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Estuarine and coastal environments have experienced dissolved oxygen (DO hereafter) depression and hypoxia due to increasingly intensified anthropogenic eutrophication and climate warming. This review compared diverse systems in Chinese coastal waters that experience DO depletion or hypoxia, aiming to identify essential aspects in advancing the abilities in comprehensively understanding DO dynamics across systems that span wide ranges of physical and biogeochemical environments. The coastal DO depression and relevant ecological consequences around the world are generally overviewed. DO depression in specific systems around Chinese coastal waters, ranging from large estuarine-coastal system to small embayment, are selected to synthetically understand the environment, the controlling processes, the evolution of eutrophication level, and the potential environmental changes under warming trend. Stressed ecosystems would be put at higher risks with high confidence due to increased complexity and uncertainty caused by future socioeconomic transformation and climate warming. This review proposes key aspects to advancing the abilities in predicting, managing, and mitigating DO stress for marine ecosystems in Chinese coastal waters, potentially providing a framework to discuss future DO changes in the coastal waters worldwide., Competing Interests: Declaration of competing interest The authors declare the following financial interests/personal relationships which may be considered as potential competing interests: Wenxia Zhang reports financial support was provided by the National Science Foundation of China. Liuqian Yu reports financial support was provided by the National Science Foundation of China. Haiyan Zhang reports financial support was provided by the National Science Foundation of China. Feng Zhou reports was provided by the National Science Foundation of China. If there are other authors, they declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier Ltd. All rights reserved.)

Nano-plastics (NPs) are emerging hazardous environmental contaminants that pose health risks with size-dependent toxic effects and are potential risk factors for hepatocellular carcinoma (HCC) and lipid metabolism disorders including non-alcoholic fatty liver disease (NAFLD). However, their underlying molecular mechanisms remain unclear. To shed more light on the causes of these risks, we developed a digestive system microphysiological platform (DS-MPP) for simulating dynamic internal-exposure of multi-size NPs in the gastrointestinal tract and liver. Multi-omics analysis based on DS-MPP revealed hepatic cells are more sensitive to 72 μg/day NPs than gastrointestinal mucosa cells. Specifically, 50 nm NPs disrupt phospholipid metabolism, promote diacylglycerol (DG) accumulation, convert more DG to phosphatidic acid (PA) than triacylglycerol (TG), thus facilitating endocytic vesicles production. Meanwhile, it can active tumorigenesis related pathway mTOR, inducing HCC marked by CAB39. Moreover, 500 nm NPs promote NAFLD by inducing insulin resistance pathways and decreasing PLD1 expression. Our results demonstrate the mechanism of disease and metabolic disorders induced by NPs vary depending on particle size. DS-MPP is a reliable platform for evaluating risk of dynamic NPs exposure and elucidating mechanisms of related metabolic diseases. This platform provides a promising method for health risk assessment caused by environmental pollutants., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier B.V. All rights reserved.)

Precise quantification of protein-ligand interaction is critical in early-stage drug discovery. Artificial intelligence (AI) has gained massive popularity in this area, with deep-learning models used to extract features from ligand and protein molecules. However, these models often fail to capture intermolecular non-covalent interactions, the primary factor influencing binding, leading to lower accuracy and interpretability. Moreover, such models overlook the spatial structure of protein-ligand complexes, resulting in weaker generalization. To address these issues, we propose Non-covalent Interaction-aware Graph Neural Network (NciaNet), a novel method that effectively utilizes intermolecular non-covalent interactions and 3D protein-ligand structure. Our approach achieves excellent predictive performance on multiple benchmark datasets and outperforms competitive baseline models in the binding affinity task, with the benchmark core set v.2016 achieving an RMSE of 1.208 and an R of 0.833, and the core set v.2013 achieving an RMSE of 1.409 and an R of 0.805, under the high-quality refined v.2016 training conditions. Importantly, NciaNet successfully learns vital features related to protein-ligand interactions, providing biochemical insights and demonstrating practical utility and reliability. However, despite these strengths, there may still be limitations in generalizability to unseen protein-ligand complexes, suggesting potential avenues for future work.

Tobacco stalks (TS) present substantial potential for biofuel and biochemical production; however, their complex lignin structures and tightly bound carbohydrates pose significant challenges for enzymatic hydrolysis due to high recalcitrance. This study explores Triton-X 100-mediated 1,4-butanediol combined with AlCl3 pretreatment for TS fractionation towards improving enzymatic hydrolysis. Optimized pretreatment conditions achieved a significant removal of 87.8% of hemicellulose and 81.0% of lignin while maintaining a high cellulose retention of 90.1%. Subsequently, the pretreated biomass recorded 91.2% glucose yield after enzymatic hydrolysis at 10% w/w solid with 12 FPU/g enzyme loadings, substantially outperforming controls. The presence of Triton-X 100 in pretreatment reduced enzyme requirements by up to 33.3%. Structural characterization of the pretreated TS indicated effective disruption of lignin-carbohydrate complexes and an increase in biomass porosity by 1.2-2.3 folds, contributing to improved cellulose accessibility and enzymatic hydrolysis efficiency. Moreover, structural characterization of lignin revealed that Triton-X 100 grafted onto lignin by etherification, yielding a 21% reduction in phenolic hydroxyl content and enhancing surface negative charge. These modifications effectively weaken both hydrogen bonding and electrostatic interactions between lignin and cellulase, thereby improving enzymatic hydrolysis efficiency. Overall, the proposed pretreatment presents a promising strategy for efficient fractionation and hydrolysis of TS biomass., (© 2025 Wiley‐VCH GmbH.)

Background: Despite the fact that morbidity and mortality rates significantly increase with tricuspid regurgitation (TR) severity, limited treatment options are available for treating severe TR., Aims: The single-arm, multicentre, prospective Confirmatory Clinical Study of Treating Tricuspid Regurgitation With K-Clip TM Transcatheter Annuloplasty System (TriStar) evaluated the 1-year outcomes of the novel transcatheter K-Clip annuloplasty system in treating secondary TR., Methods: Between May 2022 and October 2022, patients with ≥severe secondary TR despite optimal medical therapy at 11 centres in China were deemed candidates for transcatheter tricuspid repair by the local Heart Team and a multidisciplinary screening committee. Echocardiographic parameters, clinical and quality-of-life measures, and major adverse events were collected at 1 year., Results: Ninety-six patients were enrolled (mean age 72.6±7.0 years, 60.4% female, mean TRI-SCORE 5.4±2.1). The technical success rate was 97.9%. At 1 year, echocardiographic follow-up showed an average reduction in the annular septolateral diameter of 11.3% (41.9 mm vs 37.1 mm; p<0.01), compared with baseline, with marked right ventricular remodelling. A total of 82.5% of patients had ≤moderate TR, and 97.7% had a ≥1 grade reduction. Patients experienced significant clinical improvements in New York Heart Association Functional Class I/II (32.6% to 96.5%; p<0.001), the 6-minute walk distance increased by 31.9±71.8 m (p<0.001), and the overall Kansas City Cardiomyopathy Questionnaire score increased by 7.6±17.7 points (p<0.001). Neither cardiovascular death nor reintervention were recorded at the 30-day or 1-year follow-up, while severe bleeding requiring further treatment was noted in 5 patients at 1 year. The Kaplan-Meier estimates of survival and freedom from heart failure rehospitalisation were 97.8% and 95.1%, respectively, at 1 year., Conclusions: The 1-year experience using the K-Clip tricuspid annuloplasty system demonstrated high survival and low rehospitalisation rates with durable TR reduction and clinical benefits in functional status and quality-of-life outcomes.

In contemporary agriculture, the predominant strategy for managing perennial weeds within agroecosystems involves the extensive use of herbicides. Thiobencarb is widely employed to control gramineous weeds during rice cultivation. This herbicide is commonly found in terrestrial environments and agricultural products. The harmful potential of thiobencarb has been reported, along with its adverse effects in exposed species. However, few studies have explored thiobencarb toxicity, specifically in dairy cows, despite the possibility of ingestion through soil residues. Exposure to xenobiotics can reduce the viability or impair the function of bovine mammary epithelial cells (BMECs), leading to compromised immune function and reduced milk production. Despite the known cytotoxicity of thiobencarb, its specific effects on BMECs remain unclear. Herein, we aimed to investigate the effect of thiobencarb on milk production by examining its toxic effects and underlying mechanisms in BMECs. We assessed the cytotoxic effects of thiobencarb and analyzed various cellular responses upon exposure. Thiobencarb-induced apoptosis was associated with disrupted calcium homeostasis. Additionally, thiobencarb modulated AKT/MAPK proteins and increased mRNA levels of genes related to the inflammatory response. Furthermore, treatment of BMECs with thiobencarb suppressed the expression of genes related to milk production, including those encoding superoxide dismutase, tight junctions, and casein. Finally, we conducted an in silico molecular docking analysis to evaluate the binding affinity between thiobencarb and target proteins., Competing Interests: Declaration of competing interest The authors declare that there are no conflicts of interest., (Copyright © 2024 Elsevier Inc. All rights reserved.)

Mesenchymal stem cells (MSCs) have self-renewal ability and the potential for multi-directional differentiation, and their clinical application has promising prospects, but improving the migration ability of MSCs in vivo is one of the challenges. We previously determined mechanical stretch at 1 Hz with 10 % strain for 8 h can significantly promote MSC migration, however, the molecular mechanism remains poorly understood. Here, we reported that the expression and activity of yes-associated protein (YAP) are upregulated after mechanical stretch. As a classical inhibitor of the YAP-TEAD activity and YAP protein, the treatment of verteporfin (VP) suppressed mechanical stretch-promoted MSC migration. We also observed F-actin polymerization after mechanical stretch. Next, we used Latrunculin A (Lat A), the most widely used reagent to depolymerize actin filaments, to treat MSCs and we found that Lat A treatment inhibits MSC migration by suppressing YAP expression and activity. In addition, the protein expression of Piezo1 was also upregulated after mechanical stretch. Knockdown of Piezo1 suppressed mechanical stretch-promoted MSC migration by restraining F-actin polymerization. Together, these findings demonstrate the role of Piezo1/F-actin/YAP signaling pathway in MSC migration under mechanical stretch, providing new experimental evidence for an in-depth understanding the mechanobiological mechanism of MSC migration., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2025 Elsevier Inc. All rights reserved.)

Using data from NHANES for years 2005-2018, we examined temporal trends in osteoporosis prevalence and the proportion of undiagnosed osteoporosis in the United States of America. Our results suggested statistically significant increases in osteoporosis prevalence across several demographic groups. These findings carry profound implications for public health, given increased life expectancy and burden of chronic diseases., Introduction: This is the first study to assess osteoporosis prevalence trends over time and the proportion of undiagnosed osteoporosis across gender, ethnicity/race, and age groups., Methods: Observational time trend analyses were conducted using the 2005-2006, 2007-2008, 2009-2010, 2013-2014, and 2017-2018 National Health and Nutrition Examination Survey (NHANES) datasets, along with a descriptive analysis using the 2017-2018 NHANES dataset to capture the proportion of undiagnosed osteoporosis., Results: The findings showed a statistically significant increase in osteoporosis prevalence among women, non-Hispanic Whites, and all age groups (except for individuals 80 years of age and older) during the study period. A subsequent analysis examining individuals by both gender and ethnicity/race demonstrated a statistically significant increase among Other Hispanic men and non-Hispanic White women. Additional descriptive analyses found that 69.12% of individuals with osteoporosis went undiagnosed. Specifically, 86.88% of men and 84.77% of individuals 50-59 years of age with osteoporosis went undiagnosed, representing the two highest groups., Discussion and Conclusion: The substantial and increasing prevalence among certain groups and sub-groups, along with the lack of diagnostic capture of osteoporosis, highlights existing gaps in public health efforts and care delivery infrastructure. This paper highlights high-risk groups and sub-groups that may benefit most from accelerated initiatives to reduce the burden of illness associated with osteoporosis., Competing Interests: Declarations. Conflict of interest: Mr. Naso is an employee of and stockholder in Baxter International. Dr. Lin, Ms. Song, and Dr. Xue have no financial disclosures., (© 2025. The Author(s).)

Background: The gut microbiome is critical for the pathophysiology of depression, and inflammation is one of the factors contributing to depression. Fzd6 has been implicated in depression. This study aimed to elucidate the effects of the Fzd6 mutation on gut microbiota structure and the possible regulatory mechanisms involved in depression-associated neuroinflammation., Methods: Wild-type (Fzd6 WT ) and Fzd6 mutant (Fzd6 Q152E ) male mice were treated with lipopolysaccharide (LPS) for 7 days. Behavioral experiments were used to detect the behavioral changes of mice in each group, and the composition of intestinal flora and systemic inflammation levels of mice were further detected., Results: In LPS mice, the Fzd6 mutation enhanced depression-like behavior symptoms, increased the release of pro-inflammatory cytokines, decreased the release of anti-inflammatory cytokines, and caused intestinal flora disturbance. Subsequently, 16SrRNA sequencing revealed significant changes in the relative abundance of the inflammation-associated bacterial groups Ruminococcaceae and Lachnospiraceae in Fzd6 Q152E mice. In mice with depression, the levels of G protein-coupled receptors, GPR41 and GPR43, and glucagon-like peptide-1 (GLP-1) in the small intestine were down-regulated, and the expression of GLP-1 receptor (GLP-1R), peroxisome proliferators activated receptors gamma (PPAR-γ), and nuclear factor kappa-B inhibitor alpha (IκBα) in the hippocampus was also down-regulated, while the expression of nuclear factor kappa-B p65 (NF-κB p65) was up-regulated., Limitations: The size of the spleen was not studied in this model, and the Fzd6 mutation itself does not cause systemic inflammation such as IL-6., Conclusion: These results demonstrate that mutations in Fzd6 regulate the composition of the gut flora, which contributes to depression-associated inflammation., Competing Interests: Declaration of competing interest The authors declare that there are no potential conflicts of interest with respect to the research, authorship, and publication of this article., (Copyright © 2024 Elsevier B.V. All rights reserved.)

Powdery mildew, caused by the fungal pathogen Blumeria graminis (DC.) E. O. Speer f. sp. tritici Em. Marchal (Bgt), is a constant threat to global wheat (Triticum aestivum L.) production. Although ∼100 powdery mildew (Pm) resistance genes and alleles have been identified in wheat and its relatives, more is needed to minimize Bgt's fast evolving virulence. In tetraploid wheat (Triticum turgidum L.), wild emmer wheat [T. turgidum ssp. dicoccoides (Körn. ex Asch. & Graebn.) Thell.] accessions from Israel have contributed many Pm resistance genes. However, the diverse genetic reservoirs of cultivated emmer wheat [T. turgidum ssp. dicoccum (Schrank ex Schübl.) Thell.] have not been fully exploited. In the present study, we evaluated a diverse panel of 174 cultivated emmer accessions for their reaction to Bgt isolate OKS(14)-B-3-1 and found that 66% of accessions, particularly those of Ethiopian (30.5%) and Indian (6.3%) origins, exhibited high resistance. To determine the genetic basis of Bgt resistance in the panel, genome-wide association studies were performed using 46,383 single nucleotide polymorphisms (SNPs) from genotype-by-sequencing and 4331 SNPs from the 9K SNP Infinium array. Twenty-five significant SNP markers were identified to be associated with Bgt resistance, of which 21 SNPs are likely novel loci, whereas four possibly represent emmer derived Pm4a, Pm5a, PmG16, and Pm64. Most novel loci exhibited minor effects, whereas three novel loci on chromosome arms 2AS, 3BS, and 5AL had major effect on the phenotypic variance. This study demonstrates cultivated emmer as a rich source of powdery mildew resistance, and the resistant accessions and novel loci found herein can be utilized in wheat breeding programs to enhance Bgt resistance in wheat., (© 2024 The Author(s). The Plant Genome published by Wiley Periodicals LLC on behalf of Crop Science Society of America. This article has been contributed to by U.S. Government employees and their work is in the public domain in the USA.)

Selenium (Se) is an essential trace element of the utmost importance to human health. Its deficiency induces various disorders. Se species can be absorbed by organisms and metabolized to hydrogen selenide for the biosynthesis of selenoproteins, selenonucleic acids, or selenosugars. Se in mammals mainly acts as selenoproteins to exert their biological functions. The brain ranks highest in the specific hierarchy of organs to maintain the level of Se and the expression of selenoproteins under the circumstances of Se deficiency. Dyshomeostasis of Se and dysregulation of selenoproteins result in encephalopathy such as Alzheimer's disease, Parkinson's disease, depression, amyotrophic lateral sclerosis, and multiple sclerosis. This review provides a summary and discussion of Se metabolism, selenoprotein function, and their roles in modulating brain diseases based on the most currently published literature. It focuses on how Se is utilized and transported to the brain, how selenoproteins are biosynthesized and function physiologically in the brain, and how selenoproteins are involved in neurodegenerative diseases. At the end of this review, the perspectives and problems are outlined regarding Se and selenoproteins in the regulation of encephalopathy., Competing Interests: Compliance and ethics. The authors declare that they have no conflict of interest., (© 2024. Science China Press.)

Microneme protein 2 (MIC2) and its associated protein M2AP are pivotal for the gliding motility and host cell invasion by Toxoplasma gondii. In our prior work, we showed that M2AP binds specifically to the sixth TSR domain of MIC2, with this interaction mediated dominantly by the hotspot residue H620 situated at the center of TSR6. To delve deeper into the functional significance of H620 and explore the dynamic behavior of Y602, we conducted molecular dynamic (MD) simulations of the Toxoplasma TSR6-M2AP complex, encompassing both wild-type and mutant forms. Our findings underscore the critical role of H620 within TSR6, particularly its hydrogen bond interaction with K72 of M2AP. The H620A mutation disrupts the nearby hydrophobic network while minimally affecting other hydrophilic interactions. Furthermore, our data reveal a highly conserved binding pose between M2AP and TSR6 across different species, consistent with previous trans-genera studies, thereby offering insights for future strategies in infection control development., (© 2024 Wiley Periodicals LLC.)

Titanium dioxide nanoparticles (nano-TiO 2 ) can cause a reduction in sperm counts, and lactate production in Sertoli cells plays a key role in spermatogenesis. The aim of this study was to evaluate the effect of nano-TiO 2 on lactate production in mouse Sertoli cell line (TM4 cells) and to investigate whether the effect is mediated through the PI3K/AKT/HIF-1α pathway. After TM4 cells were treated with different concentrations of nano-TiO 2 for 48 h, cell viability, contents of glucose and lactate, and the expression levels of GLUT3 and key enzymes (HK1, HK2, PFKM, ENO1, LDH) during lactate production were detected. PI3K/AKT/HIF-1α pathway proteins were measured. In addition, PI3K agonist (IGF-1) was added to explore whether nano-TiO 2 regulates HIF-1α through PI3K/AKT pathway, thereby affecting the production of lactate in TM4 cells. The results showed that nano-TiO 2 significantly inhibited TM4 cell viability, increased glucose content, decreased lactate content, and downregulated the expression levels of GLUT3 and key enzymes during lactate production. Meanwhile, nano-TiO 2 decreased the expression of PI3K/AKT pathway phosphorylated proteins and HIF-1α, and IGF attenuated this effect of nano-TiO 2 . Collectively, nano-TiO 2 downregulated the expression level of proteins and enzymes related to lactate production in TM4 cells by inhibiting PI3K/AKT/HIF-1α pathway, resulting in the decrease of lactate production in TM4 cells., (© 2024 John Wiley & Sons Ltd.)

Background: Indocyanine green (ICG) fluorescence imaging technology is increasingly widely used in laparoscopic hepatectomy. However, previous studies have produced conflicting results regarding whether it is truly superior to traditional laparoscopic hepatectomy. This study investigated the clinical effect of laparoscopic hepatectomy for hepatocellular carcinoma (HCC) using ICG imaging technology., Methods: A systematic review and meta-analysis, based on the preferred reporting items for systematic reviews and meta-analysis statement, were conducted (PROSPERO: CRD42024532356). A computer search was conducted in databases including CNKI, Wanfang, PubMed, Embase, Cochrane Library, and Web of Science from January 1, 1990, to April 30, 2024., Results: A total of 17 articles were included after screening, comprising 4 randomized controlled trials and 13 case-control studies, with 1620 patients in total. Among these, there were 743 cases in the fluorescence laparoscopy group and 877 cases in the non-fluorescence laparoscopy group. Hepatectomy guided by indocyanine green fluorescence navigation significantly reduced operation time (MD = - 23.25, 95% CI: - 36.35 to - 10.15, P = 0.0005), intraoperative blood loss (MD = - 51.04, 95% CI: - 69.52 to - 32.56, P < 0.00001), and intraoperative transfusion rate (OR = 0.43, 95% CI: 0.27 to 0.69, P = 0.0004), while increasing the R0 resection rate (OR = 2.93, 95% CI: 1.73 to 4.96, P < 0.0001) and decreasing the postoperative complication rate (OR = 0.59, 95% CI: 0.43 to 0.82, P = 0.002). However, there was no statistically significant difference in postoperative length of hospital stay (MD = - 0.67, 95% CI: - 1.51 to 0.18, P = 0.12)., Conclusion: In the treatment of HCC, hepatectomy guided by indocyanine green fluorescence navigation demonstrates superior efficacy and safety, its application and promotion are warranted., Competing Interests: Declarations. Disclosures: Manqin Hu, Zhangbin Chen, Dingwei Xu, Yan Zhang, Guangna Song, Haoyang Huang, and Jie Huang have no conflicts of interest or financial ties to disclose. No (financial) support from this organization has been received for the submitted manuscript. Neither have there been any other activities nor relations that have influenced the submitted work. This work was supported by the Academic Leadership Training Program at the Second Affiliated Hospital of Kunming Medical University (Grant No. RCTDXS-202309)., (© 2025. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.)

Background: Childhood subjective socioeconomic status (operational definition of harshness) and unpredictability significantly influence life history strategies and subsequent psychological and behavioral patterns. Existing research on Chinese populations has been limited by inconsistent metrics and inadequate measurement items. This study aimed to adapt and validate the Chinese versions of the Childhood Perceived Poverty and Wealth Questionnaire (C-CPPWQ) and the Childhood Perceived Unpredictability Questionnaire (C-CPUQ), addressing cultural differences and expanding measurement subjects., Methods: We conducted Exploratory Factor Analysis (EFA) with 493 students and Confirmatory Factor Analysis (CFA) with 1217 students to validate the factor structures. Concurrent validity was assessed using correlations with life history strategies (Mini-K) and childhood trauma (CTQ-SF) and reliability were also evaluated., Results: The C-CPPWQ's two-factor model (perceived wealth and perceived poverty) demonstrated good fit (CFI = 0.95; TLI = 0.94; SRMR = 0.05; RMSEA = 0.08) and strong internal consistency (alpha = 0.90), with significant correlations with Mini-K (r = -0.28, p < 0.001) and childhood trauma (r = 0.29, p < 0.001). The C-CPUQ's three-factor model (Unpredictability of Parenting, Unpredictability of External Environment, and Unpredictability of Daily Happening) also showed a good fit (CFI = 0.96; TLI = 0.95; SRMR = 0.04; RMSEA = 0.07) and high reliability (alpha = 0.95), with significant correlations with Mini-K (r = -0.39, p < 0.001) and childhood trauma (r = 0.72, p < 0.001)., Conclusions: The newly adapted 14-item C-CPPWQ and 16-item C-CPUQ for Chinese contexts exhibit satisfactory psychometric properties, making them valuable tools for researching and evaluating childhood adversity., Competing Interests: Declarations. Ethics approval and consent to participate: All participants volunteered and received a data protection declaration in agreement with the Helsinki Declaration. They gave both, written and verbal, informed consent. The study was approved according to the ethical guidelines by the Ethical commission of Shanghai Mental health center (2023–54). Consent for publication: Not applicable. Competing interests: The authors declare no competing interests. Conflict of interest: The authors declare no conflict of interest., (© 2025. The Author(s).)

Thiol flavor compounds are a class of flavoring ingredients that contribute significantly to food flavor. However, rapid discrimination of multiple thiol-flavor compounds remain a challenge. In this study, a ratiometric fluorescent sensor (TPE-ssHPA@Cu NCs-Ce 3+ ) with dual-channel fluorescence features was developed using tetraphenylethene-embedded hyperbranched poly(amidoamine) as a template to stabilize the copper nanocluster‑cerium ions. The sensor was explored for the specific discrimination of six typical thiol flavor compounds, each producing diverse fluorescent fingerprints that were further identified using pattern recognition methods. The sensor achieved a rapid response in identifying thiol flavor compounds and multicomponent mixtures, with detection limits of 0.32-3.13 μM. Furthermore, it was successfully applied to differentiate between the different types and cooking times of meat broths., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier Ltd. All rights reserved.)

Migrasomes, newly identified organelles, play crucial roles in various physiological and pathological activities, including embryogenesis, immune responses, wound healing, and metastasis of cancer cells. Migrasome visualization is essential for the deep exploration of migrasome biology. Despite the reported labeling methods based on migrasome marker proteins, a simple and convenient method for migrasome labeling is more desirable compared to the complicated transfection technique. Here, an aggregation-induced emission (AIE) based near-infrared (NIR) molecular probe named TTCPy was presented, which can bind to the phospholipid on migrasomes and light up migrasomes with a turn-on NIR fluorescence. TTCPy allows for high-performance imaging of migrasomes in both live cells and living chorioallantoic membranes via simple and rapid staining. Moreover, TTCPy achieves live-cell super-resolution imaging of migrasomes, affording remarkedly improved spatial resolution and signal-to-background ratio. This work offers a simple yet powerful tool for migrasome visualization and will contribute to the booming hotspot of migrasome biology., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2025. Published by Elsevier Ltd.)

Chinese hamster with Chinese characteristics is used in experiments, and it is of great value in the field of medical biology research. However, at present, there is no high-efficiency method for evaluating the genetic quality of Chinese hamsters. Here, we developed a novel Chinese hamster genetic quality detection system using single-nucleotide polymorphism (SNP) markers. To find SNP loci, we conducted whole genome sequencing on 24 Chinese hamsters. Then, we employed an SNP locus screening criterion that we set up previously and initially screened 214 SNP loci with wide genome distribution and high polymorphism level. Subsequently, we developed the SNP detection system using a multitarget region capture technique based on second-generation sequencing, and a 55 SNP panel for genetic evaluation of Chinese hamster populations was developed. PopGen.32. analysis results showed that the average effective allele number, Shannon index, observed heterozygosity, expected heterozygosity, average heterozygosity, polymorphism information, and other genetic parameters of Chinese hamster population A were higher than those in population B. Using scientific screening and optimization, we successfully developed a novel Chinese hamster SNP genetic detection system that can efficiently and accurately analyze the genetic quality of the Chinese hamster population., (© 2025 The Author(s). Animal Models and Experimental Medicine published by John Wiley & Sons Australia, Ltd on behalf of The Chinese Association for Laboratory Animal Sciences.)

Indoleamine 2,3-dioxygenase 1 (IDO1) is an immunosuppressive protein that inhibits antitumor immunity through both tryptophan metabolism and nonenzymatic functions. Drugs targeting IDO1 enzyme activity have failed to improve the overall survival of patients with cancer. Developing new therapeutics that neutralize both enzyme- and nonenzyme-derived immunosuppressive IDO1 effects is therefore of high interest. We previously described a novel proteolysis targeting chimera (PROTAC), NU223612, that degrades IDO1 in cultured human glioblastoma (GBM) cells, as well as in well-established brain tumors, in vivo . In this study, we rationally optimized the structure of our lead series to create NU227326, which degrades IDO1 with a DC 50 of 5 nM in human GBM cells. Mechanistic studies showed that IDO1 degradation occurred through the ubiquitin-proteasome system and was sustained for at least 2 days, supporting NU227326 as a highly potent IDO1 PROTAC suitable for further studies in GBM and other human cancers.

Background: While previous studies have suggested a potential link between greenspace and semen quality, the effect of greenspace exposure on sperm kinematics, as well as the impact of greenspace estimation scales, remains underexplored., Objectives: This study aimed to examine the association between greenspace exposure and sperm kinematics, and to determine whether this relationship varies across different greenspace estimation scales., Methods: We conducted a retrospective longitudinal study of 5,025 semen measurements from 1,674 sperm donors recruited by the Sichuan Provincial Human Sperm Bank (SHSB) between June 2019 and December 2021. Greenspace exposure was estimated using the Normalized Difference Vegetation Index (NDVI) for four buffer zones (250m, 500m, 1000m, and 2000m) centred on the geocoded residential addresses. Linear mixed-effects models and restricted cubic spline models (knots=4) were used to assess the associations between greenspace exposure and both conventional semen parameters and sperm kinematic parameters across all buffer zones., Results: A non-linear association between NDVI-500m and progressive motility was observed for conventional semen parameters (P non-linear = 0.018). For sperm kinematics, significant non-linear associations were found between NDVI-500m and multiple measures, including LIN (P non-linear = 0.011), STR (P non-linear = 0.015), WOB (P non-linear = 0.012), and ALH (P non-linear < 0.001). Regarding the impact of greenspace estimation scales, smaller buffer zones exhibited stronger non-linear relationships for conventional semen parameters, whereas larger buffer zones revealed more pronounced non-linear relationships for sperm kinematics. There was a stable and significant linear association between greenspace exposure and sperm kinematics during the 70-90 days before ejaculation (spermatocytogenesis). PM2.5 and PM10 attenuated the negative effect of greenspace exposure on IM at a buffer scale of 250 m, while enhanced the positive effect of greenspace on kinematics at all scales., Conclusions: Greenspace exposure were significantly associated with sperm kinematics, with the strength and nature of these associations varying by buffer scale. 70-90 days before ejaculation (spermatocytogenesis) was the window of susceptibility for greenspace exposures at all buffer scales. As PM2.5 and PM10 increased, increasing levels of greenspace can improve sperm kinematics more significantly. These findings support the beneficial effect of greenspace on male fertility, and underscore the importance of considering greenspace buffer zones in urban planning to optimize health benefits effectively., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2025. Published by Elsevier Inc.)

Fenoxycarb, a carbamate insecticide, functions as a juvenile hormone agonist to inhibit pests, and its detection in aquatic environments is concerning because of its widespread application. These concerns have led to ecotoxicological studies on aquatic crustaceans; however, research on the effects of fenoxycarb on the developmental processes of organisms is limited. In the present study, the deleterious effects of fenoxycarb on zebrafish development and the related cellular mechanisms mediating this toxicity were addressed. Exposure to sublethal concentrations of fenoxycarb (0, 0.5, 1, and 2 mg/L) resulted in morphological defects in zebrafish larvae, particularly in the heart region, eyes, and body length. These defects were accompanied by an increase in the number of apoptotic cells and the upregulation of related gene expression. Moreover, fenoxycarb increased ROS production and the number of macrophages, and altered the expression of immune-related genes, thereby inducing inflammation. These results revealed various abnormalities in the heart, vasculature, liver, and pancreas, as confirmed by transgenic models, such as cmlc2:DsRed, fli1a:EGFP, and fabp10a:DsRed;elastase:GFP. These developmental impairments were associated with the altered expression levels of genes involved in the development and function of each organ. These results suggest that fenoxycarb can affect multiple organs through excessive inflammation during development and highlight its potent toxic effects on other non-target organisms., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2025 Elsevier B.V. All rights reserved.)

Epidermal electronics are extensively used in human-machine interfaces and wearable sensors. However, managing sweat and gas permeability at the skin-device interface to ensure comfort and prevent skin damage during prolonged use remains a key challenge. Inspired by the fog collection mechanism of cactus spines and trichomes, this work develops a biomimetic, flexible epidermal electronic device with high gas permeability and unidirectional water transport capability. The device exhibits excellent flexibility (Young's modulus: 0.02 MPa), breathability (electrode: 3551.63 g day -1 m -2 , substrate: 3795.38 g day -1 m -2 ), unidirectional water transport (1.09 s), and antigravity water transport (2.50 s). Notably, during continuous sweating (5 h) and extended wear (7 days), it demonstrates outstanding electromyography (EMG) signal acquisition, with a signal-to-noise ratio (SNR) approximately 58 times higher than that of commercial electrodes. This offers promising potential for advancing high-performance, wearable human-machine interface electronics.

Ferroptosis, an iron-dependent form of regulatory cell death, has garnered significant interest as a therapeutic target in cancer treatment due to its distinct characteristics, including lipid peroxide generation and redox imbalance. However, its clinical application in oncology is currently limited by issues such as suboptimal efficacy and potential off-target effects. The advent of nanotechnology has provided a new way for overcoming these challenges through the development of activatable magnetic nanoparticles (MNPs). These innovative MNPs are designed to improve the specificity and efficacy of ferroptosis induction. This Review delves into the chemical and biological principles guiding the design of MNPs for ferroptosis-based cancer therapies and imaging-guided therapies. It discusses the regulatory mechanisms and biological attributes of ferroptosis, the chemical composition of MNPs, their mechanism of action as ferroptosis inducers, and their integration with advanced imaging techniques for therapeutic monitoring. Additionally, we examine the convergence of ferroptosis with other therapeutic strategies, including chemodynamic therapy, photothermal therapy, photodynamic therapy, sonodynamic therapy, and immunotherapy, within the context of nanomedicine strategies utilizing MNPs. This Review highlights the potential of these multifunctional MNPs to surpass the limitations of conventional treatments, envisioning a future of drug-resistance-free, precision diagnostics and ferroptosis-based therapies for treating recalcitrant cancers.

Hepatocytes are the primary functional cells in the liver, and the malignant transformation of hepatocytes significantly contributes to hepatocellular carcinoma (HCC) progression. Liver fibrosis and cirrhosis caused by extracellular matrix (ECM) remodeling during liver lesions is a pivotal driver of HCC. However, the impact of matrix stiffness on hepatocytes and the underlying molecular mechanisms are not fully understood. Herein, using gelatin/sodium alginate hydrogels with different stiffnesses to simulate the change of matrix stiffness during liver lesions, we found that matrix stiffening leads to a notable decrease in the expression of hepatocyte nuclear factor 4α (HNF4α) and functional hepatocyte genes and a significant increase in the expression of interleukin 6 (IL‒6) in human hepatocyte line L‒02 cells, indicating obvious damage of hepatocyte function. In addition, matrix stiffening causes extensive DNA damage to L‒02 cells. Mechanistically, matrix stiffening upregulates piezo‒type mechanosensitive ion channel component 1 (Piezo1) expression and activates extracellular signal‒regulated kinase 1/2 (ERK1/2) signaling. Piezo1 knockdown suppresses matrix stiffening‒induced functional impairment and DNA damage in L‒02 cells. Moreover, Piezo1 knockdown blocks matrix stiffening‒activated ERK1/2 signaling in L‒02 cells. U0126 (a selective inhibitor of ERK1/2 activation) treatment could rescue matrix stiffening‒induced functional impairment and DNA damage. Taken together, these findings demonstrate that matrix stiffening induces functional impairment and DNA damage in L‒02 cells via the Piezo1‒ERK1/2 signaling pathway, which provides evidence for a better understanding of the hepatocyte function damage caused by tissue mechanical microenvironment change in liver diseases and the mechanotransduction in this process., Competing Interests: Declarations. Ethics approval and consent to participate: This article does not contain any studies with human or animal subjects. Consent for publication: Not applicable. Conflict of interest: The authors declare no competing interests., (© 2025. The Author(s) under exclusive licence to University of Navarra.)

Hematopoietic stem and progenitor cells (HSPCs) undergo rapid transcriptional transitions among distinct cell states and functional properties during development, but the underlying molecular mechanism is largely unknown. Here, we characterize the mRNA m 5 C landscape of developing HSPCs in zebrafish and found that m 5 C modification is essential for HSPC expansion through maintaining mRNA stability. Deletion of the m 5 C reader, Y-box binding protein 1 (Ybx1), significantly inhibits the proliferation of HSPCs in zebrafish and mice. Mechanistically, Ybx1 recognizes m 5 C-modified mRNAs and maintains the stability of cell-cycle-related transcripts, thereby ensuring proper HSPC expansion. This study reveals the critical role of Ybx1-mediated mRNA m 5 C modification in developmental hematopoiesis and provides new insights and epitransciptomic strategies for optimizing HSPC expansion., Competing Interests: Declaration of interests The authors declare no competing interests., (Copyright © 2025 The Author(s). Published by Elsevier Inc. All rights reserved.)

Immune checkpoint inhibitors are an effective adjuvant therapy for non-small cell lung cancer (NSCLC). Recent studies have highlighted the critical role of tumor-infiltrating B cells in tumor immunity. However, research specifically focusing on B cells in NSCLC is limited. This study aims to elucidate the role of POU2F2 + B cells in patient survival and immune cell infiltration in NSCLC. Pseudotime analysis was performed to identify B cell pseudotime-related gene sets from two single-cell RNA sequencing (scRNA-seq) datasets of NSCLC. Differentially expressed genes (DEGs) were identified from two NSCLC immunotherapy-related bulk RNA sequencing datasets. A Venn diagram was used to determine core genes shared between these datasets. Kaplan-Meier survival curves were utilized to analyze overall survival (OS). Gene ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) enrichment analyses were performed based on the differential genes between POU2F2 + and POU2F2 - B cells. CIBERSORT analysis was conducted to compare the proportions of immune cell subpopulations between groups. Multiplex immunohistochemistry (mIHC) was used to localize POU2F2 + cells and measure distances between different immune cells. Three hallmark genes, POU2F2, CD2, and CST7, were identified as being associated with B cell maturation and immunotherapy efficacy in NSCLC. High expression of POU2F2 was associated with poorer OS in both LUAD and LUSC. However, the POU2F2 + B cell score specifically correlated with the OS of LUAD but not with LUSC. Further analysis using scRNA-seq and mIHC methods revealed that POU2F2 is predominantly expressed in B cells. In LUAD tumor tissues, POU2F2 + CD20 + B cells were spatially further from PD-1 + CD8 + T cells and CD206 + CD68 + macrophages compared to POU2F2 - CD20 + B cells. In LUSC tumor tissues, POU2F2 + CD20 + B cells were spatially further from CD206 + CD68 + macrophages but showed no significant spatial difference from PD-1 + CD8 + T cells compared to POU2F2 - CD20 + B cells. In patients with high POU2F2 + B cell scores, LUAD tissues showed an increased proportion of CD8 + T cells and M1 macrophages, and a decreased proportion of M2 macrophages. In contrast, in LUSC tissues, a high POU2F2 + B cell score was associated only with an increased proportion of M1 macrophages, with no significant differences in the proportions of CD8 + T cells or M2 macrophages between groups. This study elucidates the significant role of POU2F2 + B cells in influencing survival and immune cell infiltration in NSCLC. Our findings highlight POU2F2 as a novel target for NSCLC immunotherapy. Targeting POU2F2 may modulate the tumor immune microenvironment, enhance the infiltration and activity of critical immune cells, and ultimately improve patient survival., Competing Interests: Declarations. Competing interests: The authors declare no competing interests., (© 2025. The Author(s).)

Urolithin A (UA) is a naturally occurring polyphenolic compound.Due to its remarkable efficacy in safeguarding the central nervous system, UA has emerged as a promising candidate for drug development targeting neurodegenerative diseases such as Alzheimer's. However, the source of UA is limited and the activity of UA to inhibit PDE2 needs to be further improved. Therefore, this study will be optimized on the basis of UA to seek PDE2 inhibitors with better activity. In this study, we designed a series of UA derivatives based on 4HTX as the target protein and UA as the lead compound, utilizing the binding crystal structures of 4HTX and BAY60-7550 as references. After thorough screening, we successfully identified the 8-hydroxyl group as the precise site of modification. Utilizing 2-bromo-5-hydroxybenzoic acid as our primary raw material, we synthesized a series of the 8-hydroxyl modified UA. Subsequently, we evaluated the inhibitory activity of these synthesized UA derivatives using a phosphodiesterase assay kit. Ultimately, we screened a total of 34 derivatives; among them, compounds 1f, 1q, 2d, and 2j exhibited significant inhibitory activity against PDE2 with half-maximal inhibitory concentrations of 3.05 μM, 0.67 μM, 0.57 μM, and 4.96 μM, respectively., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2025 Elsevier Ltd. All rights reserved.)

The development of synthetic receptors capable of selectively binding and transporting saccharides is crucial but highly challenging. In this study, two foldameric receptors 1 and 2, consisting of two repeating monomers, indolocarbazole and naphthyridine units, with different aromatic spacers in the middle of their sequences, have been synthesised. These receptors fold into helical conformations, and the two strands of each receptor are assembled to create domain-swapping cavities for binding monosaccharides by multiple hydrogen bonds. According to 1 H NMR, CD spectroscopy, mass spectrometry, and ITC experiments, receptor 1 forms two distinct 2 : 2 complexes with methyl β-D-galactopyranoside and methyl β-D-glucopyranoside: (1- MM ) 2 ⊃(methyl β-D-galactopyranoside·2H 2 O) 2 and (1- MP ) 2 ⊃(methyl β-D-glucopyranoside) 2 . Despite being composed of identical foldamer strands, these two complexes exhibit notably different folding and assembly modes to achieve optimal stability. The binding affinities of 1 for methyl β-D-galactopyranoside and methyl β-D-glucopyranoside are estimated to be log  K = 12.7 and 13.3, respectively, in 5% (v/v) DMSO/CH 2 Cl 2 . On the other hand, receptor 2 forms a stable 2 : 2 receptor/guest complex with methyl β-D-glucopyranoside, (2- MP ) 2 ⊃(methyl β-D-glucopyranoside) 2 , with an association constant of log  K = 13.9, which is significantly higher than that of methyl β-D-galactopyranoside (log  K = 11.1) and methyl α-D-glucopyranoside (log  K = 10.6). Furthermore, receptor 2 facilitates the selective transport of methyl β-D-glucopyranoside over other glycosides across an organic phase (CH 2 Cl 2 ) in U-tube experiments.

Despite a well-established and growing body of work on nickel(0) precatalysts, the potential of nickel(0) complexes as bifunctional precatalysts remains underexplored. In this study, we synthesized, characterized, and evaluated the catalytic activity of (Ni(0)(DQ)dtbbpy), a bifunctional, red-light-sensitive, and air-stable nickel(0) complex. Owing to its unique photophysical properties, it effectively catalyzed the etherification and amination of aryl bromides under 620-630 nm light irradiation, functioning as both a photocatalyst and an active metal catalyst. Mechanistic studies and density functional theory (DFT) calculations further confirmed the exceptional absorption properties of Ni(0)(DQ)dtbbpy in the red-light region, as well as the electron transfer process triggered by red-light irradiation.

Purpose: To explore the efficacy and safety of lenvatinib, either as a monotherapy or in combination with programmed death-1 (PD-1) blockades, as re-challenging treatment in patients with metastatic osteosarcoma following treatment failure with previous tyrosine kinase inhibitors (TKIs)., Patients and Methods: We retrospectively reviewed the data of 26 patients with metastatic osteosarcoma who received rechallenge treatment with lenvatinib monotherapy or lenvatinib plus PD-1 blockades after failure of the initial TKI treatment from January 2020 to June 2024 in our center. The primary endpoint was progression-free survival (PFS). Secondary endpoints included objective response rate (ORR), clinical benefit rate (CBR), and safety., Results: Of the 26 patients, ORR and CBR were 11.5% and 61.5%, respectively. The median duration of follow-up was 15 months (range, 4.3-25.6) with a median PFS of 7.2 months (95% CI: 1.9-12.5). A total of 14 patients received lenvatinib as a monotherapy, and 12 received a combination therapy of lenvatinib and PD-1 blockade. No significant differences were observed in ORR (0 vs 25%) and CBR (57.1 vs 66.7%) between the two groups. Additionally, the combination cohort exhibited a significantly longer PFS compared to the monotherapy cohort (8.6 [95% CI: 5.0-12.1] vs 4.0 months [95% CI: 1.0-7.0], p = 0.022). 96.2% of patients experienced grade 1 or more adverse events (AEs). Grade 3 adverse events occurred in 6 (23.1%) patients. The safety profiles of the lenvatinib and PD-1 blockade combination group were found to be comparable to those of the lenvatinib monotherapy group., Conclusion: Our data indicated that patients with metastatic osteosarcoma could potentially benefit from lenvatinib rechallenge after progress with initial TKI treatment. The combination of lenvatinib and PD-1 blockade therapy demonstrated promising survival outcomes in patients with metastatic osteosarcoma, accompanied by a manageable toxicity profile., Competing Interests: There is no conflict of interest., (© 2025 Song et al.)

ConspectusLignin, a major component of lignocellulosic biomass, accounts for nearly 30% of organic carbon on Earth, making it the most abundant renewable source of aromatic carbon. The valorization of lignin beyond low-value heat and power has been one of the foremost challenges for a long time. On the other hand, aromatic compounds, constituting a substantial segment of the chemical industry and projected to reach a market value of $382 billion by 2030, are predominantly derived from fossil resources, contributing to increased CO 2 emissions. Integrating lignin into the aromatic chemical supply chain will offer a promising strategy to reduce the carbon footprint and boost the economic viability of biorefineries. Thus, depolymerizing lignin biopolymers into aromatic chemicals suitable for downstream processing is an important starting point for its valorization. However, owing to lignin's complexity and heterogeneity, achieving efficient and selective depolymerization that yields desirable, isolable aromatic monomers remains a significant scientific challenge.The structure of lignins varies significantly in terms of subunits and linkages across plant species, leading to considerable differences in their reactivity, in the distribution of resulting monomers, and in their subsequent utilization. In this context, this Account highlights our recent studies on the catalytic hydrogenolysis of lignin into serviceable products for preparing valuable materials, fuels, and chemicals. First, we designed a series of catalytic systems for lignin hydrogenolysis specifically tailored to the structural features of lignin from wood, grass, and certain seed coats. To reduce reliance on expensive commercial catalysts like Pd/C, Ru/C, and Pt/C, we advanced heterogeneous metal catalysts by shifting from high-loaded nanostructured metals to low-loaded, atomically dispersed metals and replacing precious metals with nonprecious alternatives. This approach significantly reduces the cost of catalysts, enhances their atomic economy, and improves their catalytic activity and/or selectivity. Then, using the developed catalysts, phenolic monomers tethering a distinct side chain were selectively generated from the hydrogenolysis of lignin (from various plants), achieving yields close to the theoretical maximum. The high selectivity allowed the separation and purification of monomeric phenols from lignin reaction mixtures readily. To gain deeper insights into the cleavage of lignin C-O bonds, we designed deuterium-incorporated β-O-4 mimics (dimers and one polymer) for a mechanistic study, which excluded the pathways involving the loss of linkage protons and led to the proposal of a concerted hydrogenolysis process for β-O-4 cleavage. Finally, to enable the utilization of depolymerized lignin phenolic monomers, unconventional feedstocks in the current chemical industry, we developed a series of methods to transform them into valuable bioactive molecules, functional materials, and high-energy fuels. Overall, these contributions opened new avenues for converting lignin into serviceable products, encompassing upstream processing and downstream applications.

Compared to pristine graphene, graphene oxide (GO) has intriguing advantages for biological applications, such as high compatibility and much improved solubility in an aqueous environment. In particular, the oxygen-containing functional groups on GO enable the highly stable covalent conjugation of biomolecules, which promotes its application for developing versatile functional devices. In this work, we explored an ultraviolet/ozone (UV/O 3 ) treatment strategy to activate graphene-tape substrates (prepared by drop-casting graphene nanoplatelets on double-sided conductive carbon tapes) to achieve excellent bioconjugation capabilities. Our Fourier transform infrared spectroscopy (FTIR), wetting, and X-ray photoelectron spectroscopy (XPS) measurements confirmed the generation of high-density oxygen-containing functional groups on graphene-carbon tape, while the conductivity and electrochemical activity are merely influenced. Upon immobilizing amino-ferrocene (Fc-NH 2 ) onto the UV/O 3 -activated graphene tape via carbodiimide cross-linking, a strong pair of redox peaks (corresponding to an Fc surface density over 8.0 × 10 -9 mol/cm 2 ) was observed, indicative of its "elevated" covalent conjugation capability. More remarkably, highly efficient conjugation of glucose oxidase on UV/O 3 -treated graphene tape was achieved, which demonstrated excellent catalytic activity, as confirmed by chronoamperometry. These results augment the great potential of UV/O 3 -activated graphene tape substrates for convenient fabrication of electroactive biofunctional devices with high performance.

Surfactants are effective agents for enhancing lignocellulosic pretreatment, synergistically modifying lignin with polyols to improve substrate hydrolyzability while achieving comparable delignification. However, the mechanisms underlying the multiple modifications from dual in situ surfactant/polyols grafting that passivate lignin-cellulase interactions and their core affecting factors remain unclear. Following the previously developed polyethylene glycol (PEG) and Triton-assisted pretreatment, the intrinsic correlation among lignin structures, physical barriers, and cellulase interactions was analyzed in this study. The surfactant grafting onto lignin can significantly decrease non-productive cellulase adsorption by 5-59 % compared to the initial glycerol-modified lignin. Structurally, the changes in lignin aliphatic -OH (r > 0.93), H-OH (r > 0.98), and G-OH (r > 0.74) showed strong correlations with cellulase adsorption; the -COOH and C=O were not well-valiadted for assessing the non-productive interaction. Physically, surfactant modification also induced changes in lignin surface structure, with variations in specific surface area, pore size, and pore volume showing positive correlations (r > 0.71). The structurally modified lignin had a relatively strong affinity for exo-glucanase and β-glucosidase in enzyme cocktails, while it reduced the irreversible adsorption of lignin onto cellulases (up to 97 % of total adsorbed protein). The secondary structure of desorbed cellulases underwent obvious changes independent of lignin structural modifications, with lowering β-sheet content and increasing random coil content. Based on molecular forces, surfactant modification lowered the binding free energy of cellulases by 60.3-86.5 %, and the reduction in H-bonding interaction was predominant. This study provides mechanistic insights for constructing lignin-modified pretreatments to enhance the substrate hydrolyzability., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2025. Published by Elsevier Inc.)

Background: Given the close relationship between lipids and gestational diabetes mellitus(GDM), the present study sought to examine the association between the triglyceride high-density cholesterol-glucose body index(TyHGB) and the risk of developing GDM., Methods: In order to investigate the relationship between TyHGB and GDM, a retrospective case-control study and a prospective cohort study were conducted involving 1862 individuals. A multifactorial logistic regression model was employed to assess the relationship between TyHGB and GDM, and to reduce potential bias and confounding variables, the association between TyHGB and GDM was evaluated using 1:1 propensity score further matching (PSM) multivariate logistic regression of post-PSM data. The restricted cubic splines(RCS) was used to observe the dose-response relationship between TyHGB and GDM. Receiver operating characteristic (ROC) curves were employed to evaluate the predictive accuracy of GDM. Subsequently, likelihood ratio tests were utilized to investigate the correlation between TyHGB and GDM in specific subgroups., Results: After adjustment for all confounders, multivariate logistic regression analysis showed that TyHGB was significantly associated with the risk of developing GDM.The ROC curve shows the excellent predictive performance of the TyHGB index.TyHGB was better than other indices in predicting GDM in the first and second trimester., Conclusions: This study demonstrates that TyHGB is independently associated with GDM risk. TyHGB may be used as a screening and monitoring tool for pregnant women at high risk of GDM rather than other lipid indicators., Competing Interests: Declarations. Ethics approval and consent to participate: Ethical review and approval were waived for this study because no additional institutional review board approval was required for the secondary analysis. Prior to participation, all subjects provided written informed consent. The human trials were reviewed and approved by Guilin Medical University and the Affiliated Hospital of Guilin Medical University. Additionally, the Institutional Review Board of Seoul National University Boramae Medical Center and the Public Institutional Review Board of the Korean Ministry of Health and Welfare approved the human trials. Competing interests: The authors declare that they have no competing interests. We declare that we do not have any commercial or associative interest that represents a conflict of interest in connection with the work submitted., (© 2025. The Author(s).)

Objective: In this study, we aimed to explore the relationship between postprandial triglyceride (TG) and postprandial thyroid stimulating hormone (TSH) levels and compare the postprandial TSH levels in participants with normal lipid tolerance and reduced lipid tolerance., Methods: A total of 81 eligible participants were enrolled and given a high-fat meal of 1500 kcal, and blood samples were collected at 2, 4, 6, and 8 hours. Fasting blood glucose, total cholesterol, high-density lipoprotein cholesterol, low-density lipoprotein cholesterol, and fasting and postprandial TG, triiodothyronine (T3), tetraiodothyronine (T4), and TSH levels were tested. Based on the postprandial serum TG level, participants were divided into the normal lipid tolerance group (NFT) and the decreased lipid tolerance group (IFT)., Results: Postprandial TG levels increased in both the NFT and IFT groups and then decreased over time. A higher and delayed peak of postprandial TG was observed in the IFT group, and there were statistically significant differences in TG levels at each time point in both groups. The area under the curve (TGAUC) was an independent influencing factor for the area under the curve (TSHAUC) of TSH. Postprandial TSH levels in both groups reached a trough at 2 h and peaked at 6 h, with a higher peak in the IFT group. Except for 2 h, TSH levels were significantly different at all other time points. There was no statistically significant difference in T3 or T4 levels between the two groups, with opposite trends for TSH., Conclusion: After a high-fat meal is consumed, the postprandial TSH level is influenced by the postprandial TG level, which may be the reason for the decreased thyroid function in the population with reduced lipid tolerance., Clinical Trial Registration: http://www.chictr.org.cn/index.aspx, identifier ChiCTR1800019514., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2025 Tian, Zeng, Hou, Liu, Lu and Song.)

The current limiting control strategy of modular multilevel converters in flexible DC power grids can effectively reduce the requirements for line protection speed and the breaking capacity of DC circuit breakers (DCCB). However, it can easily lead to the interruption of power transmission at non-fault terminals and expanding the scope of the fault impact. Secondly, it did not consider the severity of matching faults, which may lead to excessive suppression of fault currents and reduce the sensitivity of the protection system. Therefore, this paper proposes an active current limiting control (ACLC) strategy with fault identification capability to further improve its selectivity and adaptability. Firstly, the starting element in the ACLC selectively identify fault areas based on the difference in the slope of the first backward traveling wave (TW) of the current. Secondly, a current limiting coefficient is constructed based on the slope of the first backward TW of current to achieve fault current limiting. On this basis, setting amplitude control to improve the adaptability of ACLC to fault resistance. Finally, a complete fault handling scheme was proposed, including ACLC, fault identification and fault isolation. The simulation results show that the proposed ACLC strategy is selective while reducing the technical requirements of DCCB. In addition, the adaptability of ACLC to fault resistance has also been improved., Competing Interests: Declarations. Competing interests: The authors declare no competing interests., (© 2025. The Author(s).)

Background: Neutrophil-to-lymphocyte ratio (NLR) can be treated as a simple indicator of patients' immune status by representing the state of the systemic inflammatory response. Immunotherapy now is the accepted second-line treatment for recurrent or metastatic nasopharyngeal carcinoma (R/M NPC). However, the significance of NLR in patients with R/M NPC undergoing treatment with PD-L1 (programmed cell death-ligand 1) inhibitors is still uncertain., Methods: We analyzed the relationship between baseline NLR with 153 patients' efficacy and survival from a multicenter, prospective, Phase 2 study. We employed restricted cubic spline plots to get the nonlinear relationship between NLR and progression-free survival (PFS) or overall survival (OS). We identified the ideal cut-off value through the analysis of the receiver operating characteristic curve (ROC curve). We used Logistic regression, Cox regression, Log-rank test, and Kaplan-Meier method to analyze the association between NLR and patients' disease control rate (DCR) and PFS or OS., Results: The ideal threshold value for NLR was 2.826. NLR was identified as a significant independent predictor of DCR (OR = 0.17, 95% CI = 0.05-0.48, p = 0.001), indicating that a higher NLR is associated with worse DCR. NLR (AUC = 0.634) showed superior predictive capability for DCR in comparison to lymphocytes (AUC = 0.602) and neutrophils (AUC = 0.593). High NLR values were risk factors both for poor PFS (HR = 2.53, 95% CI = 1.58-4.06, p < 0.001) and OS (HR = 3.89, 95% CI = 2.09-7.24, p < 0.001)., Conclusion: Elevated NLR is strongly associated with lower response to treatment and reduced survival rates in patients with R/M NPC being treated with PD-L1 inhibitors. Patients with high NLR values have poor efficacy and survival., (© 2025 Wiley Periodicals LLC.)

Objectives: Urban-rural differences in depression are evident among older adults in China but not in the United States. By comparing the two countries, this study aims to explore strategies for promoting regional equality in depression in China., Methods: Data from the China Health and Retirement Longitudinal Study (CHARLS) and the Health and Retirement Study (HRS) were utilized. Longitudinal data were used to describe urban-rural differences in depression prevalence among older adults in China (2011-2020) and the United States (2010-2020). Cross-sectional data from 2018 (CHARLS: 9840 participants; HRS: 10,381 participants) were used to identify key modifiable factors. A random forest algorithm was employed to determine the most important factors influencing depression, and comparisons between the two countries were made to identify modifiable factors. Multivariate logistic regression was used to analyze the relationship between these key modifiable factors and depression. A mediation model was applied to assess the mediating role of key modifiable factors in the relationship between residence and depression., Results: 1) From 2011 to 2020, Urban-rural differences in depression prevalence among older adults were observed in China, but not in the United States. 2) In both China and the U.S., the top five factors ranked by importance were activities of daily living disability (ADLs), instrumental activities of daily living disability (IADLs), pain levels, self-reported health (SRH), and age. However, Urban-Rural Differences in ADLs, IADLs, and SRH were present in China but not in the United States. 3) ADLs, IADLs, and SRH collectively mediated 31.6 % (95 % CI: 0.268 - 0.360) of the relationship between residence and depression scores among older adults in China., Conclusion: Urban-rural differences in physical health status (ADLs, IADLs, and self-reported health) among older adults in China are associated with Urban-Rural Differences in depression. The absence of such inequalities in the U.S. may offer insights for developing policies to promote regional equality in depression among older adults in China., Competing Interests: Declaration of Competing Interest We declare that we do not have any commercial or associative interest that represents a conflict of interest in connection with the work submitted., (Copyright © 2025. Published by Elsevier Inc.)

Simultaneous treatment of organic and inorganic pollution and the production of value-added chemicals is still a great challenge. Herein a paired electrocatalytic system using the same CuO/CF as both anode and cathode catalyst for the degradation of tetracycline (TC) in the anodic chamber and the conversion of nitrate (NO 3 - ) into ammonia (NH 3 ) by electrochemical reduction. After in-situ reduction to Cu 2 O/CuO/CF from CuO/CF, it had stronger adsorption of NO 3 - and a higher hydrogen energy barrier, enhancing cathodic reduction of NO 3 - to NH 3 with a high selectivity of 99.35 %. Attributed to the generation of singlet oxygen ( 1 O 2 ) and hydroxyl radical ( • OH), the anodic oxidation on CuO/CF could completely degrade TC within 40 min with the reaction rate constant (k = 0.253 min -1 ) that about 16.8 times faster than that on the conventional dimensionally stable anode (DSA). Moreover, this paired system saved approximately 58.1 % of energy consumption when compared with single systems of anodic oxidation and cathodic reduction. This paired electrocatalysis would provide a new strategy for the treatment of complex wastewater and the production of value-added chemicals., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2025 Elsevier B.V. All rights reserved.)

Milk protein and hyaluronic acid (HA) at different mass ratios were systemically characterized using the Maillard reaction. Combining FTIR and molecular docking results, both conjugates, α-casein-HA (α-CN-HA) and β-lactoglobulin-HA (β-Lg-HA), were prepared via hydrogen-bond interactions. Binding of HA promotes the structural folding of milk proteins and alters their secondary structures. The α-CN-HA and β-Lg-HA conjugates exhibited significantly improved solubility thermal and antioxidant activity. The functional properties of the conjugates were modulated by varying the ratio of milk proteins to HA. The α-CN:HA 1:2 ratio had the highest denaturation temperature (110.1 °C). For β-Lg-HA, the highest denaturation temperature (112.1 °C) was observed at a 1:4 ratio. Antioxidant capacity increased with decreasing HA content; the highest value was observed at a mass ratio of 3:1 for both conjugates. Our findings suggest that Maillard reaction improves the physiological and functional properties of milk proteins and HA conjugates., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2025 Elsevier Ltd. All rights reserved.)

Several studies have shown that the protein-chlorogenic acid covalent complex has better function and stability than the non-covalent. The degree of binding between the proteins and chlorogenic acids (CQA) can be enhanced by the ultrasound process. Herein, the effects of ultrasound-assisted non-enzymatic covalent binding (the free radical induction (Vc)-ultrasound combination and the alkali treatment (Alkali)-ultrasound combination) of two chlorogenic acids (neochlorogenic acid (3-CQA), cryptochlorogenic acid (4-CQA)) and β-lactoglobulin (β-LG) on proteins structure and properties were investigated. Results showed that ULG-Alkali-4CQA exhibited a 5.1 % reduction in α-helices, a 6.8 % increase in random curl and proteins structures becoming loose and disordered. The hydrophilicity and thermal stability of β-LG were effectively enhanced by the addition of 4-CQA and the effect of alkali treatment-ultrasound combination. Curcumin (CUR) and lycopene (LYC) were successfully delivered by the covalent complexes as delivery vehicles. The encapsulation efficiencies of the ULG-Vc/Alkali-4CQA + CUR and ULG-Vc/Alkali-4CQA + LYC complexes were 82.81 %, 84.16 %, 89.56 % and 90.51 %, respectively. The stabilities of CUR and LYC in the ULG-Vc/Alkali-4CQA + CUR/LYC ternary complexes were superior to those of all the measured complexes delivery systems. The study hopes to establish a theoretical foundation and serve as a reference for the advancement of a highly stable food-grade delivery system., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2025 Elsevier Ltd. All rights reserved.)

Glioblastoma-associated macrophages & microglia (GAMs) are critical immune cells within the glioblastoma (GBM) microenvironment. Their phagocytosis of GBM cells is crucial for initiating both innate and adaptive immune responses. GBM cells evade this immune attack by upregulating the anti-phagocytic molecule CD47 on their surface. Although CD47 knockdown has shown promise in reducing tumor volume and increasing survival in GBM models, the efficacy of anti-CD47 antibodies remains limited clinically, partly due to the blood-brain tumor barrier (BBTB) and the insufficient pro-phagocytosis efficacy of CD47 blockade alone. Here, we introduce CSSOssMIT@MM-PEP 20 , a PEP 20 -linked microglia membrane (MM) camouflaged CSSOssMIT prodrug micelle. The MM targets vascular cell adhesion molecule-1 on the BBTB and enhances the penetration of CSSOssMIT@MM-PEP 20 into the GBM tissue. CSSOssMIT@MM-PEP 20 disassembles into MM-PEP 20 and CSSOssMIT through the proton sponge effect in the acidic microenvironment. MM-PEP 20 blocks the CD47-SIRPα axis, disabling the 'don't eat me' signal, while CSSOssMIT releases MIT within tumor cells to promote immunogenic cell death and amplify the 'eat me' signal. In an orthotopic GBM mouse model, CSSOssMIT@MM-PEP 20 increased GAMs-mediated phagocytosis of GBM cells by 5.01-fold and enhanced CD8 + T cell infiltration by 8.63-fold, demonstrating significant GBM inhibition. Overall, this study presents a noninvasive strategy to traverse the BBTB and modulate GAMs phagocytosis, thereby facilitating effective anti-GBM chemo-immunotherapy., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier B.V. All rights reserved.)

Plasmid-encoded toxin-antitoxin (TA) systems are known for their role in plasmid maintenance via post-segregational killing. Here, we identified an inactive type II TA system, MtvT/MtvA (MtvTA), encoded on the conjugative plasmid pPAD8 from the clinical Pseudomonas aeruginosa strain PAD8. Despite its annotation as a toxin, MtvT exhibited no detectable toxicity in our assays. Interestingly, the deletion of the MtvTA significantly increased the transfer efficiency of pPAD8 from PAD8 to P. aeruginosa strain PAO1. Functional assays revealed that the MtvTA complex negatively regulates plasmid transfer by binding to the promoters of dot/icm system genes. In addition, pPAD8ΔmtvTA attenuated the pathogenicity of the host strain compared to pPAD8, highlighting a regulatory role for MtvTA in virulence. Mechanistically, the MtvTA complex positively regulates the type III and type VI secretion systems and pyocyanin biosynthesis by directly binding to the promoters of exsA and rsmY/rsmZ and indirectly influencing lasI expression, respectively. These findings provide new insights into the regulatory roles of an inactive plasmid-encoded TA system, expanding our understanding of the interplay between plasmids and their bacterial hosts., (© The Author(s) 2025. Published by Oxford University Press on behalf of Nucleic Acids Research.)

Plasmid-encoded toxin-antitoxin (TA) systems are known for their role in plasmid maintenance via post-segregational killing. Here, we identified an inactive type II TA system, MtvT/MtvA (MtvTA), encoded on the conjugative plasmid pPAD8 from the clinical Pseudomonas aeruginosa strain PAD8. Despite its annotation as a toxin, MtvT exhibited no detectable toxicity in our assays. Interestingly, the deletion of the MtvTA significantly increased the transfer efficiency of pPAD8 from PAD8 to P. aeruginosa strain PAO1. Functional assays revealed that the MtvTA complex negatively regulates plasmid transfer by binding to the promoters of dot/icm system genes. In addition, pPAD8ΔmtvTA attenuated the pathogenicity of the host strain compared to pPAD8, highlighting a regulatory role for MtvTA in virulence. Mechanistically, the MtvTA complex positively regulates the type III and type VI secretion systems and pyocyanin biosynthesis by directly binding to the promoters of exsA and rsmY/rsmZ and indirectly influencing lasI expression, respectively. These findings provide new insights into the regulatory roles of an inactive plasmid-encoded TA system, expanding our understanding of the interplay between plasmids and their bacterial hosts., (© The Author(s) 2025. Published by Oxford University Press on behalf of Nucleic Acids Research.)

Waterlogging substantially hampers the growth and development of plants. The escalating trajectory of global climate change is heightening both the frequency and intensity of waterlogging events. Peach trees are particularly vulnerable to waterlogging, with the resultant hypoxia in the rhizosphere profoundly influencing their growth and productivity. This study explored the responses of peach seedlings to waterlogging and the regulatory effects of melatonin priming. After a 24-h waterlogging treatment, a significant increase in relative electrical conductivity and an accumulation of reactive oxygen species were observed, ion permeability was markedly alleviated by melatonin priming. Transcriptomic and proteomic analyses were conducted on peach root samples to elucidate the molecular mechanisms involved in the response to waterlogging and melatonin priming. Transcriptome analysis implicated genes related to 'DNA-binding transcription factor activity', such as AP2/ERF, HSF and WRKY transcription factors, in response to waterlogging. The glycolysis/gluconeogenesis pathway was also significantly enriched, indicating its critical role in the metabolic response to waterlogging. A correlation analysis between differentially expressed genes and proteins highlighted the regulation of numerous genes at both the transcriptional and translational levels. Furthermore, core DEGs/DEPs, including heat shock proteins and stress-related proteins, were identified. Notably, ERF VII member ERF071 (Prupe.8G264900), ADH (Prupe.8G018100), and PCO (Prupe.7G011000) emerged as potential targets for genetic manipulation to enhance waterlogging tolerance in peach. This research provides targets for breeding waterlogging-tolerant varieties and strategies to mitigate waterlogging stress in peach., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2025 Gu, Lu, Gao, Fan, Song and Zhang.)

Background: Natural killer (NK) cells, as part of the group I innate lymphocytes (ILCs) are essential for tumor immune surveillance. NK cells can recognize and eliminate target cells without the need for prior sensitization or restriction of major histocompatibility complexes (MHCs) and antigens. However, the limited infiltration of metastatic NK cells poses significant challenges for advancing adoptive cell immunotherapy for solid tumors., Objective: This study aimed to explore the potential of using tumor penetrating peptide (TPP) iRGD to promote the delivery of activated NK cells to deeper layers of tumor tissue., Methods: Flow cytometry was performed to evaluate the activation, inhibition, and expression of other receptors involved in cytotoxicity. High-pressure liquid chromatography (HPLC) and mass spectrometry were used to detect the purity of iRGD. 1,2-distearoyl-sn-glycero-3- phosphoethanolamine-poly(ethylene glycol)-iRGD (DSPE-PEG-iRGD) was synthesized. Surface modification of cells was performed using DSPE-PEG-iRGD. Multicellular tumor spheroids (MCTSs) were established to evaluate permeability. In addition, in order to better simulate the physiological characteristics of solid tumors in vivo, we generated 3D spheroids from HGC27 gastric cancer cell line and BXPC-3 pancreatic cancer cell line to study the anti-tumor effect of NK cells with combination iRGD in vitro. The mouse models of gastric cancer and pancreatic cancer were used. In addition, the synergistic anti-tumor effects were evaluated in vivo based on the tumor volume and body weight of mice., Results: Initially, we treated NK cells with interleukin-2 (IL-2), resulting in significant activation as indicated by upregulation of CD56. On the 15th day, the proliferation of CD3-/56+cell population in NK cell culture containing IL-2 significantly increased, and the NK cell amplification factor was greater than 300. In addition, NK cells exhibited increased cytotoxicity towards cancer cell lines. When the ratio of effect to target was 10:1, the killing rate of NK cells against BXPC-3 was 83.1%. iRGD modification enabled NK cells to penetrate MCTSs, resulting in cytotoxicity against target HGC27 and BXPC-3 cells. In addition, NK cells modified with iRGD significantly reduced tumor growth in the xenotransplantation model of gastric cancer and pancreatic cancer mice model., Conclusion: In summary, our results indicated that NK cells exhibited higher efficacy and lifespan against cancer cell lines in vitro. Furthermore, the integration of iRGD into NK cells led to improved infiltration and targeted elimination of MCTSs. Moreover, the application of iRGDmodified NK cells has shown significant anti-tumor efficacy against solid tumors in vivo. This joint strategy may significantly improve the efficacy of NK cell immunotherapy in treating various solid tumors., (Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.net.)

Objective: Free fatty acids (FFA) can increase the expression of 11β-hydroxysteroid dehydrogenase 1 (11β-HSD1) in local tissues and organs. However, the mechanism underlying the effect of FFA on 11β-HSD1 expression remains unclear., Methods: A total of 24 male Syrian golden hamsters (SPF grade) were selected and randomly divided into a control group (Con, n = 8) fed a normal diet, and a high-fat diet group (n = 16) fed for 12 weeks. After successfully establishing the hyperlipidemia hamster model, the high-fat group was further divided into a high-fat group (HF) and a fenofibrate intervention group (Feno). Following an oral fat tolerance test (OFTT), blood lipids and FFA levels were measured. The expression levels of endoplasmic reticulum stress (ERS) marker GRP78, downstream key molecule CHOP, C/EBPα, and 11β-HSD1 were analyzed using Western blot and RT-PCR., Results: After OFTT, FFA levels in all three groups initially decreased and then increased, with the highest levels observed in the HF group (Ps < 0.05). FFA levels in the Feno group were comparable to those in the Con group (P > 0.05). Hepatic FFA, 11β-HSD1, and corticosterone levels were highest in the HF group (Ps < 0.05), while the Feno group showed no significant difference compared to the Con group (Ps > 0.05). Hepatic 11β-HSD1 and corticosterone levels were positively correlated with FFA levels (Ps < 0.05). Western blot and RT-PCR results indicated higher GRP78, CHOP, C/EBPα, and 11β-HSD1 protein and mRNA expression in the HF group compared to the Con group (Ps < 0.05). Fenofibrate intervention reduced FFA levels and downregulated these indicators in the Feno group compared to the HF group (Ps < 0.05)., Conclusion: FFA may regulate the expression of hepatic 11β-HSD1 in high-fat-fed golden hamsters via the ERS-CHOP-C/EBPα signaling pathway, thereby affecting local corticosterone levels. Fenofibrate may downregulate the levels of 11β-HSD1 and corticosterone in local tissues by reducing FFA levels., Competing Interests: Declarations. Ethics approval and consent to participate: The ethics committee of Hebei General Hospital approved the research protocol (approval number: 202226, approval date: 19 July 2022). Competing interests: The authors declare no competing interests., (© 2025. The Author(s).)

Purpose: Current commissioning of radiotherapy treatment planning systems with heterogeneous phantoms generally measures the dose delivered in solid water downstream of the lung material. The dose delivered directly in lung material is important to characterise the uncertainty of lung stereotactic body radiotherapy (SBRT) treatments, but film measurements require a correction to accurately measure dose to lung., Methods: Monte Carlo (MC) modelled corrections were applied to film measurements used for commissioning of lung SBRT. Medium dependent correction factors, k med , were established using 6 and 10 MV simulations to account for film being calibrated in water but measuring in regions of lung material. The correction factors are dependent on energy, field size, and position. To avoid the onerous requirement of modelling each individual beam to correctly match penumbra an alternative approach is presented where the correction is applied as a function of isodose level for a nominal field size., Results: Improvement in central axis dose agreements was seen for all field sizes, with the largest improvement of 7 % observed for 6MV 1 × 1 cm 2 field. Application of position dependent corrections improved the percentage of points passing a 5 %/1 mm or 3 %/1 mm gamma assessment in all cases, whilst a uniform central axis correction did not improve the passing rate in most cases., Conclusions: MC simulations provide a method for correcting dose measured in lung materials allowing more accurate comparison with treatment planning system doses. In this work a generic approach to correct small field film lung measurements as a function of isodose levels is presented., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2025. Published by Elsevier Ltd.)

Lipid nanoparticles (LNPs) encapsulating genetic material can be produced on a large scale using the bulk-mixing method. However, this approach often lacks precise control over particle size and cargo loading, limiting its efficiency in gene delivery. We have developed a membrane extrusion process that enables large-scale production of LNPs with a narrow size distribution. Initially, an ethanolic lipid solution is mixed with an aqueous buffer containing nucleic acids, forming a pre-mix of swollen LNPs. These soft, swollen LNPs are then extruded through a polycarbonate filter membrane, producing uniform LNPs, in which the ethanol concentration and extrusion pH are adjusted for LNP fluidity. Subsequent addition of citrate buffer (pH 4) enhances encapsulation efficiency by reassembling the dissociated mRNA and lipids during the extrusion process. Finally, the LNP solution is adjusted to physiological pH through buffer exchange. Optimizing the extrusion parameters allowed us to achieve highly uniform 100 nm LNPs with over 80 % encapsulation efficiency for mRNA, siRNA, and DNA. This work provides valuable insights into LNP formation, highlights critical formulation parameters, and demonstrates the potential for large-scale, controlled LNP production., Competing Interests: Declaration of competing interest The authors declare the following financial interests/personal relationships which may be considered as potential competing interests: Gi-Ra Yi reports financial support was provided by Dx&Vx Corporation. Gi-Ra Yi has patent pending to POSTECH. If there are other authors, they declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2025 Elsevier Inc. All rights reserved.)

While some research has examined the time-lagged effect of restorative soundscape in specific contexts (e.g., parks), how the time-lagged effect of noise annoyance during people's daily activities may vary across different temporal, spatial, and social contexts remains largely unknown. To address this research gap, we utilized Ecological Momentary Assessment (EMA) data to measure people's real-time noise annoyance and activity diary data to assess their time-lagged noise annoyance. Real-time noise exposure was captured by portable noise sensors. We employed fixed effects ordered panel logistic regression to examine the effects of different thresholds of noise levels on people's time-lagged noise annoyance, and how it varied across different temporal, spatial, and social contexts. The results indicated that: (1) there were significant time-lagged effects between participants' real-time noise exposure and their time-lagged noise annoyance; (2) participants' time-lagged noise annoyance associated with an activity was influenced by its temporal, spatial, and social contexts, particularly on weekdays; (3) participants' time-lagged noise annoyance was significantly associated with measured noise levels, with the highest coefficient for 65 dB, followed by 70 dB; and (4) there were significant interaction effects between noise levels and temporal-spatial-social contexts on participants' time-lagged noise annoyance (particularly when noise levels exceeded 70 dB). These findings enhance our understanding and have crucial implications for the implementation of noise control policies, which should consider not only noise levels but also the time-lagged effects of noise, particularly on weekdays, at outdoor recreational activity sites, as well as the potential vulnerabilities of individuals experiencing noise exposure in isolation., Competing Interests: Declaration of competing interest The authors declare that they have no financial and personal relationships with other people or organizations that can inappropriately influence our work., (Copyright © 2025 The Author(s). Published by Elsevier Ltd.. All rights reserved.)