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In this study, we propose a novel surface-enhanced Raman scattering (SERS) method for quantifying aflatoxin B1 (AFB1). This method relies on the target-triggered release of a SERS reporter from aptamer-sealed aminated mesoporous silica nanoparticles (MSNs). These MSNs were synthesized to accommodate 4-mercaptophenylboronic acid (4-MPBA) within their well-defined micropores, which were subsequently sealed with AFB1 aptamers. Upon specific binding of AFB1 to its aptamer, the conformational change in the aptamer is regulated by the presence of the target. Consequently, a positive linear relationship between the AFB1 concentration and the 4-MPBA SERS signal was observed. Under optimal conditions, the method exhibited a good linear relationship over the range of 0.1 to 5 ng/mL AFB1, with a limit of detection (LOD) of 0.03 ng/mL. This strategy was validated using wheat samples, yielding results comparable to high performance liquid chromatography-fluorescence detector (P > 0.05), confirming its reliability for detecting AFB1 in complex food matrices., Competing Interests: Declaration of competing interest The authors declare that they have no 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.)

This study prepared enzymatic theabrownins (TBs-e), alkaline theabrownins (TBs-a), and Pu-erh tea theabrownins (TBs-f), and investigated whether different preparation processes affected the structures, nonvolatile metabolites, and biofunctional activities of TBs. Structural characterization revealed that TBs were polymeric phenolic compounds rich in hydroxyl and carboxyl groups. Nontargeted metabolomics revealed that amino acids were the primary nonvolatile metabolites in TBs-e and TBs-a, accounting for over 70 % of the total nonvolatile content. TBs-f contained more polyphenols, caffeine, and flavonoids, accounting for 14.2 %, 3.9 %, and 0.8 % of total nonvolatile content, respectively. In vivo, at 560 mg/kg body weight, TBs-f were associated with regulation of blood glucose and lipid concentrations in mice. Moreover, 16S rRNA indicated that at 1120 mg/kg body weight, TBs-a were associated with increased numbers of microbiota linked with hypolipidemic activity. This study explores the impacts of different preparation processes on TBs and provides a theoretical foundation for the understanding of TBs., 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.)

Dietary fibers with excellent processing characteristics and water-holding capacity garnered significant attention in low-fat fried products manufacturing, but further research is lacking to elucidate fat reduction mechanisms. Three dietary fibers were added to the batter of fried batter-breaded fish nuggets, the increased maximum wavelength, fluorescence intensity, surface hydrophobicity value, and S-S/free-SH ratio revealed the enhanced exposure and interaction of hydrophobic groups within gluten. Conversion from both -SH into S-S bonds, and α-helix into β-turn confirmed the establishment of the gluten gel network and a substantially increased gel strength. X-ray diffraction demonstrated the inhibition of amylose-lipid complex formation due to the competitive amylose binding to dietary fiber. Finally, reduced oil effects were evident in surface and penetrated oil contents and oil distribution fluorescence diagram. The work clarified the interactions among dietary fiber, wheat starch and gluten, indicating the composite gel network formation and the crust characteristics alterations, ultimately inhibiting oil penetration., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could appear to influence the work reported in this paper., (Copyright © 2024 Elsevier Ltd. All rights reserved.)

Background: Mosaic chromosomal alterations are implicated in neuropsychiatric disorders, but the contribution to schizophrenia (SCZ) risk for somatic copy number variations (sCNVs) emerging in early developmental stages has not been fully established., Methods: We analyzed blood-derived genotype arrays from 9715 patients with SCZ and 28,822 control participants of Chinese descent using a computational tool (MoChA) based on long-range chromosomal information to detect mosaic chromosomal alterations. We focused on probable early developmental sCNVs through stringent filtering. We assessed the burden of sCNVs across varying cell fraction cutoffs, as well as the frequency with which genes were involved in sCNVs. We integrated this data with the PGC (Psychiatric Genomics Consortium) dataset, which comprises 12,834 SCZ cases and 11,648 controls of European descent, and complemented it with genotyping data from postmortem brain tissue of 936 participants (449 cases and 487 controls)., Results: Patients with SCZ had a significantly higher somatic losses detection rate than control participants (1.00% vs. 0.52%; odds ratio = 1.91; 95% CI, 1.47-2.49; two-sided Fisher's exact test, p = 1.49 × 10 -6 ). Further analysis indicated that the odds ratios escalated proportionately (from 1.91 to 2.78) with the increment in cell fraction cutoffs. Recurrent sCNVs associated with SCZ (odds ratio > 8; Fisher's exact test, p < .05) were identified, including notable regions at 10q21.1 (ZWINT), 3q26.1 (SLITRK3), 1q31.1 (BRINP3) and 12q21.31-21.32 (MGAT4C and NTS) in the Chinese cohort, and some regions were validated with PGC data. Cross-tissue validation pinpointed somatic losses at loci like 1p35.3-35.2 and 19p13.3-13.2., Conclusions: The study highlights the significant impact of mosaic chromosomal alterations on SCZ, suggesting their pivotal role in the disorder's genetic etiology., (Copyright © 2024 Society of Biological Psychiatry. Published by Elsevier Inc. All rights reserved.)

Detecting bolt defects on transmission lines is crucial for ensuring the safe operation of the electrical power system. However, existing methods for detecting bolt defects on transmission lines require higher detection accuracy and smaller model sizes. To address these challenges, this paper proposes a real-time bolt defect detection model based on YOLOv7, named YOLOv7-CWFD. The model integrates the Channel Shuffle Diverse Path Aggregation Network (CSDPAN), significantly reducing computational and parameter complexity while maintaining high detection accuracy. Additionally, weighted Efficient Intersection over Union (EIoU) and Normalized Wasserstein Distance (NWD) loss functions are designed to reduce the network's sensitivity to object size variations and enhance model convergence in regression tasks. The Fast Fourier Channel Attention Mechanism (FFCAM) is introduced between the backbone and neck fusion networks to mitigate excessive smoothing of detailed information and improve the network's sensitivity to objects. The DySample upsampling operator is implemented to replace the upsampling module in the neck fusion network, minimizing information loss during the upsampling process. Experiments conducted on the custom Transmission Line Bolt Defect Dataset (TLBDD) demonstrate a reduction of 10.30MB in model parameter size, along with a 2.30% increase in mean Average Precision (mAP) compared with the original YOLOV7 and a detection speed of 51.15 frames per second (FPS). Experiments on the public dataset CCTSDB further confirm the model's robust generalization capability. These experiments validate the effectiveness of the proposed algorithm., Competing Interests: Declarations. Competing interests: The corresponding author is responsible for submitting a competing interests statement on behalf of all authors of the paper. This statement must be included in the submitted article file., (© 2025. The Author(s).)

Background and Aims: Increased intestinal permeability exacerbates the development of metabolic dysfunction associated steatohepatitis (MASH), but the underlying mechanisms remain unclear. Autophagy is important for maintaining normal intestinal permeability. Here, we investigated the impact of intestinal transcription factor EB (TFEB), a key regulator of autophagy, in intestinal permeability and MASH progression., Methods: TFEB expression was analyzed in the proximal colon of 45 individuals with metabolic dysfunction associated steatotic liver disease and 23 healthy controls. We utilized immunoprecipitation-mass spectrometry toidentify TFEB-interacting proteins. Intestine-specific Tfeb knockout mice were generated by mating Tfebfl/fl mice with Villin-Cre mice. The mice were fed a high-fat, high-sucrose diet, and assessments were performed to evaluate intestinal permeability and MASH progression., Results: Intestinal TFEB levels were reduced in MASH patients and negatively correlated with intestinal permeability and hepatic toxicity. Intestine-specific TFEB deficiency increased intestinal permeability and worsened MASH severity, whereas moderate TFEB overexpression conferred protective effects. Mechanistically, the E3 ligase TRIP12 promotes the ubiquitination and degradation of nuclear TFEB, thereby inhibiting autophagic flux to aggravate intestinal barrier impairment and subsequently promote MASH progression. Importantly, a peptide PT1 designed to block the TRIP12-TFEB interaction reduced MASH progression., Conclusions: The ubiquitination of TFEB plays a pivotal role in increasing intestinal permeability and promoting the progression of MASH by inhibiting autophagy. Intestinal TFEB may represent a novel therapeutic target for the treatment of MASH., (Copyright © 2025 The Author(s). Published by Wolters Kluwer Health, Inc.)

Rapid, on-site measurement of ppm-level humidity in real time remains a challenge. In this work, we fabricated a few micrometer thick, β-ketoenamine-linked covalent organic framework (COF) membrane via interfacially confined condensation of 1,3,5-tris-(4-aminophenyl)triazine (TTA) with 1,3,5-tri-formylphloroglucinol (TP). Based on the super-sensitive and reversible response of the COF membrane to water vapor, we developed a high-performance film-based fluorescence humidity sensor, depicting unprecedented detection limit of 0.005 ppm, fast response/recovery (2.2 s/2.0 s), and a detection range from 0.005 to 100 ppm. Remarkably, more than 7,000-time continuous tests showed no observable change in the performance of the sensor. The applicability of the sensor was verified by on-site and real-time monitoring of humidity in a glovebox. The superior performance of the sensor was ascribed to the highly porous structure and unique affinity of the COF membrane to water molecules as they enable fast mass transfer and efficient utilization of the water binding sites. Moreover, based on the remarkable moisture driven deformation of the COF membrane and its composition with the known polyimide films, some conceptual actuators were created. This study brings new ideas to the design of ultra-sensitive film-based fluorescent sensors (FFSs) and high-performance actuators., (© 2024 Wiley-VCH GmbH.)

Background: Near-infrared spectroscopy (NIRS) enables a non-invasive measurement of tissue oxygen saturation (StO 2 ) in regions illuminated by near-infrared lights. Vascular occlusion test (VOT) serves as a model to artificially induce forearm ischemia-reperfusion. The combination of StO 2 monitoring and VOT allows for dynamic evaluation of the balance between oxygen delivery and consumption in tissue, as well as the functional reserve of microcirculation. However, the implications of these measurements for patient outcomes remain inadequately understood. This study aimed to investigate the association between StO 2 -VOT measurements and the occurrence of postoperative acute kidney injury (AKI), in patients undergoing cardiac surgery with cardiopulmonary bypass (CPB)., Methods: Between March 2020 and March 2021, 100 adult patients who scheduled to undergo cardiac surgery with mild hypothermic CPB were enrolled to this prospective observational study. StO 2 was continuously monitored at the right forearm and ipsilateral VOT procedure was performed before initiation of CPB, at the time before weaning from CPB, and at the end of surgery. Preoperative and intraoperative factors, along with StO 2 -VOT parameters, were evaluated for their independent association with the occurrence of AKI following cardiac surgery. StO 2 -VOT parameters were also compared between patients with hyperlactatemia (peak blood lactate ≥ 4 mmol/L) and those without hyperlactatemia., Results: In our patient population (n = 87), 13.79% (12/87) patients developed AKI after surgery. Multivariable analysis revealed that CPB time and post-CPB desaturation speed (D-speed) were independently associated with AKI. Post-CPB D-speed had an area under receiver operating characteristic (ROC) curve of 0.79 (95% CI, 0.66-0.93) with a cutoff value of 0.08%·min - 1 in predicting AKI. Patients with hyperlactatemia had longer pre-CPB T 1 and higher D-speed during CPB. However, ROC analysis indicated that T 1 and D-speed exhibited limited predictive capacity for hyperlactatemia. Patients with AKI exhibited an increased risk of prolonged ICU stays, postoperative stroke, reoperation, and in-hospital mortality., Conclusions: NIRS monitoring combined with VOT shows promise in predicting postoperative AKI in patients undergoing cardiac surgery with mild hypothermic CPB., Trial Registration: ChiCTR1900021436 with registered date 21/02/2019., Competing Interests: Declarations. Ethics approval and consent to participate: This study was approved by Ethics Committee of West China Hospital, Sichuan University (protocol number 2018480, Chengdu, China). All procedures performed in studies involving human participants were in accordance with the Helsinki declaration. Consent for publication: Not applicable. Consent to participate: Informed consent was obtained from all individual participants included in the study. Competing interests: The authors declare no competing interests., (© 2024. The Author(s).)

Background: Hospitalization is a "reachable" moment to engage people in addiction care. Addiction consult services (ACSs) have been shown to improve outcomes for hospitalized patients with substance use disorders (SUDs). Despite this, most hospital systems do not provide hospital-based addiction care or have an ACS., Objective: Characterize implementation barriers, lessons learned, and opportunities for future support of ACS implementation., Design and Participants: Semi-structured qualitative interviews with 17 "champions" leading ACS implementation at 11 institutions across the U.S., Approach: Interviews explored evolution of ACSs, including staffing, service delivery, strategic planning, and barriers and facilitators to implementation. Reflexive thematic analysis was applied to identify emergent themes., Key Results: Five dominant themes characterize ACS implementation: (1) how champions obtain buy-in from hospital leadership. Participants described the impression that ACSs are not revenue-generators as a barrier to implementation and found ways to capture monetary and non-monetary outcomes to demonstrate value; (2) specific attributes are common to ACS champions including persistence, good communication, and leadership skills. ACS champions described needing to communicate strategically with multiple stakeholders across their institution and often pitched their case multiple times before obtaining funding; (3) reliance on external resources. This included informal coaching from other ACS leaders and formal tools such as telementoring networks and published literature to learn to engage leadership and present a business case; (4) ACSs are important drivers of cultural change within institutions in the face of significant stigma and; (5) planning for sustainability. This included demonstrating improved quality of care and patient and provider satisfaction to obtain ongoing support for ACS., Conclusions: Barriers to ACS implementation are common and significant and the process of obtaining leadership support for implementation is often long and iterative. Broad adoption of ACSs will require support from hospital systems and policymakers including incentives, funding, and infrastructure to support clinical champions., Competing Interests: Declarations:. Conflict of Interest:: The authors have nothing to disclose., (© 2024. The Author(s), under exclusive licence to Society of General Internal Medicine.)

Background: Biologics are recommended for use in patients with psoriatic arthritis (PsA) after the failure of conventional systemic disease-modifying anti-rheumatic drugs (csDMARDs). However, compared to csDMARDs, biologics are significantly more expensive. The aim of this study was to evaluate the cost-effectiveness of biologic treatments for active PsA patients who have failed treatment with csDMARDs, from the perspective of the Chinese healthcare system., Research Design and Methods: A discrete event simulation model was constructed to estimate health and economic outcomes of patients. The seven biologics recommended by the Chinese psoriasis treatment guidelines were included in the evaluation. One-way and probabilistic sensitivity analysis were performed to ensure that our results were robust., Results: Our results found that compared to the standard of care (SoC) and all other biologics strategies, secukinumab (SEC) had the highest quality-adjusted life years, and at a willingness-to-pay (WTP) threshold of US $38,161 per QALY, SEC was the most cost-effective option, with an incremental cost-effectiveness ratio of $14,968 per QALY. One-way sensitivity analysis and probabilistic sensitivity analysis confirmed the robust of this result., Conclusions: From the perspective of the Chinese healthcare system, biologics are estimated to be cost-effective compared to SoC. Among these, SEC is the most cost-effective option.

Rearranged during transfection (RET) kinase is a validated therapeutic target for various cancers characterized by RET alterations. Although two selective RET inhibitors, selpercatinib and pralsetinib, have been approved by the FDA, acquired resistance through solvent-front mutations has been identified rapidly. Developing proteolysis targeting chimera (PROTAC) targeting RET mutations offers a promising strategy to combat drug resistance. Herein, we describe the design, synthesis, and evaluation of a series of RET PROTAC degraders. The representative compound QZ2135 ( 20 ) effectively degraded RET kinase and its resistant mutants, such as V804M and G810C/R. It also exhibited superior antiproliferative activity against Ba/F3 cells stably expressing oncogenic fusions of RET with solvent-front mutants, including G810C/R/S, compared to its parental inhibitor. Notably, QZ2135 demonstrated in vivo antitumor efficacy in a Ba/F3-KIF5B-RET-G810C xenograft mouse model. Together, this study provides a potential alternative strategy for overcoming acquired resistance to RET inhibitors mediated by solvent-front mutations.

Inactivation of p53 by mutations commonly occurs in human cancer. The mutated p53 proteins may escape proteolytic degradation and exhibit high expression in tumors, and acquire gain-of-function activity that promotes tumor progression and chemo-resistance. Therefore, selectively targeting of the gain-of-function p53 mutants may serve as a promising therapeutic strategy for cancer prevention and treatment. In this study, we identified cabozantinib, a multi-kinase inhibitor currently used in clinical treatment of several types of cancer, as a selective inducer of proteasomal degradation of the p53-Y220C mutant. We demonstrate that cabozantinib disrupts the interaction between p53Y220C and USP7, a deubiquitylating enzyme, resulting in the dissociation of p53Y220C protein from its binding with USP7 and subsequent ubiquitination and degradation mediated by CHIP (The carboxyl terminal of Hsp70-interacting protein). We also show that cabozantinib displays preferential cytotoxicity to p53Y220C-harboring cancer cells both in vitro and in vivo. This study demonstrates a novel, p53-Y220C mutant-targeted anticancer action and mechanism for cabozantinib, and provides the rationale for use of this drug in treatment of cancers that carry the p53-Y220C mutation., Competing Interests: Conflict of interest The authors declare no conflict of interest., (Copyright © 2025 The Authors. Published by Elsevier Inc. All rights reserved.)

Cerasus is a subgenus of Prunus in the family Rosaceae that is popular owing to its ornamental, edible, and medicinal properties. Understanding the evolution of the Cerasus subgenus and identifying selective trait loci in edible cherries are crucial for the improvement of cherry cultivars to meet producer and consumer demands. In this study, we performed a de novo assembly of a chromosome-scale genome for the sweet cherry (Prunus avium L.) cultivar 'Burlat', covering 297.55 Mb and consisting of eight chromosomes with 33,756 protein-coding genes. The resequencing and population structural analysis of 384 Cerasus representative accessions revealed that they could be divided into four groups (Group 1, Group 2, Group 3, and Group 4). We inferred that Group 1 was the oldest population and Groups 2, 3, and 4 were clades derived from it. In addition, we found selective sweeps for fruit flavor and improved stress resistance in different varieties of edible cherries (P. avium, P. cerasus, and P. pseudocerasus). Transcriptome analysis revealed significant differential expression of genes associated with key pathways, such as sucrose starch and sucrose metabolism, fructose and mannose metabolism, and the pentose phosphate pathway, between the leaves and fruits of P. avium. This study enhances the understanding of the evolutionary processes of the Cerasus subgenus and provides resources for functional genomics research and the improvement of edible cherries., Competing Interests: Declarations. Ethics approval and consent to participate: Not applicable. Consent for publication: All authors approve the manuscript and consent to the publication of the work. Competing interests: The authors declare no competing interests. Caixi Zhang is a member of the Editorial Board for Molecular Horticulture. He was not involved in the journal’s review of, and decisions related to, this manuscript., (© 2025. The Author(s).)

Salicylic acid (SA) exhibits positive effects against Citrus Huanglongbing (HLB), but how SA affects citrus resistance to HLB is currently unknown. This study conducted integrated transcriptome and metabolome analyses on SA-treated Citrus sinensis (HLB-sensitive) and Poncirus trifoliata (HLB-tolerant). The results indicated that the syntheses of flavones and flavonols were induced by SA, while the expression levels of associated genes and the contents of corresponding metabolites varied significantly between the two species after SA treatment or HLB infection. These differences may underpin the enhanced HLB management through SA treatment and the inherent HLB tolerance of P. trifoliata . Furthermore, two insertions of miniature inverted-repeat transposable element (MITE) were identified within the promoter of PtrF3'H in P. trifoliata , whereas none were found in the promoter of CsF3'H in C. sinensis . These MITE insertions notably enhanced the promoter activity of PtrF3'H in an SA-dependent manner. Our findings deepen the understanding of the correlation between SA response and HLB tolerance in Citrus .

Molecular glues are promising protein-degrading agents that hold great therapeutic potential but face significant challenges in rational design, effective synthesis, and precise targeting of tumor sites. In this study, we first overcame some of these limitations by introducing a fumarate-based molecular glue handle onto specific ligands of therapeutic kinases (TBK1, FGFR, and Bcr-Abl), resulting in the effective degradation of these important cancer targets. Despite the broad applicability of the strategy, we unexpectedly discovered potent and widespread cytotoxicity across various cell lines, including noncancerous ones, rendering it less effective in cancer therapy. To address this critical issue, we next developed a self-assembled nanoparticle-based molecular glue (nano-mGlu) based on one of the newly discovered Bcr-Abl-degrading molecular glues ( H1-mGlu ). We showed that the resulting nano-mGlu (named Cle-NP ) was able to release H1-mGlu in vitro in the presence of a high concentration of GSH or H 2 O 2 (commonly found in the tumor microenvironment). Subsequent in vivo antitumor studies with a K562-xenografted mouse model indicated that Cle-NP was highly effective in tumor-specific degradation of endogenous Bcr-Abl expressed in K562 cells, leading to eventual tumor regression while maintaining good biosafety profiles. With key advantages of generality in molecular glue design, targeted delivery (e.g., H1-mGlu ), potent antitumor activity partially induced by target-specific degradation, and minimized collateral damage to healthy tissues, our self-assembled nano-mGlu strategy thus provides a novel approach that might hold a significant promise for effective and personalized cancer therapy.

Nucleotide availability is crucial for DNA replication and repair; however, the coordinating mechanisms in vivo remain unclear. Here, we show that the circadian clock in the liver controls the activity of the pentose phosphate pathway (PPP) to support de novo nucleotide biosynthesis for DNA synthesis demands. We demonstrate that disrupting the hepatic clock by genetic manipulation or mistimed feeding impairs PPP activity in male mice, leading to nucleotide imbalance. Such defects not only elicit DNA replication stress to limit liver regeneration after resection but also allow genotoxin-induced hepatocyte senescence and STING signalling-dependent inflammation. Mechanistically, the molecular clock activator BMAL1 synergizes with hypoxia-inducible factor-1α (HIF-1α) to regulate the transcription of the PPP rate-limiting enzyme glucose-6-phosphate dehydrogenase (G6PD), which is enhanced during liver regeneration. Overexpressing G6PD restores the compromised regenerative capacity of the BMAL1- or HIF-1α-deficient liver. Moreover, boosting G6PD expression genetically or through preoperative intermittent fasting potently facilitates liver repair in normal mice. Hence, our findings highlight the physiological importance of the hepatic clock and suggest a promising pro-regenerative strategy., Competing Interests: Competing interests: The authors declare no competing interests., (© 2025. The Author(s), under exclusive licence to Springer Nature Limited.)

The emergence of novel variants of severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) continues to pose an ongoing challenge for global public health services, highlighting the urgent need for effective therapeutic interventions. Neutralizing monoclonal antibodies (mAbs) are a major therapeutic strategy for the treatment of COVID-19 and other viral diseases. In this study, we employed hybridoma technology to generate mAbs that target the BA.5 receptor-binding domain (RBD) of the SARS-CoV-2 spike protein. Through a comprehensive screening process, we identified four mAbs capable of effectively neutralizing BA.5, XBB.1.16, and related variant infections in vitro , among which ORB10 was found to neutralize BA.5 variants with a plaque reduction neutralization test (PRNT 50 ) of 8.7 ng/mL. Additionally, competitive binding assays, sequencing of heavy and light chain variable regions, and binding kinetics characterization provided insights into the epitopes and binding affinities of the identified mAbs. Moreover, in vivo experiments in the K18-hACE2 mouse model demonstrated the protective efficacy of ORB10 against both BA.5 and XBB.1.16 variants. Finally, cryo-electron microscopy structural analysis of the ORB10-RBD complex identified key residues involved in the antibody-antigen interactions, providing insights into the molecular mechanisms of neutralization and immune escape of SARS-CoV-2 Omicron variants from mAbs., Importance: The ongoing evolution of SARS-CoV-2 has led to the emergence of variants capable of evading immune responses elicited by natural infection and vaccination, especially the highly transmissible and immune-evasive Omicron variants. This study generated and characterized a panel of monoclonal antibodies (mAbs) specifically targeting the RBD of the Omicron BA.5 variant, of which the ORB10 showed efficacy against Omicron BA.5 and XBB.1.16 variants both in vitro and in vivo . Cryo-EM structural analysis further elucidated the binding epitope interactions and neutralization mechanism between ORB10 and the BA.5 RBD protein. This study enhances our understanding of antibody-mediated neutralization of SARS-CoV-2 and provides valuable insights into the development of effective therapeutic strategies to combat ongoing SARS-CoV-2 variant infections.

Tumor-initiating cells (TICs) play a key role in cancer progression and immune escape. However, how TICs evade immune elimination remains poorly characterized. Combining single-cell RNA sequencing (scRNA-seq), dual-recombinase-based lineage tracing, and other approaches, we identified a WNT-activated subpopulation of malignant cells that act as TICs in vivo. We found intensive reciprocal interactions between TICs and immune regulatory tumor-associated macrophages (Reg-TAMs) via GAS6-AXL/MERTK signaling pathways, which facilitated the immune escape of TICs. Our study employed chemical inhibitors and Axl/Mertk conditional double knockout mice to demonstrate that inhibiting the interaction between TIC-derived GAS6 and AXL/MERTK in Reg-TAMs reactivated anti-tumor immune responses. We identified CCL8 as a critical mediator of the GAS6/AXL/MERTK pathway, primarily by inhibiting regulatory T cell (Treg) infiltration into the tumor. Furthermore, the AXL/MERTK signaling blockade sensitized tumor cells to anti-PD-1 treatment. Thus, we elucidated a detailed mechanism by which TICs evade tumor immunity, providing insights into strategies to eradicate TICs that escape conventional immunotherapy.

Background: A lung cancer diagnosis has a huge impact on the psychological well-being of both patients and family caregivers. However, the current psychological stress status among dyads remains unclear. We aimed to determine the prevalence of anxiety and depression and identify the factors that influence patients with lung cancer and their caregivers., Methods: We conducted a cross-sectional study of 254 dyads of lung cancer patients and family caregivers from four tertiary hospitals in Hunan Province, China from January 2021 to June 2021. Besides, we used several instruments to collect data on depression, anxiety, illness perception, mindfulness, self-compassion, and dyadic coping. The independent samples t-test, analysis of one-way variance, Spearman's correlation analysis, and multiple linear regression analysis were employed., Results: Results showed that 21.3% of patients and 29.5% of caregivers experienced depression, while 22.0% of patients and 33.5% of caregivers reported anxiety. For lung cancer patients, patients' illness perception positively predicted their depression scores and patients' level of mindfulness and level of self-compassion negatively predicted their depression scores; patients' illness perception positively predicted their anxiety scores, and only living with children, patients' mindfulness and self-compassion levels were negatively predicted their anxiety scores. For caregivers, caregivers' level of illness perception and the number of other caregivers positively predicted their depression and anxiety scores, and caregiver's dyadic coping level, residence (county or town, and city), and caregiver's self-compassion level, were negatively predicted their depression and anxiety scores., Conclusion: The prevalence of psychological stress response of lung cancer patients and caregivers was high and influenced by family living situation, number of persons assisting in care, place of residence, patient-caregiver relationship, levels of illness perception, mindfulness, self-compassion, and dyadic coping., Trial Registration: ClinicalTrial.gov NCT06746948., Competing Interests: Declarations. Ethics approval and consent to participate: Ethical review of this study was obtained from the Behavioral Medicine and Nursing Ethics Review Committee of Central South University in January 2021 (Approval number: E202109). The Helsinki Declaration and institutional procedures guided the study. The participants signed an informed consent form and confirmed before signing that they were fully aware of the purpose of the study, the study protocol, the risks and adverse effects, the benefits and advantages, and the confidentiality of the study data. Consent for publication: Not applicable. Competing interests: The authors declare no competing interests., (© 2025. The Author(s).)

Background: Dilated cardiomyopathy (DCM) is one of the most common causes of heart failure. Infiltration and alterations in non-cardiomyocytes of the human heart involve crucially in the occurrence of DCM and associated immunotherapeutic approaches., Methods: We constructed a single-cell transcriptional atlas of DCM and normal patients. Then, the xCell algorithm, EPIC algorithm, MCP counter algorithm, and CIBERSORT method were applied to identify DCM-related cell types with a high degree of precision and specificity using RNA-seq datasets. We further analyzed the heterogeneity among cell types, performed trajectory analysis, examined transcription factor regulatory networks, investigated metabolic heterogeneity, and conducted intercellular communication analysis. Finally, we used bulk RNA-seq data to confirm the roles of M2-like2 subpopulations and GAS6 in DCM., Results: We integrated and analyzed Single-cell sequencing (scRNA-seq) data from 7 DCM samples and 3 normal heart tissue samples, totaling 70,958 single-cell data points. Based on gene-specific expression and prior marker genes, we identified 9 distinct subtypes, including fibroblasts, endothelial cells, myeloid cells, pericytes, T/NK cells, smooth muscle cells, neuronal cells, B cells, and cardiomyocytes. Using machine learning methods to quantify bulk RNA-seq data, we found significant differences in fibroblasts, T cells, and macrophages between DCM and normal samples. Further analysis revealed high heterogeneity in tissue preference, gene expression, functional enrichment, immunodynamics, transcriptional regulatory factors, metabolic changes, and communication patterns in fibroblasts and myeloid cells. Among fibroblast subpopulations, proliferative F3 cells were implicated in the fibroblast transition process in DCM, while myofibroblast F6 cells promoted the fibroblast transition to a late cell state in DCM. Additionally, two subpopulations of M2 macrophages, M2-like1 and M2-like2, were identified with distinct features. The M2-like2 cell subpopulation, which was enriched in glycolysis and fatty acid metabolism, involved in inflammation inhibition and fibrosis promotion. Cell‒cell communication analysis indicated the GAS6-MERTK axis might exhibit interaction between M2 macrophage and M2-like1 macrophage. Furthermore, deconvolution analysis for bulk RNA-seq data revealed a significant increase in M2-like2 subpopulations in DCM, suggesting a more important role for this cell population in DCM., Conclusions: We revealed the heterogeneity of non-cardiomyocytes in DCM and identified subpopulations of myofibroblast and macrophages engaged in DCM, which suggested a potential significance of non-cardiomyocytes in treatment of DCM., Competing Interests: Declarations. Ethics approval and consent to participate: Not applicable. Consent for publication: Not applicable. Competing interests: The authors declare that they have no competing interests in this section., (© 2024. The Author(s).)

SIRT6, a member of the sirtuin protein family, is recognized as a tumor suppressor. This study investigates the evolutionary history of the SIRT gene family and examines the selective pressures shaping their functional divergence. Insights into the evolution of these genes may enhance our understanding of their roles in disease pathology. Seventy-three amino acid sequences and full-length mRNA sequences from 22 vertebrate species and one invertebrate were retrieved from public databases. Phylogenetic relationships among the seven SIRT gene family members were reconstructed using Bayesian inference. Codon-based models were applied to detect site-specific positive selection, and likelihood ratio tests (LRTs) were used to compare model fits. Positively selected sites were identified using Bayesian empirical Bayes (BEB) methods. Phylogenetic analysis revealed that the seven SIRT gene family members in vertebrates originated from gene duplication events. Asymmetric evolutionary rates and natural selection were identified as the primary drivers of SIRT gene divergence. Eleven positively selected sites (23I, 310 S, 311I, 313 A, 316 K, 320 C, 321 A, 322Q, 323 H, 327E, 328P) were identified with high confidence (posterior probability ≥ 99%), suggesting critical roles in functional divergence. The evolution of the SIRT gene family is characterized by gene duplication and natural selection. The reconstructed phylogenetic tree elucidates the relationships among the seven members, with SIRT6 emerging as a key evolutionary node. Positively selected sites identified in this study may represent mutation hotspots, providing potential targets for future cancer therapy research., Competing Interests: Declarations. Competing interests: The authors declare no competing interests., (© 2025. The Author(s).)

In this study, we analyzed bioaerosol emission characteristics and potential risks of antimicrobial resistance (AMR) during composting using the impaction culture method and metagenomic sequencing. The results showed that the highly saturated water vapor in the emission gas mitigated particulate matter emission during the thermophilic period. About the bioaerosols, the airborne aerobic bacterial emissions were suppressed as composting enters the mature period, and the airborne fungi are usually present as single-cell or small-cell aggregates (< 3.3 µm). In addition, the microbial community structure in bioaerosols was stable and independent of composting time. Most importantly, the PM 2.5 in bioaerosols contained large amounts of antibiotic resistance genes (ARGs), potential pathogens, and multidrug resistant pathogens, which were diverse and present in high concentrations. Among them, ARGs concentrations encoding 21 antibiotics ranged from - 4.50 to 0.70 ppm/m 3 (Log 10 ARGs). Among the 89 potential human pathogens detected, Escherichia coli, Salmonella enterica, Klebsiella pneumoniae, and Staphylococcus aureus were the only culturable potentially multidrug resistant pathogens carrying multiple ARGs encoding resistance at high concentrations (- 0.57 to 1.15 ppm/m 3 (Log 10 ARGs)), and were more likely to persist and multiply in oligotrophic environments. Our findings indicate that composting technology can transfer AMR from solid compost to gas phase and increase the risk of AMR transmission., 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.)

This survey explores the transformative impact of foundation models (FMs) in artificial intelligence, focusing on their integration with federated learning (FL) in biomedical research. Foundation models such as ChatGPT, LLaMa, and CLIP, which are trained on vast datasets through methods including unsupervised pretraining, self-supervised learning, instructed fine-tuning, and reinforcement learning from human feedback, represent significant advancements in machine learning. These models, with their ability to generate coherent text and realistic images, are crucial for biomedical applications that require processing diverse data forms such as clinical reports, diagnostic images, and multimodal patient interactions. The incorporation of FL with these sophisticated models presents a promising strategy to harness their analytical power while safeguarding the privacy of sensitive medical data. This approach not only enhances the capabilities of FMs in medical diagnostics and personalized treatment but also addresses critical concerns about data privacy and security in healthcare. This survey reviews the current applications of FMs in federated settings, underscores the challenges, and identifies future research directions including scaling FMs, managing data diversity, and enhancing communication efficiency within FL frameworks. The objective is to encourage further research into the combined potential of FMs and FL, laying the groundwork for healthcare innovations., Competing Interests: Declarations. Ethics approval and consent to participate: Not applicable. Consent for publication: Not applicable. Competing interests: The authors declare no competing interests., (© 2025. The Author(s).)

Ovarian cancer is the leading cause of death among all gynecological malignancies, and drug resistance renders the current chemotherapy agents ineffective for patients with advanced metastatic tumors. We report an effective treatment strategy for targeting metastatic ovarian cancer involving a nanoformulation (Bola/IM)─bola-amphiphilic dendrimer (Bola)-encapsulated imatinib (IM)─to target the critical mediator of ovarian cancer stem cells (CSCs) CD117 (c-Kit). Bola/IM offered significantly more effective targeting of CSCs compared to IM alone, through a novel and tumor-specific β-catenin/HRP2 axis, allowing potent inhibition of cancer cell survival, stemness, and metastasis in metastatic and drug-resistant ovarian cancer cells. Promising results were also obtained in clinically relevant patient-derived ascites and organoids alongside high tumor-oriented accumulation and favorable pharmacokinetic properties in mouse models. Furthermore, Bola/IM displayed synergistic anticancer activity when combined with the first-line chemotherapeutic drug cisplatin in patient-derived xenograft mouse models without any adverse effects. Our findings support the use of Bola/IM as a nanoformulation to empower IM, providing targeted and potent treatment of metastatic ovarian cancer. Our study thus represents a significant advancement toward addressing the unmet medical need for improved therapies targeting this challenging disease.

Li-TFSI/t-BP is the most widely utilized p-dopant for hole-transporting materials (HTMs) in state-of-the-art perovskite solar cells (PSCs). However, its nonuniformity of doping, along with the hygroscopicity and migration of dopants, results in the devices that exhibit limited stability and performance. This study reports the use of a spherical anion of the p-dopant, regulated by its radius and shape, as an alternative to the linear TFSI- anion. The theoretical and experimental results reveal that the spherical anion significantly increases the doping of HTMs due to an enhanced electron transfer from larger dipoles. The enhanced transfer leads to a shift in the Pb-6p defect orbitals, resulting in the shallower trap states.  The linear structure of the TFSI- anion, the p-dopant anion with a larger van der Waals radius and spherical shape offers increased hydrophobicity and migration barriers protecting the perovskite. The use of sodium tetrakis(3,5-bis(trifluoro methyl)phenyl)borate results in enhanced thermal and ambient stability of PSCs. The devices fabricated with the shape- and radius-regulated p-dopant achieve remarkable efficiencies of 24.49% and 24.31% for CJ-01 and spiro-OMeTAD, respectively, representing the highest efficiency values for organic dopants to date. This study underscores the ingenious design of spherical anions as p-dopants., (© 2025 Wiley‐VCH GmbH.)

Dysregulated B-cell activation plays pivotal roles in IgG4-related disease (IgG4-RD), which makes B-cell depletion a potential strategy for IgG4-RD treatment. In this study, we aimed to investigate the feasibility of applying anti-CD19 chimeric antigen receptor T(CAR-T) cell therapy to IgG4-RD treatment in a mouse disease model based on LatY136F knock-in (Lat) mice. We constructed murine anti-CD19 CARs with either CD28 or 4-1BB as the intracellular costimulatory motif and evaluated the therapeutic function of the corresponding CAR-T cells by infusing them into Lat mice. Next, we assessed the safety of CAR-T infusion by evaluating the risk of cytokine release syndrome (CRS) and the antiviral capabilities in a mouse influenza infection model. Finally, we performed human anti-CD19 CAR-T manufacturing from IgG4-RD patients and evaluated its activation level and functional effects in vitro. Compared with 1D3 antibody treatment, the adoptive transfer of anti-CD19 CAR-T cells with CD28 costimulatory motif showed comparable B-cell-depletion effect in Lat mice. Furthermore, the transfer of syngeneic anti-CD19 CAR-T cells also decreased the percentage of plasma cells as well as IL-4 secreting Th cells, therefore attenuating the inflammation and fibrosis condition. CAR-T cells with CD28 costimulatory motif showed better therapeutic efficiency without the incidence of serious CRS events or increasing the risk of infection. In addition, we validated the feasibility of human CAR-T preparation in vitro from IgG4-RD patients. Taken together, these results show that anti-CD19 CAR-T therapy was effective in the treatment of a murine model of IgG4-RD, indicating its potential for clinical use in patients., 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.)

Aim: This study aimed to analyze the clinical efficacy and safety of autologous fascial pubovaginal sling (AFPVS) surgery in treating recurrent stress urinary incontinence (SUI) following the failure of mid-urethral sling procedures., Methods: A retrospective analysis was conducted on the clinical data of SUI patients who underwent AFPVS at our hospital between 2008 June and 2024 June following the failure of mid-urethral sling procedures. The analysis included basic information, surgical parameters, and postoperative complications. Additionally, telephone interviews using the International Consultation on Incontinence Questionnaire-Short Form (ICI-Q-SF) and the Incontinence Quality of Life Questionnaire (I-QOL) was conducted at 6-month follow-up., Results: Thirty-four patients with the mean age of 54.8 ± 15.7 years old were reviewed, and the median disease duration was 3 (2-10) years. Of the 34 patients, 20 (58.8%) were cured, 8 (23.5%) showed improvement, resulting in an overall effectiveness rate of 82.3%. Three cases experienced bladder injury, which resolved after 2 weeks of catheterization, but no patients had urethral or vaginal injuries intraoperatively. Postoperative scores on the ICI-Q-SF significantly decreased (p < 0.001), and postoperative I-QOL scores significantly increased (p < 0.001) compared to preoperative scores., Conclusion: AFPVS is a safe and effective salvage procedure for recurrent SUI following the failure of mid-urethral sling procedures., (© 2025 John Wiley & Sons Australia, Ltd.)

Current dorsal skin flap window chambers with flat glass windows are compatible with optical coherence tomography (OCT) and multiphoton microscopy (MPM) imaging. However, light sheet fluorescence microscopy (LSFM) performs best with a cylindrical or spherical sample located between its two 90° objectives and when all sample materials have the same index of refraction ( n ). A modified window chamber with a domed viewing window made from fluorinated ethylene propylene (FEP), with n similar to water and tissue, was designed. In vitro imaging of collagen gels and microsphere phantoms with and without the dome showed small decreases in signal strength and image resolution due to the dome. Using a custom mouse platform for stabilization and anesthesia support, in vivo multimodality imaging with OCT, MPM, and LSFI was demonstrated.

Primary cilia, functioning as crucial hubs for signal sensing and transduction, are integral to the development and maintenance of homeostasis across various organs. However, their roles in tooth homeostasis and repair remain inadequately understood. In this study, we reveal an indispensable role for primary cilia in regulating the homeostasis and regeneration of teeth, primarily through the regulation of cell proliferation. Using cilium-deficient mice, we demonstrate that disruption of ciliary homeostasis leads to abnormal tooth morphology, stunted growth and notably impaired tooth repair. RNA sequencing reveals a dysregulation in genes associated with various biological processes such as cell proliferation, differentiation, and cycle regulation. Furthermore, we show that cilium-deficient mice display reduced cell proliferation. Our findings highlight a critical function for primary cilia in the regulation of tooth homeostasis and regeneration and have important implications for the development of tooth regeneration therapies., (© 2024 Wiley Periodicals LLC.)

Foot ulcers are amongst the most prevalent complications of diabetes, known for their delayed healing process. Recent research indicates that the transcription factor forkhead box M1 (FOXM1) plays a role in promoting diabetic ulcer repair. However, the precise mechanisms underlying FOXM1 functions in this context remain unclear. This study aimed to clarify the role of tripartite motif-containing protein 72 (TRIM72)-mediated endoplasmic reticulum stress in FOXM1 promotive effects. Immunohistochemistry revealed that FOXM1 expression was significantly reduced in the lesion tissues of diabetic foot ulcer patients. In vitro experiments revealed a decrease in FOXM1 expression in cultured dermal fibroblasts under high glucose conditions. Activating FOXM1 with a plasmid accelerated the proliferation, migration, and differentiation of dermal fibroblasts and mitigated endoplasmic reticulum stress under high glucose conditions. Additionally, ChIP and luciferase reporter gene assays confirmed that FOXM1 suppressed TRIM72 expression transcriptionally by binding to its promoter. Furthermore, high glucose induced ubiquitination of adenosine 5'-monophosphate-activated protein kinase alpha (AMPKα), whilst inactivation of AMPKα signalling reversed the aforementioned effects of FOXM1 on cells. Finally, the FOXM1-overexpressing plasmid was transfected in vivo, which promoted wound healing in a murine diabetic ulcer model. In conclusion, FOXM1 reduces endoplasmic reticulum stress by inhibiting TRIM72-mediated AMPKα ubiquitination, thereby accelerating the healing of diabetic ulcers., (© 2024 The Author(s). Wound Repair and Regeneration published by Wiley Periodicals LLC on behalf of The Wound Healing Society.)

We report photon-phonon dressing quantization dependency on polarization. Destructive dressing polarization quantization is exhibited in fluorescence (FL) for narrowband signals, while constructive dominant dressing quantization is exhibited in fluorescence (FL) for broadband signals due to phase perturbation. Furthermore, constructive polarization quantization results due to coexistence of generation and dressing effects in strong and competitive Rabi frequency. Low power also contributes to more dressing polarization quantization, the same as in the FL region (large de-phase rate). Furthermore, linear and circular dressing quantization with polarization quantization shows inverse and direct relationships in the FL and spontaneous four-wave-mixing (SFWM) regions, respectively. Such investigations have potential in alignment of crystal field (CF) redistribution by polarization quantization at the input.

The positive hemodynamic response (PHR) during stimulation often co-occurs with a strong, sustained negative hemodynamic response (NHR). However, the characteristics and neurophysiological mechanisms of the NHR, especially in regions distal to the PHR, remain incompletely understood. Using intrinsic optical imaging (OI) and two-photon imaging, we observed that forelimb electrical stimulation evoked strong PHR signals in the forelimb region of the primary somatosensory cortex (S1FL). Meanwhile, NHR signals primarily appeared in the primary visual cortex (V1), with a delayed onset and lower amplitude relative to the PHR signals. Additionally, stimulation led to a reduction in cerebral blood flow (CBF) in the NHR region. Notably, there was an overall suppression of the calcium response in the NHR region, although a small proportion (14 %) of neurons exhibited concurrent activation. Axon tracing revealed cortico-cortical projections from S1FL to V1. These findings suggest that neuronal deactivation significantly contributes to the origin of the NHR, offering additional insights into the specific inhibitory mechanisms underlying the NHR., 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 The Authors. Published by Elsevier Inc. All rights reserved.)

Myocardial fibrosis (MF) is a key factor endangering public health worldwide. Glycyrrhiza uralensis polysaccharide (GPS) exhibits various biological activities. However, its activity against MF has not been reported. Herein, a neutral polysaccharide (GPS-1-1) was isolated from GPS through column chromatography, its structure was characterized and potential mechanism regarding anti-MF activity was evaluated. Notably, the molecular weight of GPS-1-1 was 14.073 kDa, and the monosaccharides consist of glucose, arabinose and galactose, with a → 4)-α-d-glucopyranose (Glcp)-(1 → and →4, 6)-α-D-Glcp-(1 → backbone. Western blotting and immunofluorescence showed that GPS-1-1 inhibited the expression of fibrosis-related proteins, such as Collagen, Vimentin, Fibronectin and α-SMA in TGF-β1-induced fibrosis of cardiac fibroblasts (CFs), and inhibited the expression of TGF-β1-induced CFs migration ability and matrix metalloproteinases (MMP-2 and MMP-9), thus inhibiting the deposition of extracellular matrix in CFs. Additionally, in vivo analysis showed that GPS-1-1 reduced inflammatory cell infiltration and collagen deposition in cardiac tissues of mice with MF, and it inhibited the expression of serum lactate dehydrogenase, creatine kinase, and fibrosis-related factors. Combined transcriptomics, molecular docking and Western blotting analysis showed that platelet-derived growth factor subunit B (PDGFB) was involved in the anti-fibrosis process of GPS-1-1. Furthermore, qRT-PCR and Western blotting showed that GPS-1-1 inhibited the expression of MAPK/PI3K/AKT pathway related proteins, such as ERK, p-ERK, JNK, PI3K and p-PI3K in TGF-β1-induced CFs through PDGFB. Altogether, this study showed that GPS-1-1 inhibits the activation of the MAPK/PI3K/AKT pathway by down-regulating PDGFB expression to exert its anti-MF activity and its potential to be developed as a functional food and drug., Competing Interests: Declaration of competing interest The authors declare no competing interests., (Copyright © 2024 Elsevier B.V. All rights reserved.)

Automated volumetric segmentation of the pancreas on cross-sectional imaging is needed for diagnosis and follow-up of pancreatic diseases. While CT-based pancreatic segmentation is more established, MRI-based segmentation methods are understudied, largely due to a lack of publicly available datasets, benchmarking research efforts, and domain-specific deep learning methods. In this retrospective study, we collected a large dataset (767 scans from 499 participants) of T1-weighted (T1 W) and T2-weighted (T2 W) abdominal MRI series from five centers between March 2004 and November 2022. We also collected CT scans of 1,350 patients from publicly available sources for benchmarking purposes. We introduced a new pancreas segmentation method, called PanSegNet, combining the strengths of nnUNet and a Transformer network with a new linear attention module enabling volumetric computation. We tested PanSegNet's accuracy in cross-modality (a total of 2,117 scans) and cross-center settings with Dice and Hausdorff distance (HD95) evaluation metrics. We used Cohen's kappa statistics for intra and inter-rater agreement evaluation and paired t-tests for volume and Dice comparisons, respectively. For segmentation accuracy, we achieved Dice coefficients of 88.3% (±7.2%, at case level) with CT, 85.0% (±7.9%) with T1 W MRI, and 86.3% (±6.4%) with T2 W MRI. There was a high correlation for pancreas volume prediction with R 2 of 0.91, 0.84, and 0.85 for CT, T1 W, and T2 W, respectively. We found moderate inter-observer (0.624 and 0.638 for T1 W and T2 W MRI, respectively) and high intra-observer agreement scores. All MRI data is made available at https://osf.io/kysnj/. Our source code is available at https://github.com/NUBagciLab/PaNSegNet., Competing Interests: Declaration of competing interest The authors declare the following financial interests/personal relationships which may be considered as potential competing interests: Ulas Bagci reports financial support was provided by National Institutes of Health. 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 The Authors. Published by Elsevier B.V. All rights reserved.)

Purpose: To discuss the characteristics of anterior corneal elevation asymmetry in myopic eyes and clarify which kind of asymmetry most influenced lens position., Methods: In this retrospective study of 199 consecutive myopic participants, corneal topography was used to analyse asymmetry in anterior corneal elevation. Amongst them, 65 participants (65 eyes) who underwent orthokeratology (31 and 34 with spherical and toric lenses, respectively) were re-evaluated. Stepwise multiple linear regression analysis was used to identify the contributing factors that influenced lens decentration. Receiver operating characteristic curve (ROC) analysis was employed to assess how the corneal asymmetry vector could predict decentration., Results: There were no significant differences in treatment zone decentration (TZDec) between participants wearing toric and spherical lenses (p = 0.60 and 0.64 for 1 week and 1 month of wear, respectively). Amongst the underlying factors, the magnitude of TZDec was only correlated with the amount of corneal asymmetry vector (standardised β = 0.44, 0.48, p < 0.001 for all) after 1 week and 1 month of wear, and the direction of TZDec after 1 month of lens wear was associated with the angle of the asymmetry vector (r = 0.25, p = 0.04). ROC analysis showed that the magnitude of corneal asymmetry vector produced accurate discrimination between non-severe and severe decentration for 1 week and 1 month of wear (area under the curve was 0.93 ± 0.04 and 0.89 ± 0.05, respectively, p < 0.001). Amongst participants whose corneal asymmetry vector exceeded 41.06 μm and was oriented inferiorly, 35.29% showed severe decentration after 1 month of lens wear., Conclusions: In myopic participants, corneal asymmetry existed in the 8.0 mm chord diameter. If the asymmetry vector >41.06 μm and the direction was oriented inferiorly, then practitioners must be vigilant about severe decentration which would not be alleviated by a toric design., (© 2024 College of Optometrists.)

Background and Purpose: Different types of physical training can lead to changes in brain activity and function, and these changes can vary depending on the type of training. However, it remains unclear whether there are commonalities in how different types of training affect brain activity and function. The purpose of this study is to compare the brain activity states of professional athletes with those of ordinary university students and to explore the relationship between training and differences in brain activity states., Methods: This study primarily utilizes resting-state MRI and the degree centrality metric to investigate spontaneous brain activity in 86 high-level athletes with extensive training and 74 age- and gender-matched nonathletes. Additionally, a correlation analysis between brain activity in relevant regions and years of training was conducted., Results: The analysis revealed that, compared to nonathletes, high-level athletes exhibited reduced activity in the Calcarine (a visual area) and Middle Temporal Gyrus. Furthermore, changes in the activity of the Calcarine and Middle Temporal Gyrus were significantly correlated with the number of years of professional training., Conclusions: The study results indicate that long-term physical training is associated with changes in brain activity in athletes, providing insights into the neural mechanisms underlying behavioral performance in professional athletes., (© 2024 American Society of Neuroimaging.)

Tertiary lymphoid structure (TLS) is associated with various pathologies, including those of cancers and chronic infections. Depending on the organ, multiple factors regulate the formation of TLS. However, the role of TLS in immune response and the molecules that drive its formation remain uncertain. The dental pulp, includes a few immune cells surrounded by rigid mineralized tissue, and opens to the outside through the apical foramen. Owing to this special organization, the dental pulp generates a directional immune response to bacterial infection. Considering this aspect, the dental pulp is an ideal model for comprehensively studying the TLS. In the present study, single-cell RNA sequencing of healthy and inflamed human dental pulp reveals known markers of TLS, including C-C motif chemokine ligand 19 (CCL19), lysosome-associated membrane glycoprotein 3 (LAMP3), CC chemokine receptor 7 (CCR7), and CD86, present in inflamed dental pulp. Compared with the healthy pulp, types and proportions of immune cells increase, along with enhanced cellular communication. Multiple immunofluorescence staining reveals that typical TLS emerges in dental pulp with pulpitis, consistent with the high expression of CC chemokine ligand 3 (CCL3), which may be a key driver of TLS formation. Moreover, TLS is also observed in a mouse model of pulpitis. These findings collectively offer insights into the formation and function of TLS in response to infection., (© 2024 The Author(s). Advanced Science published by Wiley‐VCH GmbH.)

Objectives: Recurrent pregnancy loss (RPL) seriously affects women's reproductive and mental health, and the incidence has increased in recent years. Insulin resistance (IR) acts as a significant contributing factor to RPL. Studies suggest that vitamin B12, folate intake, and homocysteine are correlated with IR, but the exact nature remains controversial and requires further investigation. In this study, we aimed to assess the levels and correlations between vitamin B12-folate-homocysteine and insulin resistance in RPL patients., Study Design: 73 control subjects and 256 RPL patients (144 RPL patients without IR and 112 RPL patients with IR) were included in this observational retrospective cross-sectional study. The differences in vitamin B12, folate, and homocysteine levels between RPL patients with and without IR were analyzed using a Student's t-test. Pearson correlations were utilized to examine the correlation between vitamin B12-folate-homocysteine and glucose and lipid metabolism parameters. Multivariable linear regressions were used to assess the independent correlation of each factor with HOMA-IR., Results: Compared to the control subjects, RPL patients exhibited lower vitamin B12 (p < 0.001) and folate (p < 0.001), and higher homocysteine (p = 0.001). RPL patients with IR described decreases in vitamin B12 (p = 0.003) and folate (p = 0.028), and increases in homocysteine (p = 0.033) as RPL patients without IR. Vitamin B12 in RPL patients was significantly negatively correlated with homocysteine (r = -0.348, p < 0.001), HOMA-IR (r = -0.214, p < 0.001), BMI (r = -0.160, p = 0.017), TG (r = -0.148, p = 0.039) and CHO (r = -0.149, p = 0.038) and positively correlated with folate (r = 0.217, p < 0.001). In multivariable linear regressions, after adjusting for age, strong correlations were observed between vitamin B12 (β = -0.197, p = 0.010), BMI (β = 0.466, p < 0.001), and HOMA-IR in RPL patients., Conclusion: Vitamin B12 is significantly correlated with IR in RPL patients. Circulating vitamin B12-folate-homocysteine metabolism could be a window of the pathological process of IR, obesity, and lipid metabolism disorders in RPL patients., Competing Interests: Declaration of competing interest We declare that we have no financial and personal relationships with other people or organizations that can inappropriately influence our work, there is no professional or other personal interest of any nature or kind in any product, service, and/or company that could be construed as influencing the position presented in, or the review of, the manuscript entitled., (Copyright © 2024 Elsevier Masson SAS. All rights reserved.)

This study assessed the effects of mass mixing ratio and hydrothermal temperature on the co-hydrothermal carbonization (co-HTC) of sewage sludge and rice straw regarding the yield, chemical composition, fuel properties, surface functional groups, and combustion behavior of the hydrochar. The co-HTC increased the hydrochar yield at 180 °C but decreased it at 220 and 260 °C. The co-HTC increased the hydrochar organic matter contents, higher heating values, fuel ratios, and combustion behavior (combustibility index) by 16 % to 63 %, 15 % to 85 %, 51 % to 321 %, and 30 % to 419 %, respectively. The co-HTC also enhanced the formation of oxygen-containing functional groups on the hydrochar surface. The synergistic and anti-synergistic effects of the co-HTC were more positive at 180 and 220 °C but more negative at 260 °C. The co-HTC of municipal sludge and rice straw is promising in converting waste materials into high-quality hydrochar as a clean solid fuel., 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.)

Aims: To evaluate the consistency between fractal dimensions (FD) derived from cardiac computed tomography (CT-FD) and cardiac magnetic resonance (MR-FD) in assessing left ventricular trabecular complexity., Methods: This retrospective study included 170 patients who underwent CCT and CMR scans within two weeks. Five short-axis cine images were selected at end-diastole: one basal, three mid, and one apical slice. Short-axis CCT views were reconstructed and aligned with the cine images. CT-FD and MR-FD values were calculated for each slice, with mean values determined for each patient. Severe left ventricular hypertrophy (LVH) was defined as a maximum wall thickness > 15 mm in end-diastolic cine images., Results: The diastolic CT-FD and MR-FD values exhibited high consistency, with values of 1.253 ± 0.091 and 1.250 ± 0.102, respectively (n = 535, ICC = 0.882, 95 % CI: 0.861-0.899, P < 0.001). Similarly, the systolic CT-FD and MR-FD values demonstrated good consistency, with values of 1.268 ± 0.072 and 1.286 ± 0.093, respectively (n = 390, ICC = 0.720, 95 % CI: 0.669-0.765, P < 0.001). For subgroups of systolic NLVH and LVH, the ICCs were 0.773 (n = 305, CI: 0.723-0.814, P < 0.001) and 0.565 (n = 85, 95 % CI: 0.402-0.694, P < 0.001), respectively. The diagnostic efficacy of mean CT-FD aligned with that of mean MR-FD in distinguishing abnormal cardiac conditions from the CMR-negative group., Conclusions: CCT is a feasible method for assessing left ventricular trabecular complexity, with good agreement with CMR, except in cases of severe left ventricular hypertrophy during systole., Competing Interests: Declaration of competing interest The authors declare that they have no conflicts of interest., (Copyright © 2024 Elsevier B.V. All rights reserved.)

Aluminum (Al) toxicity in acid soils poses a significant threat to rice, which exhibits highly complex genetic mechanisms for both external detoxification and internal tolerance among cereal crops. Although several genes involved Al tolerance have been identified, the molecular mechanisms underlying Al tolerance in rice remain to be fully explored. Here, we functionally characterized the gibberellin-stimulated transcription gene OsGASR1, which encodes a small cysteine-rich peptide localized to the nucleus and cytoplasm and plays a significant role in Al tolerance in rice. The expression of OsGASR1 is rapidly up-regulated by Al in rice root tips but not in the shoots. Its expression is not regulated by the central regulator Aluminum Resistance Transcription Factor 1 (ART1), indicating that OsGASR1 functions as a novel gene in rice Al resistance independent of ART1. Knockout of OsGASR1 reduced root length but did not affect Al tolerance in rice, whereas overexpression of OsGASR1 enhanced Al tolerance without affecting Al distribution and accumulation and promoted the accumulation of reactive oxygen species (ROS) in the root tips. RNA-seq analysis revealed that overexpression of OsGASR1 upregulated the expression of genes associated with cell wall modification, oxidative stress, and Al tolerance. Collectively, these findings suggest that OsGASR1 is involved in Al tolerance in rice independently of ART1, and the up-regulation of this gene is necessary for rice Al tolerance., Competing Interests: Declaration of Competing Interest The authors declare that they have no conflicts of interest., (Copyright © 2024 Elsevier B.V. All rights reserved.)

Background: Left atrioventricular coupling index (LACI) is a novel biomarker, and the prognostic value of LACI to predict cardiovascular events has been validated. The present study aimed to explore the prognostic value of LACI in patients with light-chain (AL) amyloidosis., Methods: We prospectively enrolled 179 patients with AL amyloidosis who underwent cardiovascular magnetic resonance imaging between December 2011 and January 2020. LACI was defined as the ratio between the left atrial volume and the left ventricular volume at end-diastole. The primary endpoint was all-cause mortality. Receiver operating characteristic curve was used to identify the optimal cut-off of LACI in predicting all-cause mortality. Univariable and multivariable Cox proportional hazard models were used to assess the association of LACI and primary endpoint., Results: During a median follow-up of 30 months, 118 (65.9 %) patients with all-cause mortality were documented. LACI was significantly higher in patients with primary endpoint compared to those without primary endpoint (55.4 %, interquartile range: 31.6 %-71.5 % vs. 39.4 %, interquartile range: 24.1 %-54.7 %, p = 0.001). The optimal cut-off for LACI to predict mortality was 49.3 %. In multivariate Cox regression analysis, LACI≥49.3 % (HR 1.907, 95 % CI 1.273-2.857, p = 0.002) was an independent predictor of all-cause mortality. On Kaplan-Meier analysis, patients at advanced Mayo stage (IIIa and IIIb) can be further risk stratified using LACI≥49.3 % (log-rank p = 0.035, p = 0.025)., Conclusion: The LACI provides powerful independent prognostic value in AL amyloidosis. The LACI has incremental prognostic value to predict all-cause mortality over the Mayo stage in patients at the advanced Mayo stage., Competing Interests: Declaration of competing interest None., (Copyright © 2024 Elsevier B.V. All rights reserved.)

Background: Limited understanding exists regarding the association between daily total dietary nutrient intakes and immune-inflammation states in US adults exposed to various pathogens. This study sought to examine the correlation between nutrient intakes and immune-inflammation indicators and to assess their performance in distinguishing immune-inflammation states., Methods: This study was derived from the National Health and Nutrition Examination Survey (NHANES), which included 33,804 participants aged 20 years or older between 2005 and 2018. Multivariable linear regression and restricted cubic spline regression were conducted to evaluate the association between nutrient intakes and immune-inflammation indicators. Receiver operating characteristic curve analysis was performed to evaluate the discriminatory performance of identified nutrients for various immune-inflammation states measured by the systemic immune-inflammation index (SII)., Results: Ten key nutrients were significantly associated with immune-inflammation responses, including calcium, saturated fatty acid (SFA) 4:0, SFA 6:0, SFA 12:0, SFA 14:0, SFA 16:0, vitamin B 2 , total SFAs, retinol, and lutein + zeaxanthin, which show potential as dietary indicators. The area under the curve for discriminating various immune-inflammation states was improved by at least 0.03 compared with a model that included only covariates, with all P values <0.05 in the Delong tests, indicating a significant enhancement in model performance., Conclusions: Ten nutrients, including calcium, various SFAs, vitamin B 2 , retinol, and lutein + zeaxanthin, exhibit significant association with SII and potential as dietary indicators for distinguishing between different immune-inflammation states in US adults with seropositivity to various viruses., (© 2024 American Society for Parenteral and Enteral Nutrition.)

Background: Early precise identification of high-risk dilated cardiomyopathy (DCM) phenotype is essential for clinical decision-making and patient surveillance. The aim of the study was to assess the prognostic value of enhanced cine cardiac magnetic resonance (CMR)-based radiomics in DCM., Methods: We prospectively enrolled 401 (training set: 281; test set: 120) DCM patients. Radiomic features were extracted from enhanced cine images of entire left ventricular wall and selected by the least absolute shrinkage and selection operator. Different predictive models were built using logistic regression classifier to predict all-cause mortality and heart transplantation. Model performances were compared with the area under the receiver operating characteristic curves (AUCs). Kaplan-Meier curves, log-rank test, and Cox regression were used for survival analysis., Results: Endpoint events occurred in 65 patients over a median follow-up period of 25.4 months. 13 radiomic features were finally selected. The Rad&#95;Combined model integrating clinical characteristics, CMR parameters and radiomics features achieved the best performance with an AUC of 0.836 and 0.835 in the training and test sets, respectively. High-risk groups with endpoint events defined by the Rad&#95;Combined model had significantly shorter survival time than low-risk group in both the training [Hazard Ratio (HR) = 7.74, P < 0.001] and test sets (HR = 4.84, P < 0.001)., Conclusion: The Rad&#95;Combined model might serve as an effective tool to help risk stratification and clinical decision-making for patients with DCM., Trial Registration: Chinese Clinical Trial Registry, ChiCTR1800017058 by the ethics committee of West China hospital,Sichuan University., Competing Interests: Declaration of competing interest Author Hongkun Yin is employed by the company Infervision Medical Technology Co. Author Xiaoyue Zhou and Yang Song are employed by Siemens Healthineers. All other authors have no conflicts of interest to declare., (Copyright © 2024 Elsevier B.V. All rights reserved.)

Multimodal classification algorithms play an essential role in multimodal machine learning, aiming to categorize distinct data points by analyzing data characteristics from multiple modalities. Extensive research has been conducted on distilling multimodal attributes and devising specialized fusion strategies for targeted classification tasks. Nevertheless, current algorithms mainly concentrate on a specific classification task and process data about the corresponding modalities. To address these limitations, we propose a unified multimodal classification framework proficient in handling diverse multimodal classification tasks and processing data from disparate modalities. UMCF is task-independent, and its unimodal feature extraction module can be adaptively substituted to accommodate data from diverse modalities. Moreover, we construct the multimodal learning scheme based on deep metric learning to mine latent characteristics within multimodal data. Specifically, we design the metric-based triplet learning to extract the intra-modal relationships within each modality and the contrastive pairwise learning to capture the inter-modal relationships across various modalities. Extensive experiments on two multimodal classification tasks, fake news detection and sentiment analysis, demonstrate that UMCF can extract multimodal data features and achieve superior classification performance than task-specific benchmarks. UMCF outperforms the best fake news detection baselines by 2.3% on average regarding F1 scores., 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 Ltd.)

Objective: To assess the prevalence of depression, anxiety, insomnia and somatic symptom disorder (SSD) in chronic rhinosinusitis (CRS) patients who were waiting for surgery and to predict these psychiatric disorders using the 22-item Sinonasal Outcome Test (SNOT-22)., Design: A prospective cross-sectional study., Setting: The rhinology ward at our institution, a tertiary hospital., Participants: Adult patients (> 18 years) diagnosed with CRS who were admitted to the rhinology ward for endoscopic sinus surgery and were able to understand and complete the study questionnaires., Main Outcome Measures: Patient Health Questionnaire-9 (PHQ-9), Generalised Anxiety Disorder-7 (GAD-7), Insomnia Severity Index (ISI), Patient Health Questionnaire-15 (PHQ-15) and SNOT-22., Results: Of the 159 participants recruited, 58 were at risk of depression (defined by PHQ-9 > 4, while 25 with PHQ-9 > 9), 49 were at risk of anxiety (defined by GAD-7 > 4, while 25 with GAD-7 > 9), 81 were at risk of insomnia (defined by ISI > 7, while 51 with ISI > 14) and 69 were at risk of SSD (defined by PHQ-15 > 4, while 24 with PHQ-15 > 9). The SNOT-22 score was closely correlated with the scores of psychometric tests and was an independent predictor of these psychiatric disorders. Patients with a high SNOT-22 score (> 30) are likely to be affected by comorbid psychiatric disorders and should be further evaluated by otolaryngologists., Conclusion: Depression, anxiety, insomnia and SSD are prevalent in CRS patients. Otolaryngologists should have a low threshold to ask the patient about psychiatric symptoms, especially for patients with an SNOT-22 score > 30., (© 2024 John Wiley & Sons Ltd.)

Reactive astrocyte activation in the context of cerebral ischemia/reperfusion (I/R) injury gives rise to two distinct subtypes: the neurotoxic A1 type and the neuroprotective A2 type. DJ-1 (Parkinson disease protein 7, PARK7), originally identified as a Parkinson's disease-associated protein, is a multifunctional anti-oxidative stress protein with molecular chaperone and signaling functions. SHP-1 (Src homology 2 domain-containing phosphatase-1) is a protein tyrosine phosphatase closely associated with cellular signal transduction. miR-155 is a microRNA that participates in cellular functions by regulating gene expression. Recent studies have uncovered the relationship between DJ-1 and astrocyte-mediated neuroprotection, which may be related to its antioxidant properties and regulation of signaling molecules such as SHP-1. Furthermore, miR-155 may exert its effects by influencing SHP-1, providing a potential perspective for understanding the molecular mechanisms of stroke. A middle cerebral artery occlusion/reperfusion (MCAO/R) model and an oxygen-glucose deprivation/reperfusion (OGD/R) model were established to simulate focal cerebral I/R injury in vivo and in vitro, respectively. The in vivo interaction between DJ-1 and SHP-1 has been experimentally validated through immunoprecipitation. Overexpression of DJ-1 attenuates I/R injury and suppresses miR-155 expression. In addition, inhibition of miR-155 upregulates SHP-1 expression and modulates astrocyte activation phenotype. These findings suggest that DJ-1 mediates astrocyte activation via the miR-155/SHP-1 pathway, playing a pivotal role in the pathogenesis of cerebral ischemia-reperfusion injury. Our results provide a potential way for exploring the pathogenesis of ischemic stroke and present promising targets for pharmacological intervention., (© 2024 International Society for Neurochemistry.)

Objectives: To investigate the effect of motion-compensated reconstruction (MCR) algorithm on improving the image quality of coronary computed tomography angiography (CCTA) using second-generation dual-layer spectral detector computed tomography (DLCT), and to evaluate the influence of heart rate (HR) on the motion-correction efficacy of this algorithm., Materials and Methods: We retrospectively enrolled 127 patients who underwent CCTA for suspected coronary artery disease using second-generation DLCT. We divided the patients into two subgroups according to their average HR during scanning: the "HR < 75 bpm" group and the "HR ≥ 75 bpm" group. All images were reconstructed by the standard (STD) algorithm and MCR algorithm. Subjective image quality (4-point Likert scale), interpretability, and objective image quality between the STD and MCR in the whole population and within each subgroup were compared., Results: MCR showed significantly higher Likert scores and interpretability than STD on the per-segment (3.58 ± 0.69 vs. 2.82 ± 0.93, 98.4% vs. 91.9%), per-vessel (3.12 ± 0.81 vs. 2.12 ± 0.74, 96.3% vs. 78.7%) and per-patient (2.57 ± 0.76 vs. 1.62 ± 0.55, 90.6% vs. 59.1%) levels (all p < 0.001). In the analysis of HR subgroups on a per-vessel basis of interpretability, significant differences were observed only in the right coronary artery in the low HR group, whereas significant differences were noted in three major coronary arteries in the high HR group. For objective image quality assessment, MCR significantly improved the SNR (13.22 ± 4.06 vs. 12.72 ± 4.06) and the contrast-to-noise ratio (15.84 ± 4.82 vs. 15.39 ± 4.38) compared to STD (both p < 0.001)., Conclusion: MCR significantly improves the subjective image quality, interpretability, and objective image quality of CCTA, especially in patients with higher HRs., Clinical Relevance Statement: The motion-compensated reconstruction algorithm of the second-generation dual-layer spectral detector computed tomography is helpful in improving the image quality of coronary computed tomography angiography in clinical practice, especially in patients with higher heart rates., Key Points: Motion artifacts from cardiac movement affect the quality and interpretability of coronary computed tomography angiography (CCTA). This motion-compensated reconstruction (MCR) algorithm significantly improves the image quality of CCTA in clinical practice. Image quality improvement by using MCR was more significant in the high heart rate group., Competing Interests: Compliance with ethical standards. Guarantor: The scientific guarantor of this publication is Liqing Peng. Conflict of interest: S.G. and X.Z. are affiliated with Philips Healthcare. The remaining authors declare no conflicts of interest. Statistics and biometry: No complex statistical methods were necessary for this paper. Informed consent: Written informed consent was waived by the Institutional Review Board. Ethical approval: Institutional Review Board approval was obtained. Study subjects or cohorts overlap: None. Methodology: Retrospective Observational study Performed at one institution, (© 2024. The Author(s), under exclusive licence to European Society of Radiology.)

JOURNAL/nrgr/04.03/01300535-202501000-00032/figure1/v/2024-05-14T021156Z/r/image-tiff Human brain development is a complex process, and animal models often have significant limitations. To address this, researchers have developed pluripotent stem cell-derived three-dimensional structures, known as brain-like organoids, to more accurately model early human brain development and disease. To enable more consistent and intuitive reproduction of early brain development, in this study, we incorporated forebrain organoid culture technology into the traditional unguided method of brain organoid culture. This involved embedding organoids in matrigel for only 7 days during the rapid expansion phase of the neural epithelium and then removing them from the matrigel for further cultivation, resulting in a new type of human brain organoid system. This cerebral organoid system replicated the temporospatial characteristics of early human brain development, including neuroepithelium derivation, neural progenitor cell production and maintenance, neuron differentiation and migration, and cortical layer patterning and formation, providing more consistent and reproducible organoids for developmental modeling and toxicology testing. As a proof of concept, we applied the heavy metal cadmium to this newly improved organoid system to test whether it could be used to evaluate the neurotoxicity of environmental toxins. Brain organoids exposed to cadmium for 7 or 14 days manifested severe damage and abnormalities in their neurodevelopmental patterns, including bursts of cortical cell death and premature differentiation. Cadmium exposure caused progressive depletion of neural progenitor cells and loss of organoid integrity, accompanied by compensatory cell proliferation at ectopic locations. The convenience, flexibility, and controllability of this newly developed organoid platform make it a powerful and affordable alternative to animal models for use in neurodevelopmental, neurological, and neurotoxicological studies., (Copyright © 2025 Copyright: © 2025 Neural Regeneration Research.)