Sci Rep. 2025 Mar 9;15(1):8148. doi: 10.1038/s41598-025-92605-5.

ABSTRACT

For individuals with amyotrophic lateral sclerosis (ALS), intravenous edaravone is approved as a disease-modifying medication; yet, there have been many reports of adverse events (AEs). We examined the AEs associated with edaravone in this study using actual data from the FDA's (Food and Drug Administration) adverse event reporting system (FAERS). By extracting large-scale data from the FAERS database, this study used the signals of edaravone-associated AEs were quantified using the multiitem gamma Poisson shrinker (MGPS) method based on disproportionality, the Bayesian confidence propagation neural network (BCPNN), the reporting odds ratio (ROR), and the proportional reporting ratio (PRR). In the FAERS database, this study extracted data between April 2017 and March 2024, and edaravone was identified as the "primary suspect (PS)" in 2,986 AE reports. AEs associated with edaravone specifically targeted 27 system organ types (SOCs). Unexpectedly serious AEs that weren't mentioned in the drug insert, include abnormal hepatic function, catheter site thrombosis, pain, cerebral hemorrhage, infection, cerebral infarction, poor venous access, disseminated intravascular coagulation, vein collapse and cerebral venous sinus thrombosis. Our research found possible signals of new AEs that may offer substantial backing for clinical surveillance and edaravone risk assessment, but further research and validation are needed, especially for those AE that may occur in actual usage scenarios but are not yet explicitly described in the instruction.

PMID:40059194 | DOI:10.1038/s41598-025-92605-5

Life Sci. 2025 Mar 7:123548. doi: 10.1016/j.lfs.2025.123548. Online ahead of print.

ABSTRACT

AIMS: This study explores the association between the Wnt signaling pathway and T2DM, emphasizing the role of Tankyrase1 (TNKS1) in metabolic regulation. Using network pharmacology and computational approaches, it aims to identify potential FDA-approved drugs for repurposing as Wnt inhibitors to improve insulin sensitivity and reduce fat accumulation.

MATERIALS AND METHODS: Network pharmacology analysis was performed to explore the association between the Wnt pathway and T2DM, identifying Catenin Beta 1 (CTNBB1) as a key hub gene involved in disease progression. A 2D structural similarity search was conducted using reference tankyrase inhibitors (E7449 and XAV939). Potential drug candidates were subjected to molecular docking and 100 ns molecular dynamics (MD) simulations with the Tankyrase I (PDB ID: 4W6E) protein. The shortlisted compounds were further evaluated for Wnt inhibitory activity using the TCF/LEF reporter assay, while their anti-diabetic potential was assessed through a glucose uptake assay in L6 myoblast cells.

KEY FINDINGS: Niclosamide, Capmatinib, Esomeprazole, and Fenofibrate were identified as promising candidates with strong binding affinities and stable interactions with key amino acids (Gly1185, Ser1221, Tyr1224, Asp1198, Tyr1213, and His1201). Experimental validation through in-vitro Wnt inhibition and glucose uptake assays confirmed that drugs Fenofibrate and Conivaptan exhibited significant Wnt inhibitory activity, suggesting their potential role in modulating T2DM-related pathways.

SIGNIFICANCE: This study highlights the role of the Wnt signaling pathway in T2DM pathogenesis and identifies potential drug candidates for repurposing as Tankyrase1/Wnt inhibitors. The findings provide a foundation for further in-vivo investigations into the anti-diabetic potential of the identified drugs, paving the way for novel therapeutic strategies in T2DM management.

PMID:40058577 | DOI:10.1016/j.lfs.2025.123548

Redox Biol. 2025 Mar 3:103569. doi: 10.1016/j.redox.2025.103569. Online ahead of print.

ABSTRACT

Nuclear factor erythroid 2-related factor 2 (NRF2) is a redox-activated transcription factor regulating cellular defense against oxidative stress, thereby playing a pivotal role in maintaining cellular homeostasis. Its dysregulation is implicated in the progression of a wide array of human diseases, making NRF2 a compelling target for therapeutic interventions. However, challenges persist in drug discovery and safe targeting of NRF2, as unresolved questions remain especially regarding its context-specific role in diseases and off-target effects. This comprehensive review discusses the dualistic role of NRF2 in disease pathophysiology, covering its protective and/or destructive roles in autoimmune, respiratory, cardiovascular, and metabolic diseases, as well as diseases of the digestive system and cancer. Additionally, we also review the development of drugs that either activate or inhibit NRF2, discuss main barriers in translating NRF2-based therapies from bench to bedside, and consider the ways to monitor NRF2 activation in vivo.

PMID:40059038 | DOI:10.1016/j.redox.2025.103569

Biochimie. 2025 Mar 7:S0300-9084(25)00056-2. doi: 10.1016/j.biochi.2025.03.002. Online ahead of print.

ABSTRACT

Metformin, initially prescribed as an oral hypoglycemic medication for type 2 diabetes, has recently gained attention for its potential anticancer effects. Its history dates to 1918, when guanidine, a component of the traditional European herb Galega officinalis, was found to reduce glycemia. This review precisely examines the mechanisms underlying Metformin's anticancer effects across various neoplastic conditions. This investigation explores the complex interactions between metformin and major signaling pathways associated with carcinogenesis, including AMP-activated protein kinase (AMPK), mTOR, and insulin-like growth factor (IGF) pathways. The review emphasizes Metformin's diverse effects on angiogenesis, inflammation, apoptosis, and cellular metabolism in cancer cells. Additionally, new data on metformin's capacity to alter the tumor microenvironment and enhance immune surveillance systems against cancer are examined. The review underscores Metformin's potential for repurposing in oncology, emphasizing its clinical relevance as an adjuvant therapy for various cancers. The review provides insightful information about the complex anticancer mechanisms of metformin by combining data from preclinical and clinical studies. These findings not only broaden our knowledge of the effects of metformin but also open new avenues for oncology research and treatment developments.

PMID:40058683 | DOI:10.1016/j.biochi.2025.03.002

J Cyst Fibros. 2025 Mar 8:S1569-1993(25)00070-0. doi: 10.1016/j.jcf.2025.03.002. Online ahead of print.

ABSTRACT

OBJECTIVES: Recent therapeutic advances, mainly with the advent of CFTR modulators, have been associated with an increasing number of pregnancies in females with cystic fibrosis (fwCF). This study aimed to evaluate the safety of the use of CFTR modulators, specifically elexacaftor/tezacaftor/ivacaftor (ELX/TEZ/IVA) during pregnancy.

METHODS: A nationwide cohort study was conducted using the French health insurance data warehouse (SNDS), covering nearly all singleton pregnancies ending between January 2018 and December 2023. Exposure to CFTR modulators was defined as using prescriptions through pregnancy, including one month in the preconception period. The study compared pregnancy outcomes amongst fwCF between pregnancies exposed and unexposed to CFTR modulators.

RESULTS: Among 590 pregnancies in fwCF, 148 (24.7 %) were exposed to CFTR modulators, including 136 during first trimester. Of these, 147 (99.3 %) resulted in livebirths. The most common CFTR modulator used was ELX/TEZ/IVA, in 121 (81.8 %) pregnancies. The prevalence of major birth defects was similar between exposed and unexposed fwCF (3.38 % vs. 4.66 %; p = 0.72). The rate of small for gestational age (SGA, <10th percentile) was significantly lower in pregnancies exposed compared to unexposed (6.8 % vs. 16.1 %; p < 0.01).

DISCUSSION: The study provides early reassurance about the safety of CFTR modulators during pregnancy, particularly in terms of teratogenicity and adverse pregnancy outcomes. While findings suggest potential benefits, such as halved rate of SGA, further research is required to confirm these outcomes and investigate long-term effects on the development of children prenatally exposed to CFTR modulators.

PMID:40058987 | DOI:10.1016/j.jcf.2025.03.002

Methods Cell Biol. 2025;194:119-133. doi: 10.1016/bs.mcb.2024.01.007. Epub 2024 Feb 26.

ABSTRACT

Mucosal addressin cell adhesion molecule 1 (MAdCAM-1) expression in high endothelial venules is regulated by bacterial metabolites emanating from the gut and the interaction of MAdCAM-1 with α4β7 integrin mediates lymphocyte diapedesis into gut-associated secondary lymphoid tissues. MAdCAM-1 thus controls the abundance of circulating immunosuppressive T cells that can reach malignant tissue and compromise the therapeutic efficacy of anticancer immunotherapy. Here we describe a biosensor-based phenotypic assessment that facilitates the high throughput screening (HTS)-compatible assessment of MAdCAM-1 regulation in response to exposure to bacterial metabolites. This screening routine encompasses high endothelial venule cells expressing green fluorescent protein (GFP) under the control of the MAdCAM-1 promoter combined with robot-assisted bioimaging and a multistep image analysis pipeline. Altogether this system facilitates the discovery of bacterial composites that control anticancer immunity via the sequestration of Th17-specific regulatory T cells (Treg17) in the gut.

PMID:40058956 | DOI:10.1016/bs.mcb.2024.01.007

J Obstet Gynaecol Can. 2025 Mar 7:102809. doi: 10.1016/j.jogc.2025.102809. Online ahead of print.

ABSTRACT

INTRODUCTION: Survival in cystic fibrosis (CF) is increasing and more women are considering their reproductive options, however there is limited data on pregnancy and neonatal outcomes in this population. The objectives of this study were to describe maternal and neonatal outcomes in women with CF and the general Canadian maternal population (general population).

METHODS: Maternal and neonatal clinical outcomes and healthcare utilization for in-hospital live births was retrieved from the Canadian Institute for Health Information's Discharge Abstract Database. Mothers with CF were identified using the ICD-10-CA code for CF. The observation period was fiscal year (FY) 2006-2007 to FY2020-2021 for mothers with CF, and FY2019-2020 for the general population.

RESULTS: During the 15-year observation period, there were 154 newborns from 146 deliveries among 124 mothers with CF. Relative to the general population, mothers with CF were younger (median age 28 vs. 31 years), had more comorbidities, induction of labour, epidural, assisted delivery and use of assisted reproductive technologies, but fewer cesarean sections. Nearly 85% of mothers with CF delivered in a hospital that had a CF clinic. 6.8% of mothers with CF were admitted to the intensive care unit (ICU). Neonates born to mothers with CF had high rates of multiple births, preterm delivery, and jaundice. 26.6% of neonates born to mothers with CF were admitted to the neonatal ICU.

CONCLUSIONS: While no inferential analyses were done, mothers with CF and their newborns may experience worse post-delivery outcomes and may require greater use of healthcare resources than the general population.

PMID:40058495 | DOI:10.1016/j.jogc.2025.102809

J Nippon Med Sch. 2025;92(1):69-79. doi: 10.1272/jnms.JNMS.2025_92-112.

ABSTRACT

BACKGROUND: We retrospectively examined image quality (IQ) of thin-slice virtual monochromatic imaging (VMI) of half-iodine-load, abdominopelvic, contrast-enhanced CT (CECT) by dual-energy CT (DECT) with deep learning image reconstruction (DLIR).

METHODS: In 28 oncology patients with moderate-to-severe renal impairment undergoing half-iodine-load (300 mgI/kg) CECT by DECT during the nephrographic phase, we reconstructed VMI at 40-70 keV with a slice thickness of 0.625 mm using filtered back-projection (FBP), hybrid iterative reconstruction (HIR), and DLIR; measured contrast-noise ratio (CNR) of the liver, spleen, aorta, portal vein, and prostate/uterus; and determined the optimal keV to achieve the maximal CNR. At the optimal keV, two independent radiologists compared each organ's CNR and subjective IQ scores among FBP, HIR, and DLIR to subjectively grade image noise, contrast, sharpness, delineation of small structures, and overall IQ.

RESULTS: CNR of each organ increased continuously from 70 to 40 keV using FBP, HIR, and DLIR. At 40 keV, CNR of the prostate/uterus was significantly higher with DLIR than with FBP; however, CNR was similar between FBP and HIR and between HIR and DLIR. The CNR of all other organs increased significantly from FBP to HIR to DLIR (P < 0.05). All IQ scores significantly improved from FBP to HIR to DLIR (P < 0.05) and were acceptable in all patients with DLIR only.

CONCLUSIONS: The combination of 40 keV and DLIR offers the maximal CNR and a subjectively acceptable IQ for thin-slice VMI of half-iodine-load CECT.

PMID:40058838 | DOI:10.1272/jnms.JNMS.2025_92-112

Environ Pollut. 2025 Mar 7:125937. doi: 10.1016/j.envpol.2025.125937. Online ahead of print.

ABSTRACT

In recent years, air quality levels have become a global issue with the rise of harmful pollutants and their effects on climate change. Urban areas are especially affected by air pollution, resulting in a deterioration of the environment and a surge in health complications. Research has been conducted on different studies that accurately predict future pollution concentration levels utilising different methods. This paper introduces the current physical models for air quality prediction and conducts an extensive systematic literature review on Machine Learning and Deep Learning techniques for predicting pollutants. This work compares different methodologies and techniques by grouping studies that utilise similar approaches together and comparing them. Furthermore, a distinction is made between temporal and spatiotemporal models to understand and highlight how both approaches impact future air pollutant concentration level predictions. The review differs from similar works as it focuses not only on comparing models and approaches but by analysing how the usage of external features, such as meteorological data, traffic information, and land usage, affect pollutant levels and the model's accuracy on air quality forecasting. Performances and limitations are explored for both Machine and Deep Learning approaches, and the work offers a discussion on their comparison and possible future developments in this research space. This review highlights how Deep Learning models tend to be more suitable for forecasting problems due to their feature and spatio-temporal correlation representation abilities, as well as providing different directions for further work, from models utilisation to feature inclusion.

PMID:40058557 | DOI:10.1016/j.envpol.2025.125937

Environ Res. 2025 Mar 7:121349. doi: 10.1016/j.envres.2025.121349. Online ahead of print.

ABSTRACT

Evidence linking greenspace exposure to metabolic syndrome (MetS) remains sparse and inconsistent. This exploratory study evaluate the relationship between green visibility index (GVI) and normalized difference vegetation index (NDVI) with MetS prevalence, and quantifies the potential reduction in MetS burden from increased greenspace exposure. Participants were selected from the baseline survey of the Wuhan Chronic Disease Cohort. Street-view imagry was procured within buffer zones ranging from 50 to 500-m surrounding participants' residences. GVI was extracted from street-view images using a convolutional neural network model trained on CityScapes, while the NDVI was ascertained from satellite remote sensing data. We employed generalized linear mixed-effects models to assess the associations between greenspace with the risk of MetS. Additionally, restricted cubic spline function was applied to generate exposure-response curve. Leveraging a counterfactual causal inference framework, we quantified the potential diminution in MetS cases consequent to an elevation in NDVI levels within Wuhan. Within the 150-meter buffer zone, each 0.1-unit increase in GVI and NDVI corresponded to 13% and 31% decline in the odds of MetS in the fully adjusted regression models, respectively. A negative non-linear relationship between GVI and MetS was observed when the GVI level exceeded 0.209, while a negative linear association for NDVI when its level exceeded 0.299. Assuming causality, 74,183 cases of MetS can be avoided by achieving greenness threshold of NDVI, amounting for 8.16% of total MetS prevalence in 2019. Our findings offer a compelling justification for the integration of greening policies in initiatives aimed at promoting metabolic health.

PMID:40058546 | DOI:10.1016/j.envres.2025.121349

Aust Crit Care. 2025 Mar 8;38(3):101203. doi: 10.1016/j.aucc.2025.101203. Online ahead of print.

ABSTRACT

BACKGROUND: Machine learning (ML) models represent advanced computational approaches with increasing application in predicting successful weaning from mechanical ventilation (MV). Whilst ML itself has a long history, its application to MV weaning outcomes has emerged more recently. In this systematic review, we assessed the effects of ML on the prediction of successful weaning outcomes amongst adult patients undergoing MV.

METHODS: PubMed, EMBASE, Scopus, Web of Science, and Google Scholar electronic databases were searched up to May 2024. In addition, ACM Digital Library and IEEE Xplore databases were searched. We included peer-reviewed studies examining ML models for the prediction of successful MV in adult patients. We used a modified version of the Joanna Briggs Institute checklist for quality assessment.

RESULTS: Eleven studies (n = 18 336) were included. Boosting algorithms, including extreme gradient boosting (XGBoost) and Light Gradient-Boosting Machine, were amongst the most frequently used methods, followed by random forest, multilayer perceptron, logistic regression, artificial neural networks, and convolutional neural networks, a deep learning model. The most common cross-validation methods included five-fold and 10-fold cross-validation. Model performance varied, with the artificial neural network accuracy ranging from 77% to 80%, multilayer perceptron achieving 87% accuracy and 94% precision, and convolutional neural network showing areas under the curve of 91% and 94%. XGBoost generally outperformed other models in the area under the curve comparisons. Quality assessment indicated that almost all studies had high quality as seven out of 10 studies had full scores.

CONCLUSIONS: ML models effectively predicted weaning outcomes in adult patients undergoing MV, with XGBoost outperforming other models. However, the absence of studies utilising newer architectures, such as transformer models, highlights an opportunity for further exploration and refinement in this field.

PMID:40058181 | DOI:10.1016/j.aucc.2025.101203

Brain Behav Immun. 2025 Mar 7:S0889-1591(25)00099-6. doi: 10.1016/j.bbi.2025.03.013. Online ahead of print.

ABSTRACT

BACKGROUND: Individuals raised in an urban environment (URBANs) show an exaggerated inflammatory response to the Trier Social Stress Test (TSST) compared with individuals raised in a rural environment. The underlying mechanisms are unclear but may relate to childhood animal contact. As an exaggerated immune (re)activity plays a causal role in the pathogenesis of stress-associated disorders, these findings might explain the higher prevalence of stress-associated disorders in urban vs. rural areas.

METHODS: We recruited physically and emotionally healthy male URBANs, raised in a city with more than 40,000 residents either in the absence (noPETs) or presence (PETs) of household pets. Participants were individually exposed to the TSST, and before and after the TSST, blood and saliva were collected for assessment of different stress-related parameters. An additional saliva sample before the TSST was collected for salivary microbiome analysis. Heart rate (HR) and HR variability (HRV) were recorded continuously. Mental and physical health status, early-life and perceived life stress, current animal contact, and subjective strain induced by TSST exposure were assessed using validated questionnaires.

RESULTS: Here we show that adult healthy male URBANs raised in the absence (noPETs) vs. presence (PETs) of household pets still reported less animal contact during adulthood and were characterized by deficits in their immunoregulatory and intestinal barrier function, which under basal conditions did not translate into a chronic low-grade inflammatory state. This was different under acute psychosocial stress conditions. Exposure to the TSST resulted in a facilitated mobilization of particularly neutrophil granulocytes in noPETs vs. PETs, accompanied by an enhanced pro- and compromised anti-inflammatory systemic stress response.

CONCLUSION: Together, the presence of pets seems to reduce the risk for URBANs to develop stress-associated disorders later in life (i.e., primary prevention) by facilitating immunoregulatory and barrier functions, in turn preventing an overshooting immune activation in response to acute stressors and chronic low-grade inflammation in response to repeated/chronic stressors.

PMID:40058670 | DOI:10.1016/j.bbi.2025.03.013

BMB Rep. 2025 Mar 5:6350. Online ahead of print.

ABSTRACT

Abscisic acid (ABA) is a key phytohormone that regulates multiple biological processes in plants, including seed germination, seedling growth, and abiotic stress response. ABA enhances drought tolerance by promoting stomatal closure, thereby improving crop productivity under unfavorable stress conditions. Extensive research efforts have focused on understanding ABA signaling more clearly for its potential application in agriculture. The accumulation and stability of signaling components involved in the efficient transduction of downstream ABA signaling are affected by both transcriptional regulation and post-translational modifications. Ubiquitination is a representative post-translational modification that regulates protein stability, and E3 ubiquitin ligase is a key enzyme that determines target substrates for ubiquitination. To date, many E3 ligases functioning as a monomeric form such as RING-, HECT- and Ubox-types have been known to participate in the ABA signaling process. In this review, we summarize the current understanding of ABA-related monomeric E3 ligases, their regulation, and mode of action in Arabidopsis, which will help develop a detailed and integrated understanding of the ABA signaling process in Arabidopsis.

PMID:40058874

J Biotechnol. 2025 Mar 7:S0168-1656(25)00063-X. doi: 10.1016/j.jbiotec.2025.03.006. Online ahead of print.

ABSTRACT

Transaminases have important applications in the synthesis of drug intermediates such as chiral amines. However, natural transaminases exhibit suboptimal thermal stability, limiting their further applications. Building upon an Rhodobacter sp.-derived (R)-selective transaminase (RbTA), we report a dual-region coupling engineering approach to improve thermostability of RbTA by strengthening the core hydrogen-bond networks and rigidifying the flexible surface loop. Through single strategy, we identified 4 thermostability improved single mutations, among which I249Q demonstrated the most substantial improvement, achieving a 18-fold increase in half-life (t1/240) and a 11.2 ℃ increase in T5010. Then in strategic coupling, the synergistic effect of dual-region modification was observed in both thermal stability and activity enhancement, as mutant with the best high-temperature catalytic performance, R136P/F228Y, had its T5010 improved by 7.1℃ and exhibited a 4.2-fold increase in kcat/Km towards (R)-3-amino-1-butanol. Finally, R136P/F228Y achieved a 20.5% improvement in conversion over WT in an analytical-scale synthesis in 72h at a 5 ℃ elevated catalytic temperature. Molecular dynamics simulations demonstrated that the synergy of the formation of new hydrogen bonds and decrease in flexibility accounted for the thermostability improvements. This study provides guidance for enhancing thermostability of similar fold-type enzymes without impairing enzymatic activity in an efficient manner.

PMID:40058651 | DOI:10.1016/j.jbiotec.2025.03.006

Mol Cell Proteomics. 2025 Mar 7:100934. doi: 10.1016/j.mcpro.2025.100934. Online ahead of print.

ABSTRACT

Limited proteolysis combined with mass spectrometry (LiP-MS) facilitates probing structural changes on a proteome-wide scale. This method leverages differences in the proteinase K accessibility of native protein structures to concurrently assess structural alterations for thousands of proteins in situ. Distinguishing different contributions to the LiP-MS signal, such as changes in protein abundance or chemical modifications, from structural protein alterations remains challenging. Here, we present the first comprehensive computational pipeline to infer structural alterations for LiP-MS data using a two-step approach. (1) We remove unwanted variations from the LiP signal that are not caused by protein structural effects and (2) infer the effects of variables of interest on the remaining signal. Using LiP-MS data from three species we demonstrate that this approach outperforms previously employed approaches. Our framework provides a uniquely powerful approach for deconvolving LiP-MS signals and separating protein structural changes from changes in protein abundance, post-translational modifications and alternative splicing. Our approach may also be applied to analyze other types of peptide-centric structural proteomics data, such as FPOP or molecular painting data.

PMID:40058498 | DOI:10.1016/j.mcpro.2025.100934

Hum Vaccin Immunother. 2025 Dec;21(1):2471225. doi: 10.1080/21645515.2025.2471225. Epub 2025 Mar 9.

ABSTRACT

Fear of side effects is the main motive for vaccine refusal. However, before the COVID-19 pandemic, little attention had been paid to the actual experience of adverse events and its relationship with vaccine hesitancy. This scoping review aimed to analyze the impact of VH on EAE and vice versa. We reviewed 55 articles. Most of the studies focused on COVID-19 vaccination and employed cross-sectional surveys with self-reported indicators. These studies identified significant correlations between EAE and VH. Social cognitive models shed some light on the influence of EAE on VH, while the converse is usually explained by the nocebo effect that predominately accounts for the converse. This emerging research field is hampered by significant inconsistencies in theoretical explanations, assessments of the relationship, and measurements of these two phenomena. A more comprehensive consideration of individual experience, both objective and subjective, would help develop more effective vaccine communication strategies and improve pharmacological surveillance.

PMID:40058398 | DOI:10.1080/21645515.2025.2471225

Age Ageing. 2025 Mar 3;54(3):afaf019. doi: 10.1093/ageing/afaf019.

ABSTRACT

The adoption of technology, particularly for monitoring the effects of medications in residential aged care (nursing home), has been slow. Ageing populations have led to increased demand for residential aged care globally, resulting in a growing imperative to implement technological solutions to meet the complex healthcare and medication needs of older people in residential aged care. This commentary explores the potential for and the challenges associated with implementing technological interventions within residential aged care to improve monitoring of medication effects. Drawing on insights from two implementation trials, specifically the Reducing Medicine-induced Deterioration and Adverse Reactions and A Digitally Enabled Pharmacist Service to detecT medicine harms in residential aged care, we discuss the unique challenges and opportunities arising from the real-world applications of digital technologies for medication safety in aged care.

PMID:40057985 | DOI:10.1093/ageing/afaf019

Cell Rep. 2025 Mar 7;44(3):115392. doi: 10.1016/j.celrep.2025.115392. Online ahead of print.

ABSTRACT

Streptomyces albidoflavus is a widely used strain for natural product discovery and production through heterologous biosynthetic gene clusters (BGCs). However, the transcriptional regulatory network (TRN) and its impact on secondary metabolism remain poorly understood. Here, we characterize the TRN using independent component analysis on 218 RNA sequencing (RNA-seq) transcriptomes across 88 unique growth conditions. We identify 78 independently modulated sets of genes (iModulons) that quantitatively describe the TRN across diverse conditions. Our analyses reveal (1) TRN adaptation to different growth conditions, (2) conserved and unique characteristics of the TRN across diverse lineages, (3) transcriptional activation of several endogenous BGCs, including surugamide, minimycin, and paulomycin, and (4) inferred functions of 40% of uncharacterized genes in the S. albidoflavus genome. These findings provide a comprehensive and quantitative understanding of the S. albidoflavus TRN, offering a knowledge base for further exploration and experimental validation.

PMID:40057950 | DOI:10.1016/j.celrep.2025.115392

J Allergy Clin Immunol Pract. 2025 Mar 7:S2213-2198(25)00208-9. doi: 10.1016/j.jaip.2025.02.035. Online ahead of print.

ABSTRACT

BACKGROUND: Long-acting bronchodilators can improve the control of asthma when added to inhaled corticosteroids. However, the cardiovascular safety of these drugs in patients with asthma has not been comprehensively evaluated. Notably, growing evidence has indicated a positive association between asthma and cardiovascular disease.

OBJECTIVE: To evaluate the cardiovascular safety of adding long-acting bronchodilators in patients with asthma.

METHODS: After a comprehensive search in PubMed, Embase, Cochrane Library, and Web of Science, we included randomized controlled trials that assessed the cardiovascular safety of long-acting bronchodilators in patients with asthma. The primary outcome was a comparison of the incidence of total cardiovascular adverse events (AEs). Secondary outcomes included drug-related AEs, AEs leading to discontinuation, serious AEs, and fatal AEs.

RESULTS: A total of 22 trials with 62,915 patients were included. The use of long-acting bronchodilators significantly increased the incidence of cardiovascular AEs leading to discontinuation (incidence rate ratio = 3.05; 95% CI, 1.07-8.48). The incidence of total cardiovascular AEs, drug-related AEs, serious AEs, and fatal AEs was higher in patients treated with long-acting bronchodilators, but the differences were not significant. The certainty of evidence was low for comparations of total cardiovascular AEs and fatal AEs. The certainty of evidence was very low for comparisons of drug-related AEs, AEs leading to discontinuation, and serious AEs.

CONCLUSIONS: The incidence of cardiovascular AEs was low in patients with asthma. Only the risk of AEs leading to discontinuation was significantly increased compared with those not exposed to long-acting bronchodilators. More studies are required to confirm these findings considering the potential reporting bias.

PMID:40057190 | DOI:10.1016/j.jaip.2025.02.035

Sci Rep. 2025 Mar 8;15(1):8134. doi: 10.1038/s41598-025-92531-6.

ABSTRACT

Addressing the challenge that existing deep learning models face in accurately segmenting metal corrosion boundaries and small corrosion areas. In this paper, a SegFormer metal corrosion detection method based on parallel extraction of edge features is proposed. Firstly, to solve the boundary ambiguity problem of metal corrosion images, an edge-feature extraction module (EEM) is introduced to construct a spatial branch of the network to assist the model in extracting shallow details and edge information from the images. Secondly, to mitigate the loss of target feature information during the reconstruction of the decoder, this paper adopts the gradual upsampling decoding layer design. It introduces the feature fusion module (FFM) to achieve hierarchical and progressive feature fusion, thereby enhancing the detection of small corroded areas. Experimental results show that the proposed method outperforms other semantic segmentation models achieving an accuracy of 86.56% on the public metal surface corrosion image dataset and reaching a mean intersection over union (mIoU) of 91.41% on the BSData defect dataset. On the Self-built tubing corrosion pit image dataset, the model utilizes only 3.60 MB of parameters to achieve an accuracy of 96.52%, confirming the effectiveness and performance advantages of the proposed method in practical applications.

PMID:40057599 | DOI:10.1038/s41598-025-92531-6