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Human neonatal MR1T cells have more diverse TCR repertoires but reduced bacterial recognition than adult MR1T cells
Abstract Bacterial sepsis is a leading cause of neonatal mortality. Pro-inflammatory MR1-restricted T (MR1T) cells may help protect from sepsis by recognizing bacterial pathogens producing the canonical MR1 antigen 5-OP-RU. Most adult MR1T cells are mucosal-associated invariant T (MAIT) cells expressing a semi-invariant TCRα, while neonatal MR1T cells express diverse TCRα chains. Here, we perform combined single-cell RNA-sequencing and TCR repertoire analyses on MR1/5-OP-RU tetramer-positive cells from neonatal cord blood (CB) and adult blood. Compared to adult MR1T cells, CB MR1T cells exhibit greater TCR diversity, reduced cytotoxic and proinflammatory gene expression, diminished bacterial recognition and reduced binding to MR1/5-OP-RU. Structural analysis of a CB MAIT TCR reveals decreased β chain contribution to the TCR–MR1 interface relative to an adult MAIT TCR. These findings demonstrate developmental stage-specific differences in MR1T cell repertoire, function and MAIT TCR structure with implications for neonatal sepsis.
Comparative evaluation of iodinated, nanoparticle-based, and gadolinium-based contrast agents in computed tomography for small animals
Preclinical computed tomography (CT) is extensively used for anatomical reference and multimodal imaging, but the soft tissue contrast is poor compared to clinical CT. This hinders reliable organ delineation and segmentation in small-animal studies. We present a systematic evaluation of commonly used clinical iodinated and gadolinium-based contrast agents, together with a preclinical nanoparticle-based contrast agent. This evaluation aims to enhance soft-tissue boundary definition and in vivo visibility. The study consisted of two parts. First, phantom experiments were performed to assess the relationship between contrast-agent concentration and Hounsfield Unit (HU) across multiple dilutions and CT energy settings. Second, these findings were evaluated in vivo in mice to assess organ-level enhancement. Phantom measurements demonstrated a linear relationship between HU and concentration for all agents; however, at higher dilutions, contrast enhancement became indistinguishable from the background. In vivo, clinical iodinated and gadolinium-based agents administered intraperitoneal (IP) provided enhanced soft-tissue contrast by outlining abdominal organs, whereas the intravenously administered nanoparticle agent exhibited pronounced organ-specific accumulation. Overall, IP injection of clinical iodinated contrast agents offers a cost-effective and practical strategy for enhancing organ boundary visibility in preclinical CT. For longitudinal or organ-specific imaging studies, the preclinical nanoparticle-based contrast agent remains advantageous, as its cumulative uptake allows detection over extended periods and minimizes burden from multiple injections.
Temporal risk stratification using inflammation–nutrition indices in adults with diabetes
Isotopic constraints in methane inversions reveal larger trends in wetland emissions with improved linkage to terrestrial water storage
Abstract Accurately separating the contributions of different sources to recent atmospheric methane (CH 4 ) growth is crucial for better quantifying the present and future responses of CH 4 emissions to changing climate and anthropogenic activity. Here, we run atmospheric inversions to assess global and regional CH 4 emissions from microbial, fossil, and pyrogenic sources from 2000 to 2022, using measurements of atmospheric CH 4 and its stable carbon isotope ratio ( 13 C: 12 C, expressed relative to a standard as δ 13 C-CH 4 ). We confirm that global total CH 4 emissions has increased by 15% from 2000 to 2022, with dominated contribution from microbial emissions. Both microbial and fossil emissions increased during 2007–2013 relative to 2000–2006, with the largest contributions from temperate Asia. From 2014–2017, microbial emissions from tropical regions, particularly South America and Africa, were the dominant driver of the overall increase, while fossil emissions remained stable in Europe and North America. Between 2020 and 2022, microbial emissions surged in the African and Asian tropics, whereas fossil emissions declined across most industrial regions. Notably, inversions constrained only by CH 4 observations did not capture the decline in fossil emissions during 2020–2022, a decline potentially related to the COVID-19 pandemic, policy-driven changes, and decreases in CH 4 emissions intensity, highlighting the critical role of isotopic measurements in independently verifying changes in fossil emissions. Further, our inversion with isotopic constraints estimates a more prominent increase in wetland emissions that is 20–30% more strongly correlated with variations in terrestrial water storage during 2003–2022, demonstrating the importance of climate-driven natural sources in explaining long-term CH 4 growth.
Teacher feedback VS AI-assisted peer feedback in L2 writing: A quasi-experimental study in a Chinese University
Despite the growing interest in AI-assisted peer feedback, few studies have systematically compared it with teacher feedback within a sociocultural framework. Consequently, the dynamic evolution of these two modes, their effects on micro-linguistic features, and the possibility of integrated feedback models remain largely unexplored. To address these gaps, this study, grounded in Vygotsky’s theories of scaffolding and the Zone of Proximal Development (ZPD), adopted an 8-week quasi-experimental design to conduct a multi-dimensional comparison of teacher feedback and AI-assisted peer feedback among 61 university students (244 writing texts). The innovation lies in revealing, for the first time from a “heterogeneous scaffolds” perspective, the essential differences and complementary mechanisms between the two feedback types within a sociocultural framework. The main findings are: (1) Teacher feedback demonstrated a characteristic of “comprehensive coverage and dynamic adjustment,” whereas AI-assisted peer feedback exhibited features of “sustained focus and efficient guidance.” (2) Teacher feedback produced significant short-term improvement but insufficient subsequent momentum, while AI-assisted peer feedback displayed a stable “learning-curve effect.” (3) AI-assisted peer feedback enhanced lexical diversity only in the initial task, and neither approach significantly improved syntactic complexity. In terms of practical contributions, this study proposes concrete pathways for optimizing teacher feedback and improving AI-assisted peer feedback, and constructs a hybrid “AI-Peer-Teacher” integrated feedback model, offering an actionable reform proposal for English writing instruction in application-oriented universities.
BC-AWFedAvg: blockchain-assisted adaptive federated learning for secure RAN Slicing in beyond-5G networks
Abstract The evolution of beyond-5G networks introduces new challenges for radio resource management, particularly for heterogeneous service requirements across multiple virtual network operators. This work presents BC-AWFedAvg, a layered framework for federated deep reinforcement learning in O-RAN network slicing that integrates adaptive aggregation, blockchain-based governance, secure aggregation, and differential privacy. The proposed design separates learning, governance, and storage functions to support coordinated training while preserving privacy and limiting exposure of individual updates. Simulation results in the considered setting indicate that the proposed framework improved robustness in the considered setting under several adversarial scenarios while maintaining acceptable quality-of-service performance. These findings suggest that combining complementary mechanisms may be a promising direction for secure federated learning in next-generation wireless networks.
Plate tectonic history and ocean oxygenation shaping biogeography of hydrothermal bacterial community
Circulating biomarkers of bronchoalveolar injury help predict the need for mechanical ventilation in patients with moderate to severe COVID-19 pneumonia: A prospective cohort study
Background Severe respiratory failure is a major complication of SARS-CoV-2 infection, and the need for mechanical ventilation (MV) is associated with a worse outcome. Whether some soluble biomarkers of lung injury can help predict MV requirement remains unclear. Methods This prospective, observational, monocentric cohort study consecutively enrolled patients with laboratory-confirmed COVID-19 pneumonia within 48 h of hospital admission. The serum concentrations of five key bronchoalveolar epithelial and endothelial biomarkers were determined at Day 0, 7 and 14: Krebs von den Lungen-6 (KL-6); soluble receptor for advanced glycation end-products (sRAGE); club cell protein 16 (CC16); angiopoietin-2 (Ang-2); and soluble CD146 (sCD146). The respiratory severity of COVID-19 pneumonia was defined by the maximal level of respiratory support received during hospitalization: oxygen (by mask or nasal prong); high flow oxygen therapy (HFOT); and MV. End-points were the need for MV during hospitalization and the time to liberation from oxygen. Results Fifty-four COVID-19 patients were enrolled; 23 (43%) required MV, 13 (24%) HFOT, and 18 (33%) oxygen. At inclusion, levels of KL-6, sRAGE, and CC16 were significantly higher in MV compared with non-MV patients (p < 0.05), with sRAGE showing the greatest difference (2.4-fold increase). In multivariate logistic regression, sRAGE (OR per 1000 pg/mL increase 1.316; 95% CI [1.040–1.667]; p = 0.022) and SpO 2 /F I O 2 (OR 0.984; 95% CI [0.970–0.998]; p = 0.008) were identified as independent risk factors for MV. Furthermore, patients with an sRAGE ≥ 5449 pg/mL at inclusion had a lower probability of weaning from oxygen at Day 60 (HR 0.36; 95% CI [0.19–0.67]; p = 0.001). From Day 7 to Day 14, CC16 levels increased while sCD146 levels decreased in MV patients. Conclusion Among five circulating biomarkers of bronchoalveolar injury, sRAGE showed the most favorable kinetic profile, rapidly increasing in MV patients. The early measurement of sRAGE and SpO 2 /F I O 2 upon hospital admission may effectively identify COVID-19 patients at high risk of requiring MV and prolonged oxygen support.
Cardiomyocyte lamin A re-expression via AAV-Lmna/DJ8 ameliorates cardiac dysfunction in Lmna−/− mice
Abstract Mutations in LMNA , which encodes the nuclear envelope protein lamin A/C, cause laminopathies that frequently present as dilated cardiomyopathy (DCM). We investigated whether re-expression of lamin A in cardiomyocytes can rescue the severe phenotype of Lmna −/− mice. An adeno-associated virus vector expressing wild-type Lmna (AAV- Lmna /DJ8) was administered intrathoracically to neonatal mice. Three weeks after injection, treated Lmna −/− mice exhibited robust cardiac Lmna mRNA induction and correct nuclear localization of lamin A protein, indicating efficient cardiotropic gene delivery. Compared with PBS treatment, AAV- Lmna /DJ8 treatment promoted body weight maintenance, improved left ventricular systolic function, and significantly prolonged survival in Lmna −/− mice. To explore the underlying mechanisms, we performed single-nucleus RNA sequencing of cardiomyocytes from wild-type mice, PBS-treated Lmna −/− mice, and AAV- Lmna /DJ8–treated Lmna −/− mice. AAV-mediated lamin A re-expression shifted the cardiomyocyte transcriptome toward the wild-type profile, and restored oxidative phosphorylation–related gene programs, which were diminished in untreated Lmna −/− mice. These findings demonstrate that targeted re-expression of Lmna partially ameliorates cardiac dysfunction in Lmna −/− mice and highlight the therapeutic potential of LMNA gene replacement for laminopathy-associated cardiomyopathy.
Elimination of detrimental grain boundary segregation in Garnets
Abstract Garnet Li 7 La 3 Zr 2 O 12 electrolyte is considered a key enabler of solid-state batteries with Li metal electrodes, but the grain boundaries impair its performance. To date, the understanding of grain boundary structures and its impact on performance remains elusive. Here, we show that element segregation at Li 7 La 3 Zr 2 O 12 grain boundaries critically governs Li transport and nucleation. During conventional sintering, Al, Ta, and La segregate at grain boundaries, locally depleting Li and creating space-charge layers that lower total ionic conductivity. Simultaneously, this segregation leads to higher electronic conductivity along grain boundaries, which promotes Li nucleation at grain boundary edges with increased risk of dendrite formation. The underlying mechanism of segregation is governed by both thermodynamic driving forces and diffusion kinetics. Building on this understanding, we develop a strategy to achieve segregation-free grain boundaries through a rapid sintering protocol that utilizes the onset of solid-state softening. This approach yields transparent, polycrystalline Li 7 La 3 Zr 2 O 12 with negligible grain boundary impedance and enhanced dendrite tolerance. By elucidating the structural origins and electrochemical consequences of grain boundary segregation, this work provides a guidance for the rational optimization of solid electrolytes.
Editorial Note: Malaria in Dielmo, a Senegal village: Is its elimination possible after seven years of implementation of long-lasting insecticide-treated nets?
Interplay between oxygen redox and interfacial stability of Li-rich positive electrodes in sulfide-based all-solid-state batteries
Immunization with the pan-fungal vaccine, NXT-2a, reduces fungal burden following serial intravaginal challenges with C. albicans in a non-human primate model of experimental vulvovaginal candidiasis
Worldwide, recurrent vulvovaginal candidiasis (RVVC) is estimated to affect approximately 138 million women annually. Current treatments for RVVC include azole therapies; however, these frequently fail to prevent recurrence and are limited by potential teratogenic effects and increasing azole resistance. Despite these limitations, there are no approved fungal vaccines. While rodent models have advanced our understanding of disease pathogenesis and vaccine development, their variable susceptibility to human pathogens and limited ability to recapitulate human immune responses restrict translational progress. Here, we established a nonhuman primate model of VVC reinfection in Japanese macaques ( Macaca fuscata ) and used this model to evaluate the immunogenicity and protective efficacy of the ‘pan-fungal’ vaccine candidate NXT-2. We show that like humans, Japanese macaques are susceptible to VVC infections with C. albicans and display evidence of active infection through the formation of hyphae and recruitment of polymorphonuclear cells within the vaginal lumen. Infection and reinfection induced limited anti- Candida IgG responses and did not prevent reinfection. Notably, immunization of C. albicans reinfected macaques with NXT-2 induced robust systemic and mucosal anti-NXT-2 IgG antibody titers and reduced fungal burden in the vaginal lumen following subsequent rechallenge. Together, these data establish a valuable preclinical model for investigating host responses to VVC reinfection and for vaccine development, highlighting the potential of NXT-2 as a vaccine candidate to prevent RVVC.
Enhanced invasiveness promotes the dominance of a widely-distributed carbapenem-resistant virulence-plasmid-carrying Klebsiella pneumoniae sublineage
Digital assessment of banana (Musa spp.) genotype resistance to banana weevil (Cosmopolites sordidus) compared with expert visual assessment
Accurately assessing weevil damage is critical when evaluating banana germplasm. This enables identification of genotypes resistant to the banana weevil, Cosmopolites sordidus , for use as elite parents or for advancement in banana breeding programs. Although visual observation remains the most common phenotyping approach, it is limited by individual bias. This study investigated the potential of image analyses as precise and objective alternatives for assessing weevil damage on the banana corm. ImageJ and four machine learning models, to include YOLO_v11 medium, U-Net 512, SegFormer, and MiT-b0, were explored. 260, 65, and 72 images were used to train, test, and validate the machine learning models, respectively. Phenotyping trials were set up as partially replicated (P-rep) designs with 18 test genotypes and four control genotypes. All plants were produced through tissue culture, raised in pots before infestation with the weevils. At termination, the percentage score of each of the 370 corm samples was evaluated both visually and by image analysis to compare scores across all methods. A significant genotype effect was detected, indicating differences among genotypes in resistance to banana weevils. Furthermore, a significant genotype-by-scoring-method interaction showed that genotype rankings in terms of resistance to banana weevils varied across methods. This emphasized that the choice of scoring approach can affect the magnitude of damage quantified. Visual observation agreed more closely with image analyses for smaller scores and less for larger scores. Results from genotype performance evaluation showed that machine learning methods, except for the YOLO_v11, have a strong level of agreement and can be used interchangeably, giving consistent, reliable, and repeatable measurements. We recommend and have adopted machine learning when scoring weevil damage in the banana corm to avoid individual bias and subjectivity arising from visual observation.
Extracting the transitivity backbone of bipartite networks
Women’s experiences with and preferences for contraceptive side effect counseling and management: A qualitative study from Ethiopia and Kenya
Objective The magnitude of contraceptive non-use attributed to side effects globally merits concerted attention to ensure women receive quality side effect counseling and support in line with their goals. Evidence shows comprehensive contraceptive counseling can help women navigate side effects, yet survey data reveal consistent gaps in side effect counseling quality. To elucidate women’s lived experiences with side effect counseling and management, we examined how women in Kenya and Ethiopia manage contraceptive side effects with and without help from healthcare providers, and what their preferences are for support. Methods We conducted in-depth interviews with sexually active women of childbearing age (N = 83) in Nairobi and Kisumu, Kenya, and Addis Ababa and Amhara region, Ethiopia. Participants were asked about their contraceptive experiences, including side effects, how they managed side effects, what support they received, and their preferred approaches for receiving support when experiencing side effects. We utilized a modified grounded theory approach for data collection and analysis. Results We found gaps in reported counseling quality among women in our sample, and a desire for more comprehensive counseling on side effects during initial and follow-up visits. After experiencing side effects, most participants described enduring and self-managing with over-the-counter remedies, and seeking clinical advice only when they worried about how their contraceptive method was affecting their overall health. Follow-up services often addressed participants’ immediate needs, but rarely offered additional information or comprehensive counseling. A few participants were denied a desired contraceptive device removal or shamed for not using contraception. Conclusion We identified a need to improve anticipatory contraceptive side effects counseling and proactive follow-up approaches that support women to choose methods they prefer and then navigate their use or switching. Such counseling would help health systems become more responsive to patient needs in contexts where women’s suffering is often considered acceptable, rather than cause for intervention.
Risk of incident tuberculosis after severe COVID-19: a nationwide cohort study
Abstract Severe viral infections can disrupt host immunity and increase susceptibility to secondary pathogens. Experimental and preclinical studies suggest that severe viral pneumonia may also trigger reactivation of Mycobacterium tuberculosis infection, yet population-level evidence remains limited. We conducted a nationwide retrospective cohort study in Chile, including more than 3.6 million adults with confirmed SARS-CoV-2 infection, to assess the risk of incident tuberculosis during follow-up. Individuals who developed severe COVID-19 requiring hospitalization had more than an eightfold higher hazard of tuberculosis within one year compared with those with non-severe disease. SARS-CoV-2 vaccination modified this association: the excess risk was substantially greater among unvaccinated individuals, whereas prior vaccination attenuated it. These findings indicate that severe COVID-19 is associated with an increased short- and long-term risk of tuberculosis and support the integration of targeted tuberculosis screening and preventive strategies into post-COVID-19 care, particularly among patients with severe disease.