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The rising prevalence of obesity is a global health concern. Supplementation with (S)-β-aminoisobutyric acid (L-BAIBA) has shown potential in preventing obesity and related metabolic disorders induced by high-fat diets. However, developing effective and low-toxicity BAIBA derivatives remains a challenging yet promising field. In this study, we introduce Oct-B, a novel BAIBA ester compound, which exhibits 80-fold greater efficacy than L-BAIBA in alleviating obesity in high-fat diet-fed mice. Our results demonstrate that Oct-B significantly reduces serum TG, TC, LDL-C, and the activities of ALT and AST, and also reduces TG and TC in liver, surpassing the effects of L-BAIBA. Histological analysis shows that Oct-B significantly decreases lipid accumulation in liver tissues, normalizes mast cells in white adipose tissue, and upregulates the expression of UCP1 protein in white adipose tissue. The qRT-PCR results indicated Oct-B alleviates obesity by downregulating lipogenic genes (PPARγ, ACC1, FAS), upregulating lipolysis related genes (PPARα, HSL) and thermogenic gene UCP1. Additionally, quantitative mass spectrometry reveals a marked increase in L-BAIBA levels in white fat, brown fat, serum, and muscle following Oct-B administration. These findings suggest that Oct-B is an efficient L-BAIBA substitute, offering a promising therapeutic approach for preventing and treating high-fat diet-induced obesity., Competing Interests: Declaration of Competing Interest All authors declare they have no actual or potential competing financial interest., (Copyright © 2024 The Authors. Published by Elsevier Inc. All rights reserved.)

Gastric cancer (GC) is a common malignant disease that has a fifth highest incidence and fourth highest mortality worldwide. The Warburg effect is a common phenomenon observed in tumors, which suggests that tumor cells would enhance glucose uptake by overexpressing multiple glucose transporters. Sodium glucose transporter 2 (SGLT2) is one of glucose transporters which highly expressed in several cancers, but its role in gastric cancer is still unclear. Our research found that there was a high expression level of SGLT2 in gastric cancer tissues. We found that Dapagliflozin (a SGLT2 inhibitor) could suppress gastric cancer cell proliferation and migration in vitro and tumor growth in vivo. In present study, we revealed how dapagliflozin would suppress gastric cancer progression in a novel mechanism. We proved that dapagliflozin decreased the expression level of OTU deubiquitinase 5 (OTUD5), which further increased the ubiquitination and degradation of YAP1. Overexpression of OTUD5 in gastric cancer cells partly reversed the anti-tumor effect of dapagliflozin. Our findings revealed a novel mechanism by which dapagliflozin has an antitumor effect on gastric cancer and proposed a beneficial strategy for the application of dapagliflozin in gastric cancer patients., Competing Interests: Declaration of competing interest All authors declare no conflict of interest., (Copyright © 2024 The Authors. Published by Elsevier B.V. All rights reserved.)

Cytochrome P450 enzymes (CYPs) are widely distributed among various plant groups and constitute approximately 1% of the total number of protein-coding genes. Extensive studies suggest that CYPs are involved in nearly all molecular processes that occur in plants. Over the past two decades, the identification of CYP genes has expanded rapidly, with more than 40,000 CYP genes and 819 CYP families being discovered. Copy number variation is a significant evolutionary characteristic of gene families, yet a systematic characterization of the copy evolution patterns in plant CYP gene families has been lacking, resulting in confusion and challenges in understanding CYP functions. To address these concerns, this review provides comprehensive statistics and analyses of the copy number and diversity of almost all plant CYP gene families, focusing on CYP evolution from Chlorophyta to Dicotyledoneae. Additionally, we examined the subfamily characteristics of certain CYP families with restricted copy changes and identify several CYP subfamilies that play pivotal roles in this event. Furthermore, we analyzed the structural conservation of CYPs across different taxa and compiled a comprehensive database to support plant CYP studies. Our analysis revealed differences in the six core conserved motifs of plant CYP proteins among various clans and plant taxa, while demonstrating similar conservation patterns for the ERR (Glutamic Acid-Arginine-Arginine) triad motifs. These findings will significantly facilitate the understanding of plant CYP gene evolution and metabolic diversity and serve as a valuable reference for researchers studying CYP enzymes., (© The Author(s) 2024. Published by Oxford University Press on behalf of Society for Molecular Biology and Evolution.)

Objectives: The relationship between sleep and memory has been well documented. However, it remains unclear whether a mind-body exercise, that is, Tai Chi exercise, can improve memory performance in older adults by improving their subjective and objective sleep., Methods: A randomized controlled trial was conducted with participants (M = 67.36, 56-79 years) randomly assigned to Tai Chi and control groups. The primary outcomes were sleep, both subjectively reported and objectively assessed by actigraphy, and memory performance, as well as the mediating role of sleep in memory improvement with Tai Chi practice., Results: Tai Chi exercise led to improvements in subjective sleep, as indicated by Insomnia Severity Index (ISI) (p < .001, Cohen's d = 0.62) and daytime dysfunction of the Pittsburgh sleep quality index (PSQI) (p = .02, Cohen's d = 0.80), and in actigraphy-assessed sleep onset latency (p < .01, Cohen's d = 0.61), as well as improved memory performance on digit span forward (p < .001, Cohen's d = 1.20) and visual spatial memory tasks (p < .01, Cohen's d = 0.83) compared to the control group. Importantly, Tai Chi practice improved digit span forward memory performance through parallel mediation of both subjective sleep (i.e., daytime dysfunction of the PSQI) and objective sleep (i.e., sleep onset latency; b = 0.29, p < .01)., Discussion: Our findings uncovered the potential benefits of Tai Chi exercise in relation to both subjective and objective sleep in older adults, in turn, how sleep changes played a role in the link between Tai Chi exercise and memory changes in older adults., (© The Author(s) 2024. Published by Oxford University Press on behalf of The Gerontological Society of America. All rights reserved. For commercial re-use, please contact reprints@oup.com for reprints and translation rights for reprints. All other permissions can be obtained through our RightsLink service via the Permissions link on the article page on our site—for further information please contact journals.permissions@oup.com.)

Background: Brain metastases (BMs) represents a severe neurological complication stemming from cancers originating from various sources. It is a highly challenging clinical task to accurately distinguish the pathological subtypes of brain metastatic tumors from lung cancer (LC).The utility of 2.5-dimensional (2.5D) deep learning (DL) in distinguishing pathological subtypes of LC with BMs is yet to be determined., Methods: A total of 250 patients were included in this retrospective study, divided in a 7:3 ratio into training set (N=175) and testing set (N=75). We devised a method to assemble a series of two-dimensional (2D) images by extracting adjacent slices from a central slice in both superior-inferior and anterior-posterior directions to form a 2.5D dataset. Multi-Instance learning (MIL) is a weakly supervised learning method that organizes training instances into "bags" and provides labels for entire bags, with the purpose of learning a classifier based on the labeled positive and negative bags to predict the corresponding class for an unknown bag. Therefore, we employed MIL to construct a comprehensive 2.5D feature set. Then we used the single-slice as input for constructing the 2D model. DL features were extracted from these slices using the pre-trained ResNet101. All feature sets were inputted into the support vector machine (SVM) for evaluation. The diagnostic performance of the classification models were evaluated using five-fold cross-validation, with accuracy and area under the curve (AUC) metrics calculated for analysis., Results: The optimal performance was obtained using the 2.5D DL model, which achieved the micro-AUC of 0.868 (95% confidence interval [CI], 0.817-0.919) and accuracy of 0.836 in the test cohort. The 2D model achieved the micro-AUC of 0.836 (95 % CI, 0.778-0.894) and accuracy of 0.827 in the test cohort., Conclusions: The proposed 2.5D DL model is feasible and effective in identifying pathological subtypes of BMs from lung cancer., 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.)

Bacterial pathogens manipulate host signaling pathways and evade host defenses using effector molecules, coordinating their deployment to ensure successful infection. However, host-derived metabolites as signals, and their critical role in regulating bacterial virulence requires further insights. Effective regulation of virulence, which is essential for pathogenic bacteria, involves controlling factors that enable colonization, defense evasion, and tissue damage. This regulation is dynamic, influenced by environmental cues including signals from host plants like exudates. Plant exudates, comprising of diverse compounds released by roots and tissues, serve as rich chemical signals affecting the behavior and virulence of associated bacteria. Plant nutrients act as signaling molecules that are sensed through membrane-localized receptors and intracellular response mechanisms in bacteria. This review explains how different bacteria detect and answer to secreted chemical signals, regulating virulence gene expression. Our main emphasis is exploring the recognition process of host-originated signaling molecules through molecular sensors on cellular membranes and intracellular signaling pathways. This review encompasses insights into how bacterial strains individually coordinate their virulence in response to various distinct host-derived signals that can positively or negatively regulate their virulence. Furthermore, we explained the interruption of plant defense with the perception of host metabolites to dampen pathogen virulence. The intricate interplay between pathogens and plant signals, particularly in how pathogens recognize host metabolic signals to regulate virulence genes, portrays a crucial initial interaction leading to profound influences on infection outcomes. This work will greatly aid researchers in developing new strategies for preventing and treating infections., Competing Interests: Declaration of Competing Interest None., (Copyright © 2024 The Authors. Published by Elsevier GmbH.. All rights reserved.)

Cardiomyocytes are terminal differentiated cells and have limited ability to proliferate or regenerate. Condition like myocardial infarction causes massive death of cardiomyocytes and is the leading cause of death. Previous studies have demonstrated that cardiac fibroblasts can be induced to transdifferentiate into cardiomyocytes in vitro and in vivo by forced expression of cardiac transcription factors and microRNAs. Our previous study have demonstrated that full chemical cocktails could also induce fibroblast to cardiomyocyte transdifferentiation both in vitro and in vivo. With the development of tissue clearing techniques, it is possible to visualize the reprogramming at the whole-organ level. In this study, we investigated the effect of the chemical cocktail CRFVPTM in inducing in situ fibroblast to cardiomyocyte transdifferentiation with two strains of genetic tracing mice, and the reprogramming was observed at whole-heart level with CUBIC tissue clearing technique and 3D imaging. In addition, single-cell RNA sequencing (scRNA-seq) confirmed the generation of cardiomyocytes from cardiac fibroblasts which carries the tracing marker. Our study confirms the use of small molecule cocktails in inducing in situ fibroblast to cardiomyocyte reprogramming at the whole-heart level and proof-of-conceptly providing a new source of naturally incorporated cardiomyocytes to help heart regeneration., (© 2024. The Author(s), under exclusive licence to Shanghai Institute of Materia Medica, Chinese Academy of Sciences and Chinese Pharmacological Society.)

Study Design: Retrospective, matched case-control study., Objective: To investigate the risk factors of reoperation after percutaneous endoscopic lumbar discectomy (PELD) due to recurrent lumbar disc herniation (rLDH) and to establish a set of individualized prediction models., Methods: Patients who underwent PELD successfully from January 2016 to February 2022 in a single institution were enrolled in this study. Six methods of machine learning (ML) were used to establish an individualized prediction model for reoperation in rLDH patients after PELD, and these models were compared with logistics regression model to select optimal model., Results: A total of 2603 patients were enrolled in this study. 57 patients had repeated operation due to rLDH and 114 patients were selected from the remaining 2546 nonrecurrent patients as matched controls. Multivariate logistic regression analysis showed that disc herniation type ( P < .001), Modic changes (type II) ( P = .003), sagittal range of motion (sROM) ( P = .022), facet orientation (FO) ( P = .028) and fat infiltration (FI) ( P = .001) were independent risk factors for reoperation in rLDH patients after PELD. The XGBoost AUC was of 90.71%, accuracy was approximately 88.87%, sensitivity was 70.81%, specificity was 97.19%. The traditional logistic regression AUC was 77.4%, accuracy was about 77.73%, sensitivity was 47.15%, specificity was 92.12%., Conclusion: This study showed that disc herniation type (extrusion, sequestration), Modic changes (type II), a large sROM, a large FO and high FI were independent risk factors for reoperation in LDH patients after PELD. The prediction efficiency of XGBoost model was higher than traditional Logistic regression analysis model., Competing Interests: Declaration of conflicting interestsThe author(s) declared no potential conflicts of interest with respect to the research, authorship, and/or publication of this article.

Background: Metabolic abnormalities are considered to play a key regulatory role in vascular remodeling of pulmonary arterial hypertension. However, to date, there is a paucity of research documenting the changes in metabolome profiles within the supernatants of pulmonary artery smooth muscle cells (PASMC) during their transition from a contractile to a synthetic phenotype., Methods: CCK-8 and Edu staining assays were used to evaluate the cell viability and proliferation of human PASMCs. IncuCyte ZOOM imaging system was used to continuously and automatically detect the migration of the PASMCs. A targeted metabolomics profiling was performed to quantitatively analyze 121 metabolites in the supernatant. Orthogonal partial least squares discriminant analysis was used to discriminate between PDGF-BB-induced PASMCs and controls. Metabolite set enrichment analysis was adapted to exploit the most disturbed metabolic pathways., Results: Human PASMCs exhibited a transformation from contractile phenotype to synthetic phenotype after PDGF-BB induction, along with a significant increase in cell viability, proliferation, and migration. Metabolites in the supernatants of PASMCs treated with or without PDGF-BB were well profiled. Eleven metabolites were found to be significantly upregulated, whereas seven metabolites were downregulated in the supernatants of PASMCs induced by PDGF-BB compared to the vehicle-treated cells. Fourteen pathways were involved, and pyruvate metabolism pathway was ranked first with the highest enrichment impact followed by glycolysis/gluconeogenesis and pyrimidine metabolism., Conclusions: Significant and extensive metabolic abnormalities occurred during the phenotypic transformation of PASMCs. Disturbance of pyruvate metabolism pathway might contribute to pulmonary vascular remodeling., (© 2024 The Author(s). Animal Models and Experimental Medicine published by John Wiley & Sons Australia, Ltd on behalf of The Chinese Association for Laboratory Animal Sciences.)

Background: Peer support is a promising and significant way for people living with HIV (PLWH) to improve their health outcomes. Matching PLWH with HIV peer volunteers can effectively stimulate and mobilize the function of peer support in health management. We develop the online platform Aspark, which features a precision matching function for PLWH and volunteers. This protocol provides a comprehensive overview of the randomized controlled trial design based on Aspark., Method: A parallel randomized controlled trial using block randomization will be conducted at the Beijing YouAn Home of Loving Care. The intervention group (n = 70) will have access to all 12 features of Aspark, including precise volunteer matching, health management tools, drug interaction queries, and medication reminders. The control group (n = 70) will have access to two features of informational support on Aspark. The outcomes of both groups will be evaluated at baseline and at 3, 6, 9, and 12 months after platform registration. The primary outcome is perceived social support. The secondary outcomes include mental symptoms, quality of life, self-efficacy, medication adherence, and health behaviors. Linear mixed models or generalized linear mixed models will be applied to test the intervention effects., Discussion: The Aspark trial is a randomized controlled trial designed to examine the influence of a mobile health (mHealth) application that integrates peer support and precision matching to strengthen social support for PLWH in China. This trial has the potential to significantly enhance social support for PLWH while also optimizing the delivery of peer support services and fully mobilizing the role of peer support in the overall health management of PLWH., Trial Registration: Clinical registration number: ChiCTR2300077454., (© 2024. The Author(s).)

The sericulture industry faces a significant threat from the Pebrine disease of silkworms, caused by Nosema bombycis. Nonetheless, the current microscopic diagnostic methods can be time-consuming, labor-intensive, and lacking sensitivity and accuracy. Therefore, it is crucial to develop a novel detection approach that is efficient, highly sensitive, and low-cost. In this regard, the CRISPR/Cas system has the potential to be a fast, accurate, and highly specific method of detection. Herein, using a microplate reader, a portable fluorescence detection device, and test strips as signal output tools respectively, we have efficiently developed three rapid and facile visual detection methods for N. bombycis using a CRISPR/Cas13a system with conjugation of Recombinase polymerase amplification (RPA). We evaluated the sensitivity of this combined technology by comparing it with the positive plasmid standard and the genome standard of N. bombycis. Remarkably, the sensitivity of the CRISPR/Cas13a system for N. bombycis positive plasmid standard based on the microplate reader, portable fluorescence detection device, and test strips was 1 copy/μL, 10 copies/μL, and 1 copy/μL, respectively, while for the N. bombycis genome standards, the detection sensitivity was 10 fg/μL, 10 fg/μL, and 1 fg/μL, respectively. In addition, extensive evaluations have demonstrated that the established technology can accurately detect N. bombycis without cross-reactivity with other pathogens, ensuring a specificity rate of 100%. In brief, this study will provide a practical, efficient, and affordable method for early and rapid detection of N. bombycis in various settings., (Copyright © 2024 Elsevier Ltd. All rights reserved.)

Background: Patients with coronavirus disease 2019(COVID-2019) infections may still experience long-term effects, with fatigue being one of the most frequent ones. Clinical research on the long COVID in the Chinese population after infection is comparatively lacking., Objective: To collect and analyze the long-term effects of non-severe COVID-19 infection patients and to develop a model for the prediction of fatigue symptoms., Methods: 223 non-severe COVID-19 patients admitted to one designated hospital were enrolled after finish all the self-designed clinical information registration form and nine-month follow-up. We explored the frequency and symptom types of long COVID. Correlation analysis was done on the neuropsychological scale results. After cluster analysis, lasoo regression and logistic regressions, a nomogram prediction model was produced as a result of investigating the risk factors for fatigue., Results: A total of 108 (48.4%) of the 223 non-severe COVID-19 patients reported sequelae for more than 4 weeks, and of these, 35 (15.7%) had fatigue sequelae that were scale-confirmed. Other sequelae of more than 10% were brain fog ( n  = 37,16.6%), cough ( n  = 26,11.7%) and insomnia (n = 23,10.3%). A correlation between depression and fatigue was discovered following the completion of neuropsychological scale. The duration of hospitalization, the non-use of antiviral medications in treatment, IL-6 and CD16+CD56 + cell levels in blood are the main independent risk factors and predictors of fatigue sequelae in long COVID. Additionally, the neurology diseases and vaccination status may also influence the fatigue sequelae., Conclusion: Nearly half of the patients infected with COVID-19 Omicron variant complained of sequelae, and fatigue was the most common symptom, which was correlated with depression. Significant predictors of fatigue sequelae included length of hospitalization, non-use of antiviral drug, and immune-related serum markers of IL-6 and CD16+CD56 + NK cell levels. The presence of neurology diseases and a lack of vaccination could also predict the occurrence of fatigue sequelae., 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., (© 2024 The Authors. Published by Elsevier Inc.)

Background: The gut microbiome has a significant impact on human wellness, contributing to the emergence and progression of a range of health issues including inflammatory and autoimmune conditions, metabolic disorders, cardiovascular problems, and psychiatric disorders. Notably, clinical observations have revealed that these illnesses can display differences in incidence and presentation between genders. The present study aimed to evaluate whether the composition of gut microbiota is associated with sex-specific differences and to elucidate the mechanism., Methods: 16S-rRNA-sequencing technology, hormone analysis, gut microbiota transplantation, gonadectomy, and hormone treatment were employed to investigate the correlation between the gut microbiome and sex or sex hormones. Meanwhile, genes and proteins involved bile acid signaling pathway were analyzed both in the liver and ileum tissues., Results: The composition and diversity of the microbiota from the jejunum and feces and the level of sex hormones in the serum differed between the sexes in young and middle-aged Sprague Dawley (SD) rats. However, no similar phenomenon was found in geriatric rats. Interestingly, whether in young, middle-aged, or old rats, the composition of the microbiota and bacterial diversity differed between the jejunum and feces in rats. Gut microbiota transplantation, gonadectomy, and hormone replacement also suggested that hormones, particularly testosterone (T), influenced the composition of the gut microbiota in rats. Meanwhile, the mRNA and protein level of genes involved bile acid signaling pathway (specifically SHP , FXR , CYP7A1 , and ASBT ) exhibited gender-specific differences, and T may play a significant role in mediating the expression of this pathway., Conclusion: Sex-specific differences in the structure of the gut microbiota are mediated by T through the bile acid signaling pathway, pointing to potential targets for disease prevention and management techniques by indicating that sex differences and T levels may alter the composition of the gut microbiota via the bile acid signaling pathway., 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 © 2024 Duan, Nie, Xie, Zhang, Zhu, Zhu, Chen, Xu, Zhang, Yang, Yu, Cai, Wang and Tian.)

Objective: This study aims to develop and validate SwinHS, a deep learning-based automatic segmentation model designed for precise hippocampus delineation in patients receiving hippocampus-protected whole-brain radiotherapy. By streamlining this process, we seek to significantly improve workflow efficiency for clinicians., Methods: A total of 100 three-dimensional T1-weighted MR images were collected, with 70 patients allocated for training and 30 for testing. Manual delineation of the hippocampus was performed according to RTOG0933 guidelines. The SwinHS model, which incorporates a 3D ELSA Transformer module and an sSE CNN decoder, was trained and tested on these datasets. To prove the effectiveness of SwinHS, this study compared the segmentation performance of SwinHS with that of V-Net, U-Net, ResNet and VIT. Evaluation metrics included the Dice similarity coefficient (DSC), Jaccard similarity coefficient (JSC), and Hausdorff distance (HD). Dosimetric evaluation compared radiotherapy plans generated using automatic segmentation (plan AD) versus manual hippocampus segmentation (plan MD)., Results: SwinHS outperformed four advanced deep learning-based models, achieving an average DSC of 0.894, a JSC of 0.817, and an HD of 3.430 mm. Dosimetric evaluation revealed that both plan (AD) and plan (MD) met treatment plan constraints for the target volume (PTV). However, the hippocampal D max in plan (AD) was significantly greater than that in plan (MD), approaching the 17 Gy constraint limit. Nonetheless, there were no significant differences in D 100% or maximum doses to other critical structures between the two plans., Conclusion: Compared with manual delineation, SwinHS demonstrated superior segmentation performance and a significantly shorter delineation time. While plan (AD) met clinical requirements, caution should be exercised regarding hippocampal D max . SwinHS offers a promising tool to enhance workflow efficiency and facilitate hippocampal protection in radiotherapy planning for patients with brain metastases., Competing Interests: ZL was employed by HaiChuang Future Medical Technology Co., Ltd. The remaining 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 © 2024 Li, Lu, Jiang, Sha, Luo, Xie and Ding.)

Peroxisomes are dynamic organelles involved in various cellular processes, including lipid metabolism, redox homeostasis, and intracellular metabolite transfer. Accumulating evidence suggests that peroxisomal homeostasis plays a crucial role in human health and disease, particularly in metabolic disorders and ferroptosis. The abundance and function of peroxisomes are regulated by a complex interplay between biogenesis and degradation pathways, involving peroxins, membrane proteins, and pexophagy. Peroxisome-dependent lipid metabolism, especially the synthesis of ether-linked phospholipids, has been implicated in modulating cellular susceptibility to ferroptosis, a newly discovered form of iron-dependent cell death. This review discusses the current understanding of peroxisome homeostasis, its roles in redox regulation and lipid metabolism, and its implications in human diseases. We also summarize the main mechanisms of ferroptosis and highlight recent discoveries on how peroxisome-dependent metabolism and signaling influence ferroptosis sensitivity. A better understanding of the interplay between peroxisomal homeostasis and ferroptosis may provide new insights into disease pathogenesis and reveal novel therapeutic strategies for peroxisome-related metabolic disorders and ferroptosis-associated diseases., (© 2024. The Author(s).)

Epitopes, the basic functional units of antigens, hold great significance in the field of immunology. However, the structure and composition of epitopes and their interactions with antibodies remain unclear, which limits in-depth studies on epitopes and the development of subunit vaccines. In a previous study on the localization of anti-influenza HA monoclonal antibodies (mAbs), three strains with different characteristics reacted with the same peptide. In this study, by conventional immunological assays, computer homology modeling, and molecular docking simulations, we found that (1) the peptide could bind to three strains of mAbs with different reaction characteristics utilizing different combinations of immunodominant groups. (2) By computer molecular docking and simulation methods, the immunodominant groups on the two peptides could be combined into a multi-epitope peptide bound to six strains of mAbs. We established a method for multi-epitope peptide recombination from these immunodominant groups. (3) The immune effect of the recombinant multi-epitope peptide was better than that of a single peptide. Our findings facilitate the understanding of the composition of antigen epitopes and provide a theoretical and experimental basis for developing polyvalent vaccines and understanding immune responses at the molecular level., (© 2024 Wiley Periodicals LLC.)

Metasurfaces provide an unprecedented platform for precise and subwavelength-scale modulation of optical phases, leading to innovative advancements in wavefront shaping and holography devices. This study presents a single-layer umbrella-like metasurface capable of multichannel holography, encoded with both polarization and wavelength. By leveraging a unique chiral-assisted strategy, we achieve simultaneous decoupling of wavelength and spin states through single-parameter modulation. This approach circumvents the complex structure designs and multi-parameter adjustments typically required in previous methods. Numerical simulations confirm the effectiveness of this metasurface, demonstrating wavelength- and spin-decoupled phase modulation at 1550 and 980 nm. Furthermore, we successfully demonstrate a four-channel hologram operable in both transmission and reflection modes, showcasing the potential applications of this metasurface in compact functional integration, information encryption, and 3D displays. This work paves the way for the development of multifunctional optical devices with enhanced integration and performance.

2-(2H-benzotriazol-2-yl)-4,6-di-tert-pentylphenol (UV328) is an emerging persistent organic pollutant ubiquitously found in environmental matrices. Though some advanced oxidation processes have been tested to degrade UV328 in waste streams, the degradation mechanisms are largely unknown. In this study, the degradation of UV328 by ozone (O 3 ) and peroxymonosulfate (PMS) was systemically investigated. At neutral pH, 97.0% UV328 was removed in 5 min with 6.4 mg/min O 3 and 2 mM PMS, and the degradation rate was positively correlated with the concentration of oxidants. Hydroxyl radical (•OH), sulfate radical (SO 4 •- ) and singlet oxygen ( 1 O 2 ) participated in the degradation of UV328, in which 1 O 2 played a key role. Based on the identified transformation intermediates and density functional theory simulations, three degradation pathways of dehydrogenation, cycloaddition and hydroxylation were proposed. •OH and SO 4 •- radicals could attack UV328 through hydrogen atom abstraction channel. 1 O 2 -mediated cycloaddition reaction is favorable, and •OH could react with UV328 via radical adduct formation pathway. Toxicity assessment indicated that O 3 /PMS treatment mitigated the ecological risks of UV328., 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.)

Background: Lianpu Drink (LPY) is a classic prescription for treating spleen-stomach damp-heat syndrome (SSDHS), known for its ability to clear heat and eliminate dampness. However, the underlying mechanisms of LPY in treating SSDHS remain unclear., Objectives: This study aims to use non-target metabolomics to unravel the effects and mechanisms of LPY on SSDHS., Methods: A metabolomics technique based on ultra-high-performance liquid chromatography-tandem quadrupole time-of-flight mass spectrometry (UPLC-Q-TOF/MS) was used to identify the endogenous small-molecule metabolites in the urine of SSDHS model rats and find the metabolites associated with the LPY treatment of SSDHS. Furthermore, a network pharmacological analysis and molecular docking experiments were used to screen and validate the key metabolic pathways regulated by LPY., Results: LPY exerted therapeutic effects on SSDHS by increasing the levels of motilin and gastrin, reducing the rectal temperature, alleviating the pathological changes in gastric and colonic tissues, and regulating the metabolic pattern in SSDHS rats. A total of 25 different metabolites, including L-histidine, citric acid and isocitric acid, were identified as the potential biomarkers for SSDHS via metabolomics. Among them, 11 metabolites were substantially reversed by LPY, including L-histidine, citric acid, isocitric acid, pantothenic acid, homovanillic acid sulfate, hippuric acid, indole-3-carboxilic acid-O-sulphate, 6-hydroxy-5-methoxyindole glucuronide, 2-phenylethan-ol glucuronide, 3-hydroxydodecanedioic acid and 3-methoxy-4-hydroxy-phenylethyleneglyclol sulfate. The results of network pharmacological analysis and molecular docking experiments validated that LPY ameliorated SSDHS by regulating the citrate cycle and histidine metabolism., Conclusion: We preliminarily investigated the effects and mechanisms of LPY on SSDHS at the level of endogenous small-molecule metabolites. Furthermore, this study provides a novel perspective for objectively evaluating the therapeutic effects, and exploring the mechanisms of Chinese medicinal formulas on SSDHS., 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 Author(s). Published by Elsevier B.V. All rights reserved.)

The precise and safe treatment of bioorthogonal prodrug system is hindered by separate administration of prodrug and its activator, which often results in poor therapeutic effects and severe side effects. To address above issues, we herein construct a single bioorthogonal-activated co-delivery system for simultaneous PROTAC prodrug (proPROTAC) delivery and controlled, site-specific activation for tumor-specific treatment. In this co-delivery system (termed AuPLs), prodrug (proPROTAC) and water-soluble Pd-catalyst are first encapsulated by gold nanocubes (AuNCs), which are further coated with a layer of phase-change material (lauric acid/stearic acid, LA/SA). Below 39 °C, the solid state of LA/SA prevents the activation of Pd-mediated bioorthogonal reaction due to the solidification of Pd-catalyst and proPROTAC. Nevertheless, once over 42 °C, the phase change of LA/SA into liquid state, enabled by the photothermal effect of AuNCs, triggers the simultaneous release of proPROTAC and Pd-catalyst and initiates the in situ bioorthogonal reaction for proPROTAC activation. In the tumor-bearing mouse models, the systemic administration of AuPLs results in the accumulation in tumor region, where the photothermal effect activates and controls the tumor-specific bioorthogonal reaction to degrade BRD4 protein, leading to anti-tumor effects with minimized side effects. Overall, the co-delivery proPROTAC and Pd-catalyst and controlled activation by photothermal effects provide a precise way for biorthogonal-based anticancer prodrugs., Competing Interests: Declaration of competing interest The authors declare no conflict of interest., (Copyright © 2024 Elsevier B.V. All rights reserved.)

Protease-activated receptors (PARs) are a unique group within the G protein-coupled receptor superfamily, orchestrating cellular responses to extracellular proteases via enzymatic cleavage, which triggers intracellular signaling pathways. Protease-activated receptor 1 (PAR1) is a key member of this family and is recognized as a critical pharmacological target for managing thrombotic disorders. In this study, we present cryo-electron microscopy structures of PAR1 in its activated state, induced by its natural tethered agonist (TA), in complex with two distinct downstream proteins, the G q and G i heterotrimers, respectively. The TA peptide is positioned within a surface pocket, prompting PAR1 activation through notable conformational shifts. Contrary to the typical receptor activation that involves the outward movement of transmembrane helix 6 (TM6), PAR1 activation is characterized by the simultaneous downward shift of TM6 and TM7, coupled with the rotation of a group of aromatic residues. This results in the displacement of an intracellular anion, creating space for downstream G protein binding. Our findings delineate the TA recognition pattern and highlight a distinct role of the second extracellular loop in forming β-sheets with TA within the PAR family, a feature not observed in other TA-activated receptors. Moreover, the nuanced differences in the interactions between intracellular loops 2/3 and the Gα subunit of different G proteins are crucial for determining the specificity of G protein coupling. These insights contribute to our understanding of the ligand binding and activation mechanisms of PARs, illuminating the basis for PAR1's versatility in G protein coupling., (© 2024. The Author(s).)

Ferroptosis is a form of cell death that is induced by iron-mediated accumulation of lipid peroxidation. The involvement of ferroptosis in different pathophysiological conditions has offered new perspectives on potential therapeutic interventions. Natural products, which are widely recognized for their significance in drug discovery and repurposing, have shown great promise in regulating ferroptosis by targeting various ferroptosis players. In this review, we discuss the regulatory mechanisms of ferroptosis and its implications in different pathological conditions. We dissect the interactions between natural products and ferroptosis in cancer, ischemia/reperfusion, neurodegenerative diseases, acute kidney injury, liver injury, and cardiomyopathy, with an emphasis on the relevance of ferroptosis players to disease targetability., (© 2024. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature.)

Background: Prolonged use of anti-arrhythmic drugs (AAD) beyond the post-ablation blanking period to maintain sinus rhythm has been adopted in clinical practice but without sufficient evidence. Dronedarone is an AAD valid for maintaining sinus rhythm with fewer side effects than other AAD for long-term use., Objective: We sought to investigate the effect of prolonged use of dronedarone on the recurrence of non-paroxysmal AF patients beyond 3 months within the first year after ablation., Methods: Non-paroxysmal AF patients will receive dronedarone for 3 months after radiofrequency ablation. Patients without drug side effects and atrial tachyarrhythmia (AT) recurrence will then be randomly divided into dronedarone and placebo groups and followed up until 1 year after ablation. The primary endpoint is the cumulative nonrecurrence rate post 3 months to 1 year after ablation. Patients will receive 7-day Holter monitoring (ECG patch) at 6, 9, and 12 months after ablation to evaluate AT recurrence. Secondary endpoints include dronedarone withdrawal due to side effects or intolerance of AT recurrence, time to the first recurrence, repeat ablation, electrical cardioversion, unscheduled emergency room visit, or re-hospitalization., Conclusion: This trial will evaluate whether prolonged use of dronedarone effectively reduces the recurrence rate after ablation in non-paroxysmal AF patients. The result of this trial will provide evidence for optimizing post-ablation anti-arrhythmic therapy., Trial Registration: ClinicalTrials.gov ; NCT05655468, 19-December-2022., (© 2023. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.)

Telomeres are repetitive DNA sequences and associated protein complexes located at the end of chromatin. As a result of the DNA replication ending issue, telomeric DNA shortens during each cell cycle. The shelterin protein complex caps telomeric ends and forms a high-order protein-DNA structure to protect telomeric DNA. The stability of telomeres is critical for cellular function and is related to the progression of many human diseases. Telomeric repeat-containing RNA (TERRA) is a noncoding RNA transcribed from telomeric DNA regions. TERRA plays an essential role in regulating and maintaining the stability of telomeres. Heterogeneous nuclear ribonucleoproteins (hnRNPs) are RNA-binding proteins associated with complex and diverse biological processes. HnRNPA1 can recognize both TERRA and telomeric DNA. Previous research reported that hnRNPA1, TERRA, and POT1, a component of the shelterin complex, worked coordinately and displaced replication protein A from telomeric ssDNA after DNA replication, promoting telomere capping to preserve genomic integrity. However, the detailed molecular mechanism has remained unclear for over twenty years. Our study revealed the molecular structure through which the hnRNPA1 UP1 domain interacts with TERRA. Through structural analysis, we identified critical residues on the interacting surface between UP1 and TERRA. Furthermore, we proved that nucleic acids significantly increase the phase separation ability of hnRNPA1 and disrupting the UP1-TERRA interaction extraordinarily affects hnRNPA1 droplet formation both in vitro and in vivo. Taken together, these data revealed the molecular mechanism of the droplet formation of hnRNPA1 and TERRA and the possible function of the droplets for maintaining genomic stability., (© The Author(s) 2024. Published by Oxford University Press on behalf of Institute of Biochemistry and Cell Biology, Shanghai Institutes for Biological Sciences, Chinese Academy of Sciences.)

Sorghum is the world's fifth-largest cereal crop, and anthracnose (Colletotrichum sublineola) is the main disease affecting sorghum. However, systematic research on the cellular structure, physiological and biochemical, and genes related to anthracnose resistance and disease resistance evaluation in sorghum is lacking in the field. Upon inoculation with anthracnose (C. sublineola) spores, disease-resistant sorghum (gz93) developed a relative lesion area (RLA) that was significantly smaller than that of the disease-susceptible sorghum (gz234). The leaf thickness, length and profile area of leaf mesophyll cells, upper and lower epidermal cells decreased in the lesion area, with a greater reduction observed in gz234 than in gz93. The damage caused by C. sublineola resulted in a greater decrease in the net photosynthetic rate (Pn) in gz234 than in gz93, with early-stage reduction due to stomatal limitation and late-stage reduction caused by lesions. Overall, the activities of superoxide dismutase (SOD) and catalase (CAT), the content of proline (Pro), abscisic acid (ABA), jasmonic acid (JA), salicylic acid (SA), and gibberellic acid (GA 3 ), are higher in gz93 than in gz234 and may be positively correlated with disease resistance. While malondialdehyde (MDA) may be negatively correlated with disease resistance. Disease-resistant genes are significantly overexpressed in gz93, with significant expression changes in gz234, which is related to disease resistance in sorghum. Correlation analysis indicates that GA 3 , MDA, peroxidase (POD), and disease-resistance genes can serve as reference indicators for disease severity. The regression equation RLA = 0.029 + 8.02 × 10 -6 JA-0.016 GA 3 can predict and explain RLA. Principal component analysis (PCA), with the top 5 principal components for physiological and biochemical indicators and the top 2 principal components for disease-resistant genes, can explain 82.37% and 89.11% of their total variance, reducing the number of evaluation indicators. This study provides a basis for research on the mechanisms and breeding of sorghum with resistance to anthracnose., (© 2024. The Author(s).)

Fueled by the rapid advancement of nanofabrication, metasurface has provided unprecedented opportunities for 3D holography. Large depth 3D meta-holography not only greatly increases information storage capacity, but also enables distinguishing of the relative spatial relationship of 3D objects, which has important applications in fields like optical information storage and medical diagnosis. Although the methods based on Fresnel diffraction theory can reconstruct the real depth information of 3D objects, the maximum depth is only 2 mm. Here, we develop a 3D meta-holography based on angular spectrum diffraction theory to break through the depth limit. By developing the angular spectrum diffraction theory into meta-holography, the metasurface structure with independent polarization control is used to create a polarization multiplexing 3D meta-hologram. The fabricated amorphous silicon metasurface increases the depth range by 47.5 times and realizes 0.95 dm depth reconstruction for polarization independent and different color 3D meta-hologram in visible. Such polarization controlled large-depth color meta-holography is expected to open avenue for data storage, display, information security and virtual reality., (© 2024. The Author(s).)

Heavy metal stress threatens plant growth and productivity. In this study, we investigated the effects of CuSO 4 and ZnSO 4 toxicity on sorghum seedlings, focusing on their impact on biomass, germination rates, growth parameters, antioxidant enzyme activities, gene expression profiles, and stress resistance mechanisms. As a result, eight sorghum superoxide dismutase (SOD) genes were identified, and their evolutionary relationships with cis-acting regulatory elements and their expressional patterns were evaluated. Integrating transcriptomic data revealed a key SOD member SbCSD1 that might contribute to plant abiotic stress resistance. Furthermore, SbCSD1 overexpression enhanced plant tolerance to CuSO 4 and ZnSO 4 stress by regulating SOD activity and interacting with copper chaperone for superoxide dismutase 1 (CCS1) in the plant nucleus and cytoplasm. Meanwhile, silencing CCS1 in SbCSD1-overexpressing plants revealed that SbCSD1 and CCS1 synergistically contribute to Cu stress tolerance. By integrating transcriptomic and genetic data, herein we provide novel insights into the orchestration of plant responses to heavy-metal stress in sorghum by SOD., 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.)

Cancer poses a substantial global health challenge, necessitating the widespread use of chemotherapy and radiotherapy. Despite these efforts, issues like resistance development and severe side effects remain. As such, the search for more effective alternatives is critical. Andrographolide, a naturally occurring compound, has recently gained attention for its extensive biological activities. This review explores the role of andrographolide in cancer therapy, especially focusing on the molecular mechanisms that drive its anti-tumor properties. It also examines innovative methods to enhance andrographolide's bioavailability, thus boosting its effectiveness against cancer. Notably, andrographolide has potential for use in combination with various clinical drugs, and both preclinical and clinical studies provide strong evidence supporting its broader anticancer applications. Additionally, this paper proposes future research directions for andrographolide's anti-cancer effects and discusses the challenges in its clinical usage along with current research efforts to address these issues. In summary, this review underscores andrographolide's potential roles and contributes to the development of improved cancer treatment strategies., Competing Interests: Declaration of Competing Interest The authors declare that there are no conflict of interests, we do not have any possible conflicts of interest., (Copyright © 2024 The Authors. Published by Elsevier Masson SAS.. All rights reserved.)

Plastic additive-related chemicals, particularly in polyvinyl chloride (PVC) plastics, have become a key issue in plastic pollution. Although addressing plastic pollution through the life-cycle approach is crucial, the environmental impacts of typical plastic additive-related chemicals in PVC plastics during the cradle-to-gate stage remain unexplored. Consequently, managing the life-cycle environmental impacts of these additives remains challenging. Herein, the environmental impacts of 23 typical plastic additive-related chemicals and six PVC plastic products were evaluated throughout the cradle-to-gate life-cycle stage using a life cycle assessment-material flow analysis (LCA-MFA) coupled model. The results indicate that plastic additives significantly contribute to the environmental impacts of PVC plastic products across various end point indicators, ranging from 8.7 to 40.6%. Additionally, scenario analysis (SA) reveals that conventional strategies for addressing plastic pollution may not be highly effective in mitigating the environmental impacts associated with plastic additives. Specifically, compared to primary polymers, these additives exhibit 4 to 13% lower mitigation potential under the same policy scenarios. However, technical adjustment strategies targeting additives show a mitigation potential of 12 to 39%, suggesting that guiding the plastic additive industry toward green transformation is a key strategy for reducing environmental impacts.

Background: Vascular endothelial growth factor (VEGF) is a candidate mediator of blood-brain barrier (BBB) disruption in depression. However, previous studies have mainly focused on peripheral blood VEGF levels, and the results are heterogeneous. Here we use astrocyte-derived extracellular vesicles (ADEVs) isolated from plasma to explore the in vivo changes of VEGF levels in patients with major depressive disorder (MDD)., Methods: Thirty-five unmedicated patients with MDD and 35 healthy controls (HCs) were enrolled, and plasma ADEVs were isolated from each participant. VEGF levels in ADEVs and glial fibrillary acidic protein (GFAP) in plasma were measured. Additionally, Alix and CD81, two established extracellular vesicle markers, were quantified in ADEVs., Results: At baseline, MDD patients exhibited significantly increased levels of VEGF in ADEVs and GFAP in plasma. Following four weeks of selective serotonin reuptake inhibitor treatment, these target protein levels did not significantly change. ROC curve analysis revealed an AUC of 0.711 for VEGF in ADEVs. In exploratory analysis, VEGF levels in ADEVs were positively correlated with Alix and CD81., Limitations: Multiple factors regulate BBB permeability. This study focused solely on VEGF and the sample size for longitudinal analysis was relatively small., Conclusion: Our study is the first to confirm increased ADEV-derived VEGF levels in patients with MDD, thereby providing preliminary evidence supporting the hypothesis that the BBB is disrupted in depression., Competing Interests: Declaration of competing interest All authors declare that they have no conflicts of interest., (Copyright © 2024 Elsevier B.V. All rights reserved.)

It is important to attain red hot exciton materials applicable in highly efficient organic light-emitting diodes with low-efficiency roll-off, but their development is restricted by the energy gap law. Herein, the sulfur atom was replaced by a heavier selenium atom based on benzothiadiazole to obtain a new benzoselenadiazole acceptor with a heavy atom effect and stronger electron-withdrawing ability. Two novel red hot exciton materials named BSe-DtBuTPA and BSe-2PhCz-d 24 were designed and synthesized based on the benzoselenadiazole unit. Benefiting from the heavy-atom effect of selenium and the small Δ E S 1 T 2 , both emitters exhibited ultrafast high-lying reverse intersystem crossing rate constants (7.00 × 10 7 and 1.17 × 10 7 s -1 ). The devices based on BSe-DtBuTPA and BSe-2PhCz-d 24 demonstrated maximum external quantum efficiencies of 4.81 and 7.15% with emission peaks at 653 and 596 nm, respectively. The device based on deep-red BSe-DtBuTPA exhibited negligible efficiency roll-off of 18.5% at 10000 cd/m 2 .

Vacuum collected toilet wastewater (VCTW) contains high and fluctuating contents of organics and nitrogen, which exerts technological challenges to biological treatment processes. A partial nitrification-denitrification and anammox (PND-AMX) process was developed in sequencing batch reactor (SBR) and moving bed biofilm reactor (MBBR) to achieve effective nitrogen removal in VCTW at low ambient temperature. Stable PND was achieved, and nitrogen removal efficiency in SBR could be manipulated by adjusting influent COD/N ratios. As temperature ≥18 °C, 91.0% nitrogen was removed in PND-AMX process. In spite of the decreased anammox activity at 13-18 °C, more than 90% nitrogen removal could be obtained by adjusting SBR influent COD/N to 2.43 ± 0.32 with methanol. In MBBR reactor, Candidatus Kuenenia was the dominant anammox bacteria and contributed to more than 90% nitrogen removal capacity. Co-existing anammox and denitrifying bacteria synergistically contributed to the removal of ammonium, nitrite, nitrate, and COD in MBBR., 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.)

Floquet engineering is a promising tool to manipulate quantum systems coherently. A well-known example is the optical Stark effect, which has been used for optical trapping of atoms and breaking time-reversal symmetry in solids. However, as a coherent nonlinear optical effect, Floquet engineering typically requires high field intensities obtained in ultrafast pulses, severely limiting its use. Here, we demonstrate using cavity engineering of the vacuum modes to achieve orders-of-magnitude enhancement of the effective Floquet field, enabling Floquet effects at an extremely low fluence of 450 photons/μm 2 . At higher fluences, the cavity-enhanced Floquet effects lead to 50 meV spin and valley splitting of WSe 2 excitons, corresponding to an enormous time-reversal breaking, non-Maxwellian magnetic field of over 200 T. Utilizing such an optically controlled effective magnetic field, we demonstrate an ultrafast, picojoule chirality XOR gate. These results suggest that cavity-enhanced Floquet engineering may enable the creation of steady-state or quasi-equilibrium Floquet bands, strongly non-perturbative modifications of materials beyond the reach of other means, and application of Floquet engineering to a wide range of materials and applications., (© 2024. The Author(s).)

Background: Acute myeloid leukemia (AML) is an immunosuppressive hematologic malignancy with a poor prognosis. An immunosuppressive microenvironment blunts AML therapy. However, the prognostic and therapeutic roles of the factors that mediate immunosuppression in AML remain elusive., Methods: S100 calcium-binding protein A4 (S100A4) was identified as an immunosuppression-mediating factor by analyzing The Cancer Genome Atlas AML project (TCGA-LAML) transcriptome data and data from AML-bearing mice and AML patients. The S100A4-mediated signaling pathway in myeloid-derived suppressor cells (MDSCs) was evaluated., Results: Elevated S100A4 expression was positively associated with worse survival of AML patients, MDSCs, macrophages and immune checkpoints. S100A4 silencing downregulated the expression levels of MDSC-associated CD14, CCR2 and CCL2, reduced MDSC expansion and impaired MDSC-mediated inhibition of T cell activation and proliferation. S100A4-based prognostic signature (SPS) was an independent risk factor for AML patients. The high-risk group based on SPS was not only associated with adverse survival, MDSCs and macrophages and immune checkpoints but also insensitive to 25 chemotherapy drugs. It was also found that CCAAT enhancer binding protein beta (CEBPB) mediated S100A4 transcription. CEBPB silencing downregulated the expression levels of MDSC-associated CD14, CCR2 and CCL2. Mechanistically, S100A4 activated GP130/JAK2/STAT3 signaling in MDSCs by interacting with the cytokine-binding domain of GP130. Moreover, S100A4 mediated MDSC expansion through JAK2/STAT3 signaling., Conclusion: This study uncovers the critical role of S100A4 in MDSC accumulation, and S100A4-based prognostic signature may guide chemotherapy sensitivity in patients with AML., 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 B.V.)

Purpose: To investigate the neuroplasticity hypothesis of depression by measuring brain-derived neurotrophic factor (BDNF) levels in plasma astrocyte-derived extracellular vesicles (ADEVs) and to evaluate their potential as biomarkers for depression compared with plasma BDNF levels., Patients and Methods: Thirty-five patients with major depressive disorder (MDD) and 35 matched healthy controls (HCs) were enrolled. Plasma ADEVs were isolated using a combination of ultracentrifugation and immunoaffinity capture. Isolated ADEVs were validated using transmission electron microscopy, nanoparticle tracking analysis, and Western blotting. BDNF levels were quantified in both ADEVs and plasma. ALG-2-interacting protein X (Alix) and cluster of differentiation 81 (CD81) levels, two established extracellular vesicle markers, were measured in ADEVs., Results: After false discovery rate correction, patients with MDD exhibited higher CD81 levels ( P FDR = 0.040) and lower BDNF levels ( P FDR = 0.043) in ADEVs than HCs at baseline. BDNF levels in ADEVs normalized to CD81 ( P FDR = 0.002) and Alix ( P FDR = 0.040) remained consistent with this finding. Following four weeks of selective serotonin reuptake inhibitor treatment (n=10), CD81 levels in ADEVs decreased ( P FDR = 0.046), while BDNF levels normalized to CD81 increased ( P FDR = 0.022). BDNF levels in ADEVs were more stable than in plasma. Exploratory analysis revealed no correlation between BDNF levels in ADEVs and plasma ( ρ =0.117, P = 0.334)., Conclusion: This study provides human in vivo evidence supporting the neuroplasticity hypothesis of depression by demonstrating altered BDNF levels in ADEVs. ADEVs may be more suitable for developing biomarkers of depression than plasma-derived biomarkers., Competing Interests: The authors report no conflicts of interest in this work., (© 2024 Li et al.)

Our previous study has identified that glutamate in the red nucleus (RN) facilitates the development of neuropathic pain through metabotropic glutamate receptors (mGluR). Here, we further explored the actions and possible molecular mechanisms of red nucleus mGluR Ⅰ (mGluR1 and mGluR5) in the development of neuropathic pain induced by spared nerve injury (SNI). Our data indicated that both mGluR1 and mGluR5 were constitutively expressed in the RN of normal rats. Two weeks after SNI, the expressions of mGluR1 and mGluR5 were significantly boosted in the RN contralateral to the nerve injury. Administration of mGluR1 antagonist LY367385 or mGluR5 antagonist MTEP to the RN contralateral to the nerve injury at 2 weeks post-SNI significantly ameliorated SNI-induced neuropathic pain. However, unilateral administration of mGluRⅠ agonist DHPG to the RN of normal rats provoked a significant mechanical allodynia, this effect could be blocked by LY367385 or MTEP. Further studies indicated that the expressions of TNF-α and IL-1β in the RN were also elevated at 2 weeks post-SNI. Administration of mGluR1 antagonist LY367385 or mGluR5 antagonist MTEP to the RN at 2 weeks post-SNI significantly inhibited the elevations of TNF-α and IL-1β. However, administration of mGluR Ⅰ agonist DHPG to the RN of normal rats significantly enhanced the expressions of TNF-α and IL-1β, these effects were blocked by LY367385 or MTEP. These results suggest that activation of red nucleus mGluR1 and mGluR5 facilitate the development of neuropathic pain by stimulating the expressions of TNF-α and IL-1β. mGluR Ⅰ maybe potential targets for drug development and clinical treatment of neuropathic pain., Competing Interests: Declaration of competing interest The authors have approved the manuscript entitled “Red nucleus mGluR1 and mGluR5 facilitate the development of neuropathic pain through stimulating the expressions of TNF-α and IL-1β” and agreed with the submission to Neurochemistry International. All 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 Ltd.. All rights reserved.)

Background: Hypoxic pulmonary vascular remodeling (HPVR) is a key pathological feature of hypoxic pulmonary hypertension (HPH). Oxygen-sensitive potassium (K + ) channels in pulmonary artery smooth muscle cells (PASMCs) play a crucial role in HPVR. Luteolin (Lut) is a plant-derived flavonoid compound with variety of pharmacological actions. Our previous study found Lut alleviated HPVR in HPH rat., Purpose: To elucidate the mechanism by which Lut mitigated HPVR, focusing on oxygen-sensitive voltage-dependent potassium channel 1.5 (Kv1.5)., Methods: HPH rat model was established using hypobaric chamber to simulate 5000 m altitude. Isolated perfused/ventilated rat lung, isolated pulmonary arteriole ring was utilized to investigate the impact of Lut on K + channels activity. Kv1.5 level in lung tissue and pulmonary arteriole of HPH rat was assessed. CyclinD1, CDK4, PCNA, Bax, Bcl-2, cleaved caspase-3 levels in lung tissue of HPH rat were tested. The effect of Lut on Kv1.5, cytoplasmic free calcium concentration ([Ca 2+ ] cyt ), CyclinD1, CDK4, PCNA, Bax/Bcl-2 was examined in PASMCs under hypoxia, with DPO-1 as a Kv1.5 specific inhibitor. The binding affinity between Lut and Kv1.5 in PASMCs was detected by drug affinity responsive target stability (DARTS). The overexpression of KCNA5 gene (encoding Kv1.5) in HEK293T cells was utilized to confirm the interaction between Lut and Kv1.5. Furthermore, the impact of Lut on mitochondrial structure, SOD, GSH, GSH-Px, MDA and HIF-1α levels were evaluated in lung tissue of HPH rat and PASMCs under hypoxia., Results: Lut dilated pulmonary artery by directly activating Kv and Ca 2+ -activated K + channels (K Ca ) in smooth muscle. Kv1.5 level in lung tissue and pulmonary arteriole of HPH rat was upregulated by Lut. Lut downregulated CyclinD1, CDK4, PCNA while upregulating Bax/Bcl-2/caspase-3 axis in lung tissue of HPH rat. Lut decreased [Ca 2+ ] cyt , reduced CDK4, CyclinD1, PCNA, increased Bax/Bcl-2 ratio, in PASMCs under hypoxia, by upregulating Kv1.5. The binding affinity and the interaction between Lut and Kv1.5 was verified in PASMCs and in HEK293T cells. Lut also decreased [Ca 2+ ] cyt and inhibited proliferation via targeting Kv1.5 of HEK293T cells under hypoxia. Furthermore, Lut protected mitochondrial structure, increased SOD, GSH, GSH-Px, decreased MDA, in lung tissue of HPH rat. Lut downregulated HIF-1α level in both lung tissue of HPH rat and PASMCs under hypoxia., Conclusion: Lut alleviated HPVR by promoting vasodilation of pulmonary artery, reducing cellular proliferation, and inducing apoptosis through upregulating of Kv1.5 in PASMCs., Competing Interests: Declaration of competing interest We declare that we do not have any commercial or associative interest that represents a conflict of interest in connection with the work submitted., (Copyright © 2024 Elsevier GmbH. All rights reserved.)

The myelin sheath plays crucial roles in brain development and neuronal functions. In the central nervous system, myelin is generated by oligodendrocytes, that differentiate from oligodendrocyte progenitor cells (OPC). In demyelinating diseases, the differentiation capacity of OPC is impaired and remyelination is dampened. Boosting remyelination by promoting OPC differentiation is a novel strategy for the treatment of demyelinating diseases. The opioid system, which consists of four receptors and their ligands, has been implicated in OPC differentiation and myelin formation. However, the exact roles of each opioid receptor and the relevant pharmacological molecules in OPC differentiation and myelin formation remain elusive. In the present study, specific agonists and antagonists of each opioid receptor were used to explore the function of opioid receptors in OPC differentiation. Nociceptin/orphanin FQ receptor (NOPR) specific antagonist LY2940094 was found to stimulate OPC differentiation and myelination in both in vitro and in vivo models. Unexpectedly, other NOPR ligands did not affect OPC differentiation, and NOPR knockdown did not mimic or impede the effect of LY2940094. LY2940094 was found to modulate the expression of the oligodendrocytes differentiation-associated transcription factors ID4 and Myrf, although the exact mechanism remains unclear. Since LY2940094 has been tested clinically to treat depression and alcohol dependency and has displayed an acceptable safety profile, it may provide an alternative approach to treat demyelinating diseases., 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 Author(s). Published by Elsevier Inc. All rights reserved.)

Background: Hepatocellular Carcinoma (HCC) is the most common digestive system malignancy, with unclear pathogenesis and low survival rates. AP1M2 is associated with tumor progression, but its role and molecular mechanisms in HCC remain poorly understood and require further investigation., Methods: We utilized the Gene Expression Omnibus (GEO) and Expression Analysis Interactive Hub (XENA) databases to assess AP1M2 mRNA expression levels in HCC patients. Additionally, we employed the Cancer Genome Atlas (TCGA) database to identify pathways associated with both AP1M2 and HCC development. To evaluate the effect of AP1M2 on HCC cell proliferation and migration, we employed various techniques including EdU, CCK-8, Colony formation assay, and Transwell assays. Furthermore, Western blot analysis was conducted to examine the signaling pathways influenced by AP1M2., Results: AP1M2 expression was significantly increased at the mRNA level in HCC tissues(P<0.001). Importantly, overall survival (OS) analysis confirmed the association between higher AP1M2 expression and a poorer prognosis in HCC patients compared to those with lower AP1M2 expression (P<0.019).Multivariate Cox regression analysis showed that AP1M2 was an independent prognostic factor and a valid predictor for HCC patients. Furthermore, GSEA results indicated differential enrichment of lipid, metal metabolism, and coagulation processes in HCC samples demonstrating a high AP1M2 expression phenotype. In vitro experiments supported these findings by demonstrating that AP1M2 promotes HCC cell proliferation and migration, while activating the JNK/ERK pathway., Conclusion: Our findings indicate that AP1M2 expression may serve as a potential molecular marker indicating a poor prognosis for HCC patients. Furthermore, we have demonstrated that AP1M2 significantly influences HCC cell proliferation and migration, with the JNK/ERK signaling pathway playing a key role in AP1M2-mediated regulation in the context of HCC., 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.)

As a reactive sulfur species, sulfur dioxide (SO 2 ) and its derivatives play crucial role in various physiological processes, which can maintain redox homeostasis at normal levels and lead to the occurrence of many diseases at abnormal levels. So, the development of a suitable fluorescent probe is a crucial step in advancing our understanding of the role of SO 2 derivatives in living organisms. Herein, we developed a near-infrared fluorescent probe (SP) based on the ICT mechanism to monitor SO 2 derivatives in living organisms in a ratiometric manner. The probe SP exhibited excellent selectivity, good sensitivity, fast response rate (within 50 s), and low detection limit (1.79 µM). In addition, the cell experiment results suggested that the SP has been successfully employed for the real-time monitoring of endogenous and exogenous SO 2 derivatives with negligible cytotoxicity. Moreover, SP was effective in detecting SO 2 derivatives in mice., 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.)

Enhancing soil organic matter characteristics, ameliorating physical structure, mitigating heavy metal toxicity, and hastening mineral weathering processes are crucial approaches to accomplish the transition of tailings substrate to a soil-like substrate. The incorporation of biomass co-pyrolysis and plant colonization has been established to be a significant factor in soil substrate formation and soil pollutant remediation. Despite this, there is presently an absence of research efforts aimed at synergistically utilizing these two technologies to expedite the process of mining tailings soil substrate formation. The current study aimed to investigate the underlying mechanism of geochemical changes and rapid mineral weathering during the process of transforming tailings substrate into a soil-like substrate, under the combined effects of biomass co-smoldering pyrolysis and plant colonization. The findings of this study suggest that the incorporation of smoldering pyrolysis and plant colonization induces a high-temperature effect and biological effects, which enhance the physical and chemical properties of tailings, while simultaneously accelerating the rate of mineral weathering. Notable improvements include the amelioration of extreme pH levels, nutrient enrichment, the formation of aggregates, and an increase in enzyme activity, all of which collectively demonstrate the successful attainment of tailings substrate reconstruction. Evidence of the accelerated weathering was verified by phase and surface morphology analysis using X-ray diffraction and scanning electron microscopy. Discovered corrosion and fragmentation on the surface of minerals. The weathering resulted in corrosion and fragmentation of the surface of the treated mineral. This study confirms that co-smoldering pyrolysis of biomass, combined with plant colonization, can effectively promote the transformation of tailings into soil-like substrates. This method has can effectively address the key challenges that have previously hindered sustainable development of the mining industry and provides a novel approach for ecological restoration of tailings deposits., 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 © 2023. Published by Elsevier B.V.)

In 2019, we conducted a cross-sectional study for polio virus seroprevalence in Guangdong province, China. We assessed the positivity rates of poliomyelitis NA and GMT in serum across various demographic groups, and the current findings were compared with pre-switch data from 2014. Using multistage random sampling method, four counties/districts were randomly selected per city, and within each, one general hospital and two township hospitals were chosen. Healthy individuals coming for medical checkups or vaccination were invited. A total of 1318 individual samples were collected and tested. In non-newborn population, age-dependent positivity rates ranged from 77.8% to 100% for PV1 NA and 70.3% to 98.9% for PV3 NA ( p  < .01). The lowest GMT values for both types (17.03 and 8.46) occurred in the 20 to <30 years age group, while peak GMTs for PV1 and PV3 were observed in 1 to <2 (340.14) and 0 to <1-year (168.90) age groups, respectively. GMTs for PV1 ( P  = .002) and PV3 ( P  = .007) in Eastern Guangdong were lower than those in the other three regions. Male participants showed higher GMTs than females ( P  = .016 and .033, respectively). In newborn population, both males and females showed higher PV1 NA positivity rates and GMTs compared to PV3 ( p  < .05). Post-switch PV3 NA positivity rates were higher than pre-switch rates ( p  = .016). GMTs of both PV1 and PV3 were significantly higher post-switch ( p  < .001). The positivity rates of NAs and GMTs remain high level, which play an important role in resisting poliomyelitis infection. Effect of the converted immunization program was more pronounced than that before.

Because ascorbic acid (AA) is one of the basic elements to maintain the normal physiological functions of human body, it is urgent to develop a material that can achieve efficient, rapid and in-situ detection for AA. A new fluorescence organic compound 4',4'''-(benzo[c][1,2,5]thiadiazole-4,7-diyl)bis([1,1'-biphenyl]-4-carboxylic acid) (H 2 BTBC) based on benzothiadiazole group has been synthesized, which can detect Fe 3+ ions by fluorescence turn-off effect with a detection limit of 0.015 μM, as well as recognize linear amines by fluorescence turn-on effect. Moreover, a highly stable Tb(III) metal-organic framework has been solvothermally prepared with H 2 BTBC, namely {[(CH 3 ) 2 NH 2 ] 2 [Tb 2 (BTBC) 4 ]∙solvents} n (JXUST-39), which can selectively detect AA among biological fluids by fluorescence enhancement effect with a detection limit of 0.077 μM. In addition, the mechanism for JXUST-39 detecting AA is possibly the cooperative effect of absorbance-caused enhancement and charge transfer between JXUST-39 and AA. Moreover, LED lamp beads, fluorescent films and fluorescent detection test paper based on JXUST-39 were prepared to achieve portable detection via fluorescence enhancement effect., 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.)

Background: Arginine vasopressin (AVP) has been reported to regulate insulin secretion and glucose homeostasis in the body. Previous study has shown that AVP and its receptor V1bR modulate insulin secretion via the hypothalamic-pituitary-adrenal axis. AVP has also been shown to enhance insulin secretion in islets, but the exact mechanism remains unclear., Results: In our study, we unexpectedly discovered that AVP could only stimulates insulin secretion from islets, but not β cells, and AVP-induced insulin secretion could be blocked by V1bR selective antagonist. Single-cell transcriptome analysis identified that V1bR is only expressed by the α cells. Further studies indicated that activation of the V1bR stimulates the α cells to secrete glucagon, which then promotes glucose-dependent insulin secretion from β cells in a paracrine way by activating GLP-1R but not GCGR on these cells., Conclusions: Our study revealed a crosstalk between α and β cells initiated by AVP/V1bR and mediated by glucagon/GLP-1R, providing a mechanism to develop new glucose-controlling therapies targeting V1bR., (© 2024. The Author(s).)

The formation of memory T cells is a fundamental feature of adaptative immunity, allowing the establishment of long-term protection against pathogens. Although emerging evidence suggests that metabolic reprogramming is crucial for memory T cell differentiation and survival, the underlying mechanisms that drive metabolic rewiring in memory T cells remain unclear. Here, we found that up-regulation of the nuclear receptor peroxisome proliferator-activated receptor β/δ (PPARβ/δ) instructs the metabolic reprogramming that occurs during the establishment of central memory CD8 + T cells. PPARβ/δ-regulated changes included suppression of aerobic glycolysis and enhancement of oxidative metabolism and fatty acid oxidation. Mechanistically, exposure to interleukin-15 and expression of T cell factor 1 facilitated activation of the PPARβ/δ pathway, counteracting apoptosis induced by antigen clearance and metabolic stress. Together, our findings indicate that PPARβ/δ is a master metabolic regulator orchestrating a metabolic switch that may be favorable for T cell longevity.

A copper-catalyzed arylation or alkenylation of quinoline N -oxides with aryl- or alkenylboronates, respectively, has been developed, which provides an efficient route for C2-substituted oxygenated quinolines under mild reaction conditions. The reaction shows a broad substrate scope for both quinoline N -oxides and aryl/alkenylboronates, mild reaction conditions, and high reaction efficiency. The formation of an aryl- or alkenyl-copper species as the key intermediate was suggested to be involved in this reaction.

The pyroptosis of renal tubular epithelial cells leads to tubular loss and inflammation and then promotes renal fibrosis. The transcription factor Krüppel-like factor 4 (KLF4) can bidirectionally regulate the transcription of target genes. Our previous study revealed that sustained elevation of KLF4 is responsible for the transition of acute kidney injury (AKI) into chronic kidney disease (CKD) and renal fibrosis. In this study, we explored the upstream mechanisms of renal tubular epithelial cell pyroptosis from the perspective of posttranslational regulation and focused on the transcription factor KLF4. Mice were subjected to unilateral ureteral obstruction (UUO) surgery and euthanized on D7 or D14 for renal tissue harvesting. We showed that the pyroptosis of renal tubular epithelial cells mediated by both the Caspase-1/GSDMD and Caspase-3/GSDME pathways was time-dependently increased in UUO mouse kidneys. Furthermore, we found that the expression of the transcription factor KLF4 was also upregulated in a time-dependent manner in UUO mouse kidneys. Tubular epithelial cell-specific Klf4 knockout alleviated UUO-induced pyroptosis and renal fibrosis. In Ang II-treated mouse renal proximal tubular epithelial cells (MTECs), we demonstrated that KLF4 bound to the promoter regions of Caspase-3 and Caspase-1 and directly increased their transcription. In addition, we found that ubiquitin-specific protease 11 (USP11) was increased in UUO mouse kidneys. USP11 deubiquitinated KLF4. Knockout of Usp11 or pretreatment with the USP11 inhibitor mitoxantrone (3 mg/kg, i.p., twice a week for two weeks before UUO surgery) significantly alleviated the increases in KLF4 expression, pyroptosis and renal fibrosis. These results demonstrated that the increased expression of USP11 in renal tubular cells prevents the ubiquitin degradation of KLF4 and that elevated KLF4 promotes inflammation and renal fibrosis by initiating tubular cell pyroptosis., (© 2024. The Author(s), under exclusive licence to Shanghai Institute of Materia Medica, Chinese Academy of Sciences and Chinese Pharmacological Society.)

Recent years have seen a surge of machine learning (ML) in chemistry for predicting chemical properties, but a low-cost, general-purpose, and high-performance model, desirable to be accessible on central processing unit (CPU) devices, remains not available. For this purpose, here we introduce an atomic attention mechanism into many-body function corrected neural network (MBNN), namely, MBNN-att ML model, to predict both the extensive and intensive properties of molecules and materials. The MBNN-att uses explicit function descriptors as the inputs for the atom-based feed-forward neural network (NN). The output of the NN is designed to be a vector to implement the multihead self-attention mechanism. This vector is split into two parts: the atomic attention weight part and the many-body-function part. The final property is obtained by summing the products of each atomic attention weight and the corresponding many-body function. We show that MBNN-att performs well on all QM9 properties, i.e., errors on all properties, below chemical accuracy, and, in particular, achieves the top performance for the energy-related extensive properties. By systematically comparing with other explicit-function-type descriptor ML models and the graph representation ML models, we demonstrate that the many-body-function framework and atomic attention mechanism are key ingredients for the high performance and the good transferability of MBNN-att in molecular property prediction.