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Effective coordination of multi-echelon supply chains is vital in dynamic markets, yet traditional methods fail to address inherent complexity and uncertainties. This study proposes a novel discrete event simulation (DES) and genetic algorithm (GA) integration to optimize production planning and scheduling. The DES model simulates real-world dynamics, including demand fluctuations and delays, while the GA optimizes critical decisions (production schedules, inventory levels) through iterative learning. A hierarchical framework combines mathematical supply chains modelling, DES-based scenario testing, and GA-driven decision refinement. Experimental results demonstrate significant improvements: 15-22 % cost reduction, 10-18 % shorter lead times, and 12-20 % higher service levels compared to conventional methods. This approach advances supply chain management by bridging dynamic simulation with metaheuristic optimization, offering enterprises a scalable tool for adaptive decision-making under uncertainty. The work underscores the value of integrating simulation and AI to tackle complex supply chain challenges. [ABSTRACT FROM AUTHOR]

Adaptive immunity is critical in eliminating tumors, but cancer-intrinsic factors can subvert this function. Melanoma antigen-A4 (MAGE-A4), a cancer-testis antigen, is expressed in solid tumors and correlates with poor survival, but its role in tumorigenesis and antitumor immunity remains unclear. We found that expression of MAGE-A4 was highly associated with the loss of PTEN, a tumor suppressor, in human non-small cell lung cancers (NSCLC). Here, we show that constitutive expression of human MAGE-A4 with Pten loss in mouse airway epithelia results in metastatic adenocarcinoma. Tumors showed distinct enrichment in IgA+ CD138+ CXCR4+ plasma cells (PCs) and increased expression of CXCL12 in endothelial cells. Consistently, human NSCLC expressing MAGE-A4 showed increased CD138+ IgA+ PCs surrounding tumors. Abrogation of PCs decreased tumor burden, increased activated T cell infiltration, and reduced CD163+CD206+ macrophages in the MAGE-A4- induced lung tumors. These findings suggest MAGE-A4 promotes NSCLC tumorigenesis, in part, through the recruitment and retention of IgA+ PCs in the lungs. [ABSTRACT FROM AUTHOR]

Abstract The progression of malignant tumors leads to the development of secondary tumors in various organs, including bones, the brain, liver, and lungs. This metastatic process severely impacts the prognosis of patients, significantly affecting their quality of life and survival rates. Research efforts have consistently focused on the intricate mechanisms underlying this process and the corresponding clinical management strategies. Consequently, a comprehensive understanding of the biological foundations of tumor metastasis, identification of pivotal signaling pathways, and systematic evaluation of existing and emerging therapeutic strategies are paramount to enhancing the overall diagnostic and treatment capabilities for metastatic tumors. However, current research is primarily focused on metastasis within specific cancer types, leaving significant gaps in our understanding of the complex metastatic cascade, organ-specific tropism mechanisms, and the development of targeted treatments. In this study, we examine the sequential processes of tumor metastasis, elucidate the underlying mechanisms driving organ-tropic metastasis, and systematically analyze therapeutic strategies for metastatic tumors, including those tailored to specific organ involvement. Subsequently, we synthesize the most recent advances in emerging therapeutic technologies for tumor metastasis and analyze the challenges and opportunities encountered in clinical research pertaining to bone metastasis. Our objective is to offer insights that can inform future research and clinical practice in this crucial field.

Yaopian Chen,1 Fu Su,2 Haixia Xiang,1 Jinhong Xia3 1Department of Sleep Medicine, Wenzhou Seventh People’s Hospital, Wenzhou, Zhejiang Province, 302003, People’s Republic of China; 2Psychology Major, Clark University, Worcester, MA, 01610, USA; 3Department of Nursing, Wenzhou Seventh People’s Hospital, Wenzhou, Zhejiang Province, 302003, People’s Republic of ChinaCorrespondence: Yaopian Chen, Department of Sleep Medicine, Wenzhou Seventh People’s Hospital, Ouhai District, Wenzhou, Zhejiang Province, 302003, People’s Republic of China, Tel +86 13738325171, Email yaopianchencyp@126.comObjective: To assess the sleep status and prevalence rate of the elderly in southeast coastal areas of China, and analyze related factors.Methods: A questionnaire survey was conducted among elderly individuals in Wenzhou City, Zhejiang Province, situated in the southeast coastal areas of China, using a multi-stage random sampling method. A total of 903 elderly people aged ≥ 60 years were selected for the survey. The questionnaire aimed to assess their sleep status using PSQI and to evaluate related factors using Self-designed General Information and Health Behavior Questionnaires, SAS, GDS-15, ESS, AD8, SHAP, WHOQOL-BREF, among other tools. Logistic regression was applied to analyze the influencing factors of sleep disorders.Results: Among the 903 elderly individuals who participated in the survey, 316 cases (35.0%) had a PSQI score > 7. Females exhibited a higher prevalence rate of poor subjective sleep quality (24.9% vs 17.6%) and difficulty falling asleep (32.8% vs 22.5%) compared to males. Drinking green tea (OR = 0.1.841, 95% CI, 1.220– 2.777, P < 0.05) had the strongest association with poor sleep. The duration of nap time ranging from 30 to 90 minutes (OR = 0.492, 95% CI= 0.340– 0.713, P < 0.001) and specifically a 90-minute nap (OR = 0.441, 95% CI = 0.234– 0.832, P < 0.05) were both significantly associated with a decreased risk of experiencing poor sleep quality.Conclusion: The prevalence in this population is 35%. Several factors contribute to this prevalence, including tea consumption, anxiety, daytime sleepiness, cognitive decline, environmental influences, awareness of sleep health, knowledge about sleep, and detrimental habits. Specifically, the consumption of green tea negatively impacts sleep quality, while taking naps longer than 30 minutes is associated with a reduced risk of poor sleep. These findings can inform the development of targeted preventive strategies and interventions aimed at mitigating sleep disorders in the elderly population.Keywords: elderly, sleep disorders, related factors, Pittsburgh Sleep Quality Index, cross-sectional study

To enhance the retention of compost nutrients, specifically in nitrogen metabolism and humification, compound microbial agents were added during the aerobic composting of bagasse pith and buffalo manure. The introduction of the microbial agent successfully colonized the mixture, boosted the degradation capacity of organic matter, and facilitated the formation of nitrogenous substances and humic substances (HSs). The incorporation of a composite microbial inoculum led to a substantial rise in total Kjeldahl nitrogen (TKN) by 62.04%, nitrate nitrogen (NO- 3-N) by 291.65%, and amino acid (AA) by 78.77%. Furthermore, this intervention resulted in achieving a humic acid (HA) to fulvic acid (FA) ratio of 1.64. Metagenomic sequencing revealed enhanced synergistic interactions among microorganisms through inoculation, increasing the abundance of functional genes related to nitrification and nitrogen fixation compared to the uninoculated control. Spearman correlation analysis identified unclassified&#95;c&#95;&#95;Deltaproteobacteria, unclassified&#95;f&#95;&#95;Planctomycetaceae, Chryseosolibacter, unclassified&#95;f&#95;&#95;Hyphomicrobiaceae as the principal producers of HA. This research provides insights into the interactions between nitrogen metabolism and humification in composting, aiming to effectively retain compost nutrients and support the long-term sustainability of agriculture., 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.)

Developing next generation batteries necessitates a paradigm shift in the way to engineering solutions for materials challenges. In comparison to traditional organic liquid batteries, all-solid-state batteries exhibit some significant advantages such as high safety and energy density, yet solid electrolytes face challenges in responding dimensional changes of electrodes driven by mass transport. Herein, the critical mechanical parameters affecting battery cycling duration are evaluated based on Spearman rank correlation coefficient, decoupling them into strength, ductility, stiffness, toughness, elasticity, etc. Inspired by the statistical results to apply the materials with stress-relief mechanisms, we propose an elastic solid electrolyte based on the multi-scale mechanical dissipation mechanism. The Li 6.4 La 3 Zr 1.4 Ta 0.6 O 12 /thermoplastic polyurethanes curled fibrous framework is designed and prepared by side-by-side electrospinning technique, serving as elastic source and ion-transport pathways for the composite with poly(ethylene oxide) matrix. Dominated sequentially by electrolyte deformation, network orientation, extendable fibers and molecular chain unfolding, the prepared elastic electrolyte exhibits excellent resilience, compression and puncture resistance. Meanwhile, the curled fast ion conductor fibers can also provide the transport pathways along the component of transmembrane direction, endowing the composite electrolyte with an ionic conductivity of 1.46 × 10 -4  S cm -1 at 30 °C. A low capacity decay of 0.011 % per cycle at 2 C in assembled LiFePO 4 /Li battery and an excellent lifespan of 1000 cycles at 50 °C in LiNi 0.8 Mn 0.1 Co 0.1 O 2 /Li battery can be achieved. The elastic electrolyte system presents a promising strategy for enabling stable operation of high-energy all-solid-state lithium batteries., 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 Inc. All rights reserved.)

Hydroxyl radical is the most oxidizing type of reactive oxygen species (ROS), which is closely related to body health. In this work, a novel turn-on fluorescent probe BIJ-H for OH with high sensitivity was reported. BIJ-H was synthesized by a three-step reaction, and the pure product was obtained by only washing with poor solvents. In a neat aqueous solution containing BIJ-H, after adding OH, the probe was oxidized to BIJ, which produced fluorescence emission at 625 nm under the excitation with 550 nm. This sensing behavior can be achieved under physiological pH conditions. The detection limit of BIJ-H for OH was as low as 0.1379 μM. Thanks to the good analytical properties of BIJ-H, the probe has been applied to fluorescence imaging of OH in HepG2 cells and in acute liver injury induced by acetaminophen. The probe BIJ-H is expected to be used in the qualitative and quantitative detection of OH in physiological or pathological processes., 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.)

Ethnopharmacological Relevance: Xiangshao Sanjie Oral Liquid (XSSJ) is a traditional Chinese medicine formulation used clinically for the treatment of mammary gland hyperplasia (MGH), yet its mechanism remains obscure., Aim of the Study: The purpose of this study was to explore the therapeutic mechanism of XSSJ on MGH using a comprehensive strategy of plasma metabolomics and network pharmacology., Materials and Methods: The rat model of MGH was established, and the multiple indicators were employed for efficacy evaluation. Then, a metabolomics strategy was established to find plasma metabolites and metabolic pathways that may be important in inducing MGH. In addition, UPLC-Q-TOF-MS and network pharmacological analysis were used to identify the prototype compounds of XSSJ in rat plasma and target genes that may cause the effect. Finally, the results were integrated and verified by RT-qPCR and Western Blot (WB)., Results: XSSJ has a therapeutic effect on MGH. 29 differential metabolites of XSSJ in the treatment of MGH were identified by metabolomics. After administration of XSSJ, 16 prototype compounds were found in the rat plasma, which were associated with 179 potential therapeutic targets. Comprehensive analysis revealed that XSSJ reversed the mRNA expression of EGFR, ESR1, AKT1, SRC and PTPN11 in MGH rats. In addition, different doses of XSSJ inhibited the expression of p-PI3K and p-AKT proteins., Conclusion: This study combined metabolomics and network pharmacology to reveal the regulatory effect of XSSJ on MGH through PI3K/AKT pathway, which provided further support for the clinical application of XSSJ., 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.)

Silicon monoxide (SiO x , x ≈ 1) has been a promising candidate of anode materials for next-generation lithium-ion batteries due to its high specific capacity (∼2600 mA h g -1 ). However, huge volume expansion and the resultant repeated destruction of the solid electrolyte interphase (SEI) are key challenges to the practical application of the SiO x anode. In this work, a highly elastic quasi-solid polymer electrolyte (QSPE) is demonstrated for batteries employing an SiO x anode, which is prepared via in situ cationic ring-opening polymerization employing 1,3,5-trioxane (TXE) as the monomer, 1,3,2-dioxathiolane 2,2-dioxide (DTD) as both the initiator and film-forming additive, and fluoroethylene carbonate as the plasticizer. This TXE-based QSPE possesses excellent ionic conductvity properties, including an extremely low glass-transition temperature of -94.3 °C, a high ionic conductivity of 1.36 mS cm -1 at 25 °C, and a high Li + transference number of 0.66. The long poly-TXE skeleton endows the polymer electrolyte with a high elastic modulus of 42 MPa, helping to effectively suppress the volume expansion of the SiO x anode during cycling. DTD participates in the construction of a robust SEI containing Li 2 SO x species, mitigating the structural collapse of SiO x particles. As a result, the cyclic stability of the SiO x anode has been remarkably enhanced─the Li||SiO x half-battery with the in situ TXE-based QSPE achieves 81.9% capacity retention after 200 cycles at 0.5C, exhibiting significant improvement over its liquid-state counterparts and showing promising application potential.

Objectives: This study investigated the therapeutic effects of stigmasterol (STG), derived from Cornus officinalis , on osteoporosis in rats with type 2 diabetes mellitus (T2DM)., Methods: Twenty-four Male Sprague-Dawley rats (6 weeks old) were used to establish a T2DM model and were divided into four groups: normal diet (ND), high-fat diet (HFD), low-dose STG (STG-L, 100 mg/kg), and high-dose STG (STG-H, 200 mg/kg). The rats received daily gavage treatments for four weeks. Therapeutic effects were assessed by examining femoral bone structure, serum bone formation markers (P1NP, osteocalcin, and osteoprotegerin), bone resorption indices (CTX-1 and RANKL), and osteogenic protein expression (Runx2, osteopontin, and COL1A1)., Results: STG significantly reduced fasting blood glucose levels and improved insulin resistance in T2DM rats. It enhanced trabecular bone microstructure, with the STG-H group demonstrating superior effects. Compared to the HFD group, STG increased bone mineral density, bone volume fraction (BV/TV), and trabecular thickness, while reducing bone surface-to-volume ratio (BS/BV) and trabecular separation. STG also elevated serum levels of P1NP, osteocalcin, and osteoprotegerin, while reducing CTX-1 and RANKL. Western blot analysis revealed increased expression of Runx2, osteopontin, and COL1A1 in femoral tissues., Conclusions: STG appears to alleviate osteoporosis in diabetes by improving bone microstructure, promoting bone formation, and reducing bone resorption, indicating its potential as a therapeutic option for managing osteoporosis., Competing Interests: The authors have no conflict of interest.

Background: Anemia is common among HIV/AIDS patients, impacting prognosis. Particulate matter (PM) exposure is an understudied, potentially modifiable risk factor in this group., Methods: We gathered 36,266 hemoglobin (Hb) measurements from 6808 HIV/AIDS patients from the HIV/AIDS Comprehensive Response Information Management System from 1 January 2004 to 31 December 2021. We evaluated the relationship between Hb levels and short-term PM exposure using linear mixed-effects models. We used logistic regression to estimate the association of long-term PM exposure with baseline anemia prevalence and time-varying Cox models to estimate the association of long-term PM exposure with follow-up incidence of anemia. Mediation analysis explored the role of chronic kidney disease (CKD) in the association between PM exposure and anemia., Results: For every 5 µg/m³ increase in 28-day average PM 1 , Hb levels decreased by 0.43 g/l. For a 10 µg/m³ increase in PM 2.5 , Hb decreased by 0.55 g/l; for the same increase in PM 10, Hb decreased by 0.35 g/l. A 5 µg/m³ increase in 1-year average PM 1 corresponded to a 7% higher prevalence of anemia at baseline, a 10 µg/m³ increase in PM 2.5 to 8% higher prevalence, and a 10 µg/m³ increase in PM 10 to 6% higher prevalence. These rises in average PM concentrations during follow-up were associated with increased incident anemia by 54% (PM 1 ), 72% (PM 2.5 ), and 51% (PM 10 ). CKD partially mediated the positive associations between PM exposure and the incidence of anemia., Conclusion: PM exposure was associated with lower Hb levels and higher incidence of anemia in HIV/AIDS patients and CKD with mediating estimated effects in PM-induced anemia., Competing Interests: Disclosure: The authors report no conflicts of interest., (Copyright © 2024 Wolters Kluwer Health, Inc. All rights reserved.)

Aim: To explore clinician, child and parent acceptability and usability of the Smileyscope VR device in the context of addressing the unique pain and distress needs of young burn patients., Design: A survey comprising closed and open-ended questions., Method: Descriptive statistics analysed participant characteristics, pain and analgesia. Qualitative content was collected from April 2022-August 2022 and analysed to identify barriers and enablers. Categories were then mapped onto the Capabilities, Opportunities and Motivation-Behaviour Wheel (COM-B) framework., Results: Smileyscope was found to be effective for reducing pain and anxiety during dressing changes by both patients (n = 39) and parents (n = 37). Clinicians (n = 35) reported high self-efficacy and willingness to reuse the device. However, concerns arose regarding the device's fit and the need for age-appropriate programmes., Conclusion: Smileyscope demonstrated promise in reducing procedural pain and distress. The device is well accepted by all participants implying ease of implementation. Feedback suggests further program development and fitting optimisation is required., Implications for the Profession And/or Patient Care: Improved procedural pain has proven to decrease wound healing times, decreasing possible need for further scar management and long-term consequences after sustaining a burn injury. Smileyscope use in rural hospitals presents valuable opportunities for optimising early paediatric burn pain., Impact: Increased burn pain can delay wound healing and have long term physical and psychological impact on patients. Smileyscope was well received within this cohort; however, improvements in device design and programmes were suggested. This study shows the potential for use of Smileyscope as a non-pharmacological approach to improving paediatric burn pain and distress., Patient or Public Contribution: While our study included patients, parents and clinicians as research participants, there was no patient or public contribution in the design or conduct of the study, analysis or interpretation of the data., (© 2024 The Author(s). Journal of Advanced Nursing published by John Wiley & Sons Ltd.)

This study aimed to investigate the underlying mechanisms by which physical exercise mitigates muscle atrophy induced by Dexamethasone (Dex). A muscle atrophy model was established in the mouse C2C12 cell line and 8-week-old mice treated with Dex, with subsequent verification of phenotype and atrogene expression. The potential benefits of combined aerobic and resistance exercise in mitigating muscle atrophy were then examined. To elucidate the involvement of Histone deacetylase 4 (HDAC4) in the protective effects of exercise against muscle loss, a combination of RT-PCR, Western blotting, immunoprecipitation, and immunofluorescence staining techniques were employed. The upregulation of HDAC4 was observed following Dex-induced muscle atrophy in vitro and in vivo. Inhibition of HDAC4 in C2C12 cells resulted in an increase in myotube diameter and fusion index, along with a decrease in the expression of Atrogin-1 and MuRF1. Treatment with Tasquinimod, an HDAC4 inhibitor, effectively prevented muscle wasting and dysfunction in mice induced by Dex. After a 6-week exercise intervention, the Dex-Exercise group exhibited significant improvements in body fat level, hyperinsulinemia, muscle mass and function in comparison to the Dex-Sedentary group. Mechanistically, we discovered that HDAC4 bound to and deacetylated Forkhead box protein O 3a (FoxO3a) within the nucleus, leading to decreased phosphorylation of FoxO3a at Ser 253. This interaction subsequently facilitated the expression of downstream atrogene Atrogin-1 and MuRF1, resulting in muscle atrophy. Conversely, exercise was found to potentially mitigate muscle atrophy by inhibiting the HDAC4/FoxO3a pathway. These findings suggest that HDAC4 may be a potential therapeutic target for exercise to combat Dex-induced muscle atrophy., 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. Published by Elsevier Inc.)

Sepsis is often a cause of mortality in patients admitted to the intensive care unit. Notably, the heart is the organ most susceptible to the impact of sepsis and this condition is referred to as sepsis‑induced cardiomyopathy (SIC). Low triiodothyronine (T3) syndrome frequently occurs in patients with sepsis, and the heart is one of the most important target organs for the action of T3. Phospholamban (PLN) is a key protein associated with Ca 2+ ‑pump‑mediated cardiac diastolic function in the myocardium of mice with SIC, and PLN is negatively regulated by T3. The present study aimed to explore whether T3 can protect cardiac function during sepsis and to investigate the specific molecular mechanism underlying the regulation of PLN by T3. C57BL/6J mice and H9C2 cells were used to establish in vivo and in vitro models, respectively. Myocardial damage was detected via pathological tissue sections, a Cell Counting Kit-8 assay, an apoptosis assay and crystal violet staining. Intracellular calcium levels and reactive oxygen species were detected by Fluo‑4AM and DHE fluorescence. The protein and mRNA expression levels of JNK and c‑Jun were measured by western blotting and reverse transcription‑quantitative PCR to investigate the molecular mechanisms involved. Subsequently, 100 clinical patients were recruited to verify the clinical application value of PLN in SIC. The results revealed a significant negative correlation between PLN and T3 in the animal disease model. Furthermore, the expression levels of genes and proteins in the JNK/c‑Jun signaling pathway and PLN expression levels were decreased, whereas the expression levels of sarcoplasmic reticulum calcium ATPase were increased after T3 treatment. These results indicated that T3 alleviated myocardial injury in SIC by inhibiting PLN expression and its phosphorylation, which may be related to the JNK/c‑Jun signaling pathway. Accordingly, PLN may have clinical diagnostic value in patients with SIC.

Chirality is a fundamental property of nature. Herein, we demonstrate a straightforward strategy to build a new kind of metal-induced distally axial chirality based on vertical binuclear platinum(II) complexes. The strong and balanced steric hindrance between the four methyl substituents of sym-tetraacetylethane bridging ligand causes the two Pt-containing hexatomic rings in these binuclear Pt(II) complexes to be vertically linked by a C-C single bond. Although the two heterobidentate 2-phenylpyridine (C^N) ligands are spatially distant from the C-C single bond, they are strictly orthogonal to each other, resulting in metal-induced distally axial chirality. Moreover, such distally axial chirality can reduce the synthesis difficulty of asymmetric bridging ligands, extend axially chiral plane without distorting the coordination configuration, and enhance rotational barriers for high phosphorescent quantum yield and racemization energy barrier. The enantiomers of complexes can be separated by chiral high-performance liquid chromatography (HPLC) and their absolute configurations were confirmed by X-ray diffraction, circular dichroism, and density functional theory calculation. Furthermore, without the use of chiral HPLC, enantiopure complexes can be prepared using chiral binaphthalene- and estrone-based C^N ligands through chirality self-sorting. The estrone groups can also facilitate the formation of supramolecular gels by self-assembly., (© 2025 Wiley‐VCH GmbH.)

Methicillin-resistant Staphylococcus aureus (MRSA), a principal causative agent of infections worldwide, urgently requires innovative interventions to counter its increasing risk. The present study revealed the profound impact of farrerol (FA), a robust bioactive agent, on the virulence and resistance mechanisms of MRSA. Our in-depth investigation revealed that FA significantly mitigated the β-lactam resistance of MRSA USA300, an achievement attributed to its precise interference with the BlaZ and Pbp2a protein. Additionally, FA indirectly diminishes the oligomerization of PBP2a by disrupting pigment synthesis, further contributing to its efficacy. In addition, FA extends its functional footprint beyond resistance modulation, exhibiting substantial antivirulence efficacy through selective inhibition of the accessory gene regulator (Agr) system, thereby significantly curbing MRSA pathogenicity in A549 cell and murine models. This study comprehensively explored the multiple impacts of FA on MRSA, shedding light on its versatile role as a BlaZ suppressor, pigment synthesis regulator, and AgrA activity modulator. These intricate findings firmly position FA as a compelling therapeutic candidate for addressing MRSA infections in the clinic.

Objective: CIDEB (Cell death-inducing DNA fragmentation factor alpha-like effector B), a family member of CIDEs (Cell death-inducing DFF45-like effectors), is well known as a crucial regulator for lipid metabolic signaling pathways in various metabolic tissues and secretory glands. However, its role in regulating intramuscular fat (IMF) deposition in goat remains unclear., Methods: The expression vector pcDNA3.1-CIDEB was constructed and transfected into goat intramuscular preadipocytes; the overexpression and interference efficiency and expression of genes related to lipid metabolism were measured by Real-time PCR; the effect of overexpression of CIDEB and interfering with CIDEB on lipid droplet formation was observed by Oil Red O staining and GPO-Trinder enzymatic reaction. Then RNA-Seq was used to investigate the metabolic pathway of CIDEB affecting adipocyte deposition in goat intramuscular preadipocytes., Results: Overexpression of CIDEB significantly promoted the lipid droplets accumulation and the triglyceride deposition, and significantly upregulated the expression of genes related to lipid metabolism. After overexpression of CIDEB in goat intramuscular preadipocytes, in total 171 differentially expressed genes (DEGs) were found, including 122 up-regulated and 49 down-regulated DEGs, and the top three significantly changed pathways filtered by Kyoto Encyclopedia of Genes and Genomes (KEGG) analysis were Cocaine addiction, Amphetamine addiction and Malaria pathways. Conversely, the silencing of CIDEB significantly reduced lipid accumulation in goat intramuscular preadipocytes, meanwhile changed the expression of lipid metabolism genes. For CIDEB silencing, a total of 2140 DEGs were found, including 1252 up-regulated and 888 down-regulated DEGs, and the top three significantly changed pathways filtered by KEGG analysis were Ribosome, Thyroid hormone signaling pathway and Alzheimer disease., Conclusion: The expression of CIDEB can significantly promote lipid deposition of intramuscular adipocytes in goats, and these results provide important data to support further clarifying the mechanism of CIDEB gene on the regulation of intramuscular adipogenesis, and the IMF formation in goat.

Non-adiabatic molecular dynamics (NAMD) simulations have become an indispensable tool for investigating excited-state dynamics in solids. In this work, we propose a general framework, N 2 AMD (Neural-Network Non-Adiabatic Molecular Dynamics), which employs an E(3)-equivariant deep neural Hamiltonian to boost the accuracy and efficiency of NAMD simulations. Distinct from conventional machine learning methods that predict key quantities in NAMD, N 2 AMD computes these quantities directly with a deep neural Hamiltonian, ensuring excellent accuracy, efficiency, and consistency. N 2 AMD not only achieves impressive efficiency in performing NAMD simulations at the hybrid functional level within the framework of the classical path approximation (CPA), but also demonstrates great potential in predicting non-adiabatic coupling vectors and suggests a method to go beyond CPA. Furthermore, N 2 AMD demonstrates excellent generalizability and enables seamless integration with advanced NAMD techniques and infrastructures. Taking several extensively investigated semiconductors as the prototypical system, we successfully simulate carrier recombination in both pristine and defective systems at large scales where conventional NAMD often significantly underestimates or even qualitatively incorrectly predicts lifetimes. This framework offers a reliable and efficient approach for conducting accurate NAMD simulations across various condensed materials., Competing Interests: Competing interests: The authors declare no competing interests., (© 2025. The Author(s).)

Horse domestication revolutionizes human civilization by transforming transportation, agriculture, and warfare patterns. Despite extensive studies on modern domestic horse origins, the intricate demographic history and genetic signatures underlying pony size remain unexplored. Here, a high-quality genome assembly of the Chinese Debao pony is presented, and 452 qualified individuals from 64 horse breeds worldwide are extensively analyzed. The authors' results reveal the conservation of ancient components in East Asian horses and close relationships between Asian horses and Western pony lineages. Genetic analyses suggest an Asian paternal origin for European pony breeds. These pony-sized horses share close genetic affinities, potentially attributed to their early expansion and adaptation to local environments. In addition, promising cis-regulatory elements influencing horse withers height by regulating genes such as RFLNA and FOXO1 are identified. Overall, this study provides insightful perspectives on the dispersal history and genetic determinants underlying body size in ponies, offering broader implications for horse population management and improvement., (© 2025 The Author(s). Advanced Science published by Wiley‐VCH GmbH.)

Understanding wetland change is critical to establishing and implementing international conservation and management conventions. With such knowledge, supporting sustainable development, making management decisions, improving policies, and conducting scientific research become possible. However, consistent information on changes in Chinese wetlands has been unavailable. We applied the hybrid object-based and hierarchical classification approach to ∼53,000 scenes of Landsat images acquired between 1980 and 2020 and created a national wetland mapping product (China&#95;Wetlands) for six periods (e.g., 1980, 1990, 2000, 2010, 2015, and 2020). China&#95;Wetlands revealed diverse changes in Chinese wetlands and their trajectories in response to climate change and human impacts over the past four decades. Specifically, there was a substantial shrinkage in wetland area before 2015, with a small rebound between 2015 and 2020. The net loss was ∼60.9 × 10 3  km 2 , which represents 12% of the area in 1980. However, the loss of natural wetlands was hidden by human-made wetland gain with an offset of 15.6 × 10 3  km 2 . Additionally, the expansion of surface water extent approximately 14.0 × 10 3  km 2 obscured the loss of vegetated wetlands. Wetland loss in hotspot areas (e.g., Sanjiang Plain and Yangtze River Delta) should not be neglected. The sustainable management and effective conservation of wetlands in China should target wetland areas, landscape structures, and small wetlands delivering important ecosystem services. Moreover, the conversion of wetland types and the invasion of alien species need to be monitored and regulated. China&#95;Wetlands will be a critical wetland dataset for ecological research and the assessment of national and global environmental objectives (e.g., the United Nation's sustainable development goals)., (Copyright © 2024 Science China Press. Published by Elsevier B.V. All rights reserved.)

Ischemic stroke (IS) presents a significant challenge to global health, as conventional reperfusion strategies aimed at restoring cerebral circulation paradoxically exacerbate neurological damage. This injury primarily results from the excessive production of reactive oxygen species (ROS) and the initiation of a widespread neuroinflammatory response. In this study, mercaptosuccinic acid (MSA)-coated bimetallic clusterzymes, containing an optimized ratio of Au 7 Ag 1 nanoclusters (NCs), are developed for the targeted treatment of IS reperfusion injury. The ultrafine particle size of bimetallic nanoclusters facilitates the penetration across the blood-brain barrier (BBB) and enhances catalytic capacity and enzymatic activity through synergistic effects. Comprehensive in vitro and in vivo studies demonstrate that Au 7 Ag 1 NCs provide neuroprotection by efficiently scavenging ROS and modulating microglial polarization, alleviating oxidative stress-induced injury. Furthermore, Au 7 Ag 1 NCs play a crucial role in reducing brain tissue damage following reperfusion and promoting long-term neurological function recovery. Notably, RNA sequencing reveals that Au 7 Ag 1 NCs impact key molecular pathways linked to apoptosis and inflammation. In summary, this study demonstrates the potential of Au 7 Ag 1 NCs as a novel therapeutic approach for IS reperfusion injury and highlights a promising pathway for nanomedicine-based interventions targeting ischemic cerebral disorders., (© 2025 Wiley‐VCH GmbH.)

Immunogenic programmed cell death effectively triggers acute inflammatory responses, thereby enhancing antitumor immunity. The advancement of biodegradable nonmetallic dual inducers represents a promising strategy. Herein, a biodegradable organomolecular ferroelectric nanoplatform (C 60 -TCNQ, CT) is designed to facilitate effective ferroelectric catalysis, thereby augmenting tumor immunotherapy through apoptosis and ferroptosis. CT-mediated ultrasound-triggered ferroelectric catalysis promotes ferroelectric polarization and significantly increases the production of reactive oxygen species, leading to substantial tumor cell apoptosis. Moreover, the polycyano group of CT nanoparticles selectively reacts with cysteine under mild conditions, resulting in redox imbalances and the accumulation of lipid peroxides, which contribute to the induction of ferroptosis in tumor cells. Additionally, the apoptosis and ferroptosis induced by CT stimulate immunogenic cell death progression, eliciting robust immune responses. In vivo evaluation using a bilateral tumor model demonstrates the capacity of CT to sensitize anti-PD-L1 therapy under ultrasound irradiation, achieving an impressive antitumor response rate of 96.2% against malignant melanoma and an 80% inhibition of tumor metastasis. RNA sequencing analysis revealed that treatment with CT resulted in a downregulation of gene signatures associated with the immune-related Jak-Stat signaling pathway. This study opens a novel avenue to developing organomolecular ferroelectric nanomedicines for effective tumor immunotherapy., (© 2025 Wiley‐VCH GmbH.)

3-Nitropropionic acid (3-NP) is a naturally occurring mycotoxin produced by various fungi and plants. Despite reports on its toxicity, the potential impact of 3-NP exposure on reproductive health remains elusive. To this end, we conducted an in vitro study to investigate the toxic effects of 3-NP on the developmental processes of mouse embryos. Our results suggested that exposure to 50 μM 3-NP resulted in significant pre-implantation developmental arrest , with most embryos arrested at the 2-cell stage, indicating disruption of normal development. Further analysis indicated that 3-NP exposure altered embryonic gene expression, disrupted zygotic genome activation and maternal gene degradation, and inhibited maternal-zygote transition. Moreover, it impaired mitochondrial dysfunction, causing dysfunctional cellular energy metabolism and elevated intracellular oxidative stress, culminating in increased DNA damage. Additionally, 3-NP exposure caused aberrant epigenetic modifications, particularly the upregulation of histone methylation levels, including elevated H3K27me3 and H3K9me3, which are strongly related to gene expression silencing. In summary, this study elucidates the in vitro toxic effects of 3-NP on mouse embryo development and highlights its potential adverse effects on female reproductive health., 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.)

Slow-release fertilizers show great promise for advancing agricultural sustainability by enhancing nutrient efficiency and mitigating environmental impacts. Herein, we propose an approach that embeds chitosan hydrogel membranes with metal-modified biochars to encapsulate N-P-K compound fertilizers, referred to as CS-MBC-SRFs. Our results demonstrate that CS-MBC-SRFs exhibit superior slow-release performance for N, P, and K compared to others (commercial NPK compound fertilizers, chitosan-coated, and biochar-embedded chitosan-coated fertilizers). Over a 33-day soil column test, CS-MBC-SRFs showed cumulative leaching ratios of <8.93 % for N, 18.4 % for P, and 14.4 % for K. Incorporating metal-modified biochar into the chitosan hydrogel membrane significantly enhances its swelling and mechanical properties while maintaining biodegradability and water-retention capacity. Mechanistic investigations reveal that nutrient release from CS-MBC-SRFs primarily occurs via diffusion through the hydrogel membrane, with the metal-modified biochar surface enhancing nutrient adsorption and delaying release. Additionally, the metal-modified biochars improved swelling and mechanical properties of the chitosan hydrogel membrane, significantly reducing nutrient diffusion. Pot tests demonstrated that CS-MBC-SRFs effectively promoted chili plant growth, ensuring high N-P-K utilization and improving chili fruit nutritional indices. Economic analysis further highlights the promising application prospects of CS-MBC-SRFs., 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.)

The efficacy of the G-protein is influenced by N-linked glycosylation, which serves as the sole immunogen of the rabies virus vaccine. However, achieving satisfactory immune-protection efficacy remains challenging, owing to the heterogeneous glycosylation of G-proteins. Within molecular dynamics, examining the impact of N-glycan heterogeneity on the structural characteristics of G-proteins provides insights into the relationship between antigens and the efficacy of rabies virus vaccines. Glycosylation is regulated by host cells. In rabies virus cultured in Vero cells (VRV), all N-glycosylation sites of the G-protein underwent modification. In contrast, rabies virus G-protein cultured in KMB17 cells (human diploid cell vaccine [HDCV]) was only modified by N-glycans at amino acid positions 247 and 319. Furthermore, treatment of VRV with de-glycosylation significantly improved its immune-protective efficacy, whereas de-glycosylation did not alter the immune-protective efficacy of HDCV. To support the impact of glycosylation on VRV efficacy, the structures and dynamics of G-proteins were analyzed using GROMACS. Specifically, the hydrophobicity, flexibility, and radius of gyration of the G-protein trimer in VRV were significantly altered by excessive hydrogen bonds formed by the three-branched hybrid glycan at the aa 319 site. These changes increase the instability of the G-protein trimer and may lead to a decrease in vaccine protective efficacy. Ultimately, we determined that N-glycan heterogeneity affects the immune-protection effect of antigen proteins by altering their dynamic characteristics, enhancing our understanding of the correlation between antigen structural characteristics and efficacy., Importance: N-glycosylation of rabies virus glycoprotein dynamically regulates protein folding, stability, and antigenicity. Therefore, regulation of N-glycan modification is key to improving vaccine stability and protective efficacy. How the type and modification sites of N-glycans affect the protective efficacy of rabies vaccines remains unclear. Our research indicates that there are differences in the protective efficacy of rabies virus G-proteins modified with different N-glycans. Moreover, the modification of the three-branched hybrid glycan at the aa 319 site of G-protein significantly altered the hydrophobicity, flexibility, and radius, and increased its trimeric antigen instability through molecular dynamics demonstrations. These findings update the current understanding of the impact of glycans on vaccine antigenicity and develop a system to evaluate the stability of antigen glycoproteins based on molecular dynamics.

Low back pain (LBP) resulting from sciatic nerve compression presents major challenges in pain management, as traditional therapies provide only short-term relief and pose risks of systemic toxicity. In this study, an innovative Fe 3 O 4 @ZIF-8-RVC (FZR) dual-responsive nanoplatform is introduced that integrates magnetic targeting with pH-sensitive, sustained drug release to overcome these limitations. The FZR nanoplatform encapsulates ropivacaine (RVC) within the ZIF-8-coated Fe 3 O 4 core, enabling precise and prolonged analgesia at the injury site through magnetic guidance and acid-triggered release. In vitro and in vivo assessments indicate that FZR achieves high drug loading, sustained release in acidic environments, and excellent biocompatibility, significantly extending analgesic effects in chronic nerve injury models while minimizing systemic exposure. Behavioral tests and molecular analyses in LBP rat models confirm that FZR effectively suppresses pain-related neuronal activity and central sensitization markers. This dual-responsive nanoplatform FZR offers a safe, long-lasting, and targeted therapeutic approach, holding strong potential for advancing pain relief in LBP and related neuropathic pain conditions., (© 2025 Wiley‐VCH GmbH.)

Objective: Compared with conventional synthetic disease-modifying antirheumatic drugs (csDMARDs), biologics are more effective and are recommended to be included in the sequential treatment for psoriatic arthritis (PsA) patients. However, biologics are expensive and the cost-effectiveness of sequential biologic therapy in China remains unknown. The purpose of this study is to evaluate the cost-effectiveness of different sequential treatment option for PsA patients who have not responded to csDMARDs from the perspective of Chinese healthcare system., Methods: We constructed a discrete event simulation model to evaluate the cost-effectiveness of 7 monotherapy treatments and 32 sequential treatments. In sequential therapy, two different types of biologics were used as first-line and second-line treatments, respectively, with the best supportive care (BSC) as the third-line treatment. The primary outcomes included total treatment costs, quality-adjusted life years (QALYs), and incremental cost-effectiveness ratios (ICERs). One-way and probability sensitivity analyses were performed to explore the uncertainty of our model., Results: Compared to all other strategies, initiating with secukinumab followed by etanercept (SEC-ETN) provided the highest health benefits. At a willingness-to-pay (WTP) threshold of US $38,161 per QALY, SEC-ETN was the most cost-effective strategy, with an ICER of $20,837 per QALY. One-way sensitivity analysis and probabilistic sensitivity analysis results confirmed the robust of this conclusion., Conclusions: In China, SEC-ETN may be the most cost-effective strategy for patients who have failed treatment with csDMARDs and have not previously used biologics. The results provide evidence for identifying the optimal biologic treatment strategy for PsA patients in China. Key Points • Compared with conventional synthetic disease-modifying antirheumatic drugs (csDMARDs), biologics are more effective and are recommended to be included in the sequential treatment for psoriatic arthritis (PsA) patients. However, the cost-effectiveness of sequential biologic therapy in China remains unclear. • At a willingness-to-pay threshold of $38,161, initiating with secukinumab followed by etanercept (SEC-ETN) was cost-effective strategy, outperforming other strategies. • From the perspective of the Chinese healthcare system, the optimal biologic treatment strategy was SEC-ETN in China., Competing Interests: Compliance with ethical standards. Ethics approval: The manuscript does not contain clinical studies or patient data. Disclosures: None., (© 2025. The Author(s), under exclusive licence to International League of Associations for Rheumatology (ILAR).)

Osteogenesis of renal tubular epithelial cells (RTEC) is an important trigger for calcium oxalate (CaOx) kidney stone formation, but whether macrophages are involved in RTEC osteogenesis is unclear. The purpose of this study was to investigate the role and mechanism of macrophages in CaOx kidney stones on RTEC osteogenesis. Oxalate or ethylene glycol was used to construct in vitro and in vivo CaOx kidney stone models, respectively. Macrophage-derived conditioned medium was used to induce osteogenesis in HK-2 cells, and genetic controls and pharmacological interventions were used to investigate the underlying mechanism. The results demonstrated that macrophage-conditioned medium under oxalate intervention facilitated the increase of alkaline phosphatase and calcium salts as well as the upregulation of osteogenic marker genes (BMP2 and RUNX2) expression in HK-2 cells. On the one hand, the knockdown of the JAK2 gene in HK-2 cells reverses the role of macrophage-derived conditioned medium in promoting osteogenesis in HK-2 cells. On the other hand, inhibition of prostaglandin E2 (PGE2) generation in macrophages reverses osteogenesis in HK-2 cells. Moreover, inhibition of PGE2 generation would cure ethylene glycol-induced renal injury and calcium salt deposition, as well as osteogenesis of RTEC. This study illustrates that in the presence of oxalate, macrophages secret PGE2 to activate JAK2/STAT3 signaling in RTEC, which could trigger osteogenesis. It provides new insights into the mechanism of CaOx kidney stone formation., 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.)

Utilizing agricultural waste is a sustainable approach to reduce the production cost of bio-based products. Here, we report a novel haloalkaliphilic strain, Halomonas nigrificans X339, which exhibits an exceptional ability to utilize various low-cost carbon sources. Compared to other halophiles, X339 could be cultivated at an optimal salinity as low as 2 % (w/v). X339 accumulated extraordinarily large granules of polyhydroxybutyrate (PHB). In open batch fermentation, X339 produced 5.11 g/L of PHB from wheat straw hydrolysate (WSH) at 3 % salinity and pH 9, with a PHB/carbon source conversion rate of 0.30 g/g. This represents the highest PHB yield reported from straw hydrolysates in shake-flask fermentation by halophiles. Additionally, whole genome of X339 was sequenced to identify candidate genes related to carbon source utilization. Our findings will benefit researchers in developing a suitable chassis for Next Generation Industrial Biotechnology, and offer a sustainable and eco-friendly solution for bio-based products., 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 The Authors. Published by Elsevier Ltd.. All rights reserved.)

Fluorene-9-bisphenol (BHPF), a prevalent substitute for bisphenol A (BPA), has become a widespread endocrine disruptor found in numerous consumer products. Despite extensive research on its toxicological profile, the specific effects of BHPF on reproduction, particularly during early embryonic development, remain unclear. Therefore, in our study, we used an in vitro culture system of mouse embryos to treat fertilized eggs with different concentrations of BHPF, and applied immunofluorescence, cell live staining and transcriptome sequencing to explore the effects of BHPF on early embryonic development and related mechanisms. Our study demonstrates that BHPF exposure causes significant developmental arrest in early embryonic stages. Transcriptomic analysis revealed that BHPF exposure altered gene expression at the 2-cell stage, notably impairing zygotic genome activation and maternal mRNA degradation, which disrupted the maternal-to-zygotic transition. Furthermore, BHPF exposure impaired mitochondrial function, as illustrated by altered mitochondrial distribution, reduced membrane potential, and decreased ATP production. Oxidative stress and DNA damage in 2-cell embryos were linked to the accumulation of reactive oxygen species and superoxide anions induced by BHPF. Additionally, BHPF-treated embryos exhibited altered histone modification patterns, suggesting epigenetic disruptions. Overall, these results indicate that BHPF has the potential to disrupt early embryonic development, raising concerns regarding its safety as a BPA substitute., 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 future applications of organic solar cells (OSCs) necessitate a thorough consideration of their ambient stability and processability, particularly for large area air-processed engineering, but water-induced degradation of active layer critically restricts its development. To surmount this hurdle, a water-obstructing guest (WOG) strategy is proposed to attenuate the interaction of the active layer with water molecules, reduce defects in blend films, and enhance the devices stability under high relative humidity (RH) conditions by introducing a siloxane-containing polymer D18-SiO. In addition to suppressing trap density, the WOG with hydrophobic and low surface free energy characteristics, forms a capping layer that blocks moisture penetration while preserving ideal nano-micromorphology with high crystallinity and tight packing properties. Power conversion efficiencies (PCE) of >19% is reported for spin coating OSCs fabricated across an RH range of 20 to 90%, and PCE of >17% blade coating OSCs at 90% RH. The D18-SiO, serves as a protective barrier to enhance the device stability, and the corresponding unencapsulated OSCs retained 80.7% of its initial performance in air (≈ 40% RH) after 600-h maximum power point tracking under continuous light illumination, showcasing great potential in designing WOG strategy for large-scale production of air-processed OSCs., (© 2024 The Author(s). Advanced Science published by Wiley‐VCH GmbH.)

A critical challenge in wearable electrothermal textiles is achieving effective insulation while maintaining sheath flexibility, which is essential for enhancing the mechanical properties and durability of conductive materials under everyday conditions, such as washing, stretching, and twisting. In this work, we employ a coaxial tubular braiding technique to coat a high-conductivity carbon nanotube (CNT) yarn with a high-strength insulation layer made of ultra-high-molecular-weight polyethylene (UHMWPE) multifilaments, resulting in a core-sheath-structure CNT yarn with excellent electrothermal performance. By adjusting the number of UHMWPE multifilaments and the sheath braiding angle, we achieve high flexibility, high tensile strength, and abrasion and wash resistance, as well as improved electrical stability for the CNT yarns. Additionally, the CNT yarns with an insulation layer effectively prevent short-circuiting during use and achieve superior thermal management, with a significant increase in steady-state temperature under operational conditions, exhibiting significant potential for applications in wearable electronic devices.

Climate change and air pollution pose significant global health threats, including impacts on diabetes risk; however, their long-term effects on insulin resistance (IR), a key determinant in diabetes pathophysiology, remain unclear. This study investigated whether exposure to heatwaves, temperature fluctuations, and warm-season ozone (O 3 ) contributes to or exacerbates IR and explored the potential mediating role of biological aging. The study enrolled 6901 participants and assessed both traditional and novel IR indicators: estimated glucose disposal rate (eGDR), triglyceride-glucose (TyG) index, triglyceride to high-density lipoprotein cholesterol ratio (TG/HDL-c), metabolic score for IR (METS-IR), TyG-body mass index (TyG-BMI), TyG-waist circumference (TyG-WC), waist-to-height ratio (WHtR), TyG-WHtR, and lipid accumulation product (LAP). Ordinary least squares regression models were applied to evaluate the long-lasting effects of heatwaves, temperature fluctuation, and warm-season O 3 on IR, incorporating Huber-White robust standard errors for model stability. Causal mediation analysis was utilized to investigate the mediating effects of biological aging. We found that exposure to heatwaves and higher concentrations of warm-season O 3 was associated with elevated IR levels, with males, smokers, drinkers, and low-income individuals being more vulnerable. Accelerated biological aging (including body age, metabolomic aging rate, etc.) could significant mediate the long-lasting effects of heatwaves and warm-season O 3 . Our findings suggest that climate change and air pollution could amplify the vulnerability of glucose metabolism, particularly in males, smokers, drinkers, and individuals with low-income. More importantly, our findings reveal the importance of mitigating biological aging to prevent IR in the future, as global diabetes prevalence escalates rapidly., 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: Gastrointestinal endoscopy with sedation is frequently complicated by hypoxemia. Nasal cannulas have limitations in eliminating hypoxemia. We hypothesized that the combination of nasal clips and nasal cannulas would improve the inspired oxygen concentrations and prevent hypoxemia compared with the use of nasal cannulas alone., Methods: A total of 600 adult patients were randomly assigned to receive supplemental oxygen through single-lumen nasal cannulas or through the combination of nasal clips and nasal cannulas. The primary outcome was the incidence of hypoxemia. Additionally, subclinical respiratory depression and severe hypoxemia, duration of hypoxemia, lowest SpO 2 level, measures to increase oxygen saturation level, and adverse events such as cough and hiccups were compared as secondary outcomes., Results: Three hundred patients in the nasal clip group and 296 patients in the nasal cannula group were included in the intention-to-treat analysis. Nasal clips significantly decreased the incidence of hypoxemia from 25.0-17.7%(RR = 0.707, 95% CI = 0.516 to 0.967, P = 0.029). The median and interquartile range of lowest SpO 2 in the nasal clip group (96 [92 to 98]) was significantly greater than that in the nasal cannula group (95 [89 to 97]; median difference = 1.000, 95% CI = 0.000 to 2.000, P = 0.004). No significant differences were found between the two groups in subclinical respiratory depression or severe hypoxemia, duration of hypoxemia, adverse events or measures taken to increase oxygen saturation., Conclusions: The combination of nasal clips and cannulas reduces hypoxemia during gastrointestinal endoscopy with sedation, demonstrating a significant advantage over the sole use of nasal cannulas, with tolerable adverse events., Trial Registration: Chinese Clinical Trial Registry (ChiCTR2200065407)., Competing Interests: Declarations. Ethics approval and consent to participate: This study was approved by the Medical Ethics Committee of Taizhou Enze Medical Centre (Group) Enze Hospital, Taizhou, Zhejiang, China (approval no. K20220307) on 28 March 2022. All participants provided written informed consent before participation. The trial followed the Consolidated Standards of Reporting Trials (CONSORT) reporting guidelines and was registered before patient recruitment at the Chinese Clinical Trial Registry (registration no. ChiCTR2200065407; date of registration: November 4, 2022). Consent for publication: Not applicable. Competing interests: The authors declare no competing interests., (© 2025. The Author(s).)

The effect of oat β-glucan (OG) on the structure, interfacial behavior and emulsion rheological properties of sea bass myofibrillar protein (MP) was investigated. Fourier transform infrared spectroscopy demonstrated that adding OG decreased the α-helix content in MP from 27% to 22% and increased the β-sheet content, suggesting that OG facilitated MP unfolding. When the OG content was 1.2%, the interfacial tension decreased by approximately 20%, and the diffusion rate increased by approximately 1.5-fold. These changes augmented the physical stability of emulsions. Rheological analysis showed that 3% OG promoted the energy storage modulus (G') of the emulsion. These changes enhanced MP adsorption and rearrangement at the oil-water interface, which enhanced viscoelasticity in the interfacial film and further increased the emulsion stability. These findings augment the understanding of protein-polysaccharide interactions and provide guidance for improving protein emulsion stability., 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.)

Mixed-halide perovskite plays important role in wide-color gamut displays as a vital material for three primary colors. However, halide segregation and caused unstable spectra are the intrinsic problem in mixed-halide perovskite light-emitting diodes (PeLEDs) originating from the lattice strain and the resulting defects in perovskite quantum dots (PQDs). Here, smaller transition metal cations are applied to replace Pb 2+ and release lattice strain, which avoids halogen escaping/halide vacancies forming to ensure high photoluminescence quantum yield (PLQY) and stable spectra. However, the actual doping amount is limited by ionic size and chemical environment, which will affect the improvement of optoelectronic performance. Thus, this study proposes a strategy by introducing tri-n-octylphosphine to coordinate strongly with metal cations and catch them to participate the nucleation-growth process. Through doping transition metal cations effectively, the CsPb(BrI) 3 PQDs show high PLQY (92%) and long lifetime (107.83 ns). Further, highly efficient pure-red PeLEDs with highest external quantum efficiency of 16.86% is fabricated and the spectrum can be stabilized at 630 nm with only 1 nm red-shift under bias, showing the promising potential of PQDs for next-generation display., (© 2025 Wiley‐VCH GmbH.)

Methods for catalytically constructing of N-N axially chiral scaffolds have garnered significant attention since such compounds are widely present in natural products, bioactive molecules, and organic materials. Herein, we report a highly diastereoselective and enantioselective organocatalyzed [4 + 1] annulation method for synthesizing diverse valuable isoindolinones that possessing N-N axial and central chiralities. This methodology uses a chiral phosphoric acid as a bifunctional catalyst to promote a cascade sequence involving two nucleophilic additions, dehydration, and dearomatization processes. Control experiments and DFT calculations revealed a possible mechanism in which the stereoselectivity-determining step is likely to involve the irreversible formation of a hydroxy biaryl intermediate. Additionally, preliminary biological activity studies showed that some of these N-N axially chiral isoindolinones have potential in suppressing tumor-cell proliferation., Competing Interests: Competing interests: The authors declare no competing interests., (© 2025. The Author(s).)

Type-II multiferroicity, where electric polarization is induced by specific spin patterns, is crucial in fundamental physics and advanced spintronics. However, the spin model and magnetoelectric coupling mechanisms in prototypical type-II multiferroic CuFeO&#95;{2} and Al-doped CuFeO&#95;{2} remain unclear. Here, by considering both spin and alloy degrees of freedom, we develop a magnetic cluster expansion method, which considers all symmetry allowed interactions. Applying such method, we not only obtain realistic spin model that can correctly reproduce observations for both CuFeO&#95;{2} and CuFe&#95;{1-x}Al&#95;{x}O&#95;{2}, but also revisit well-known theories of the original spin-current (SC) model and p-d hybridization model. Specifically, we find that (i) a previously overlooked biquadratic interaction is critical to reproduce the ↑↑↓↓ ground state and excited states of CuFeO&#95;{2}; (ii) the combination of absent biquadratic interaction and increased magnetic frustration around Al dopants stabilizes the proper screw state; and (iii) it is the generalized spin-current (GSC) model that can correctly characterize the multiferroicity of CuFeO&#95;{2}. These findings have broader implications for understanding novel magnetoelectric couplings in, e.g., monolayer multiferroic NiI&#95;{2}.

Background: The association of protein from different food sources and different plasma amino acids with risk of chronic kidney disease (CKD) is unclear., Objectives: We aimed to investigate longitudinal relationships of dietary protein intake from different sources and quantity of plasma amino acids with new-onset CKD in the general population., Methods: Participants (mean age: 56 y) without CKD at baseline were included in the UK Biobank. A total of 176,980 were included in the analysis for protein intakes and 99,061 participants were included in the analysis for plasma amino acids. Information on dietary protein was collected based on a 24-h dietary recall from the previous day. Plasma amino acid concentrations were measured by a high-throughput NMR-based metabolic biomarker profiling platform. The study outcome was new-onset CKD., Results: During a median follow-up of 12 y (beginning between 2006 and 2010 and ending in 2021), 3542 participants (2,128,626 person-year) developed new-onset CKD. Higher intakes of dairy-derived and fish-derived protein were associated with lower incidence of CKD [per standard deviation, SD increment, adjusted hazard ratio, HR (95% confidence interval, 95% CI): 0.95 (0.91, 0.98) and 0.95 (0.92, 0.99), respectively], but protein intake from other foods was not (P-trend > 0.1). Moreover, incident CKD was lower among those with higher plasma histidine (per SD increment; adjusted HR = 0.90; 95% CI: 0.86, 0.95), tyrosine (0.90; 0.87, 0.94), isoleucine (0.89; 0.85, 0.92), leucine (0.89; 0.85, 0.93), and valine (0.89; 0.85, 0.93)., Conclusions: The protein intake from dairy and fish, as well as the concentration of plasma histidine, tyrosine, isoleucine, leucine, and valine, was inversely associated with new-onset CKD., Competing Interests: Conflict of interest SRS is a member of the Journal’s Editorial Board. All other authors report no conflicts of interest., (Copyright © 2025 American Society for Nutrition. Published by Elsevier Inc. All rights reserved.)

Endothelial lipase (LIPG), a member of the triglyceride lipase family, plays an essential role in human diseases and lipid metabolism. However, its function in goat intramuscular fat (IMF) deposition remains unclear. In this study, we investigated the role of the LIPG gene in IMF deposition by knocking down and overexpressing it in goat intramuscular preadipocytes. We successfully cloned the full-length LIPG gene, which spans 2,131 bp, including a 94 bp 5' untranslated region (5'UTR), a 1,503 bp coding sequence (CDS), and a 534 bp 3' untranslated region (3'UTR). Tissue expression profiles showed that LIPG is expressed in the heart, liver, spleen, Kidney, longest dorsal muscle, and small intestine tissues of goats. LIPG knockdown significantly inhibited both the proliferation of intramuscular preadipocytes and lipid deposition. Moreover, LIPG knockdown markedly decreased mRNA expression of FASN, LPL, CPT1A, CPT1B, FABP3, while increasing the mRNA expression of ATGL, ACOX1, FADS1, and ELOVL6. These findings were further corroborated through LIPG overexpression experiments. Using RNA sequencing (RNA-seq), we identified 1695 differentially expressed genes (DEGs) between the negative control (NC) and LIPG knockdown (Si-LIPG) groups, with KEGG pathway analysis revealing significant enrichment in the PPAR signaling pathway. Additionally, LIPG knockdown significantly upregulated the expression of both mRNA and protein levels of PPARα. The PPARα agonist WY14643 was able to reverse the enhanced lipid deposition induced by LIPG overexpression. In conclusion, our study highlights a key role for LIPG in the regulation of goat intramuscular preadipocyte proliferation and lipid deposition, potentially through the PPARα signaling pathway. These findings provide new insights into the regulatory mechanisms governing IMF deposition and suggest potential strategies for improving goat meat quality., Competing Interests: 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 Wang et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.)

To promote collaborative governance of PM2.5 and O3 pollution, understanding their spatiotemporal patterns and determining factors is crucial to control air pollution in China. Using the ground-monitored data encompassing PM2.5 and O3 concentrations in 2019 across 337 Chinese cities, this study explores the spatiotemporal patterns of PM2.5 and O3 concentrations, and then employed the Multi-scale Geographically Weighted Regression (MGWR) model to examine the socioeconomic and natural factors affecting PM2.5 or O3 concentrations. The results show that PM2.5 and O3 concentrations exhibit distinct monthly U-shaped and inverted U-shaped temporal fluctuation patterns across Chinese cities, respectively. Spatially, both pollutants manifest spatial clustering characteristic and a certain degree of bivariate spatial correlation. Elevated PM2.5 concentrations are predominantly concentrated on north and central China, as well as the Xinjiang Autonomous Region, whereas higher O3 concentrations are distributed widely across north, east, and northwest China. The MGWR model outperforms traditional OLS and global spatial regression models, evidenced by its enhanced goodness-of-fit metrics. Specifically, the R2 values for the PM2.5 and O3 MGWR models are notably high, at 0.842 and 0.861, respectively. Socioeconomic and natural factors are found to have multi-scale spatial effects on PM2.5 and O3 concentrations in China. On average, PM2.5 concentrations show positively correlations with population density, the proportion of the added value of secondary industry in GDP, wind speed, relative humidity, and atmospheric pressure, but negatively relationship with per capita GDP, road density, urban greening, air temperature, precipitation, and sunshine duration. In contrast, O3 concentrations are also positively associated with population density, the proportion of the added value of secondary industry in GDP, energy consumption, precipitation, wind speed, atmospheric pressure, and sunshine duration, but negatively correlated with per capita GDP, road density, and air temperature. Our findings offer valuable insights to inform the development of comprehensive air pollution management policies in in developing countries., Competing Interests: The authors have declared that no competing interests exist., (Copyright: © 2025 Zhan et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.)

Background: The precise prediction of multi-origin malignant cervical lymphadenopathy is limited by the low inter-reader reproducibility of imaging interpretation, and a quantitative method to improve this aspect is lacking. This study aimed to develop and validate an artificial intelligence framework integrating quantitative vascular features for assessing cervical lymphadenopathy and explore its utility among radiologists., Methods: For this retrospective study, a total of 21,298 ultrasound images of 10,649 cervical lymph nodes (LNs) from 10,386 patients and 2366 images of 1183 LNs from 1151 patients at the Sun Yat-sen University Cancer Center between January 2011 and July 2022 were used for model development and internal testing, respectively. For external model testing, we used 776 images of 388 LNs from 360 patients at the Chongqing University Cancer Hospital between January and December 2022. Quantitative features used to characterize the vascular distribution and degree of richness were fused with morphological and semantic features on B-mode and color Doppler ultrasound images to develop a dual-modality, multi-feature, fusion lymph node network (DMFLNN). Subsequently, the performance of DMFLNN was compared with that of six radiologists, and its auxiliary value was assessed in test cohorts., Findings: DMFLNN achieved an area under the receiver operating characteristic curve (AUC) of 0.937 for the internal test cohort and 0.875 for the external test cohort. Using the internal test cohort with assistance from DMFLNN, the average AUC improved from 0.814 to 0.836 for senior radiologists ( P  = 0.00018), and from 0.778 to 0.847 for junior radiologists ( P  < 0.0001). Additionally, the average inter-radiologist agreement improved from fair to moderate (improvement in kappa: from 0.590 to 0.696 for senior radiologists; from 0.571 to 0.750 for junior radiologists). Similar trends were observed for the external test cohort. Moreover, the radiologists' average false-positive rate decreased by 3.8% and 9.8% for the internal and external test cohorts, respectively., Interpretation: DMFLNN could improve radiologists' performance and potentially reduce unnecessary biopsies of cervical lymphadenopathy. However, further testing is warranted before its wide adoption in clinical practice., Funding: The National Natural Science Foundation of China (82171955; 62371476; 82441027); the China Department of Science and Technology (2023YFE0204300); and the R&D project of Pazhou Lab (HuangPu) (2023K0606)., Competing Interests: All authors declare no competing interests., (© 2025 The Author(s).)

In this study, lignocellulose-degrading microbes were added to cattle manure and bagasse co-compost through initial- and two-stage inoculations. A comparison was made between the effects of the two inoculations on compost humification parameters, and an investigation was conducted into the dynamic succession of the microbial community, microbial interactions, and amino acid metabolism to uncover the underlying mechanisms. The results showed that two-stage inoculation increased the humus (HS) and humic acid (HA) contents to 86.59 mg/g and 25.80 mg/g, respectively, and achieved a germination index (GI) of 128.77%. At the genus level, it stimulated the growth of Corynebacterium, Thermobifida, and Aspergillus during the high-temperature period, and Luteimonas, Pseudomonas, Actinomadura, and Rhizopus during the maturity period. Two-stage inoculation increased the stability of the bacterial network and microbial cooperation within the fungal network. Additionally, from the cooling to the maturity period, it boosted ten amino acid synthesis pathways. In conclusion, two-stage inoculation is an effective method to promote the maturation and stabilization of co-compost., 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.)

Introduction: Haemonchus contortus ( H. contortus ) infection has a significant impact on the health of pregnant ewes and adversely affects fetal development, highlighting the critical need for a non-toxic feed additive as an alternative and sustainable control strategy. Tannin is a kind of polyphenol compound, which has certain antiparasitic. The objective of this study was to evaluate the impact of dietary tannin supplementation on fecal egg count (FEC), packed cell volume (PCV), complete blood count (CBC), hormone levels, inflammatory markers, placental inflammation, and fetal growth and development in pregnant ewes infected with H. contortus ., Methods: Hulunbuir ewes were randomly divided into three groups: control group (CON), gastrointestinal nematode infection group (GIN), and tannin group, which was infected by H. contortus with tannin feeding therapy (TAN). After artificial insemination was completed, and the ewes were confirmed for pregnancy and infection; stools were collected for FEC, and blood samples were collected for PCV and CBC, hormonal, and inflammation levels. The mRNA levels of hypothalamic-pituitary-ovarian axis-related hormone receptors and placental tissue inflammation genes were detected by quantitative reverse transcription polymerase chain reaction (RT-qPCR). Finally, fetal weights were measured, and fetal ovarian tissue samples were taken for transcriptomic analysis., Results: The results showed that tannins increased the levels of gonadotropin-releasing hormone (GnRH), follicle-stimulating hormone (FSH), luteinizing hormone (LH), estrogen (E 2 ), progesterone (P 4 ), human chorionic gonadotropin (hCG), red blood cell (RBC) counts, packed cell volume (PCV), and mRNA levels of gonadotropic axis receptors in pregnant ewes infected with H. contortus ( p  < 0.05). In addition, tannin reduced fecal egg count (FEC), leukocyte counts, and mRNA levels of inflammatory markers ( p  < 0.05). In addition, fetal ovarian sequencing further showed that tannin may alleviate the delay in fetal growth and development induced by H. contortus infection ( p  < 0.05)., Conclusion: In summary, tannins have anthelmintic effects, restore reproductive hormone levels in pregnant ewes, reduce inflammation levels, and alleviate fetal growth retardation caused by H. contortus infection. Therefore, tannin is a suitable potential alternative to antibiotics as a feed additive., 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 Li, Xiang, Liang, Han, Zhong, Liu and Fang.)

Kidney stones are a common urological disease worldwide, imposing a significant burden on healthcare systems. Calcium oxalate stones are the predominant form of urinary calculi, with two main theoretical models explaining their pathogenesis: the fixed particle and free particle models. Regardless of the model, the formation of calcium oxalate kidney stones is inseparably linked to crystal nucleation, growth, aggregation, and adhesion in urine. Growing evidence highlights the significant role of urinary proteins, particularly matrix proteins, in the development of calcium oxalate stones. The review classifies urinary proteins impacting calcium oxalate stone formation into three groups: inhibitors, promoters, and dual-regulators, outlining their contributions to the formation process., Competing Interests: Declarations. Competing interests: The authors declare no competing interests., (© 2025. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature.)

Streptococcus suis , a significant zoonotic pathogen, annually caused substantial economic losses in the swine industry and had intensified threat to public health due to the recent emergence of human-associated clade. In this study, we discovered that the rare-earth metal-based metal-organic frameworks (Y-BTC) possessed excellent ECL capabilities. After prereduction at high voltage, its ECL intensity was enhanced by two times. Subsequently, we developed an efficient CRISPR/Cas12a-mediated electrochemiluminescence resonance energy transfer (ECL-RET) biosensor utilizing Y-BTC for the detection of the human-associated S. suis clade. Y-BTC was employed as the ECL-RET donor and ECL emitter, and the spherical nucleic acid Au NP was utilized as the ECL-RET receptor. In the presence of the target, isothermal amplification was triggered to generate a large number of amplicons, which subsequently activated the trans -cleavage activity of Cas12a. Cas12a cleaved the nucleic acid shell on the surface of Au NPs, reducing the spatial distance between Au NPs and Y-BTC due to electrostatic adsorption, thereby quenching the ECL of Y-BTC via ECL-RET. Consequently, the presence of targets can be observed by a reduced ECL signal. The sensor exhibited a detection range of 25 pM to 50 nM, with a detection limit as low as 17 pM. The practical utility was verified through actual sample testing. Our proposed ECL-RET sensing strategy provides a new avenue for the sensitive detection of S. suis . The universality has also been demonstrated using Fusobacterium nucleatum , Salmonella pullorum , and Listeria monocytogenes , holding great promise in the field of food safety and public health.