In addition, the other mutations took an occupation of greater than 50% in the MA17 passage.

    Mouse adapted mutation enhances the polymerase activity of the RNP complex

    To investigate the impact of mouse-adapted mutations in the PB2, PB1, PA, and NP genes on polymerase activity, we analyzed the activity of the RNP complex from these gene combinations. As shown in Fig. 2, the relative polymerase activity of the RNP complex containing PB2-S590R, PB1-I682V, PA-K615E, or NP-G384R ranged from 120 to 136%, which is higher than that of the A(H3N2)-WT, set at 100%. Specifically, the polymerase activity of the combination with PA-K615E and NP-G384R, as well as the combination with PB2-S590R and PA-K615E, was greater than that of A(H3N2)-WT. The activity levels of the combination of PB2-S590R, PA-K615E, and NP-G384R and the combination of PB2-S590R, PB1-I682V, and PA-K615E were comparable and significantly higher than A(H3N2)-WT (P < 0.05). Ultimately, the polymerase activity of the combination with PB2-S590R, PB1-I682V, PA-K615E, and NP-G384R was also significantly higher than A(H3N2)-WT (P < 0.05). These results indicated that the mouse-adapted mutations in the PB2, PB1, PA, and NP genes enhanced the polymerase activity, which may affect the replication and virulence of A(H3N2) virus in mice.

    Fig. 2
    figure 2

    Polymerase activity of ribonucleoprotein (RNP) complexes of the A(H3N2)-WT and A(H3N2)-MA strains. A The polymerase activities of the RNP complexes for the WT and MA strains were detected using a dual-luciferase reporter system with PB2, PB1, PA, and NP expression vectors in HEK-293T cells. The blue and red rectangles represent the gene from A(H3N2)-WT and A(H3N2)-MA, respectively. Values represent the mean ± SD from three independent experiments and are standardized to those of A(H3N2)-WT measured in HEK-293T cells. Blue asterisks indicate statistical significance between the wild-type group and the other groups. Statistical significance between groups was analyzed by the Kruskal–Wallis test with Dunn’s multiple comparisons. *, P < 0.05. B NP protein expression was detected in the HEK-293T cell lysis supernatant by Western blotting

    Pathogenic and replication characteristics of A(H3N2)-MA and A(H3N2)-WT strains in mice

    The mouse-adapted A(H3N2) strain, A/Kansas/14/2017/H3N2-MA, was generated through three rounds of plaque purification of the viruses from lung homogenate of the MA17 passage in MDCK cells. We first investigated the pathogenic characteristics of the A(H3N2)-MA and A(H3N2)-WT strains based on the MLD50 (Fig. 1A). The mice were infected with the A(H3N2)-WT strain of 108 EID50 and the A(H3N2)-MA strain of different infection doses (from 103 to 106 EID50, to tenfold dilution), respectively. The results showed that mice infected with A(H3N2)-MA of 103 EID50 experienced a 10% decrease in body weight at 7 dpi, and later began to increase. The body weights of mice infected with 104 EID50 of A(H3N2)-MA decreased by approximately 20% at 8 dpi, and two of five mice died at 9 dpi (Fig. 3A and B). Most mice infected with 105 EID50 and 106 EID50 of A(H3N2)-MA lost body weights of greater than 25% at 7 dpi, and all mice succumbed at 8 and 7 dpi, respectively. In contrast, mice infected with the maximum titer of 108 EID50 of A(H3N2)-WT showed no significant body weight loss, and all five mice survived (Fig. 3A and B). Therefore, the MLD50 value for the A(H3N2)-MA strain is 104.167 EID50/50 μL, and for the A(H3N2)-WT is greater than 108.0 EID50/50 μL, indicating that the virulence of A(H3N2)-MA is higher than A(H3N2)-WT in the mouse model.

    Fig. 3
    figure 3

    Pathogenicity and replicability of the A(H3N2)-WT and A(H3N2)-MA strains in mice. Five mice of each group were intranasally infected with tenfold serial dilutions containing 106 to 103 EID50 of A(H3N2)-MA or with a dose of 108 EID50 of A(H3N2)-WT, respectively. The control group was intranasally inoculated with an equal volume of sterile PBS. A Changes in body weight and (B) survival rates of mice were monitored for 14 dpi. In addition, two groups of 20 mice were intranasally inoculated with 104.5 EID50/50 μL A(H3N2)-MA or A(H3N2)-WT, respectively, and (C) body weight changes and (D) survival rate of mice were measured daily. Five mice per group were euthanized at 3, 5, and 7 dpi, respectively. Virus RNA loads in the lung (E) and nasal turbinate (F) of the mice were determined by qRT-PCR. The dashed horizontal lines indicate the lowest limit of detection (E, F). Statistical significance between groups was analyzed using Kruskal–Wallis test with Dunn’s multiple comparisons (E, F). The grey asterisks represent statistical significance between the A(H3N2)-MA and the control group. The blue asterisks represent statistical significance between the A(H3N2)-MA and A(H3N2)-WT groups. Error bars indicate mean ± SD. **, P < 0.01

    Furthermore, we compared the pathogenicity of A(H3N2)-MA and A(H3N2)-WT in the mouse model infected with the same dose of 104.5 EID50/50 μL. In the A(H3N2)-MA group, the body weights gradually decreased to approximate 77% of initial weight at 8 dpi, and two of five mice died at 8 dpi, with a survival rate of 60% (Fig. 3C and D). Conversely, mice infected with A(H3N2)-WT exhibited no body weight loss compared to the control group, and all mice survived (Fig. 3C and D). Furthermore, the mean values of lung viral RNA loads of the mice infected with A(H3N2)-MA were 109.82, 1010.84, and 109.69 copies/mL at 3, 5, and 7 dpi, respectively (Fig. 3E), meanwhile virus loads in the nasal turbinate were 108.15, 108.91, and 108.17 copies/mL (Fig. 3F). In contrast, no viral RNA were detected in the lung and nasal turbinate of mice in the A(H3N2)-WT group at 3, 5, and 7 dpi. These findings indicated that the pathogenicity and replication capacity of the A(H3N2)-MA strain were significantly greater than those of the A(H3N2)-WT strain.

    Tissue tropism of A(H3N2)-MA and A(H3N2)-WT in the mouse model

    To evaluate tissue tropism of the A(H3N2)-MA and -WT strains, we also measured the virus RNA loads in seven tissues (including the heart, liver, spleen, kidney, intestine, stomach, and brain) from the infected mice with 104.5 EID50 at 3, 5, and 7 dpi. The results exhibited that no viral RNA was detected in these seven tissues, regardless of the A(H3N2)-MA or A(H3N2)-WT strains (Fig. S1). These findings suggested that the tissue tropism of A(H3N2)-MA has not changed compared to the WT strain, although the replication ability of the MA strain significantly increased in the respiratory system.

    Lung pathology and cytokine changes in mice infected with A(H3N2)-MA and A(H3N2)-WT

    Next, we compared the pathological and inflammatory factor changes in the lungs of the mice infected with A(H3N2)-MA and A(H3N2)-WT viruses. At 7 dpi, lung tissue infected with A(H3N2)-MA showed more severe pathological damage than those with A(H3N2)-WT. In the A(H3N2)-MA group, greater infiltration of inflammatory cells into the alveoli, blood vessels, and bronchioles, as well as increased shedding of bronchiolar epithelial cells were observed (Fig. 4A). Consistently, the histopathological score for the A(H3N2)-MA group was significantly elevated compared with the A(H3N2)-WT group. But no significant difference was observed between the A(H3N2)-WT and the control groups (Fig. 4B).

    Fig. 4
    figure 4

    Lung histopathology and inflammatory factors in mice infected with A(H3N2)-MA and A(H3N2)-WT. Mice were intranasally infected with 104.5 EID50/50 μL A(H3N2)-MA or A(H3N2)-WT, respectively. The control mice were intranasally inoculated with an equal volume of sterile PBS. A Histopathological changes in the lungs of mice were analyzed at 7 dpi. The scale bar represents 100 μm, and the magnification is 100x. B Histopathological scores for the lungs at 7 dpi. The levels of cytokines and chemokines (C) IL-6, (D) TNF, (E) MCP-1, and (F) IFN-γ in the lungs of mice were measured at 3, 5, and 7 dpi, respectively. Five mice were in each group. Statistical significance between groups was analyzed using the Kruskal–Wallis test with Dunn’s multiple comparisons (B, C, D, E, F). The grey asterisks represent statistical significance between the A(H3N2)-MA and the control group. The blue asterisks represent statistical significance between the A(H3N2)-MA and A(H3N2)-WT groups. Error bars represent mean ± SD. *, P < 0.05; **, P < 0.01; ***, P < 0.001

    We then assessed the levels of cytokines and chemokines in the mouse lungs from the A(H3N2)-MA, A(H3N2)-WT, and control groups. Pro-inflammatory factors including IL-6 (Fig. 4C), TNF (Fig. 4D), and MCP-1 (Fig. 4E) were significantly higher in the A(H3N2)-MA group than in the A(H3N2)-WT group at 3, 5, and 7 dpi. Additionally, the level of the pro-inflammatory factor, IFN-γ, was significantly higher in the A(H3N2)-MA group compared with the A(H3N2)-WT group at 5 dpi and 7 dpi (Fig. 4F). These results suggested that the infection of A(H3N2)-MA induced more severe lung pathological damage and inflammatory response than the A(H3N2)-WT.

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  • Lost Your Job? Xbox Exec Says Talk to a Chatbot About Your Feelings – PCMag

    1. Lost Your Job? Xbox Exec Says Talk to a Chatbot About Your Feelings  PCMag
    2. Laid-off workers should use AI to manage their emotions, says Xbox exec  The Verge
    3. Xbox Producer Offers Laid-Off Devs to Use AI For ‘Emotional Clarity & Confidence’  80 Level
    4. Xbox executive producer offers “best advice I can” to those caught up in Microsoft’s latest lay-off spree – AI prompts to “help reduce the emotional and cognitive load that comes with job loss”  GamesRadar+
    5. Xbox Producer Recommends Laid Off Workers Should Use AI To ‘Help Reduce The Emotional And Cognitive Load That Comes With Job Loss’  aftermath.site

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  • Pakistan taught India an unforgettable lesson: Ishaq Dar

    Pakistan taught India an unforgettable lesson: Ishaq Dar



    Pakistan


    Credits military success, national unity, and diplomacy for Pakistan’s standing on the global stage





    LAHORE (Dunya News) – Deputy Prime Minister Ishaq Dar stated that on May 9 and 10, Pakistan taught India a lesson it will never forget.

    Speaking to the media outside Data Darbar in Lahore, he said that Pakistan emerged successful against Indian aggression and the global community recognised Pakistan’s role.

    Dar expressed gratitude to God for Pakistan’s success, saying that Pakistan defeated a much larger adversary. “We downed six Indian fighter jets during the conflict. God granted Pakistan both respect and victory. The civil and military leadership defended the country with great success,” he said.

    Refuting rumours about a meeting between Nawaz Sharif and Imran Khan, Dar said, “These are mere speculations and not based on facts. Any reports of Nawaz visiting Adiala Jail are purely speculative.”

    He added, “When India attacked, we reached out to all political parties. The world heard our united voice. We are ready to work with political parties, and legal accountability will follow if anyone violated the law in the past.”

    Praising the armed forces, he said: “We are proud of our military. Pakistan currently holds the presidency of the UN Security Council. We condemned Israeli aggression against Iran. The Iranians—our Muslim brothers—expressed deep gratitude to Pakistan. We aim for peace and prosperity in this region.”

    He emphasised that Pakistan is now on a path of development. “Inflation is decreasing, prosperity is returning, and employment opportunities will rise. In 2022, the country was in deep crisis, and without a change in leadership, we could have defaulted. We bore political losses to put the country first.”

    Dar added that Prime Minister Shehbaz Sharif is working tirelessly to ensure the country’s progress.

    “The economy is stabilising, and we are proud of our armed forces, who are bravely fighting terrorism. Our soldiers are sending extremists to hell.”

    He concluded by saying, “Iran has realised that Pakistan is its true friend. Iranian parliament chanted ‘Thank You Pakistan’ slogans, and Pakistani flags were seen at the funerals of Iranian martyrs.”

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  • Ant genes show how evolution created perfect teamwork

    Ant genes show how evolution created perfect teamwork

    Ants, with their unique genes, outnumber people by roughly 2.5 million to one. Their combined dry mass, about 12 million tons of carbon, rivals one‑fifth of humanity’s weight on land.

    An international research team has compared 163 ant genomes to show how these insects turned cooperative living into an evolutionary engine. They reshuffled DNA while guarding key caste genes for more than 100 million years.

    Genetic clues to colony life


    Dr. Lukas Schrader of the University of Münster helped coordinate the project and still sounds amazed by its scope.

    Charles Darwin once fretted over sterile workers, calling them a “special difficulty” because natural selection seemed unable to favor individuals that never breed.

    Inclusive‑fitness theory, formalized in 1964, solved the logic by showing that workers spread their genes by helping sisters.

    The new data add genetic proof to that idea: worker‑specific gene clusters stayed almost identical across lineages, hinting that any mutation hurting brood care was swiftly purged.

    Ant colonies behave like bodies

    Biologists label an ant colony a superorganism because its members behave like cells of one body.

    The new dataset spans army ants with millions of workers, species such as Camponotus japonicus whose queens dwarf their tiniest laborers more than 100‑fold, and even parasites that have lost workers altogether.

    Researchers sequenced 145 species from 25 countries and folded in 18 earlier genomes to reach chromosome‑level quality for 17 of them. That’s no small feat when many ants are smaller than a comma.

    “The publication is a milestone in our understanding of the molecular and genetic foundations of ants and probably also other social insects such as honeybees,” said Schrader.

    Across the tree, queen and worker blueprints sit side by side. Yet workers never hatch reproductive organs because development is rerouted by hormones and gene‑regulation circuits embedded in the shared DNA.

    Ants keep critical survival genes

    The study tracked synteny, the order of genes along a chromosome. Whole blocks had flipped, fused, or fractured at a rate up to four times that seen in vertebrates. Ant groups with the fastest breakage spawned the most species.

    Even so, 970 tiny gene clusters, street blocks in the genetic city, remained frozen across 80 percent of species. Many code for metabolism and caste traits, suggesting that breaking them would cripple colony function.

    One conserved block houses two vitellogenin genes vital for queen egg yolk and sits unchanged in 148 genomes. Another links fatty‑acid enzymes to worker‑biased expression, underlining how diet and labor intertwine.

    Holding those modules steady while the surrounding landscape rearranged let ants explore new lifestyles without losing the caste machinery that keeps colonies alive.

    Hormones decide jobs and stability

    A single molecule can tip a larva toward royalty or toil. Juvenile hormone has long been that switch, and gene copies for the enzyme JHAMT rise in species with extreme queen‑worker size gaps. 

    Insulin and MAPK signaling join the act. In the jumping ant Harpegnathos, blocking MAPK with the drug trametinib makes workers grow larger, echoing lab findings that this pathway expands ovaries when workers become egg‑laying gamergates. 

    The new comparison shows MAPK genes under intensified selection in lineages where workers can still replace a queen, but relaxed selection where caste roles are rock‑solid.

    That fits the idea that plastic colonies need fine hormonal tuning, while rigid ones lock their switches.

    Hormone receptors for juvenile hormone and insulin sit inside conserved synteny islands. This hints that the entire endocrine toolkit rode through deep time as a connected package.

    Ant genes shift with colony size

    Bigger colonies and steeper queen‑worker dimorphism marched together in evolution; both correlate with trails, trophallaxis, and worker polymorphism.

    Genes tied to brain development, such as GCM and the muscarinic receptor mAChR‑A, show worker‑type biased activity and signs of adaptive change in species sporting soldiers beside tiny foragers.

    Where workers lost ovaries altogether, selection on oogenesis genes like otu relaxed, but those same genes stay under pressure in species whose workers can still lay male eggs.

    Social parasites flip the pattern. Workerless inquilines shed odorant‑receptor genes and rack up chromosomal breaks, mirroring their narrow ecological niche and tiny population sizes.

    Ant genes explain social evolution

    Many themes, hormonal control, preserved gene neighborhoods, break‑induced innovation, also shape honeybees, wasps, and higher termites. Ants simply had a 150‑million‑year head start, offering a living time machine for social evolution.

    Knowing which genes stay linked during caste splits could aid synthetic‑biology efforts that aim to engineer division of labor in microbes or even tissues.

    The study also reminds us that nature can be both flexible and conservative: colonies reinvent chromosome layouts yet keep critical circuits intact, a balance worth emulating in adaptive technologies.

    Ants may be tiny, but their genomes read like manuals on how cooperation rewires life. Future research will test whether the same genetic choreography repeats whenever individual interests yield to collective success.

    The study is published in the journal Cell.

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  • Children Die, and Parents Go On Living

    Children Die, and Parents Go On Living

    Jenessa Abrams reviews Yiyun Li’s “Things in Nature Merely Grow.”

    Things in Nature Merely Grow by Yiyun Li. Farrar, Straus and Giroux, 2025. 192 pages.

    ONCE YOU ARE a mother, you are a mother forever. You are a mother before your child is born, you are a mother once your child becomes too large to fit in your arms, you are a mother when your child no longer needs you. You are a mother when your child leaves this earth before you do.

    Yiyun Li is a mother who has lost both of her children—her two sons: Vincent, who died at age 16 in 2017, and James, who died at age 19 in 2024. Each chose to end their lives by suicide. I use the language of “suicide” intentionally here; Li makes her disdain for euphemisms clear, given that their primary function is to make other people feel more comfortable. That is not her responsibility. Her responsibility is to her children. Should it be your desire to be made to feel more comfortable, should “a mother using the word ‘died’ or ‘death’ offen[d] your sensibilities,” then, “dear readers,” as Li writes near the beginning of her new book, Things in Nature Merely Grow, “this is a good time for you to stop reading.”

    Losing both of your children, no longer having their living physical forms as proof of their existence, does not mean that the relationship between mother and child ends. Instead, it must take a different form. Li, whose medium is writing, uses words to conjure up her children again in the pages of two books, each constructed with respect to both of her sons’ ways of existing within and experiencing the world.

    The first, Where Reasons End, written in the wake of Vincent’s suicide and published in 2019, is structured as an imagined conversation between a mother and her dead son. The volume was published as fiction “because it could only be called that: no dead child has ever come back to have an argument with his mother.” The second, Things in Nature Merely Grow, is the book Li wrote after James’s suicide and published this spring, a work of nonfiction in which she uses language to reconstruct thought, attempting to reconfigure the particular, astonishing complexity of her son’s mind—all the while knowing that it will be merely that: a reconstruction.

    Li’s project evokes the title of Elizabeth McCracken’s masterful 2008 memoir of the stillbirth of her first child: An Exact Replica of a Figment of My Imagination. I’ve always taken that title to mean that the living child McCracken later births is a replica of the dead child who lived only in her imagination. For Li, perhaps, the books she has written for her two sons are precisely that: replicas of them as they continue to live in her imagination. The “book for Vincent,” as Li often refers to it, is a book that captures his curiosity, his tenacious spark, their passionate mother-son sparring; it “was as much written for Vincent as it was written by Vincent.” James, on the other hand, “resisted metaphor and evaded attention,” making the task of summoning his essence in literature effectively impossible. Li understands this from the outset but chooses to write the book anyway. It is this understanding of the inherent impossibility of bringing James back that makes the resulting piece of writing so remarkable: “Anything I write for James,” she acknowledges,

    is bound to be a partial failure. Sooner or later there will come the moment when my understanding parts ways with his essence. I can ask questions—answerable or unanswerable—but it is likely that by the end of the book I will have failed to find the right questions, just as I will have failed to pinpoint the exact moment when James’s contemplation of suicide shifted from Vincent’s to his own.

    Within those sentences, which appear near the beginning of Things in Nature Merely Grow, Li arrives at what I believe is the essential project of the book: the conflation of her inability to recreate James in writing and her inability to have predicted his suicide. And yet, with painstaking care, Li resists reflecting on James’s death as if it had been preventable. Her work, and perhaps also her life, is dedicated to honoring her children and respecting the choices they made, which means not only writing in the vein of the distinct lives each lived but also repeatedly referring to their deaths as deaths, using the word suicide, again and again, so that we must acknowledge what it is that happened to them, what they chose, that they existed. That they exist still.

    ¤

    Things in Nature Merely Grow has an organically cyclical nature. There are refrains and repetitions, like mathematical equations, like philosophical conceits, like musical compositions—like James. Two of the most hauntingly affecting are products of one another, a play on a line in Camus’s Caligula (1944), which James had been rereading before his death: “Men die; and they are not happy.” As Li observes,

    Half of the line is a fact; the other half, a conjecture. There is no cause and effect emphasized: do men die because they are not happy, or are they not happy because they have to die someday? The two statements, existing together, are like two hands kept close, either barely touching or with their fingers intertwined.

    Li reinvents the line as “Children die, and parents go on living,” and she often returns to the image of two hands “barely touching or with fingers intertwined.” Each time these lines appear, they mean something slightly different. Each time, that meaning is clearer.

    Another unexpectedly compelling facet of Things in Nature Merely Grow’s composition is the frequent inclusion of voices outside of Li’s, in the form of emails, conversations, and telephone calls from close friends—which feel like her conduit for communication much in the same way her son James, who had a predilection for silence, turns toward logic, philosophy, and existentialist literature in order to speak. The book is given weight from the people who kept Li and her husband alive after the death of their children. That is never explicitly stated, but one feels the intensity of what these interlocutors mean to Li: people willing to look with her to see her dead children, to name them, to wonder into Vincent’s and James’s lives and their respective decisions to end them.

    There are two such inclusions—one near the beginning of the book and the other near the end—that serve as pillars holding the project together. The first arrives in the form of an email to Li “precisely an hour and a half after [James’s] death” from a friend who was one of James’s professors. “You did everything you could to help James find his place in life, but he wanted to leave and one must let go.” Li repeats the line in italics, ruminating on how deeply the friend understands James and understands the unforgiving nature of life itself. Like Li, I found myself repeating the line and rereading it countless times, feeling the words somewhere underneath my skin, knowing what it means to love someone fiercely whose experience of the world brings them astonishing pain. Recognizing that your desire for them to live is a desire that does not account for their suffering.

    Li’s decision to braid the narrative of James’s life and his death with fragments of speech and writing she received in the wake of his suicide is one of the many stylistic choices that ensures the book transcends genre conventions. Things in Nature Merely Grow is a textured, living record of Li’s unfathomable loss. Beyond that, it is an invitation to the reader to carry the unimaginable with her. It is an insistence: rather than turning away from the horror or gawking from a distance, it is necessary to sit inside the room where she and her husband are greeted by police officers for a second time to learn that their last living child has died.

    ¤

    At one point in the book, Li invokes the concept of assisted suicide, choosing to refer to it with that precise term rather than the elegant, somewhat poetically veiled death with dignity. I pondered this as I read. What does it mean for society to embrace one’s decision to wield power or to assert control over the end of their life when faced with a terminal physical illness in late adulthood, and why are we comparatively unable to understand that some younger people live every day of their lives with a pain that is unspeakable, a pain that makes living no less of a torment? “Those who have learned swimming in their childhood tend to swim unthinkingly,” Li reflects, after beginning swimming lessons following her sons’ deaths. “For some people, the same must be true in life; for them living is a natural process. This has never been the case for me or for my children.”

    Just as the mother character in Where Reasons End never asks her dead son, a portrait of the late Vincent, why he has killed himself, Li rarely wonders in Things in Nature Merely Grow why James has ended his life. The answer to that question will not change his death, and the answer, for her, is not unfamiliar. Toward the book’s close, Li describes a visit from a friend who asks “how much [Li] thought James’s suicide was connected to Vincent’s.” “Do you think,” the friend ventures, “that Vincent’s suicide might have given James a sense of possibility?” Another mother might fall apart at this question or become enraged, but Li feels gratitude. Her friend is willing to stare directly into the abyss of child loss with her, to ask a potentially off-limits question, which then allows Li—who is moving through the book as James might, leading with logic and reason—to ask herself: “How did my suicide attempts affect Vincent? Did I, by trying to end my life, also make him see that as a possibility to end his own suffering? Was I the person to have pointed at what separates life from death and said, Look, that partition is not as solid as people make it out to be?”

    Exercising (as ever) extraordinary control and restraint, Li refrains from opening this line of inquiry until the very end of Things in Nature Merely Grow. Before this inclusion, knowing that Li has been open, in the past, about her own suicide attempts, I felt shadows of the shield Joan Didion put up in Blue Nights (2011), the memoir she wrote after the death of her only child, her daughter Quintana. While Didion’s posture of distance is a signature of her style, I’ve always found Blue Nights less narratively satisfying than Didion’s earlier memoir The Year of Magical Thinking (2005), which follows her husband John’s unexpected death. In the latter, Didion exhibits traces of vulnerability that undercut her persona, but Blue Lights seems less interested in contending with the thorny complexities of a parent outliving their child. Li is a very different writer from Didion, though they share an aversion to sentimentality and are each masters in their own right. Li, for her part, chooses to see and see and see and see, reflecting and refracting the image of her hospitalizations for suicidal ideation and her sons’ successful attempts.

    A reader, naturally, might ask, following the logic Li herself embeds in the narrative: What might have happened had Li been able to write these books for her children before? To capture their essence while they were living, trace the shadows of their deaths earlier? Which, invoking Li’s preference for bluntness, is another way of asking: Could she have prevented their suicides? But it’s a false question, or, to use a term from the book, it is a pebble of a question: “Better kick the pebble out of your way instead of letting it stop you.” It is a pebble of a question because it presupposes that the deaths of Li’s children are her fault, it places the blame—the responsibility—on the mother. It puts the onus on her children living on her; it disregards the very likely possibility that they were deeply loved and that even that was not enough to make the pain of their lives livable. It disrespects James and Vincent’s choices as much as it does Li’s own.

    ¤

    Li does not discuss her suicide attempt fully until the second half of the book. She similarly waits until we’ve become familiar with James in the pages of Things in Nature Merely Grow before, indirectly, mentioning certain aspects of his identity that might provide fodder for investigation or assumptions about his decision to die. Initially, when these details appeared, my mind returned to Didion as I contemplated whether Li was protecting herself by withholding; then, I was reminded that, just as Li’s every word is painstakingly chosen, her every decision is measured, calculated, and weighed. Here, she ensures that the reader does not assume the role of detective to try to find clues or answers about James’s death, because doing so is a reductive act. His life is not a puzzle to be solved. Any attempt to do so is dismissive and pathologizing. The answer to his death is not what this book is about.

    This book is about James. At the same time, it is, in some ways, about Vincent and in others, about Li herself. Li has long alluded to the unhappiness of her childhood in communist China and her mother’s inhumane cruelty, but it is in Things in Nature Merely Grow that she lays bare her mother’s astonishing abuse. I suppose it is naive to consider a mother inflicting pain on her child as astonishing, but what is certainly astonishing is that in all of Li’s work, it is here, in this book for James, that she most bluntly presents her mother’s staggering violence.

    In a late section titled “Things I Never Told My Children,” Li writes about the beatings she endured at the whims of her mother. While the physical violence is devastating, what is arguably more devasting is the psychological violence Li’s mother inflicted, including inventing a game of isolation in which an imagined twin of Li is a child finally worthy of love. Throughout her childhood, Li’s mother asked her: “[D]o you want a dead mother or a mad mother?” In response, Li now writes: “Nobody knew that I had always thought a dead mother would be better than a mad mother,” adding, “That thought too was on my mind when I felt too bleak to live: it’s not my children’s job to keep me alive; in fact, it’s my job to protect them from myself, if I cannot save my sanity.” After Li’s suicide attempt, her mother’s response was “Why did you do that to me?” The question positions Li’s mother herself at the center of her daughter’s pain, rather than attempting to understand or acknowledge it.

    Intergenerational trauma defies language. We hold the wounds of our parents inside us: whether or not we’re aware of it, the violence is there, and our children may well feel it. Li’s decision to write about her mother now, then, in the wake of her children’s suicides, reads like an act of defiance, an act of freedom. It is a direct rejection of her mother’s question; just as Li is not responsible for the deaths of her sons, her sons are not responsible for the pain she experiences as she goes on living.

    ¤

    Toward the book’s close, Li includes a section titled “Minor Comedies—for James,” whose tone takes on an almost childlike glee—if one can ethically use the word “glee” in the space of child loss. Still, glee is the word that occurs to me each time I recall the section of text in which Li seems to inhabit the joy James might’ve felt had he been able to witness her dedicating a substantial portion of the book to publicly exposing the people who have behaved horrifically toward their family in the wake of the children’s deaths—so horrifically that their actions verge on comedy. There is a freeness to the prose in this section that feels shocking for a writer who is an artist of precision.

    The way Li playfully embraces vengeance feels both refreshing and somewhat dangerous. Suddenly, no one and nothing is safe: in a scathing paragraph of uncharacteristic catharsis, Li directly addresses the Chinese media and tabloids who ran salacious and crude headlines about the deaths of her children in conjunction with her perceived role in their suicides as well as the many visitors she and her husband were forced to host who inflicted their own harm. Most notable is the mother of one of Vincent’s friends, who came to “file a complaint about [Li’s] dead son.” To them, she now writes: “I am sorry for whatever losses you have suffered or whatever deficiencies you were born with that make you, unavoidably, who you are and what you are.” The descriptions of utter inhumanity serve as a reminder of the difficulty inherent in being human, a feeling Li and her children know intimately.

    There is no redemption arc in Things in Nature Merely Grow, no hero’s journey, no arrival at a deeper meaning of life after the compounding tragedies of Vincent and James’s suicides. Instead, there is an astonishing act of what Li refers to as “radical acceptance,” the only form of control she can assert on the tragedies of her life, which is to acknowledge them, which is not to try to play a god that she does not believe in, which is not to try to imagine (at least not for long and with very little indulgence) what might have happened if she had mothered her sons differently, what might have happened if her sons had discovered a world in which they could live—though, of course, they have one now. It is the world she has made in the books she wrote for them.

    LARB Contributor

    Jenessa Abrams is a writer, literary translator, and practitioner of narrative medicine. Her fiction, literary criticism, and creative nonfiction have appeared in publications such as The Atlantic, The New York Times, the Chicago Review of Books, BOMB, and elsewhere.

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    • Ultimately, “Where Reasons End” is a tremendous act of empathy.

    • Jenessa Abrams reviews “Liars” by Sarah Manguso in the wake of Andrea Skinner’s essay about her sexual abuse at the hands of her stepfather, and her mother Alice Munro’s silence.

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    LARB publishes daily without a paywall as part of our mission to make rigorous, incisive, and engaging writing on every aspect of literature, culture, and the arts freely accessible to the public. Help us continue this work with your tax-deductible donation today!

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  • Infinix Hot 60 5G+ is launching next week with ‘One-Tap AI Button’

    Infinix Hot 60 5G+ is launching next week with ‘One-Tap AI Button’

    Infinix recently unveiled the Hot 60i with the Helio G81 Ultimate chip at the helm, and now it has announced that it will soon launch the Hot 60 5G+ featuring a “One-Tap AI Button.”

    The image shared by Infinix with us shows that the One-Tap AI Button will be located on the right side of the Hot 60 5G+ below the volume rocker and power button. Infinix says it’s a “smart and seamless shortcut that redefines user interaction” with the device and is designed for professionals, gamers, students, and regular users alike.

    The One-Tap AI Button supports single press, double press, and long press, and can be customized for over 30 apps. Moreover, the AI Button adapts to an individual’s usage patterns to provide relevant, real-time assistance.

    The One-Tap AI Button can also be used to summarize articles, trigger Circle to Search, or get explanations of the on-screen content. It can also launch personalized tools based on the content displayed on the phone’s screen.

    Infinix hasn’t revealed anything else about the Hot 60 5G+, but said the smartphone will launch in India on July 11 and will be sold online exclusively through Flipkart.

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  • Why are heart attacks less deadly then they used to be

    Why are heart attacks less deadly then they used to be

    A day before my 47th birthday last month, I took the subway to Manhattan’s Upper East Side for a coronary artery calcium scan (CAC).

    For those who haven’t entered the valley of middle age, a CAC is a specialized CT scan that looks for calcium deposits in the heart and its arteries. Unlike in your bones, having calcium in your coronary arteries is a bad thing, because it indicates the buildup of plaque comprised of cholesterol, fat, and other lovely things. The higher the calcium score, the more plaque that has built up — and with it, the higher the risk of heart disease and even heart attacks.

    A couple of hours after the test, I received a ping on my phone. My CAC score was 7, which indicated the presence of a small amount of calcified plaque, which translates to a “low but non-zero cardiovascular risk.” Put another way, according to one calculator, it means an approximately 2.1 percent chance of a major adverse cardiovascular event over the next 10 years.

    2.1 percent doesn’t sound high — it’s a little higher than the chance of pulling an ace of spades from a card deck — but when it comes to major adverse cardiovascular events, 2.1 percent is approximately 100 percent higher than I’d like. That’s how I found myself joining the tens of millions of Americans who are currently on statin drugs, which lower levels of LDL cholesterol (aka the “bad” cholesterol).

    I didn’t really want to celebrate my birthday with a numerical reminder of my creeping mortality. But everything about my experience — from the high-tech calcium scan to my doctor’s aggressive statin prescription — explains how the US has made amazing progress against one of our biggest health risks: heart disease, and especially, heart attacks.

    A dramatic drop in heart attack deaths

    A heart attack — which usually occurs when atherosclerotic plaque partially or fully blocks the flow of blood to the heart — used to be close to a death sentence. In 1963, the death rate from coronary heart disease, which includes heart attacks, peaked in the US, with 290 deaths per 100,000 population. As late as 1970, a man over 65 who was hospitalized with a heart attack had only a 60 percent chance of ever leaving that hospital alive.

    A sudden cardiac death is the disease equivalent of homicide or a car crash death. It meant someone’s father or husband, wife or mother, was suddenly ripped away without warning. Heart attacks were terrifying.

    Yet today, that risk is much less. According to a recent study in the Journal of the American Heart Association, the proportion of all deaths attributable to heart attacks plummeted by nearly 90 percent between 1970 and 2022. Over the same period, heart disease as a cause of all adult deaths in the US fell from 41 percent to 24 percent. Today, if a man over 65 is hospitalized with a heart attack, he has a 90 percent chance of leaving the hospital alive.

    By my calculations, the improvements in preventing and treating heart attacks between 1970 and 2022 have likely saved tens of millions of lives. So how did we get here?

    In 1964, the year after the coronary heart disease death rate peaked, the US surgeon general released a landmark report on the risks of smoking. It marked the start of a decades-long public health campaign against one of the biggest contributing factors to cardiovascular disease.

    That campaign has been incredibly successful. In 1970, an estimated 40 percent of Americans smoked. By 2019, that percentage had fallen to 14 percent, and it keeps declining.

    The reduction in smoking has helped lower the number of Americans at risk of a heart attack. So did the development and spread in the 1980s of statins like I’m on now, which make it far easier to manage cholesterol and prevent heart disease. By one estimate, statins save nearly 2 million lives globally each year.

    When heart attacks do occur, the widespread adoption of CPR and the development of portable defibrillators — which only began to become common in the late 1960s — ensured that more people survived long enough to make it to the hospital. Once there, the development of specialized coronary care units, balloon angioplasty and artery-opening stents made it easier for doctors to rescue a patient suffering an acute cardiac event.

    Our changing heart health deaths

    Despite this progress in stopping heart attacks, around 700,000 Americans still die of all forms of heart disease every year, equivalent to 1 in 5 deaths overall.

    Some of this is the unintended result of our medical success. As more patients survive acute heart attacks and life expectancy has risen as a whole, it means more people are living long enough to become vulnerable to other, more chronic forms of heart disease, like heart failure and pulmonary-related heart conditions. While the decline in smoking has reduced a major risk factor for heart disease, Americans are in many other ways much less healthy than they were 50 years ago. The increasing prevalence of obesity, diabetes, hypertension, and sedentary behavior all raise the risk that more Americans will develop some form of potentially fatal heart disease down the line.

    Here, GLP-1 inhibitors like Ozempic hold amazing potential to reduce heart disease’s toll. One study found that obese or overweight patients who took a GLP-1 inhibitor for more than three years had a 20 percent lower risk of heart attack, stroke, or death due to cardiovascular disease. Statins have saved millions of lives, yet tens of millions more Americans could likely benefit from taking the cholesterol-lowering drugs, especially women, minorities, and people in rural areas.

    Lastly, far more Americans could benefit from the kind of advanced screening I received. Only about 1.5 million Americans received a CAC test in 2017, but clinical guidelines indicate that more than 30 million people could benefit from such scans.

    Just as it is with cancer, getting ahead of heart disease is the best way to stay healthy. It’s an astounding accomplishment to have reduced deaths from heart attacks by 90 percent over the past 50-plus years. But even better would be preventing more of us from ever getting to the cardiac brink at all.

    A version of this story originally appeared in the Good News newsletter. Sign up here!

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  • Vizsla Silver Corp.’s (TSE:VZLA) market cap touched CA$1.4b last week, benefiting both individual investors who own 59% as well as institutions

    Vizsla Silver Corp.’s (TSE:VZLA) market cap touched CA$1.4b last week, benefiting both individual investors who own 59% as well as institutions

    • The considerable ownership by individual investors in Vizsla Silver indicates that they collectively have a greater say in management and business strategy

    • The top 25 shareholders own 36% of the company

    • Insiders have been selling lately

    This technology could replace computers: discover the 20 stocks are working to make quantum computing a reality.

    To get a sense of who is truly in control of Vizsla Silver Corp. (TSE:VZLA), it is important to understand the ownership structure of the business. And the group that holds the biggest piece of the pie are individual investors with 59% ownership. In other words, the group stands to gain the most (or lose the most) from their investment into the company.

    While individual investors were the group that reaped the most benefits after last week’s 5.6% price gain, institutions also received a 34% cut.

    Let’s delve deeper into each type of owner of Vizsla Silver, beginning with the chart below.

    See our latest analysis for Vizsla Silver

    TSX:VZLA Ownership Breakdown July 5th 2025

    Institutional investors commonly compare their own returns to the returns of a commonly followed index. So they generally do consider buying larger companies that are included in the relevant benchmark index.

    Vizsla Silver already has institutions on the share registry. Indeed, they own a respectable stake in the company. This suggests some credibility amongst professional investors. But we can’t rely on that fact alone since institutions make bad investments sometimes, just like everyone does. If multiple institutions change their view on a stock at the same time, you could see the share price drop fast. It’s therefore worth looking at Vizsla Silver’s earnings history below. Of course, the future is what really matters.

    earnings-and-revenue-growth
    TSX:VZLA Earnings and Revenue Growth July 5th 2025

    We note that hedge funds don’t have a meaningful investment in Vizsla Silver. Our data shows that Sprott Inc. is the largest shareholder with 7.0% of shares outstanding. In comparison, the second and third largest shareholders hold about 4.2% and 3.1% of the stock. In addition, we found that Michael Konnert, the CEO has 0.7% of the shares allocated to their name.

    Our studies suggest that the top 25 shareholders collectively control less than half of the company’s shares, meaning that the company’s shares are widely disseminated and there is no dominant shareholder.

    Researching institutional ownership is a good way to gauge and filter a stock’s expected performance. The same can be achieved by studying analyst sentiments. There are plenty of analysts covering the stock, so it might be worth seeing what they are forecasting, too.

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  • Heavy rain forecast across Punjab on Ashura

    Heavy rain forecast across Punjab on Ashura

    Listen to article

    A fresh spell of monsoon rains has entered Punjab, with the Pakistan Meteorological Department forecasting heavy showers in Lahore and several other districts across the province on Ashura (Muharram 10).

    The Provincial Disaster Management Authority (PDMA) has issued an alert for possible rainfall on Ashura, warning of intense downpours in Lahore, Rawalpindi, Gujranwala, Gujrat, Sialkot, Sargodha, and Faisalabad.

    Experts have predicted that the current monsoon system could persist until July 10, potentially raising water levels in rivers and streams.

    Rescue 1122 teams have been placed on full alert, while the Disaster Response Force has been instructed to remain fully equipped and ready. Citizens are urged to follow safety precautions and contact the PDMA helpline (1129) in case of emergencies.

    Meanwhile, after a hot and humid day in Lahore, the provincial capital is expected to receive heavy rain with thunder and lightning late at night. Temperatures in the city are forecast to range between 30°C and 37°C.

    The Met Office has warned that rainfall of varying intensity—ranging from light to heavy—is expected in multiple areas of Punjab due to the re-entry of a rain-bearing monsoon system. Strong winds and further downpours are likely to continue in the coming days.

    Residents of Lahore have expressed concern over the slow pace of infrastructure development projects, warning that incomplete work could lead to severe disruptions during heavy monsoon rains.

    Read More: NDMA issues new alert for heavy rain, storms across country

    Overnight, heavy rain lashed the twin cities of Rawalpindi and Islamabad, prompting the Water and Sanitation Agency (WASA) to issue a high alert and declare a rain emergency amid fears of water accumulation in low-lying areas.

    Saidpur received the highest rainfall with 80 mm recorded, followed by 40 mm at PMD, 20 mm at Shamsabad, and 15 mm at Pirwadhai.

    According to the National Disaster Management Authority (NDMA), flash floods and heavy rainfall have claimed 64 lives and injured 117 people nationwide over the past week.

    Khyber Pakhtunkhwa has been the worst-hit region, with 23 fatalities, including 10 children. In Punjab, 21 people lost their lives, while Sindh and Balochistan reported 15 and five deaths, respectively.


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  • Heavy rain forecast across Punjab on Ashura

    Heavy rain forecast across Punjab on Ashura

    Listen to article

    A fresh spell of monsoon rains has entered Punjab, with the Pakistan Meteorological Department forecasting heavy showers in Lahore and several other districts across the province on Ashura (Muharram 10).

    The Provincial Disaster Management Authority (PDMA) has issued an alert for possible rainfall on Ashura, warning of intense downpours in Lahore, Rawalpindi, Gujranwala, Gujrat, Sialkot, Sargodha, and Faisalabad.

    Experts have predicted that the current monsoon system could persist until July 10, potentially raising water levels in rivers and streams.

    Rescue 1122 teams have been placed on full alert, while the Disaster Response Force has been instructed to remain fully equipped and ready. Citizens are urged to follow safety precautions and contact the PDMA helpline (1129) in case of emergencies.

    Meanwhile, after a hot and humid day in Lahore, the provincial capital is expected to receive heavy rain with thunder and lightning late at night. Temperatures in the city are forecast to range between 30°C and 37°C.

    The Met Office has warned that rainfall of varying intensity—ranging from light to heavy—is expected in multiple areas of Punjab due to the re-entry of a rain-bearing monsoon system. Strong winds and further downpours are likely to continue in the coming days.

    Residents of Lahore have expressed concern over the slow pace of infrastructure development projects, warning that incomplete work could lead to severe disruptions during heavy monsoon rains.

    Read More: NDMA issues new alert for heavy rain, storms across country

    Overnight, heavy rain lashed the twin cities of Rawalpindi and Islamabad, prompting the Water and Sanitation Agency (WASA) to issue a high alert and declare a rain emergency amid fears of water accumulation in low-lying areas.

    Saidpur received the highest rainfall with 80 mm recorded, followed by 40 mm at PMD, 20 mm at Shamsabad, and 15 mm at Pirwadhai.

    According to the National Disaster Management Authority (NDMA), flash floods and heavy rainfall have claimed 64 lives and injured 117 people nationwide over the past week.

    Khyber Pakhtunkhwa has been the worst-hit region, with 23 fatalities, including 10 children. In Punjab, 21 people lost their lives, while Sindh and Balochistan reported 15 and five deaths, respectively.


    Continue Reading