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Microplastics exposures in cataract surgery and potential clinical concerns
Long-Term Survivorship After Chimeric Antigen Receptor T-Cell Therapy for Hematologic Malignancies
Clinical trials and real-world evidence have established the benefit of chimeric antigen receptor (CAR) T-cell therapy to reduce progression of hematologic malignancies and, in some settings, increase overall survival. However, recent studies have highlighted that patients in long-term remission remain at risk of morbidity and nonrelapse mortality, primarily because of infections and subsequent myeloid malignancies. In addition, these patients may also be survivors of chemotherapy, radiation, and/or stem-cell transplant, with broad survivorship needs. Here, we provide a roadmap for the care of patients in long-term remission after CAR-T-cell therapies and discuss avenues for future research.
Evolutionary trade-offs under stochastic water stress shape xylem vulnerability to drought
Damage to the water supply system in plants (xylem) during water stress is a major cause of plant mortality under drought. However, theory is lacking for the evolutionary emergence of, and variation in, the ability of xylem to resist damage when the maximum water stress experienced each year is stochastic. We determine optimal xylem vulnerability to water stress that balances trade-offs among water transport for photosynthetic carbon gains, carbon costs of constructing xylem that is resistant to damage, and the likelihood of experiencing water stress. Higher water stress optimally selects for higher resistance to water stress, loss of functional xylem over a larger range of water stress, greater water use efficiency, and, counterintuitively, higher chances of complete loss of xylem function despite larger hydraulic safety margins. The greater hydraulic safety observed in gymnosperms over angiosperms is most likely because of less severe increases in the cost of xylem that can withstand higher water stress. Species with longer-lived xylem are predicted to be especially vulnerable to increased mortality if transitions to a drier climate occur faster than adaptation. Our stochastic water stress theory shows that a relative metric of hydraulic safety, the hydraulic safety index, coupled with climate variability, better reflects the likelihood of hydraulic failure than does the widely used hydraulic safety margin. By placing water stress in a stochastic framework, our theory provides insights into adaptive xylem vulnerability and the risk of hydraulic failure.
Functional study of two flexible regions of the hepatitis E virus ORF1 replicase
Hepatitis E virus (HEV), like other positive-sense RNA viruses, encodes a multidomain protein essential for replication, termed ORF1. However, the number, organization, and functions of its domains remain debated. Using AlphaFold2-based structural modeling, we investigated two structurally disordered regions with potential regulatory functions: (i) a 16-residue linker between the Helicase (Hel) and RNA-dependent RNA polymerase (RdRp) domains, proposed as a cleavage site and/or a flexible hinge, and (ii) the RdRp C-terminal tail, suggested to modulate polymerase activity through conformational plasticity. We performed mutagenesis of the Hel/RdRp linker and analyzed the impact of mutations on ORF1 maturation, subcellular localization, and replication efficiency. Using an extensive antibody panel combined with precise protein sizing, we found that ORF1 is predominantly expressed as a full-length protein with an apparent molecular weight of ~235 kDa by SDS-PAGE, together with several low-abundance truncated products, including the previously described HEV-derived SMAD activator (HDSA) fragment. These results suggest that ORF1 likely undergoes post-translational modifications and partial maturation by cellular proteases and/or spontaneous truncations in exposed regions. Importantly, Hel/RdRp linker mutations did not alter the ORF1 expression profile or subcellular localization, arguing against cleavage within this region. However, substitutions of conserved residues in the linker strongly impaired HEV replication, highlighting the functional importance of this disordered segment for viral genome replication. Boltz-1 structural modeling suggests a direct involvement of the Hel-RdRp linker in positioning the two enzymes, particularly for synthesis of the subgenomic RNA. Similarly, deletions or substitutions within the last 20 C-terminal RdRp residues abolished or severely impaired HEV replication. This demonstrates that the conformational flexibility of the RdRp C-terminal segment is likely critical for ORF1 function, e.g., for polymerase activity. In conclusion, although ORF1 likely undergoes tightly regulated processing, cleavage is unlikely to occur within the Hel/RdRp linker. Nevertheless, this segment and the conformational dynamics of the RdRp C-terminus emerge as key regulatory elements required for efficient HEV replication, pointing to novel mechanistic layers of control in the HEV replication process.
Correction: Discovery of novel disulfide-containing PD-1/PD-L1 inhibitor with in vivo influenza therapeutic efficacy
Erratum: Efficacy and Biomarker Study of Bevacizumab for Hearing Loss Resulting From Neurofibromatosis Type 2–Associated Vestibular Schwannomas
Climate-driven divergence in biophysical and economic impacts of agrivoltaics
Increasing global demands for food and energy necessitate innovative land-use solutions. Agrivoltaics, colocating solar photovoltaics with agriculture, shows promise, but its widespread adoption faces complex biophysical and economic trade-offs in a changing climate. Here, we develop an integrated biophysical–economic modeling framework to quantify how agrivoltaics affect biophysical and economic impacts across the Midwestern United States under both current and project climate conditions. We find strong regional divergences driven by climate gradients. In the humid eastern Midwest, solar panel shading limits photosynthesis, leading to reduced yields (maize −24%; soybean −16%) and lower farmers’ profitability (maize −16%; soybean −2%) compared to conventional agriculture. Conversely, in the semiarid western region, shading alleviates heat and water stress, moderating yield reductions for maize (−12%) and even boosting soybean yields (+6%), resulting in improved economic returns (−6% for maize; +9% for soybean), for a scenario with 33% photovoltaic ground coverage ratio. Although agrivoltaics generate substantial electrical energy across all regions, high upfront installation costs challenge solar developers compared to standalone solar photovoltaics. However, our analysis identifies “win-win” opportunities where soybean-based agrivoltaics in the semiarid region produce economic benefits for both farmers and solar developers, highlighting the necessity for region-specific designs tailored to local climate conditions. Critically, future climate projections indicate eastward expansion of semiarid conditions, broadening areas where agrivoltaics can mitigate crop yield penalties (even boosting yield) and improve overall profitability, especially under high-emission scenarios. The results provide a mechanistic and economically integrated understanding essential for developing evidence-based and region-specific strategies to scale agrivoltaics in a changing climate.
The biodegradable mGnRHa-Poly[lactic-co-glycolic acid] microparticles enhances semen quality in multi-stripped rainbow trout
To reduce reproduction costs, broodstock undergo multiple stripping, during which semen quality gradually declines toward the end of the spawning season. One potential solution is the use of slow-release delivery systems such as mGnRHa-PLGA (Poly[lactic-co-glycolic acid]) microparticles to prolong the spermiation period. In this study, mGnRHa microparticles with an average size of 14.77 ± 8.09 µm were prepared using an oil-in-water emulsion that release more than 72% of the mGnRHa within 61 days at 12°C. For the in vivo trial, during the end of the natural spawning season, 50 mature rainbow males (738.60 ± 104.86 g and 40.09 ± 2.03 cm) were randomly divided into 5 groups. The control group (C) received 1 mL kg -1 physiological saline. The second group (10A) received 10 μg kg -1 mGnRHa. The third to fifth groups (10M, 20M, and 40M) received 10, 20, and 40 μg kg -1 mGnRHa in the form of mGnRHa-PLGA microparticles, respectively. Semen and blood samples were collected at 0, 9, 21, 47, and 61 days days post injection (dpi) for semen quality and sex steroid hormones assessments. Only 40M group continued to release semen until 61 dpi. The 40M group showed the highest semen volume and sperm density throughout the experimental period, while no significant differences were observed between C, 10A, and 10M groups. At 21, 47, and 61 dpi, the 40M group exhibited the highest sperm density, semen volume, and plasma testosterone levels among all groups. At 61 dpi, 40M group showed the highest GSI and the largest surface area occupied by spermatids and spermatozoa. Finally, while the acute mGnRHa failed to enhance spermiation parameters under multiple stripping conditions, the 40M were capable of increasing the duration of semen release and boosting semen volume at the end of spawning season. This study provided aquaculturists with novel information to improve reproductive performance in rainbow trout hatcheries.
Correction: The effect of weight-bearing status on kinematics and cruciate ligament force in normal knees
Reply to: Enhancing Representation and Reporting of Body Mass Index in Cancer Randomized Clinical Trials
Ocean warming enhances iron use efficiencies of marine ammonia-oxidizing archaea
Ammonia-oxidizing archaea (AOA) are among the most abundant microorganisms in the ocean, playing a fundamental role in the marine nitrogen cycle. Although temperature and trace metal availability each individually influence the growth and activity of marine AOA, there is only a very limited understanding of the interactive effects of these two major factors on AOA in the rapidly changing ocean. Here, we show that the iron requirements of the model marine AOA species Nitrosopumilus maritimus SCM1 are highly sensitive to temperature changes. A 5 °C increase in growth temperature reduced SCM1 iron requirements by >80%, and was associated with a substantial increase in iron use efficiencies (IUE, mol C fixed/h/mol cellular Fe) under iron-limited and warming conditions. A thermally enhanced IUE enables SCM1 to more efficiently utilize scarce available iron supplies to support its growth. Whole-cell proteomic analysis revealed that iron limitation decreased expression of a ferredoxin and increased expression of a copper-dependent plastocyanin that became more pronounced with warming, suggesting coordinated electron transport response regulation under combined iron and temperature stress. The global impacts of these temperature-dependent changes to AOA iron demands were assessed using sensitivity experiments with a state-of-the-art biogeochemical model. Simulations showed that impacts on nitrification were concentrated at higher latitudes, but the alterations to ammonia concentrations were redistributed toward lower latitudes by mode and intermediate water transport. These findings reveal a previously unrecognized mechanism by which ocean warming may alleviate iron limitation of AOA, enhance their ecological competitiveness, and reshape ocean nitrogen cycling throughout marine ecosystems.
Systemic inflammatory response index is associated with acute kidney injury following cardiac surgery: A retrospective cohort study using the MIMIC database
Purpose This study aimed to investigate the association between the Systemic Inflammatory Response Index (SIRI) and acute kidney injury (AKI) following cardiac surgery using the Medical Information Mart for Intensive Care (MIMIC) database, and to evaluate whether SIRI could serve as a potential risk marker associated with post-cardiac surgery AKI. Methods We conducted a retrospective cohort study of 2,884 cardiac surgery patients from the MIMIC-IV database. SIRI was calculated as (neutrophil count × monocyte count)/ lymphocyte count. The primary outcome was AKI occurrence within seven days post-surgery. Logistic regression models and restricted cubic spline (RCS) analysis were used to assess the association between SIRI and AKI risk. Subgroup analyses were performed to evaluate potential effect modifiers. Results Higher SIRI levels were significantly associated with increased AKI risk, even after adjusting for potential confounders (OR for highest vs. lowest quartile: 1.35, 95% CI: 1.04–1.77). A dose-response relationship was observed between SIRI and AKI severity (P for trend < 0.001). The association between SIRI and AKI risk was more pronounced in patients with a history of myocardial infarction (OR: 1.261, 95% CI: 1.084–1.467) and those not using loop diuretics (OR: 2.306, 95% CI: 1.200–4.434). Conclusion SIRI showed a modest but significant association with AKI following cardiac surgery. Its integration of multiple inflammatory cell types provided a comprehensive assessment of inflammatory status. The varying strength of association across different patient subgroups suggested the need for individualized risk assessment strategies. Further research is warranted to validate these findings and explore the underlying mechanisms.
Indoor environmental factors and pneumonia in preschool children in Haikou China
Ethics of Backfilling in Early-Phase Oncology Trials
Dynamics of the attentional blink in preverbal infants
In the first months postterm, human infants are traditionally viewed as passive to their environment, unable to focus or sustain attention on specific objects. Here, we asked whether 4-mo-old infants could engage their attention strongly enough in a visual task to block the perception of a subsequent interesting stimulus—a phenomenon known as attentional blink, which in adults reflects a serial processing bottleneck for accessing a central workspace. We presented three successive visual events: a central teddy bear (T1) followed by a lateralized face and scrambled face (T2) at varying stimulus onset asynchrony (SOAs: 400, 800, and 1,200 ms), then the same face reappeared after 1,600 ms (T3). We monitored saccades toward the face, pupil size, and electroencephalic (EEG) responses to the flickering background. Our behavioral and EEG results showed that infants missed the lateralized face at the shortest SOA (400 ms). At 800 ms, detection occurred only when the face appeared in the left hemifield, while detection in the right hemifield required 1,200 ms, suggesting a hemispheric asymmetry in face processing. Furthermore, at SOAs where T2 should be visible, a trial-by-trial metric based on event-related variability revealed that the depth of attentional engagement to T1 predicted access to T2, despite identical visual input. These findings support the presence of a global workspace in early infancy, though with slower dynamics.
Correction: Endocrine advantages of PD-1/PD-L1 therapy: Comparative analysis of FAERS-JADER
Hybrid intelligence-powered secure clustering with trust-optimized routing for next-generation MANET communication
Erratum: BR.31 Trial: Adjuvant Durvalumab as the Third Contender in Resected Non–Small Cell Lung Cancer
Head-to-head comparison of brain-derived pTau217 and total pTau217 for brain amyloid and tau pathology classification
Phosphorylated-tau 217 (pTau217) is currently the most promising blood-based biomarker for accurately detecting Alzheimer’s disease (AD) pathology. However, interference from peripheral tau species in the kidneys or peripheral nerves can hinder diagnostic precision. Recently developed brain-derived pTau217 (BD-pTau217) assays emerge as highly specific tools for detecting AD-related pathological changes in the brain. In this study, we conducted a head-to-head comparison of the NULISAqpcr BD-pTau217 assay and Simoa ALZpath total p-Tau217 assay in two independent, amyloid-PET–characterized Chinese cohorts. Our results demonstrate a strong correlation between BD-pTau217 and total pTau217 (ρ = 0.89 to 0.90), with BD-pTau217 showing significantly reduced interference from kidney dysfunction, as evidenced by weaker associations with blood levels of urea (ρ BD-pTau217 = 0.02 to 0.06, ρ Total-pTau217 = 0.06 to 0.12) and creatinine (ρ BD-pTau217 = 0.03 to 0.08, ρ Total-pTau217 = 0.16 to 0.18). Moreover, BD-pTau217 is more strongly associated with amyloid-PET Centiloid values (ρ BD-pTau217 = 0.78 to 0.80, ρ Total-pTau217 = 0.74 to 0.77) and exhibits superior classification performance for amyloid-β (Aβ) pathology (area under the curve [AUC] BD-pTau217 = 0.96 to 0.98, AUC Total-pTau217 = 0.94 to 0.97). Furthermore, BD-pTau217 outperforms total pTau217 for identifying tau-positive individuals within the Aβ-positive group (AUC BD-pTau217 = 0.89, AUC Total-pTau217 = 0.78), facilitating more accurate disease staging. These findings underscore BD-pTau217 as a highly sensitive and specific blood-based biomarker for AD that has significant potential for early detection, precise classification, and staging of AD-related brain pathology in clinical practice.