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Adoption of soil and water conservation practices among smallholder farmers in the Somali Regional State of Ethiopia

Study on the mechanism of action of HuaZhuoKeLi in modulating LCN2-mediated cellular pyroptosis to ameliorate ulcerative colitis

Concurrent optimization of fracture toughness, thermal conductivity, and tribological behavior in Cf/Si3N4 composites via phase driven selection

Abstract Carbon fiber–reinforced silicon nitride (C f /Si 3 N 4 ) composites were fabricated by spark plasma sintering (SPS) using α-, β-, and γ-Si 3 N 4 powders to clarify the influence of the initial Si 3 N 4 phase on microstructural evolution and functional properties. The results show that the starting phase significantly affects densification behavior, phase transformation, and mechanical and tribological performance. The composite derived from α-Si 3 N 4 achieved the highest relative density (96.53%) and exhibited an optimal balance of fracture toughness (10.87 MPa m 0.5 ), thermal conductivity (66 W/m K), and stable friction behavior (COF ≈ 0.46). This performance is attributed to the in-situ formation of a self-reinforced β-Si 3 N 4 microstructure during the α → β phase transformation, which promotes crack deflection, crack bridging, and effective load transfer in synergy with carbon fibers. In contrast, β- and γ-Si 3 N 4 –based composites showed lower densification or excessive hardness associated with increased porosity and secondary phase formation. These findings demonstrate that controlling the initial Si 3 N 4 phase provides an effective microstructural design strategy for developing high-performance C f /Si 3 N 4 composites for thermostructural applications such as aerospace brake discs.

Total and regional skeletal muscle mass measured by magnetic resonance imaging in Japanese children aged 7–11 years

Abstract The aims of this study were to obtain representative data on total and regional skeletal muscle (SM) mass in prepubertal Japanese children using magnetic resonance imaging (MRI), and to examine sex differences in SM mass and its distribution. A total of 129 healthy prepubertal Japanese children (78 boys and 51 girls), aged 7–11 years and classified as Tanner stage 1, were enrolled. Contiguous MRI scans were acquired from the first cervical vertebra to the ankle joint. SM volume was calculated by summing digitised cross-sectional areas and dividing them into discrete anatomical regions. Age was significantly correlated with total, arm, trunk, thigh, and lower leg SM mass in both sexes. Total SM mass ranged from approximately 7 to 11 kg in boys and 6 to 10 kg in girls across the age range, increasing by roughly 1 kg per year in both groups. Boys had significantly higher intercepts in the regression lines between age and total, arm, trunk, and thigh SM mass compared to girls ( p  < 0.05), except for the lower leg. While no sex differences were observed in the slopes of the regression lines for total, arm, trunk, and lower leg SM mass, boys demonstrated a significantly steeper slope for thigh SM mass. This study provides detailed MRI-based reference representative data on SM mass and regional distribution in prepubertal children, contributing to a better understanding of early developmental differences between sexes.

Underlying structure and measurement invariance by sex of the state trait anxiety inventory: A psychometric analysis in Ecuador

Anxiety is currently one of the most prevalent and investigated psychological symptoms requiring precise and reliable instruments for its assessment. The current study evaluates the psychometric properties of the State-Trait Anxiety Inventory (STAI) in an Ecuadorian sample, focusing on the factor structure and potential methodological artefacts, especially those introduced by reverse-scored items. Employing exploratory and confirmatory factor analyses (EFA and CFA), along with structural equation modelling (SEM), the research examines the presence of two distinct factors: genuine anxiety and a secondary factor related to reversed items. Findings indicate that the expected two-factor model fits the data more accurately than a unidimensional model. Notably, cross-loadings suggest the second factor may represent a substantive positive, anxiety-free state rather than solely a methodological effect. Additionally, multigroup CFA confirmed strict measurement invariance across sex, supporting the scale’s utility for group comparisons. These results suggest that the STAI’s total score represents a composite of anxiety and well-being. While the STAI remains a robust tool for evaluating anxiety in clinical contexts, researchers seeking pure measures of anxiety symptomatology should consider analysing the subscales separately.

Reputation and trust in health insurance: A scoping review of key drivers and outcomes

Background Reputation is a critical factor in the health insurance industry, impacting business performance and public health outcomes. However, despite its acknowledged importance, the reputation of health insurers has received limited attention in both academic research and industry practice. Gaining a comprehensive understanding of health insurers’ reputation could help insurers strategically manage their public image while providing policymakers with valuable insights to develop policies that improve health outcomes. Objective This study aims to identify the factors shaping the reputation of health insurers and to assess the broader impacts of reputation within the industry and the health care system. Design A scoping review was conducted to map the existing literature on the reputation of health insurers. Using the PRISMA-ScR framework, it identified key determinants and outcomes of health insurer reputation, clarified concepts of reputation and trust, and highlighted gaps in the current body of literature. Results A total of 3385 records were identified, of which 397 were fully screened for eligibility, resulting in the inclusion of 45 studies. The majority of the included studies conducted surveys (n = 40), while the minority employed qualitative interviews (n = 6) and focus group discussions (n = 7). The total number of participants involved in the included studies is 31’344. The analysis identified 23 descriptives themes, which were organised into two main analytical categories: determinants and outcomes. The determinants included 17 descriptive themes which have been further classified into three groups based on whether they pertain to policyholders, insurers or providers. The outcomes consist of six key descriptive themes. Conclusion This review provides a thorough analysis of research that have investigated different aspects of health insurance reputation and identify significant gaps in the literature. It maps key determinants of reputation – such as corporate culture, product structure, and service quality – that insurers can directly influence. Additionally, factors like the quality of healthcare providers and targeted communication efforts may also be linked to reputation. The analysis underscores the importance of reputation for core business activities (e.g., client acquisition and retention) and its role in preventive healthcare. Notably, there is a lack of research on the regulatory implications of insurers’ reputation, suggesting a need for further studies to enhance preventive strategies and integrate insurers into a broader public health framework.

Contact, cognition, and taiwanese youths’ attitudes toward local and Chinese culture

Classical contact theory posits that intergroup contact can reduce perceived threats and hostility between in-groups and out-groups, thereby laying the foundation for the formation of subsequent friendships and deeper forms of identification. However, in a cross-Strait context that is highly politicized and in which exchanges are deliberately obstructed by the Democratic Progressive Party, whether contact experience alone is sufficient to trigger changes in Taiwanese youths’ attitudes toward Chinese culture remains an open question requiring further examination. Drawing on data from the 2018 Taiwan Social Change Survey, this study analyzes a sample of youths aged 18–45 and constructs an index of attitudes toward “Taiwan’s local culture” to examine the effects of two independent variables, namely Taiwanese youths’ contact with the Chinese mainland and increases in Taiwanese youths’ cognition of the Chinese mainland, on their cultural attitudes. The results show that experience of contact with the Chinese mainland alone does not have a statistically significant effect on attitudes toward local culture. By contrast, individuals with higher levels of cognition of the Chinese mainland exhibit a significantly lower Taiwan’s Local Cultural Attitude Index. These findings suggest that under conditions in which cross-Strait exchanges are constrained, contact per se may be insufficient to induce shifts in cultural attitudes. Instead, its effects are more likely to operate through increases in cognition.

Inflammation in osteonecrosis of the femoral head: Evaluation of hematological biomarkers and potential prognostic value

Increasing evidence suggests that inflammation and immune imbalance are associated with osteonecrosis of the femoral head (ONFH). This study aimed to investigate peripheral inflammatory biomarkers in patients with nontraumatic ONFH and assess their potential prognostic value. A retrospective analysis was conducted on 80 patients with nontraumatic ONFH and 110 control individuals without ONFH. Peripheral blood cell counts, C-reactive protein (CRP), and derived inflammatory indices including neutrophil-to-lymphocyte ratio (NLR), monocyte-to-lymphocyte ratio (MLR), platelet-to-lymphocyte ratio (PLR), and systemic immune-inflammation index (SII) were compared between groups and among different disease stages. Diagnostic performance was assessed using receiver operating characteristic (ROC) curve analysis. The results showed that ONFH patients showed significantly higher CRP, monocyte count (cM), monocyte percentage (pM), MLR, and platelet count (PLT). ROC analysis revealed that CRP (AUC = 0.700, sensitivity = 71.3%, specificity = 65.5%) and cM (AUC = 0.690, sensitivity = 82.5%) had the highest diagnostic accuracy. CRP levels differed significantly across disease stages, peaking at stage II (P = 0.0107), while other indices remained stable. These findings support the concept that both systemic and local inflammatory mechanisms contribute to the pathogenesis of ONFH. CRP and monocyte indices may serve as inexpensive, accessible adjuncts for early disease screening and monitoring.

Outcomes of hyperglycaemia in pregnancy in Africa: Systematic review and meta-analysis

Objective The global prevalence of type 2 diabetes mellitus has significantly risen in recent decades, leading to a corresponding increase in the incidence of diabetes-complicated pregnancies. Hyperglycaemia in pregnancy (HIP), the most common metabolic complication encountered during pregnancy, is associated with a range of adverse maternal and foetal outcomes. This systematic review comprehensively examined the maternal, foetal, neonatal, childhood, and long-term maternal outcomes of HIP in Africa. Methods A systematic review of all studies investigating HIP outcomes in Africa from January 1998 to February 2025 was undertaken. We searched PubMed-MEDLINE, Cochrane Library, Scopus, CINAHL (EBSCOhost), Embase and Web of Science databases for eligible studies. Studies were included if they were observational studies describing outcomes of HIP in Africa. For each outcome, study results were synthesised using an inverse variance heterogeneity meta-analysis with the Freeman-Tukey transformation. Heterogeneity was assessed using the I 2 statistic, and publication bias was assessed using Doi plots. Results Thirty studies were included in the review, comprising 9742 participants. These studies were conducted across the following African countries: South Africa (n = 11), Ethiopia (n = 4), Nigeria (n = 3), Sudan (n = 3), Uganda (n = 2), and one each from Ghana, Algeria, Morocco, Democratic Republic of Congo, Zimbabwe, Togo, and Egypt. The most common adverse pregnancy outcomes for gestational diabetes mellitus (GDM) were caesarean section (CS) (overall prevalence 46.0%, 95% CI 35.7–56.4, I 2  = 95.6%), preterm delivery (overall prevalence 25.2% (95% CI 12.7–40.2, I 2  = 96.7%) and neonatal intensive care unit (NICU) admission (overall prevalence 25.9% (95% CI 13.7–40.2, I 2  = 85.7%). The most common adverse pregnancy outcomes for women with preexisting type 1 diabetes (T1DM) were CS (overall prevalence 57.5%, 95% CI 44.9–69.7, I 2  = 81.2%), preterm delivery (overall prevalence 50.7%, 95% CI 16.3–84.8, I 2  = 92.6%), and neonatal hypoglycaemia (overall prevalence 20.2%, 95% CI 0.0–61.4, I 2  = 94.6%). CS (overall prevalence 60.6%, 95% CI 45.5–74.8, I 2  = 93.6%) and preterm delivery (overall prevalence 35.2%, 95% CI 29.5–41.1, I 2  = 49.3%) were the most prevalent adverse pregnancy outcomes for women with preexisting type 2 diabetes (T2DM). Postpartum T2DM was the most common long-term adverse outcome of women who had GDM or hyperglycaemia first detected in pregnancy (HFDP). There was significant heterogeneity across most outcomes. Conclusions The prevalence of adverse outcomes of HIP in Africa is high, in particular CS, preterm delivery and neonatal hypoglycaemia, with higher frequencies in pregestational T1DM and T2DM compared to GDM. Additionally, T2DM prevalence in women post-GDM is about 50%. The outcome data predominantly come from a few studies, indicating the necessity for more high-quality research to improve HIP-related maternal and child health in Africa. The high heterogeneity across most outcomes suggests that their prevalence varies across populations and underscores the need for more high-quality data. PROSPERO Registration Number: CRD42020184573.

Efficacy of a combined diving and mindfulness program on emotional eating in adults with obesity: Randomised controlled trial with standard care

Background Emotional eating is considered as a mediator between depression and obesity. Combining mindfulness and sport activities can improve obesity-related psychological disorders but inconsistencies in effect and duration have been reported. We aimed to evaluate the effects of a combined mindfulness-diving Bathysmed® program on emotional eating scores in participants with obesity. Methods This unblinded randomized controlled trial was performed in the community setting, Montpellier, France. Adults with a BMI > 30 kg/m2 were randomly assigned (1:1) to a Bathysmed® 2-month program (intervention group) therapeutic scuba-diving protocol with mindfulness exercises plus standard care, or stand-alone standard care including dietary and psychological support (control group). The primary outcome was the mean change in the emotional eating subscale of the Dutch Eating Behaviour Questionnaire (DEBQ-EE) at 2-months as intention to treat. Findings Between July-August 2022, 63 participants were randomised, with 31 in the intervention group. One participant from each group were excluded. Fifty-five (87·3%) were female, median age 46 [35.5;54] and BMI 35.46 [33.45;39.48]. There was a statistically significant reduction of DEBQ-EE at 2 months in the intervention group (−0·82 (SD 0·81)) versus control group (−0·27 (SD 0·61) p = 0·004). This effect was maintained at 5 and 8-month follow up. There was a significant reduction in weight self-stigma, stress, and quality of life change scores in the intervention group. Interpretation This combined diving and mindfulness program effectively reduces emotional eating, self-stigma and quality of life scores in participants with obesity, with sustained benefits. Health policies should integrate physical activity and psychological therapies for obesity management. Trial registration Clinicaltrials NCT06882200 .

Employing in-context learning prompts with large language models for drone routing in delivery services

Autonomous Aerial Vehicles (AAVs) – known as drones – employment in delivery services is one of the promising transformative technologies. The AAV industry has taken significant steps to develop drones to fulfill the needs of delivery services. However, AAVs have limitations related to the flight range and payload capacity. Therefore, drone route planning is crucial to reducing the effectiveness of these challenges. The recent emergence of Large Language Models (LLMs) has opened new possibilities for solving combinatorial problems using in-context learning (ICL). Unlike traditional machine learning models, LLMs can generate solutions without requiring task-specific fine-tuning by leveraging solved examples within their input prompts. In this study, we explore the application of LLMs to the Drone Routing Problem (DRP), leveraging various ICL strategies to generate optimized delivery routes. Our solution ensures that drone routes are planned to reduce the traveling distance for the full route. Notably, it ensures that drones don’t mess any delivery points and fast delivery routes. Through extensive experimentation, we evaluate the effectiveness of different prompt engineering techniques in guiding LLMs to produce high-quality, non-hallucinated route plans. We compared our model results to heuristic-based generated routes to demonstrate the variation between our technique and other techniques. The results demonstrate that LLMs, when properly prompted, can reliably generate valid routing solutions, highlighting their potential as a flexible and adaptive tool for drone logistics planning. Project link: https://github.com/ahmed-abdulhuy/Solve-TSP-using-GPT3.5.git

Prediction of vegetation indices from down-sampled hyperspectral data using machine learning: A novel framework for olive crop monitoring

Accurate plant health monitoring relies on hyperspectral imagery to extract vegetation spectral signatures and compute vegetation indices (VIs), which are critical for phenotyping and crop condition assessment. However, the requirement for high spectral resolution significantly increases the cost and complexity of data acquisition. In this study, we proposed a novel machine learning-based framework for predicting VIs from down-sampled hyperspectral reflectance data. The aim was to reduce the dependency on high-resolution spectral imagery without compromising prediction accuracy. The framework integrated correlation-based feature selection with four regression models to identify and utilize the most informative spectral bands from coarsely sampled data. The system was trained and validated using a data set consisting of 555 spectral signatures collected from olive leaves at five stages of dehydration, with spectral resolutions ranging from 1 to 100 nm. A total of 25 vegetation indices, commonly used in the estimation of water stress, chlorophyll, and nitrogen, were predicted on various sampling scales. Experimental results show that even with 100 nm spectral resolution, the proposed framework achieves high prediction accuracy, with coefficients of determination reaching 0.99 for RVSI, VOPT, and SPADI indices. These findings demonstrate that accurate vegetation index estimation is achievable with significantly fewer spectral bands, offering a cost-effective solution for large-scale plant health monitoring. This framework lays the groundwork for the development of low-cost, data-efficient remote sensing systems for precision agriculture, especially in crops such as olives, where health dynamics are sensitive to water and nutrient status.

Early contraceptive discontinuation and associated factors among married women initiating long-acting and short-acting contraceptives in humanitarian settings in Ethiopia: A retrospective cohort study

Background The sexual and reproductive health (SRH) service provision in conflict-affected populations has been continually overlooked. International and local relief organizations have begun to recognize the neglect of women’s SRH needs; however, SRH services and humanitarian responses remain suboptimal. Contraceptive discontinuation is a significant public health issue with considerable impact on family planning (FP) programs, as well as on women’s SRH and population growth. There is scarce information regarding the dynamics of contraceptive use in refugee areas. Evidence on contraceptive use dynamics is vital, especially now, as the global refugee crisis grows. Therefore, this study aimed to examine first-year contraceptive discontinuation and associated factors among married women initiating long-acting reversible contraceptives (LARC) and short-acting contraceptives (SAC) in selected refugee populations in Ethiopia. Methods A retrospective cohort study was conducted among 551 married women in selected refugee populations in Ethiopia. After reviewing FP registries, all eligible women who initiated a contraceptive method 12–18 months before data collection were included in the study. Through computer-assisted face-to-face interviews, data on the socio-demographic, reproductive, and contraceptive use history of women were collected. Key characteristics of SAC acceptors and LARC acceptors were compared using chi-square statistics and t-tests. A multivariable Cox proportional hazards model identified the predictors of time to contraceptive discontinuation during the first year of use. In addition, adjusted hazard ratios (aHR), 95% CI, and P-values were calculated to determine the magnitude and precision of the association. Results The 12-month discontinuation rate for all contraceptive methods was 41.2% (95% CI: 37.2–45.4). The discontinuation rate for SAC (44.94%) was higher than LARC (32.32%) (P ≤ 0.001). The factors associated with 12-month discontinuation include method type (aHR = 1.50;95% CI:1.06–2.12), residence (aHR = 1.83;95% CI:1.24–2.70), husband occupation (aHR = 0.49;95% CI:0.29–0.84), length of stay in the refugee camp (aHR = 0.95;95% CI:0.92–0.99), and intention to use contraceptives in the future (aHR = 0.15;95% CI:0.11–0.21). Conclusion A high rate of early contraceptive discontinuation was documented among refugee women, with a higher discontinuation rate among SAC acceptors. To improve contraceptive service provision and maintain continuous use of the methods initiated, targeted interventions, such as improved counselling and promotion of long-acting contraceptive methods, especially among urban refugee women, are crucial.

Contrasting effects of SARS-CoV-2 vaccination vs. infection on antibody and TCR repertoires

Antibodies and helper T cells play important roles in SARS-CoV-2 infection and vaccination. We sequenced B- and T-cell receptor repertoires (BCR/TCR) from the blood of 251 infectees, vaccinees, and controls to investigate whether features of these repertoires could predict subjects’ SARS-CoV-2 neutralizing antibody titer (NAbs), as measured by enzyme-linked immunosorbent assay (ELISA). We sequenced recombined immunoglobulin heavy-chain (IGH), TCRβ (TRB), and TCRδ (TRD) genes in parallel from all subjects, including select B- and T-cell subsets in most cases, with a focus on their hypervariable CDR3 regions, and correlated this AIRRseq data with demographics and clinical findings from subjects’ electronic health records. We found that age affected NAb levels in vaccinees but not infectees. Intriguingly, we found that vaccination and infection are associated with longer non-productively recombined IGHs, suggesting an effect that precedes clonal selection. We found that TRB repertoires’ binding capacity to known SARS-CoV-2-specific CD4+ TRBs performs as well as the best hand-tuned approximate or “fuzzy” matching at predicting a protective level of NAbs, while also being more robust to repertoire sample size and not requiring hand-tuning. The overall conclusion from this large, unbiased, clinically well annotated dataset is that B- and T-cell adaptive responses to SARS-CoV-2 infection and vaccination are surprising, subtle, and diffuse. We discuss methodological and statistical challenges faced in attempting to define and quantify such strong-but-diffuse repertoire signatures and present tools and strategies for addressing these challenges.

On the potential sources of a low-frequency sound percept that only a few can perceive

A small percentage of the general population reports almost constant humming or pulsing low-frequency sound percepts (LFSPs), while others in their vicinity, such as family members, often do not perceive these sounds. The origin of these LFSPs remains to be elucidated and may, or may not, be related to external sound sources. The underlying causes of these perceptions could also be subjective and belong to the tinnitus family, especially in cases where no external sound source sufficiently explaining the LFSP can be found. The present study puts forth two hypotheses to explain the phenomenon, based on both subjective and objective auditory phenomena: an unusually high auditory sensitivity to low-frequency sound, and hearing one’s own low-frequency spontaneous otoacoustic emissions (SOAEs), sounds actively produced by the inner ear as a normal, physiological by-product of cochlear amplification. The present study employed high-resolution, low-frequency hearing threshold measurements and SOAE measurements in 28 individuals with LFSPs and in control groups devoid of LFSPs. LFSP complainants self-reported hearing an LFSP at a median frequency of 50 Hz, obtained with a frequency-matching procedure. With a few clear exceptions, complainants most often did not present unusually sensitive low-frequency hearing thresholds. Furthermore, hearing threshold microstructure was comparable to that of the control group. In addition, no SOAEs in the low-frequency range could be measured. Based on our results, while cases of hearing physical external sound sources are not ruled out, we suggest that subjective tinnitus in the low-frequency range is often the reason behind hearing these LFSPs.

Prognostic value of cardiac magnetic resonance–derived global longitudinal strain in LGE-negative dilated cardiomyopathy

Background Dilated cardiomyopathy (DCM) is a major cause of heart failure and sudden cardiac death (SCD), with a 5-year survival rate of approximately 45%–50%. Current risk stratification is predominantly dependent on left ventricular ejection fraction (LVEF), which has limited sensitivity and specificity. Hence, more effective biomarkers should be used in late gadolinium enhancement (LGE)-negative patients. Methods A total of 378 consecutive patients with LGE-negative DCM were enrolled from four hospitals between December 2016 and December 2022. Cardiac magnetic resonance imaging-derived strain parameters (global radial strain, global circumferential strain, and global longitudinal strain [GLS]) were assessed against the primary (SCD and related events) and secondary (heart failure, appropriate implantable cardioverter-defibrillator therapy) endpoints. Internal validation was performed using stratified bootstrap resampling with Harrell’s optimism correction to report the optimism-corrected C-index. Data were accessed for research purposes from 15/06/2023–30/12/2023, and all records were de-identified prior to analysis. Results Over a median follow-up of 59.78 months, 35 (9.26%) and 72 (19.0%) patients presented with the primary and secondary endpoints, respectively. Based on the multivariate Cox analysis, GLS, LVEF, and age were independent prognostic factors. However, only GLS (HR = 1.37; P  = 0.041) remained significant in the LVEF <20% subgroup. A model integrating GLS and LVEF had a better discrimination ability for SCD than LVEF strata alone (apparent C-index 0.756 vs 0.714, P  < 0.001). This advantage persisted after bootstrap internal validation (B = 1000; optimism-corrected C-index 0.754 vs 0.711, Holm adjusted P  = 0.048). Further inclusion of age and New York Heart Association (NYHA) classification enhanced the model’s performance (model 4): apparent C-index 0.801; optimism-corrected C-index 0.785). Conclusion GLS is an independent predictor of SCD-related events in LGE-negative DCM. Incorporating GLS with conventional indicators such as age, NYHA classification, and LVEF significantly enhances prognostic discrimination and model robustness, indicating potential value for future clinical risk stratification.

Poly(heptazine imide): Crystalline Allotrope of Polymeric Carbon Nitrides for Solar to Chemical Energy Conversion

ABSTRACT Polymeric carbon nitride (PCN), an emerging semiconductor photocatalyst, has drawn intense interest for solar to chemical energy conversion, owing to advantages of metal‐free contents, visible‐light response, and robust stability. However, the amorphous melon‐based PCN formed by conventional thermal‐induced polymerization exhibits moderate photocatalytic performance, that is, restricted by its high exciton binding energy. In recent years, poly(heptazine imide) (PHI), a crystalline allotrope of PCN with high crystallinity and visible‐light absorption, has been widely investigated in various photocatalytic applications due to its enhanced performance. In this mini‐review, we have summarized the progress in the synthesis, modification, and photocatalytic applications of PHI. We have presented the synthetic protocols, electronic structure, and structural identification of PHI. This review summarizes and provides a detailed analysis of four main strategies for modifying PHI: crystal structure, nanostructure, molecular structure, and atomic composition. Finally, the article discusses the challenges and potential future directions for optimizing and advancing the functions of state‐of‐the‐art PHI photocatalysts. These insights are expected to offer valuable perspectives for driving the development of PHI and related conjugated polymers.

5-HT1B receptor agonists promote Schwann cell myelination

Congenital demyelinating peripheral neuropathy causes severe sensorimotor defects, affecting patient mobility. To identify therapeutic compounds for peripheral hypomyelinating neuropathy, we performed an unbiased screening of annotated compound library by in vitro myelination culture model using Trembler (Tr-Ncnp) -derived dorsal root ganglia explants. Among the compounds identified in the screening, we confirmed that zolmitriptan, a 5-hydroxytryptamine 1B/1D receptor agonist, promotes myelination in culture. Zolmitriptan up-regulated myelin-related genes in primary Schwann cells and increased proliferating Schwann cells along axons in DRG explant cultures of Tr-Ncnp mice. Furthermore, we observed that chronic administration of zolmitriptan ameliorates sensorimotor dysfunction in Tr-Ncnp mice. Collectively, these results suggest that 5-HT1B/1D receptor agonists may increase Schwann cells participating in myelination, and consequently ameliorate myelination impairment in peripheral neuropathy.

Chemical Proteomics Identifies Ketogenesis‐Mediated Cysteine Modifications Regulating Redox Function

Abstract All the studies of ketogenesis‐dependent post‐translational modifications (PTMs), notably those mediated by ketone bodies, β‐hydroxybutyrate (Bhb) and acetoacetate (Acac), have focused on lysine acylations. However, given the chemically diverse and reactive nature of metabolites generated, it remains unclear whether non‐lysine modifications can also happen. Here, we develop an acetoacetate‐alkyne (Acac‐alkyne) chemical probe that enables efficient metabolic labeling, robust fluorescent visualization, and site‐specific identification of Acac‐modified proteins. By combining chemical proteomics with open‐search strategy, we showed that Acac induces previously uncharacterized cysteine modifications in mammalian cells. Notably, cysteine crotonation (Ccr) is validated by employing both probe‐based and standard peptide‐based co‐elution assays. Metabolic pathway tracing further identifies BDH1 and ECHS1 as key enzymes that generate Ccr formation. We further demonstrate that Ccr at PRDX3 C229 site impairs dimerization and redox activity, linking this newly discovered modification to the regulation of cellular reactive oxygen species. Together, these findings establish ketone metabolism as a novel source of cysteine modifications and provide an alternative mechanistic pathway to explain the profound biological effects of ketone bodies.

Dynamic response and failure mechanism of rural masonry structures impacted by debris flow containing boulders

Rural masonry structures in mountainous regions are highly vulnerable to debris flow impacts. However, their dynamic failure mechanisms remain poorly quantified. To address this knowledge gap and enhance the debris flow resilience of such structures in the Three Gorges Reservoir Area, a Fluid-Structure Interaction model was established and validated using ANSYS Workbench. The model simulated the impact of debris flows containing boulders and incorporated the Drucker-Prager constitutive model for the masonry material. Parametric analysis revealed a bimodal dynamic response, characterized by the peak boulder force lagging behind the peak slurry force. A critical flow velocity of 5 m/s was identified: above this threshold, slurry force dominated ( F slurry  >  F boulder ), while below it, the boulder force was greater ( F slurry  <  F boulder ). The critical failure parameters were quantified as follows: At a flow depth of 1.5 m, the critical velocities for local and global collapse were 5 m/s and 9 m/s, respectively. Conversely, at a flow velocity of 5 m/s, the critical depth for severe damage was 3 m. Stress analysis showed that boulder impact induced significant stress concentration, with the peak von Mises stress ( σ boulder ) 114.29% higher than that from the slurry ( σ slurry ). A damage grading standard and corresponding displacement prediction formulas were proposed based on the inter-story displacement angle. Collectively, these findings provide a theoretical and practical foundation for designing rural masonry structures that are resilient to debris flow disasters.