Nevin Manimala

Zhonghua Lao Dong Wei Sheng Zhi Ye Bing Za Zhi. 2026 Apr 20;44(4):241-246. doi: 10.3760/cma.j.cn121094-20250704-00267.

ABSTRACT

Objective: To evaluate the causal association between serum albumin and carpal tunnel syndrome (CTS) and to investigate the mediating role of leptin in this relationship. Methods: In April 2025, data on serum albumin, leptin (adjusted for body mass index), and CTS from Genome-Wide Association Studies (GWAS) and FinnGen public databases were collected for a two-way, two-sample Mendelian randomization (MR) analysis. Causal analyses were performed using inverse variance weighted (IVW), weighted median estimator, MR-Egger, simple mode, and weighted mode methods. The robustness of the results was tested using Cochran’s Q statistic, MR-Egger intercept test, Mendelian randomization pleiotropy residual sum and outlier (MR-PRESSO) test. A two-step approach was used to analyze the mediating effect of leptin between serum albumin and CTS. Results: The IVW analysis showed that elevated serum albumin levels significantly increased the risk of CTS (OR=1.18, 95%CI: 1.00-1.38, P=0.045), and the results from the weighted median estimator and weighted mode method were consistent with the IVW direction and the differences were statistically significant (P<0.05). Mediation analysis revealed a significant negative causal effect between serum albumin and leptin (OR=0.44, 95%CI: 0.28-0.68, P<0.001), and elevated leptin levels significantly reduced the risk of CTS (OR=0.79, 95%CI: 0.68-0.94, P=0.006). Leptin played a key mediating role in the path of serum albumin affecting CTS (β(indirect)=0.190, P=0.027), with a mediation proportion of 118%. Reverse MR analysis showed that the causal effect of CTS on serum albumin was not statistically significant (OR=1.00, 95% CI: 0.97-1.04, P=0.889). There were no statistically significant differences in the heterogeneity test (Cochran’s Q=20.68, P=0.079) and multi-effect test (MR-Egger intercept value -0.004, P=0.684; MR-PRESSO global P=0.067) . Conclusion: There is a positive causal relationship between serum albumin level and the risk of CTS, and leptin level plays an important mediating role in this pathway, suggesting that albumin may indirectly increase the risk of CTS through the modulation of leptin, and provide new genetic clues for the identification of people at high risk of CTS.

PMID:42092244 | DOI:10.3760/cma.j.cn121094-20250704-00267

Biochem Biophys Res Commun. 2026 Apr 29;821:153785. doi: 10.1016/j.bbrc.2026.153785. Online ahead of print.

ABSTRACT

BACKGROUND: Inhibiting hepatic stellate cells (HSCs) activation, which represents the initial step of liver fibrosis, is a key strategy for fibrosis treatment. Sorafenib has been repurposed as an antifibrotic agent; however, its reported effects largely rely on cytotoxic mechanisms. The antifibrotic mechanisms induced by minimally cytotoxic sorafenib remain unclear. We aimed to elucidate the dynamic changes in gene expression and lipid metabolites that occur during HSC inactivation using low-concentration sorafenib.

METHODS: Human HSCs (LX-2) were activated by treatment with transforming growth factor (TGF)-β to create a fibrotic environment. The activated cells were treated with sorafenib and then subjected to transcriptomic and lipidomic analyses. In the transcriptomic analysis, statistical significance was assessed using adjusted P-values based on the Benjamini-Hochberg method, whereas significance in the lipidomic analysis was evaluated using MetaboAnalyst.

RESULTS: During fibrogenesis, we observed upregulation of extracellular matrix-related genes (COL1A1 (P < .001), FN1 (P < .001), THBS1 (P < .001), P4HA3 (P < .01)) and CXCL12 (P < .01), which is an upstream regulator of the Raf/MEK/ERK and PI3K/AKT signaling pathways. Meanwhile, dihydroceramide (dhCer) and dihydrosphingomyelin (dhSM) levels decreased (both P < .001). In contrast, sorafenib-induced antifibrotic conditions significantly reversed these molecular and lipidomic trends (all P < .01).

CONCLUSIONS: In light of the observed trends, we propose that activating the dhSM synthesis pathway may play a regulatory role in fibrosis. Collectively, our study provides novel lipid-based insights into the molecular mechanisms underlying antifibrotic responses.

PMID:42092220 | DOI:10.1016/j.bbrc.2026.153785

J Infect Public Health. 2026 Apr 29;19(6):103236. doi: 10.1016/j.jiph.2026.103236. Online ahead of print.

ABSTRACT

BACKGROUND: Despite significant progress in tuberculosis (TB) prevention, China remains the third-highest TB burdened country globally, with ongoing concerns about drug-resistant tuberculosis (DR-TB) and HIV/TB co-infection.

METHOD: The study utilized data from the Global Burden of Disease (GBD) 2021, applying the Age-Period-Cohort (APC) model to analyze age, period, and cohort effects on the incidence and mortality of TB, DR-TB, and HIV/TB co-infection. The Bayesian Age-Period-Cohort (BAPC) model projected future trends from 2022 to 2035.

RESULT: Age effects indicated an increased incidence and mortality risk for TB and DR-TB with age, while younger and middle-aged groups were more affected by HIV/TB co-infection. Period effects demonstrated decreasing risks for TB and DR-TB, but an increasing trend for HIV/TB co-infection. Cohort effects similarly indicated a decline for TB and DR-TB, with a slight rise for HIV/TB co-infection among individuals born between 1990 and 2006. BAPC projections indicate that by 2035, the age-standardized incidence rate (ASIR) for TB, DR-TB, and HIV/TB co-infection will be 21.86, 1.04, and 1.21 per 100,000 person-years, respectively, while the age-standardized mortality rate (ASMR) will be 0.90, 0.09, and 0.12 per 100,000 person-years, respectively. None of these projections fulfill the End TB targets.

CONCLUSION: Current strategies are unlikely to meet the End TB targets by 2035 in China, suggesting a need for preventive treatment for latent tuberculosis infection (LTBI) and improved screening for HIV and TB in high-risk populations.

PMID:42092213 | DOI:10.1016/j.jiph.2026.103236

Int J Hyg Environ Health. 2026 May 5;275:114811. doi: 10.1016/j.ijheh.2026.114811. Online ahead of print.

ABSTRACT

Knowledge of infectious agents, modes of transmission, and routes of spread play a central role in planning and performing infection prevention and control (IPC) procedures. The European Hygeia survey involved an online questionnaire that was administered from March 2025 to August 2025 to nurses from acute Hospitals and long-term facilities in Italy, Spain, Sweden and Turkey, to monitor their training on hygiene and related topics, in order to provide them up-to-date, reliable and easily accessible professional education and training to strengthen their knowledge on IPC procedures. A total of 438 nurses were included in the study; their median age was 42 years and 368 (84%) were women and 66 (15%) men; 4 (1%) not stated. Most nurses attended at least one hygiene course (321, 75%), 364 (84%) nurses were interested in attending a hygiene course. There were a few statistically significant differences in education level, in particular, nurses with university degree had a greater self-perceived knowledge in hygiene and prevention with adjusted Odds Ratios (aOR) = 3.77, CI: 1.38-10.30, p = 0.010 and infections (aOR = 2.96, CI: 1.09-8.01, p = 0.033) than nurses with diploma. Our study showed most nurses had a good self-perceived knowledge in hygiene prevention and protection measures and were willing to take part in future courses on this subject. Greatest knowledge deficiencies were related to disinfection and sterilization and infection control fields, future education courses should aim to address this issue.

PMID:42092211 | DOI:10.1016/j.ijheh.2026.114811

J Environ Radioact. 2026 May 5;297:108024. doi: 10.1016/j.jenvrad.2026.108024. Online ahead of print.

ABSTRACT

The ²¹⁰Pb dating technique is widely applied for reconstructing sediment accumulation in aquatic environments. However, its reliability depends strongly on appropriate age model and independent validation. In this study, previously reported sedimentation rates for the highly dynamic coastal environment of Sorsogon Bay, Philippines, derived using the Constant Initial Concentration (CIC) model, were reassessed to validate and improve chronological robustness. Guided by statistical and physical assumptions, and supported by the results of CF:CS and CRS age model, the evaluation of regression intervals of excess ²¹⁰Pb activity concentration profiles, the average sedimentation rates of the three sediment cores SO-01 (CAS), SO-03 (CAD), and SO-07 (SAM) were determined to be the best fit. Results of Mann-Whitney U test revealed the influence of natural disturbances, such as eruptions of Mt. Bulusan and major typhoon events that hit the Bicol Region, to sediment characteristics particularly dry bulk density (DBD) and calculated mass accumulation rate (MAR). This further strengthen the qualitative analysis of peak association of DBD and MAR to the documented natural disturbances. This study demonstrates the importance of multi-proxy validation and Mann-Whitney U test in strengthening ²¹⁰Pb-derived chronologies, which are critical for a more robust foundation for investigating land-use change, coastal evolution, pollution histories, climate variability, and other natural and anthropogenic drivers of sediment dynamics over the past century.

PMID:42092209 | DOI:10.1016/j.jenvrad.2026.108024

Sci Rep. 2026 May 6. doi: 10.1038/s41598-026-51981-2. Online ahead of print.

ABSTRACT

The malicious URLs have been a constant threat to cybersecurity because hackers are constantly creating phishing, malware, spam, and defacement links that resemble authentic Web layouts and bypass static security measures. Despite very promising results of machine learning (ML) and deep learning (DL) models in URL classification, the effectiveness of these models is usually limited by high dimensional spaces of features that have redundant and irrelevant qualities, which leads to increased computation costs and potentially less generalization ability. To cope with this, this study will present a wrapper-based Bat Algorithm (BA) feature selection model to determine small and discriminative subsets of features in detecting malicious URLs. The bio-inspired metaheuristic BA offers a good tradeoff of exploration and exploitation in high dimensional optimization issues and thus is useful in feature subset selection. The proposed BA model is tested on ensemble ML (XGBoost, AdaBoost, Gradient Boosting, CatBoost and LightGBM) and DL (CNN, RNN, LSTM and CNN-LSTM) architectures with two datasets the multi-class ISCX-URL-2016 dataset and the more recent URL Phishing (2026) dataset. Experiments results indicate that BA has a significant dimensionality reduction: It reduces original feature space on ISCX-URL-2016 by 51.90% in the case of Defacement, by 67.09% in the case of Malware, by 49.37% in the case of Phishing, by 59.49% in the case of Spam, and 45.91% in the case of Phishing on URL Phishing (2026). This reduction notwithstanding, BA shows consistent improvements in the classification of both datasets. BA-enhanced LightGBM had the best overall results of all the tested models, with an accuracy of 99.92% on ISCX-URL-2016 and 98.17% on URL Phishing (2026), and high values of ROC-AUC and good computational efficiency. A statistical analysis also supports the fact that the improvements noticed are significant. Altogether, the proposed BA-based feature selection model is an efficient, scalable, and reliable solution to malicious URL detection intelligent, with good possibilities of being implemented into real-world systems in terms of cybersecurity.

PMID:42092159 | DOI:10.1038/s41598-026-51981-2

Nature. 2026 May 6. doi: 10.1038/s41586-026-10443-5. Online ahead of print.

ABSTRACT

Cognitive flexibility refers to the adaptive neural processes that adjust learned behaviours as circumstances shift, supporting optimal decision-making and behavioural control. This includes the capacity to modify specific behaviours as the contingency between cues and rewards degrades. Across species^1-4, the medial prefrontal cortex (mPFC) has a well-established role in controlling contingency degradation⁵; however, the precise neural circuit mechanisms underlying this cognitive process remain unclear. To address this gap, we developed a quantitative model of cognitive flexibility that incorporates a meta-learning parameter into an established reward prediction error learning model^6,7. Our meta-reward prediction error model significantly improves accurate representation of mouse cue-evoked licking behaviour in response to degraded or enhanced cue-reward associations. Using longitudinal two-photon calcium imaging and single-cell holographic optogenetics, we found that a subset of neurons in the mPFC specifically encode the contingency degradation in a significant and causal manner. Recognizing that behavioural flexibility probably requires interactions between the mPFC and canonical reward learning circuitry, we then examined how mPFC neural signalling during contingency degradation interacts with the ventral tegmental area (VTA)-a critical hub for reward processing⁸. Our imaging and optogenetics data show that mPFC sends this signal to VTA, with most mPFC→VTA neurons reflecting this transmission, and that selective optogenetic stimulation of these ensembles accelerates contingency degradation. These findings reveal how prefrontal circuits facilitate flexibility, selectively halting learned behaviours through connections with subcortical reward networks.

PMID:42092148 | DOI:10.1038/s41586-026-10443-5

Nature. 2026 May 6. doi: 10.1038/s41586-026-10477-9. Online ahead of print.

ABSTRACT

The existence of abundant post-starburst and quiescent galaxies just about 1-2 Gyr after the Big Bang challenges our current model of galaxy evolution^1-3. Cosmological simulations suggest that quasar feedback is likely the most promising mechanism responsible for this rapid quenching^4-6. Here we report a high detection rate (6/27) of exceptionally fast and powerful galaxy-scale outflows traced by [O III] emission in z ≈ 5-6 luminous quasars as shown by the James Webb Space Telescope, with velocity up to about 8,400 km s^-1 and order-of-magnitude kinetic energy outflow rates up to around 260% of the observed quasar bolometric luminosities. This fraction is >3.9 and 8.8 times that in comparison samples at z ≈ 1.5-3.5 and z < 1, respectively. These extreme outflows are comparable to or even faster than the most rapid [O III] outflows reported at z ≲ 3, and could reach the circumgalactic medium or even the intergalactic medium. The average kinetic energy outflow rate of our sample is more than 2 dex higher than that of the lower-redshift comparison samples. The substantially higher frequency of outflows with energetics well above the threshold for negative feedback in our sample strongly suggests that quasar feedback plays an important part in efficiently quenching and regulating early massive galaxies.

PMID:42092143 | DOI:10.1038/s41586-026-10477-9

Nature. 2026 May 6. doi: 10.1038/s41586-026-10459-x. Online ahead of print.

ABSTRACT

A major scientific drive is to characterize the protein-coding genome, which is a primary basis for studying human health. But the fundamental question remains of what has been missed in previous analyses. Over the past decade, the translation of non-canonical open reading frames (ncORFs) has been observed across human cell types and disease states^1-3, with major implications for biomedical science. However, a key gap in knowledge has been which ncORFs produce small microproteins or alternative protein molecules that contribute to the human proteome. Here we report the collaborative efforts of the TransCODE Consortium⁴ to produce a consensus landscape of protein-level evidence for ncORFs. We show that about 25% of a set of 7,264 ncORFs gives rise to detectable peptides in a large-scale analysis of 95,520 proteomics experiments. We develop an annotation framework for ncORF-encoded microproteins as human proteins and codify the new conceptual model of ‘peptideins’ as microproteins that have indeterminate potential as functional proteins. To probe the biological implications of peptideins, we create an evolutionary analysis approach, termed ORF relative branch length (ORBL), and determine that evolutionary constraint is common and associates with observation of ncORF-derived peptides. We then characterize a pan-essential cellular phenotype for one peptidein from the OLMALINC long non-coding RNA. Overall, we generate public research tools supported by GENCODE and PeptideAtlas and advance biomedical discovery for understudied components of the human proteome.

PMID:42092140 | DOI:10.1038/s41586-026-10459-x

Nature. 2026 May 6. doi: 10.1038/s41586-026-10498-4. Online ahead of print.

ABSTRACT

Stability can be desirable for many natural and social systems. Temporal stability, the invariability of a system over time, can be enhanced by resisting displacement during perturbations, accelerating recovery after them, or both^1-4. Likewise, resilience (sensu proximity to unperturbed levels after a perturbation^5-10) also has components of withstanding (resistance) and recovering after perturbations^11,12. Here we develop and test new predictions for how temporal stability and resilience depend on their resistance and recovery components. We find that temporal stability could often be predicted from resistance, even without information about how quickly the system recovers. By contrast, resilience is predicted to depend at least as much on recovery as on resistance, as in earlier theory^11,12. Using plant productivity data from the world’s longest-running biodiversity experiment, we find that long-term temporal stability, quantified over a quarter century at the ecosystem or species level, is predicted with moderate accuracy from single-year estimates of resistance alone, with only slight improvement by also considering recovery. Resilience was predicted with moderate accuracy by a combination of resistance and recovery at the ecosystem level. We also find that ecosystem drought resistance can be forecasted by monitoring temporal stability before the drought. Our results reveal that long-term temporal stability and short-term resistance may often be predicted from one another and clarify how resistance and recovery can be leveraged to enhance the stability of both natural and managed systems.

PMID:42092138 | DOI:10.1038/s41586-026-10498-4