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Zi Wang,1 Xiaoyu Li,1 Qing Xu,1 Yao Yao,1 Xiaoye Li,1 Hongmei Yan,2 Qianzhou Lv1 1Department of Pharmacy, Zhongshan Hospital, Fudan University, Shanghai, People’s Republic of China; 2Department of Endocrinology and Metabolism, Zhongshan Hospital, Fudan University, Shanghai, People’s Republic of ChinaCorrespondence: Qianzhou Lv, Department of Pharmacy, Zhongshan Hospital, Fudan University, Shanghai, People’s Republic of China, Email lv.qianzhou@zs-hospital.sh.cn Hongmei Yan, Department of Endocrinology and Metabolism, Zhongshan Hospital, Fudan University, Shanghai, People’s Republic of China, Email yan.hongmei@zs-hospital.sh.cnBackground: The influence of genetic variants on the glucose-lowering effects of dapagliflozin remains unclear. This study aims to investigate the impact of polymorphisms in solute carrier family 5 member 2 (SLC5A2), uridine diphosphate glucuronosyltransferase 1A9 (UGT1A9), solute carrier family 2 member 2 (SLC2A2) and member 4 (SLC2A4) on the anti-hyperglycemic effect of dapagliflozin in patients with type-2 diabetes mellitus (T2DM).Methods: A total of 141 patients with T2DM were included in this prospective cohort study. Twenty-nine single nucleotide polymorphisms (SNPs) were selected and genotyped using the Sequenom MassArray platform or Sanger sequencing. Glycated hemoglobin (HbA1c) and fasting blood glucose (FBG) levels were compared before and after the treatment with dapagliflozin.Results: Among the 29 SNPs selected, 27 were successfully analyzed. After three months of dapagliflozin treatment, FBG levels were significantly reduced (8.00 mmol/L (5.45– 10.71) mmol/L vs 6.40 mmol/L (5.45– 9.20) mmol/L, p = 0.003) in patients with T2DM. However, there was no significant change in HbA1c levels (8.10% (6.88– 10.00)% vs 8.10% (6.83– 10.00)%, p = 0.452). Analysis of covariance showed that patients with the minor allele homozygote or heterozygote of rs12471030 (CT/TT), rs12988520 (AC/CC) or rs2602381 (TC/CC) had higher FBG levels compared to those with the major allele homozygote (p = 0.014, p = 0.024, and p = 0.044, respectively). After adjusting for baseline FBG level, age, gender, body mass index, use of insulin and use of metformin, three SNPs—rs12471030, rs12988520 and rs2602381—were associated with the anti-hyperglycemic effect of dapagliflozin. However, using a stringent significance threshold (p < 0.002 with Bonferroni correction), none of these selected SNPs were significantly associated with FBG and HbA1c levels after dapagliflozin treatment.Conclusion: After adjusting for confounding variables, polymorphisms in SLC5A2, UGT1A9, SLC2A2 and SLC2A4 genes were not associated with the anti-hyperglycemic effect of dapagliflozin in the Chinese population.Clinical Trial Registration Number: ChiCTR2200059645.Keywords: dapagliflozin, fasting blood glucose, glycated hemoglobin, polymorphisms, UGT1A9

Aiming Lv,1,2 Tong Ding,2 DeQiong,2 DaWaZhuoMa,2 Long Cai,2 Yutong Zhang,2 Jinyu Yin,2 SeZhen,2 Qiubo Lv1 1Department of Obstetrics and Gynecology, Beijing Hospital, National Center of Gerontology, Institute of Geriatric Medicine, Chinese Academy of Medical Sciences, Beijing, People’s Republic of China; 2Women and Children’s Hospital of Tibet Autonomous Region, Lhasa, Tibet Autonomous Region, People’s Republic of ChinaCorrespondence: Qiubo Lv, Department of Obstetrics and Gynecology, Beijing Hospital, National Center of Gerontology, Institute of Geriatric Medicine, Chinese Academy of Medical Sciences, No. 1 DaHua Road, Dong Dan, Beijing, 100730, People’s Republic of China, Tel +86 13801192185, Fax +86 10 85136220, Email lvqiubo@yeah.netPurpose: Pelvic floor disorder (PFD) seriously affects the everyday life of women. This cross-sectional study aimed to evaluate the prevalence and risk factors for postpartum PFD in women living in the Tibet Autonomous Region (TAR).Methods: Parous women who attended the outpatient gynaecology clinic at our hospital between June 2022 and August 2022 were screened in this study. The demographic and clinical data of these women were collected. Their pelvic floor functions were evaluated via a pelvic organ prolapse (POP) quantification examination, the Pelvic Floor Distress Inventory Questionnaire-20 (PFDI-20) and the Overactive Bladder Symptom Score (OABSS).Results: A total of 201 women were included in this study, of whom 81.09% (163/201) were Tibetan. Twenty-seven women (13.43%) were diagnosed with POP stage ≥ 2 and 27 women (13.43%) with an OABSS score ≥ 3. The median PFDI-20 total score was 4.17 (range 0– 43.75). Han women (n = 38) in the TAR had much lower PFDI-20 total scores, compared with Tibetan women (n = 163) (p < 0.05). The results of the multiple linear regression models showed that the PFDI-20 scores obtained from women living in the TAR were closely related to parity, history of heavy weight lifting, age, history of instrumental deliveries, ethnicity and number of caesarean sections.Conclusion: Pelvic floor disorder is common among parous women living in the TAR. Ethnicity, parity, history of heavy weight lifting, age, history of instrumental deliveries and number of caesarean sections are the factors closely related to the PFDI-20 scores.Keywords: pelvic floor disorder, Tibet Autonomous Region, pelvic organ prolapse, urinary incontinence, overactive bladder symptoms

Both tea polyphenols (TP) and Lactobacillus rhamnosus have been shown to alleviate obesity, and regulate lipid metabolism. However, the combined effects and their underlying mechanisms of action remain elusive. In the present work, the effects of TP, Lactobacillus rhamnosus R5 (R5), and TP+R5 on blood lipids and the gut microbiota of mice fed with a high-fat diet were compared. Results showed that the combination of TP and R5 effectively increased the serum levels of high-density lipoprotein cholesterol (HDL-C), and decreased total cholesterol (TC) levels, low-density lipoprotein cholesterol (LDL-C) levels, and the atherosclerosis index (AI) in mice fed with a high-fat diet. The combination treatment resulted in a modification of the structure of the gut microbiota in mice, as evidenced by a decrease in the F/B ratio, and an increase in the abundance of beneficial genera, such as Akkermansia muciniphila, Faecalibaculum rodentium, and Ruminococcus_uncultured bacterium. Additionally, the contents of SCFAs (acetic, propionic, and butyric acids) in faeces also increased. These could provide new ideas for anti-obesity methods, and a theoretical basis for the development of foods combining probiotics and tea polyphenols. [ABSTRACT FROM AUTHOR]

Background: Major depressive disorder (MDD) is a serious and disabling condition characterized by abnormal mood changes. Clinical guidelines for depression treatment recommend antidepressant medications, with benzodiazepines acting as short-term synergists. However, little is currently known about the prevalence and associated clinical risk factors of benzodiazepine use among Chinese patients with MDD. This study aimed to explore the prevalence and clinical risk factors associated with benzodiazepine use in this population., Methods: A total of 2742 patients with MDD (males/females = 816/1926, aged 14-60 years) participated in this cross-sectional observational study. General information and psychosis assessments were collected online. Depressive symptoms were assessed using the Patient Health Questionnaire-9 (PHQ-9), anxiety symptoms using the Generalized Anxiety Disorder-7 (GAD-7), and sleep problems and suicidal tendencies using the third and ninth items of the PHQ-9. Multivariable logistic regression analysis models were employed to identify factors associated with benzodiazepine use., Results: The prevalence of benzodiazepine use among patients with MDD was 42.9 %. Among these patients, 99.6 % used a single benzodiazepine, with oxazepam being the most frequently prescribed. Age, severity of sleep problems, depressive symptoms, and anxiety symptoms were significantly correlated with benzodiazepine use (all P < 0.001)., Limitations: The cross-sectional design of this study precludes establishing causal relationships., Conclusion: Our findings indicate a high prevalence of benzodiazepine use among Chinese patients with MDD. Factors such as severe depressive symptoms, anxiety symptoms, age, and sleep problems appear to be associated with benzodiazepine use. These results underscore the importance of vigilance regarding benzodiazepine use in patients with MDD., Competing Interests: Declaration of competing interest The authors declare that they have no conflicts with any financial interests., (Copyright © 2024 The Authors. Published by Elsevier B.V. All rights reserved.)

The goat, an early domesticated ruminant, is a reliable source of cashmere, meat and milk in global agricultural production. Despite this, the genome of cashmere-rich goats has yet to be characterized. Here, we assembled the nearly complete genome of a cashmere goat from a highly economically valuable Inner Mongolian Cashmere buck, utilizing a combination of PacBio HiFi, ONT ultra-long reads, and Hi-C technologies. The size of this genome is 2.76 Gb, with a contig N50 of 95.22 Mb. All assembled sequences were anchored onto 29 autosomes and both sex chromosomes, with only two gaps present on the X chromosome. We identified 1,333.29 Mb (48.26%) of repetitive sequences and predicted 22,480 protein-coding genes. Assembly quality assessment of the genome demonstrated that our assembled cashmere goat genome surpasses the continuity, completeness, and accuracy of other published goat genomes. Taken together, we provided the first cashmere goat assembly, bridging the gap in the genome of important economic breeds of domestic goats, and providing a valuable reference resource for goat genetics and genome research., (© 2024. The Author(s).)

Aims: Cisplatin (CDDP) is still one of the most commonly used first-line treatments for advanced and recurrent oral squamous cell carcinoma patients in clinical practice. However, the decrease in tumor sensitivity to CDDP weakens its therapeutic effect. There is still limited research on the effect of METTL3-mediated methylation of m6A on CDDP sensitivity in oral squamous cell carcinoma (OSCC). TMEM30A widely exists in biomembranes and regulates the lipid asymmetry of the membrane, but there is no report on its function in OSCC. This study aims to explore the specific mechanism by which METTL3 regulates m6A methylation of TMEM30A and affects the occurrence and development of OSCC, and further investigate the effects of METTL3 and TMEM30A on the anti-tumor activity of CDDP., Key Findings: In oral squamous cell carcinoma, METTL3 plays a pro cancer role and weakens the anti-tumor efficacy of CDDP; METTL3 positively regulates the expression of TMEM30A by m6A methylation modification and binding to TMEM30A; The abnormally high expression of TMEM30A in tumors not only weakens CDDP sensitivity, but also enhances the malignant evolution of cancer cells, regulates the metabolic balance of ATP and lactate in cells, and is a potential oncogenic gene., Significance: TMEM30A promotes malignant progression of tumors through METTL3 mediated m6A methylation modification, participates in maintaining the balance of tumor ATP and lactate metabolism, and thus reduces the anti-tumor activity of CDDP. TMEM30A is a potential gene target for CDDP anti-tumor activity in OSCC., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024. Published by Elsevier Inc.)

Introduction: This study aims to explore the impact of smoking on intrinsic brain activity among high-altitude (HA) populations. Smoking is associated with various neural alterations, but it remains unclear whether smokers in HA environments exhibit specific neural characteristics., Methods: We employed ALFF and fALFF methods across different frequency bands to investigate differences in brain functional activity between high-altitude smokers and non-smokers. 31 smokers and 31 non-smokers from HA regions participated, undergoing resting-state functional magnetic resonance imaging (rs-fMRI) scans. ALFF/fALFF values were compared between the two groups. Correlation analyses explored relationships between brain activity and clinical data., Results: Smokers showed increased ALFF values in the right superior frontal gyrus (R-SFG), right middle frontal gyrus (R-MFG), right anterior cingulate cortex (R-ACC), right inferior frontal gyrus (R-IFG), right superior/medial frontal gyrus (R-MSFG), and left SFG compared to non-smokers in HA. In sub-frequency bands (0.01-0.027 Hz and 0.027-0.073 Hz), smokers showed increased ALFF values in R-SFG, R-MFG, right middle cingulate cortex (R-MCC), R-MSFG, Right precentral gyrus and L-SFG while decreased fALFF values were noted in the right postcentral and precentral gyrus in the 0.01-0.027 Hz band. Negative correlations were found between ALFF values in the R-SFG and smoking years., Conclusion: Our study reveals the neural characteristics of smokers in high-altitude environments, highlighting the potential impact of smoking on brain function. These results provide new insights into the neural mechanisms of high-altitude smoking addiction and may inform the development of relevant intervention measures., 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.)

Cold stress is one of the major abiotic stress factors affecting rice growth and development, leading to significant yield loss in the context of global climate change. Exploring natural variants that confer cold resistance and the underlying molecular mechanism responsible for this is the major strategy to breed cold-tolerant rice varieties. Here, we show that natural variations of a SIMILAR to RCD ONE (SRO) gene, OsSRO1c, confer cold tolerance in rice at both seedling and booting stages. Our in vivo and in vitro experiments demonstrated that OsSRO1c possesses intrinsic liquid-liquid phase-separation ability and recruits OsDREB2B, an AP2/ERF transcription factor that functions as a positive regulator of cold stress, into its biomolecular condensates in the nucleus, resulting in elevated transcriptional activity of OsDREB2B. We found that the OsSRO1c-OsDREB2B complex directly responds to low temperature through dynamic phase transitions and regulates key cold-response genes, including COLD1. Furthermore, we showed that introgression of an elite haplotype of OsSRO1c into a cold-susceptible indica rice could significantly increase its cold resistance. Collectively, our work reveals a novel cold-tolerance regulatory module in rice and provides promising genetic targets for molecular breeding of cold-tolerant rice varieties., (Copyright © 2024 The Author. Published by Elsevier Inc. All rights reserved.)

Thymoma, a rare tumor from thymic epithelial cells, presents diagnostic challenges because of the subjective nature of traditional methods, leading to high false-negative rates and long diagnosis times. This study introduces a thymoma classification technique that integrates hyperspectral imaging with deep learning. We initially capture pathological slice images of thymoma using a hyperspectral camera and delineate regions of interest to extract spectral data. This data undergoes reflectance calibration and noise reduction. Subsequently, we transform the spectral data into two-dimensional images via the Gramian Angular Field (GAF) method. A variant residual network is then utilized to extract features and classify these images. Our results demonstrate that this model significantly enhances classification accuracy and efficiency, achieving an average accuracy of 95%. The method proves highly effective in automated thymoma diagnosis, optimizing data utilization, and feature representation learning., (© 2024 Wiley‐VCH GmbH.)

In addition to inducing xylem embolism, freeze-thaw events can cause frost fatigue phenomena. Freezing temperature, freezing times, number of freeze-thaw cycles and frost drought can affect the level of freeze-thaw-induced embolism, but it is unknown whether there is an effect on frost fatigue. We assessed whether these frost-related factors changed frost fatigue in the three diffuse-porous species by simulating freeze-thaw treatments under different conditions. We also proposed a new metric, embolism area, in place of embolism resistance, to more accurately quantify the shift of the vulnerability curve after experiencing freeze-thaw-induced embolism and refilling. Frost fatigue caused vulnerability curves of all species to change from S-shaped to double S-shaped or even R-shaped curves. When exposed to a freeze-thaw event, Acer truncatum showed strong resistance to frost fatigue; in contrast, Populus (I-101 × 84 K) and Liriodendron chinense were more vulnerable. Changing freezing temperature and times did not impact the response to frost fatigue in the three species, but a greater number of freeze-thaw cycles and more severe frost drought significantly exacerbated their fatigue degree. Considering that frost fatigue may be a widespread phenomenon among temperate diffuse-porous species, more work is needed in the future to reveal the mechanisms of frost fatigue., (© The Author(s) 2024. Published by Oxford University Press. All rights reserved. For permissions, please e-mail: journals.permission@oup.com.)

Antimicrobial resistance (AMR) is a growing global health concern, necessitating innovative strategies beyond the development of new antibiotics. Here, we employed NdYVO 4 :Eu 3+ nanoparticles, which can persistently produce reactive oxygen species (ROS) after stopping the light, as a model of photodynamic nanoparticles and demonstrated that the photodynamic effect can serve as an adjuvant with antibiotics to effectively reduce their minimum inhibitory concentration. These preirradiated nanoparticles could penetrate the bacterial cell membrane, significantly enhancing the potency of antibiotics. We showed that the synergy effect could be attributed to disrupting crucial cellular processes by ROS, including damaging cell membrane proteins, interfering with energy supply, and inhibiting antibiotic metabolism. Our findings suggested that complementing the photodynamic effect might be a robust strategy to enhance antibiotic potency, providing an alternative antibacterial treatment paradigm.

Background: TRIM8 -related neuro-renal syndrome (NRS), caused by pathogenic variants of the TRIM8 gene, is characterized by epilepsy, developmental delay (DD) and renal disorders. The severity of the neurological effects as well as the presence of renal disorders is variable among patients. Here, we report three additional patients with clinical features compatible with NRS and summarize the association between the variants' loci and phenotype of TIRM8 -related NRS., Methods: A retrospective analysis was conducted for three Chinese children with NRS due to TRIM8 variants identified through whole-exome sequencing (WES). Previous reports of patients with TRIM8 -related NRS were reviewed systematically. Demographic and clinical data were collected from these patients., Results: Two de novo TRIM8 truncating variants in three NRS patients were identified in our study, including c.1327&#95;c.1328delCCinsTG (p. Arg443*) and c.1375C>T (p.Gln459*). Our three patients all exhibited drug-resistant epilepsy and early-onset DD, and two of whom developed electrical status epilepticus during sleep (ESES). Brain magnetic resonance imaging (MRI) showed periventricular leukomalacia in one patient and normal in the other two. All three patients demonstrated nephrotic range proteinuria (NRP) or nephrotic syndrome (NS) with normal renal function during follow-up. There was a total of 27 patients with TRIM8 -related NRS have been identified to date. The most common clinical features are renal diseases (89%), DD (89%), followed by epilepsy (78%). 67% of patients eventually progressed to end-stage renal disease (ESRD). Focal seizure was the most frequent seizure type (57%). 52% of patients presented drug-resistant epilepsy. 64% of patients exhibited non-specific brain MRI abnormalities. Brain atrophy was the most common change (50%). Two patients with TRIM8 variants closer to the N-terminal had neurological diseases without renal damage. Five patients with TRIM8 variants closer to the C-terminal had no severe neurological diseases. Seven patients had Gln459* variant which is the most common variant (7/27, 25.9%). The severity of the renal and neurological damage of the seven patients was variable., Conclusion: This study expands the number of individuals with confirmed NRS due to pathogenic variants in TRIM8 . Neurological and renal phenotype with the same variant locus differed in their severity. Further research is needed to explore the relationship between genotype and phenotype of TRIM8 variants., 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 Lv, Niu, Xu, Qin and Yang.)

Aim: This study investigates changes in immune cell subsets in peripheral blood of ankylosing spondylitis (AS) patients with colitis or terminal ileitis. It aims to explore the connection between changes in lymphocyte subsets and gut inflammation, providing insights for early detection., Methods: Overall, 50 AS patients undergoing colonoscopy were enrolled. Flow cytometry was employed to analyze lymphocyte subsets, including T and B cells, in peripheral blood. Disease activity was assessed using CRP, ESR, BASDAI, ASDAS-CRP, and ASDAS-ESR., Results: Compared to AS patients without gut inflammation, those with colorectal inflammation showed a significant increase in total T cells (p < .05), an increase in exhausted CD4 + T cells (p < .05), and a decrease in Th2 cells and total Tc cells (p < .05). Notably, in AS patients with terminal ileitis, there was an increase in total B cells and classic switched B cells (p < .05), with a decrease in double-positive T cells (p < .05). However, no significant differences were observed in the distribution of Tfh-cell subpopulations (Tfh1, Tfh2, Tfh17) and Tc-cell subpopulations (Tc1, Tc2, Tc17) between AS patients with either colorectal inflammation or terminal ileitis (p > .05). We explored the relationship between disease activity scores, ESR, CRP, and lymphocyte subsets, but found no statistically significant correlation between them., Conclusion: Distinct immune patterns may exist in AS with different types of intestinal inflammation. Colitis in AS is primarily characterized by a significant increase in exhausted CD4 + T cells, along with a decrease in Th2 cells. In contrast, terminal ileum inflammation in AS is marked by an increase in total B cells and classic switched B cells. These findings offer new insights for early detection and therapeutic intervention., (© 2024 Asia Pacific League of Associations for Rheumatology and John Wiley & Sons Australia, Ltd.)

Objectives: This retrospective study aimed to investigate the clinical characteristics and genetic findings in paediatric patients with gastrointestinal involvement in Behçet's disease (BD), elucidating the spectrum of autoinflammatory syndromes mimicking BD in this young population., Methods: Fifty paediatric patients diagnosed with BD between January 2016 and December 2022, including 24 (48%) with gastrointestinal involvement, underwent comprehensive analysis. Clinical presentations, laboratory examinations, gastrointestinal endoscopy, and genetic tests were conducted, with patients stratified based on genetic results for rigorous comparative clinical analysis., Results: The cohort, with a median age of disease onset at 4.0 years, predominantly manifested with recurrent oral ulcers (100%). Gastrointestinal symptoms were prevalent in 83.3%, with abdominal pain (70%) and haematochezia (16.7%) being notable. Endoscopic evaluations unveiled lesions primarily in the terminal ileum and ileocecal region, with diverse ulcers across various anatomical sites. While 70.8% initially met ICBD criteria, only 41.6% fulfilled new paediatric classification criteria. Genetic analysis in 18 patients unveiled pathogenic variants in 7, with the genetic-positive group exhibiting earlier onset and more atypical symptoms. Noteworthy cases included X-linked deficiency in ELF4, A20 haploinsufficiency, and Majeed syndrome, with two cases revealing chromosomal abnormalities such as trisomy 8 syndrome. Comparative analysis underscored earlier disease onset, heightened inflammatory markers, and distinctive gastrointestinal lesions in the genetic-positive cohort., Conclusions: Identification of monogenic diseases and chromosomal abnormalities resembling BD underscores the imperative of precise diagnosis for tailored treatment and genetic counselling. Expanding genetic screening initiatives holds promise for enhancing our comprehension of the genetic landscape associated with BD.

The gut microbiome has been implicated in various human diseases, though findings across studies have shown considerable variability. In this study, we reanalyzed 6314 publicly available fecal metagenomes from 36 case-control studies on different diseases to investigate microbial diversity and disease-shared signatures. Using a unified analysis pipeline, we observed reduced microbial diversity in many diseases, while some exhibited increased diversity. Significant alterations in microbial communities were detected across most diseases. A meta-analysis identified 277 disease-associated gut species, including numerous opportunistic pathogens enriched in patients and a depletion of beneficial microbes. A random forest classifier based on these signatures achieved high accuracy in distinguishing diseased individuals from controls (AUC = 0.776) and high-risk patients from controls (AUC = 0.825), and it also performed well in external cohorts. These results offer insights into the gut microbiome's role in common diseases in the Chinese population and will guide personalized disease management strategies., (© 2024. The Author(s).)

Objectives: As populations age, the issue of social participation among older adults has gained prominence. Studies indicate variability in social participation trajectories among this demographic, yet the transition patterns and their effects on depression remain unclear. This longitudinal study aims to explore the latent classes and transition patterns in social participation among older adults and to evaluate their effects on depression., Methods: Data from the Chinese Longitudinal Healthy Longevity Survey (CLHLS) in 2014 (T1) and 2018 (T2) were analyzed, including 2293 older adults. Latent class analysis (LCA) and latent transition analysis (LTA) were employed to identify latent classes of social participation at T1 and T2, as well as the transition probabilities between these classes. Multinomial logistic regression was used to examine predictors of transitions, and depression levels at T2 were compared across transition patterns., Results: The LCA results supported a 3-class model labeled as low, moderate, and high social participation. The probabilities of remaining stable and transitioning to other classes were similar across the three classes (ranging from 0.50 to 0.54). Age, gender, and other baseline characteristics emerged as significant predictors of transition patterns. Older adults experiencing positive transitions exhibited reduced depression compared to those in their original class over time, while those with negative transitions showed increased depression., Conclusions: This research prompts a deep understanding of social participation dynamics in older adults and their effects on depression. Identifying social participation classes and transition patterns could inform interventions to enhance social participation and reduce depression among older adults., Competing Interests: Declaration of competing interest No conflict of interest has been declared by the authors., (Copyright © 2024 Elsevier Inc. All rights reserved.)

Disposable plastic tableware was widely used and it was particularly important to identify potential hazardous substances in it and evaluate the risk to humans health. In this study, 85 substances were identified in 60 samples (22 bowls, 20 sporks, and 18 straws) by methanol extraction and non-targeted analysis using GC-Orbitrap HRMS. Subsequently, 14 high-risk substances were further screened and their migration in the samples was measured in three food simulants. Finally, based on the proposed safety limit assessment scheme for EU- authorized and unauthorized substances, the risk assessment of exposure to high-risk substances in disposable plastic tableware was performed for three age groups. The results showed that the dibutyl phthalate and bis(2-ethylhexyl) phthalate in some samples exceeded the safety limit value. Overall, the risk of bowls was lower than spock and straws, and the potential exposure risk for young children was higher than that of adults and older children., 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.)

Drought stress poses a substantial challenge to plant growth and agricultural productivity worldwide. Upon water depletion, plants activate an abscisic acid (ABA) signaling pathway, leading to stomatal closure to reduce water loss. The MYB family of transcription factors plays diverse roles in growth, development, stress responses, and biosynthesis, yet their involvement in stomatal regulation remains unclear. Here, we demonstrate that ABA significantly upregulates the expression of MYB41, MYB74, and MYB102, with MYB41 serving as a key regulator that induces the expression of both MYB74 and MYB102. Through luciferase assays, chromatin immunoprecipitation (ChIP) assays, and electrophoretic mobility shift assays (EMSA), we reveal that MYB41 engages in positive feedback regulation by binding to its own promoter, thus amplifying its transcription in Arabidopsis (Arabidopsis thaliana). Furthermore, our investigation showed that MYB41 recruits BRAHMA (BRM), the core ATPase subunit of the SWI/SNF complex, to the MYB41 promoter, facilitating the binding of HISTONE DEACETYLASE 6 (HDA6). This recruitment triggers epigenetic modifications, resulting in reduced MYB41 expression characterized by elevated H3K27me3 levels and concurrent decreases in H3ac, H3K27ac, and H3K14ac levels in wild-type plants compared to brm knockout mutant plants. Our genetic and molecular analyses show that ABA mediates autoregulation of the MYB41-BRM module, which intricately modulates stomatal movement in A. thaliana. This discovery sheds light on a drought response mechanism with the potential to greatly enhance agricultural productivity., Competing Interests: Conflict of interest statement. None declared., (© The Author(s) 2024. Published by Oxford University Press on behalf of American Society of Plant Biologists. 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.)

The exploration of environmentally friendly slow-release fertilizer (SRF) based on natural bio-polymers is of great importance in the development of modern agriculture and horticulture. Herein, a novel starch carbamate (SC) modified sodium alginate (SA) hydrogel (SC/SAH) was prepared utilizing as-synthesized SC and natural SA through the cationic ions crosslinking method and ultimately the corresponding slow-release fertilizer (SC/SAH-SRF) was successfully developed by immersing the dried SC/SAH matrix into saturated urea solution. Due to the low gelation temperature and high viscosity of the synthesized SC, the formed SC/SAH exhibits significantly enhanced properties including excellent water absorbency up to 8.02 g/g with considerable repeatability, abundant pore structure and high hydrophilicity compared with the neat SAH and natural starch based hydrogel (NS/SAH). Accordingly, the SC/SAH leads to higher urea loading amount ∼ 1.28 g/g. Importantly, the resultant SC/SAH-SRF also shows superior slow-release performance, yielding a cumulative urea release of only 61.6 % within 10 h and almost completely release >16 h in water, what's more, only 58.5 % of the urea releases within 25 days and exceeding 50 days for complete release in soil column assays. The slow-release of urea from SC/SAH-SRF well complies for the first-order kinetics and accomplishes via a non-Fickian diffusion process. Moreover, the pot experiment demonstrates that the SC/SAH-SRF has higher growth promotion role for the maize seedlings than those of others. Consequently, this work provides a novel strategy for preparing environmentally friendly SRF by blending modified starch and hydrogel., 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.)

Endomucin (MUC14), encoded by EMCN gene, is an O-glycosylated transmembrane mucin that is mainly found in venous endothelial cells (ECs) and highly expressed in type H vessels of bone tissue. Its main biological functions include promoting endothelial generation and migration through the vascular endothelial growth factor (VEGF) signaling pathway and inhibiting the adhesion of inflammatory cells to ECs. In addition, it induces angiogenesis and promotes bone formation. Due to the excellent functions of Endomucin in the above aspects, it provides a new research target for the treatment of vascular inflammatory-related diseases and bone diseases. Based on the current understanding of its function, the research of Endomucin mainly focuses on the above two diseases. As it is known, the progression of cancer is closely related to angiogenesis. Endomucin recently is found to be differentially expressed in a variety of tumors and correlated with survival rate. The biological role of Endomucin in cancer is opaque. This article introduces the research progress of Endomucin in vascular inflammatory-related diseases and bone diseases, discusses its application value and prospect in the treatment, and collects the latest research situation of Endomucin in tumors, to provide meaningful evidence for expanding the research field of Endomucin., (© 2024 Wiley‐VCH GmbH.)

Osteoarthritis (OA) is a prevalent joint disease characterized by cartilage degeneration and subchondral bone homeostasis imbalance. Effective topical OA therapy is challenging, as therapeutic drugs often suffer from insufficient penetration and rapid clearance. We develop miniature polydopamine (PDA) nanocapsules (sub-60 nm), which are conjugated with collagen-binding polypeptide (CBP) and loaded with an anabolic drug (i.e., parathyroid hormone 1-34, PTH 1-34) for efficient OA treatment. Such multifunctional polymeric nanocapsules, denoted as PDA@CBP-PTH, possess deformability when interacting with the dense collagen fiber networks, enabling the efficient penetration into 1 mm cartilage in 4 h and prolonged retention within the joints up to 28 days. Moreover, PDA@CBP-PTH nanocapsules exhibit excellent reactive oxygen species scavenging property in chondrocytes and enhance the anabolism in subchondral bone. The nanosystem, as dual-mode treatment for OA, demonstrates rapid penetration, long-lasting effects, and combinational therapeutic impact, paving the way for reversing the progression of OA for joint health care., Competing Interests: Declaration of competing interest None., (Copyright © 2024. Published by Elsevier B.V.)

The activation of nuclear factor erythroid 2-related factor 2 (NRF2) has been observed in various cancers. Yet its exact contribution to the development of head and neck squamous cell carcinoma (HNSCC) remains undetermined. We previously found that NRF2 signaling is critical for the differentiation of squamous basal progenitor cells, while disruption of NRF2 causes basal cell hyperplasia. In this study, we revealed a correlation between elevated NRF2 activity and poor outcomes in HNSCC patients. We demonstrated that NRF2 facilitates tumor proliferation, migration, and invasion, as evidenced by both in vitro and in vivo studies. Significantly, NRF2 augments the expression of the antioxidant enzyme GPX2, thereby enhancing the proliferative, migratory, and invasive properties of HNSCC cells. Activation of GPX2 is critical for sustaining cancer stem cells (CSCs) by up-regulating NOTCH3, a key driver of cancer progression. These results elucidate that NRF2 regulates HNSCC progression through the NRF2-GPX2-NOTCH3 axis. Our findings proposed that pharmacological targeting of the NRF2-GPX2-NOTCH3 axis could be a potential therapeutic approach against HNSCC., (© 2024. The Author(s).)

Organic materials with thermally activated delayed fluorescence (TADF) and room-temperature phosphorescence (RTP) dual emission have attracted great attention in recent years, but the regulation mechanism via internal and external heavy atoms is not clear enough. Here, we carry out a systematic theoretical investigation on the photophysical properties of the materials by introducing aliphatic or aromatic bromine atoms. The molecule with aromatic bromine atoms exhibits obvious TADF owing to the effective reverse intersystem crossing (RISC) with matchable energy levels and enhanced spin orbit couplings, the molecule with aliphatic bromine atoms shows a long RTP lifetime because of the reduced nonradiative transition of triplet excitons, and the molecule with both aliphatic and aromatic bromine atoms presents balanced TADF and RTP emissions thanks to the synergy internal and external heavy-atom effects. Besides, the internal and external heavy atoms induce multisite intermolecular interactions, effectively suppressing the nonradiative process in the solid phase. The efficient RISC process and the suppressed nonradiative process of triplet excitons should be key to regulating the dual emission property. These findings and insights are of great importance for revealing the structure-performance relationship, providing theoretical guidance for the design of TADF and RTP dual emission molecules via internal and external heavy-atom effects.

Background/objectives: As a hyperaccumulator of selenium (Se), Cardamine violifolia ( Cv ) and its peptide extract could ameliorate the negative effects of a high-fat diet (HFD). However, the effects of the coaccumulation of cadmium (Cd) in Se-enriched Cv ( Cv2 ) and the potential confounding effect on the roles of enriched Se remain unknown. We aimed to investigate whether Cv2 could alleviate HFD-induced lipid disorder and liver damage., Methods: Three groups of 31-week-old female mice were fed for 41 weeks ( n = 10-12) with a control Cv -supplemented diet ( Cv1 D, 0.15 mg Se/kg, 30 µg Cd/kg, and 10% fat calories), a control Cv -supplemented HFD ( Cv1 HFD, 45% fat calories), and a Cv2 -supplemented HFD ( Cv2 HFD, 1.5 mg Se/kg, 0.29 mg Cd/kg, and 45% fat calories). Liver and serum were collected to determine the element concentrations, markers of liver injury and lipid disorder, and mRNA and/or protein expression of lipid metabolism factors, heavy metal detoxification factors, and selenoproteins., Results: Both Cv1 HFD and Cv2 HFD induced obesity, and Cv2 HFD downregulated Selenoi and upregulated Dio3 compared with Cv1 D. When comparing Cv2 HFD against Cv1 HFD, Cv2 increased the liver Se and Cd, the protein abundance of Selenoh, and the mRNA abundance of 10 selenoproteins; reduced the serum TG, TC, and AST; reduced the liver TG, lipid droplets, malondialdehyde, and mRNA abundance of Mtf1 and Mt2 ; and differentially regulated the mRNA levels of lipid metabolism factors., Conclusions: Cv2 alleviated HFD-induced lipid dysregulation and liver damage, which was probably associated with its unique Se speciation. However, further research is needed to explore the interaction of plant-coenriched Se and Cd and its effects on health.

Crying is one of the primary means by which infants communicate with their environment in the early stages of life. These cries can be triggered by physiological factors such as hunger or sleepiness, or by pathological factors such as illness or discomfort. Therefore, analyzing infant cries can assist inexperienced parents in better caring for their babies. Most studies have predominantly utilized a single-speech feature, such as Mel Frequency Cepstral Coefficients (MFCC), for classifying infant cries, while other speech features, such as Mel Spectrogram and Tonnetz, are often overlooked. In this study, we manually designed a hybrid feature set, MMT (including MFCC, Mel Spectrogram, and Tonnetz), and explored its application in infant cry classification. Additionally, we proposed a convolutional neural network based on residual connections and long short-term memory (LSTM) networks, termed ResLSTM. We compared the performance of different deep learning models using the hybrid feature set MMT and the single MFCC feature. This study utilized the Baby Crying, Dunstan Baby Language, and Donate a Cry datasets. The results indicate that the hybrid feature set MMT outperforms the single MFCC feature. The MMT combined with the ResLSTM method achieved the best performance, obtaining accuracy rates of 94.15%, 92.92%, and 95.98% on the three datasets, respectively., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 The Voice Foundation. Published by Elsevier Inc. All rights reserved.)

A novel approach of visible light-emitting diode (Vis-LED) radiation was employed to activate permanganate (Mn(VII)) for efficient organic micropollutant (OMP) removal. The degradation rates of OMPs by Vis-LED/Mn(VII) were 2-5.29 times higher than those by Mn(VII) except for benzoic acid and atrazine. Increasing wavelengths (445-525 nm) suppressed the degradation of diclofenac (DCF) and 4-chlorophenol (4-CP) owing to the decreased quantum yields of Mn(VII). Comparatively, light intensity and Mn(VII) dosage had a positive effect on the degradation of DCF and 4-CP. Experimental data revealed that Mn(V) dominated the DCF degradation whereas Mn(III) was the active oxidant in the 4-CP degradation. Mn(V) and Mn(III) formed from the photo-decomposition of Mn(VII), meanwhile, Mn(III) also formed from the Mn(V) photo-decomposition. The increase in solution pH inhibited DCF degradation but had a positive impact on 4-CP degradation, mainly due to the changing speciation of DCF and 4-CP. Inorganic anions (Cl - and HCO 3 - ) had little impact on DCF and 4-CP degradation, while humic acid (HA) showed a positive impact because of the π-π interaction between HA and DCF/4-CP. The transformation products of DCF and 4-CP were identified and transformation pathways were proposed. Finally, the Vis-LED/Mn(VII) exhibited great degradation performance in various authentic waters. Overall, this study boosts the development of Mn(VII)-based oxidation processes., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier B.V. All rights reserved.)

Background: In 2020, the WHO proposed the global strategic goal of accelerating the elimination of cervical cancer (CC). One of the key strategies is that, by 2030, 90% of girls will complete HPV vaccination by age 15. In 2017, HPV vaccines were first marketed in China., Objectives: This study aimed to explore the changes in parents' knowledge about CC, HPV, HPV vaccines, and acceptance of HPV vaccination 5 years after the introduction of HPV vaccines into China. Associated factors and reasons for refusal by parents were also explored., Methods: A school-based follow-up study was conducted among parents in China from May 2018 to May 2023. Comparison using Chi-square tests was performed to measure the changes. Univariate and multivariate analyses were used to explore factors associated with HPV vaccination among teenage girls., Results: The overall cognitive level in terms of CC- and HPV-related knowledge among parents increased, and they expressed more willingness to vaccinate their daughter (35.4% in 2018 vs. 56.6% in 2023). The HPV vaccination rate among teenage girls remained at a low level (4.4% in 2018, 9.8% in 2023). The main obstacles reported by parents were limited knowledge (42.0%), scarcity of the HPV vaccine (29.2%), waiting until their daughter was older (27.5%), safety concerns (14.7%), high cost (9.0%), and effectiveness concerns (4.6%). Parents who are elderly, local residents, have received HPV vaccines themselves, have had experience of vaccinating their children with influenza vaccines, and have a higher knowledge level of CC, HPV and HPV vaccines are more likely to vaccinate their children with HPV vaccines., Conclusions: Although we observed an increment in parents' knowledge level in terms of CC, HPV, HPV vaccines, and HPV vaccine uptake over the past 5 years, the HPV vaccine coverage among girls still falls short of the WHO's 2030 target. Comprehensive intervention strategies, including tailored health education among adolescents and their parents, doctor recommendations, and providing financial subsidies or free HPV vaccines are needed in China.

Complex organic lateral heterostructures (OLHs) with spatial distribution of two or more chemical components are crucial for designing and realizing unique structure-dependent optoelectronic applications. However, the precise design of well-defined OLHs with flexible domain regulation remains a considerable challenge. Herein, we present a stepwise solution self-assembly method to synthesize two-dimensional (2D) OLHs with a central rhombus domain and a lateral region featuring tunable blue and green emission based on the sequential nucleation and growth of 2D crystals. By controlling the initial crystallization time of 2,6-diphenylanthracene, the rhombic length ratio (α) of the multicolor-emissive part of the 2D OLHs is precisely modified. Furthermore, a third lateral layer is constructed on the resulting OLHs, demonstrating scalable lateral regulation. Significantly, these prepared 2D OLHs exhibit great excitation position-dependent waveguide characteristics and enable a 0.06 dB/μm low-loss waveguiding, which are conducive to photon transport and conversion for photonic integrated circuits. This work provides a stepwise strategy for the accurate fabrication of 2D OLHs, fabricating the developments of next-generation optoelectronics devices.

In computational molecular and materials science, determining equilibrium structures is the crucial first step for accurate subsequent property calculations. However, the recent discovery of millions of new crystals and super large twisted structures has challenged traditional computational methods, both ab initio and machine-learning-based, due to their computationally intensive iterative processes. To address these scalability issues, here we introduce DeepRelax, a deep generative model capable of performing geometric crystal structure relaxation rapidly and without iterations. DeepRelax learns the equilibrium structural distribution, enabling it to predict relaxed structures directly from their unrelaxed ones. The ability to perform structural relaxation at the millisecond level per structure, combined with the scalability of parallel processing, makes DeepRelax particularly useful for large-scale virtual screening. We demonstrate DeepRelax's reliability and robustness by applying it to five diverse databases, including oxides, Materials Project, two-dimensional materials, van der Waals crystals, and crystals with point defects. DeepRelax consistently shows high accuracy and efficiency, validated by density functional theory calculations. Finally, we enhance its trustworthiness by integrating uncertainty quantification. This work significantly accelerates computational workflows, offering a robust and trustworthy machine-learning method for material discovery and advancing the application of AI for science., (© 2024. The Author(s).)

Aims: To explore the inter-eye retinal microvascular density asymmetry of patients on hydroxychloroquine (HCQ) therapy through optical coherence tomography angiography (OCTA)., Methods: 40 subjects were enrolled in this cross-sectional study, including 20 systemic lupus erythematasus patients currently treated with HCQ (40 eyes) and 20 age- and sex-matched normal controls (NCs, 40 eyes). OCTA images were obtained to measure macular and peripapillary mircrovasculatures and microstructures, including vessel density, retinal nerver fiber layer thickness, and peripapillary ganglion cell-inner plexiform layer thickness. The absolute values of the difference between right and left eyes were taken as a measure of inter-eye asymmetry., Results: Macular whole image vessel density (wiVD-M) and perifoveal vessel density (pfVD) of superficial capillary plexus (SCP) were notably reduced in both the right and left eyes of the HCQ treatment group compared with NCs. Specifically, SLE patients treated with HCQ have higher inter-eye asymmetry of wiVD-M of SCP (2.28 ± 1.03 vs 1.27 ± 0.79, p < 0.01) and pfVD of SCP (2.55 ± 1.26 vs 1.78 ± 1.06, p = 0.04) compared with NCs. There were no significant differences in inter-eye asymmetry of structure parameters. Inter-eye asymmetry of wiVD-M of SCP (AUC = 0.80, p < 0.01) and pfVD of SCP (AUC = 0.71, p = 0.02) exhibited greater discrimination power., Conclusion: SLE Patients treated with HCQ exhibited a notably higher inter-eye vessel density asymmetry compared to that of NCs. Thus, inter-eye vessel density asymmetry could be used to screen for HCQ retinal toxicity., Competing Interests: Declaration of competing interest All 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 Elsevier Inc. All rights reserved.)

Exploring highly efficient ultrasound-triggered catalysts is pivotal for various areas. Herein, we presented that Ba 2+ doped brookite TiO 2 nanorod (TiO 2 : Ba) with polarization-induced charge separation is a candidate. The replacement of Ba 2+ for Ti 4+ not only induced significant lattice distortion to induce polarization but also created oxygen vacancy defects for facilitating the charge separation, leading to high-efficiency reactive oxygen species (ROS) evolution in the piezo-catalytic processes. Furthermore, the piezocatalytic ability to degrade dye wastewater demonstrates a rate constant of 0.172 min -1 and achieves a 100 % antibacterial rate at a low dose for eliminating E. coli. This study advances that doping can induce piezoelectricity and reveals that lattice distortion-induced polarization and vacancy defects engineering can improve ROS production, which might impact applications such as water disinfection and sonodynamic therapy., 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.)

Background: Right ventricular (RV) involvement has been reported in type 2 diabetes mellitus (T2DM). The relationship between glycemic control and RV function remains unknown. We aimed to investigate the association between glycemic control and RV function assessed by two-dimensional speckle-tracking echocardiography (2D-STE) and three-dimensional echocardiography (3DE) in T2DM individuals., Methods: This study prospectively enrolled 207 patients with T2DM and 84 individuals with normal glucose metabolism (NGM). T2DM patients were divided into two subgroups according to glycated hemoglobin (HbA1c) level: controlled (HbA1c < 7.0%, n = 91) and uncontrolled subgroup (HbA1c ≥ 7.0%, n = 116). RV free wall longitudinal strain (RVFWLS) was acquired by 2D-STE, RV volumes and RV ejection fraction (RVEF) were assessed using 3DE. RV coupling to pulmonary circulation was defined as the ratio of RVFWLS/pulmonary artery systolic pressure (PASP)., Results: Controlled and uncontrolled T2DM subgroups had impaired RV function as reflected by reduced RVFWLS and RVEF compared to the NGM group. The reduction in RVFWLS was more pronounced in the uncontrolled subgroup than in the controlled subgroup (P < 0.001), whereas no significant difference was found in RVEF between these two T2DM subgroups. Higher PASP and lower RVFWLS/PASP ratio were also noted in uncontrolled T2DM patients. Additionally, the incidence of RV dysfunction was significantly higher in the uncontrolled T2DM patients than in the controlled subgroup (43.1% vs 17.6%, P < 0.001). After adjustment for potential clinical confounders, PASP and left ventricular parameters, HbA1c level was independently associated with RVFWLS (β = 0.290, P = 0.003) and RVFWLS/PASP ratio (β = 0.028, P = 0.006)., Conclusions: Subclinical RV myocardial dysfunction is present in T2DM patients and is more pronounced in patients with uncontrolled blood glucose. HbA1c level is independently associated with subclinical RV myocardial dysfunction, providing further insight into a possible link between poor glycemic control and diabetic cardiomyopathy., (Copyright © 2024. Published by Elsevier Inc.)

The continuous emergence of novel infectious diseases poses a significant threat to global public health security, necessitating the development of small-molecule inhibitors that directly target pathogens. The RNA-dependent RNA polymerase (RdRp) and main protease (Mpro) of SARS-CoV-2 have been validated as potential key antiviral drug targets for the treatment of COVID-19. However, the conventional new drug R&D cycle takes 10-15 years, failing to meet the urgent needs during epidemics. Here, we propose a general multimodal deep learning framework for drug repurposing, MMFA-DTA, to enable rapid virtual screening of known drugs and significantly improve discovery efficiency. By extracting graph topological and sequence features from both small molecules and proteins, we design attention mechanisms to achieve dynamic fusion across modalities. Results demonstrate the superior performance of MMFA-DTA in drug-target affinity prediction over several state-of-the-art baseline methods on Davis and KIBA data sets, validating the benefits of heterogeneous information integration for representation learning and interaction modeling. Further fine-tuning on COVID-19-relevant bioactivity data enhances model predictions for critical SARS-CoV-2 enzymes. Case studies screening the FDA-approved drug library successfully identify etacrynic acid as the potential lead compound against both RdRp and Mpro. Molecular dynamics simulations further confirm the stability and binding affinity of etacrynic acid to these targets. This study proves the great potential and advantages of deep learning and drug repurposing strategies in supporting antiviral drug discovery. The proposed general and rapid response computational framework holds significance for preparedness against future public health events.

In this study, genome-wide association analysis was performed on the growth traits (body height, body length, chest circumference, chest depth, chest width, tube circumference, and body weight) of Inner Mongolian cashmere goats (Erlangshan type) based on resequencing data. The population genetic parameters were estimated, haplotypes were constructed for the significant sites, and association analysis was conducted between the haplotypes and phenotypes. A total of two hundred and eighty-four SNPs and eight candidate genes were identified by genome-wide association analysis, gene annotation, and enrichment analysis. The phenotypes of 16 haplotype combinations were significantly different by haplotype analysis. Combined with the above results, the TGFB2 , BAG3 , ZEB2 , KCNJ12 , MIF , MAP2K3 , HACD3 , and MEGF11 functional candidate genes and the haplotype combinations A2A2, C2C2, E2E2, F2F2, I2I2, J2J2, K2K2, N2N2, O2O2, P2P2, R1R1, T1T1, W1W1, X1X1, Y1Y1, and Z1Z1 affected the growth traits of the cashmere goats and could be used as molecular markers to improve the accuracy of early selection and the economic benefits of breeding.

Lithium metal batteries have garnered significant attention due to their high energy density and broad application prospects. However, the practical use of traditional liquid electrolytes is constrained by safety and stability challenges. In the exploration of novel electrolytes, solid-state electrolyte materials have emerged as a focal point. Covalent organic frameworks (COFs), with their large conjugated structures and unique electronic properties, are gradually gaining attention as an emerging class of solid-state electrolyte materials. In recent years, outstanding electrochemical performance has been achieved through the design and synthesis of various types of COF-based solid-state electrolytes, along with successful integration with other functional materials. This review will provide an overview of the research progress on COFs as solid-state electrolyte materials for lithium metal batteries and offer insights into their future potential in battery technology.

A variety of abnormal epithelial cells and immature and mature immune cells in thymic epithelial tumors (TETs) affect histopathological features, the degree of malignancy, and the response to treatment. Here, gene expression, trajectory inference, and T cell antigen receptor (TCR)-based lineage tracking are profiled in TETs at single-cell resolution. An original subpopulation of KRT14 + progenitor cells with a spindle cell phenotype is shown. An abnormal infiltration of immature T cells with a TCR hyper-rearrangement state is revealed, due to the lack of CCL21 + medullary epithelial cells. For thymic carcinoma, the novel biomarkers of MSLN, CCL20, and SLC1A5 are identified and observed an elevated expression of LAG3 and HAVCR2 in malignant tumorn-infiltrating mature T cells. These common features based on the single-cell populations may inform pathological reclassification of TETs. Meanwhile, it is found that macrophages (MACs) attract thymic tumor cells through the LGALS9-SLC1A5 axis, providing them with glutamine to elicit metabolic reprogramming. This MAC-based metabolic pattern can promote malignancy progression. Additionally, an interactive immune environment in TETs is identified that correlates with the infiltration of abnormal FOXI1 + CFTR - ionocytes. Collectively, the data broaden the knowledge of TET cellular ecosystems, providing a basis for tackling histopathological diagnosis and related treatment., (© 2024 The Author(s). Advanced Science published by Wiley‐VCH GmbH.)

Objective: Research indicates that cognitive control is compromised in individuals with internet gaming disorder (IGD). However, the neural mechanisms behind it are still unclear. This study aims to investigate alterations in resting-state brain networks in adolescents with IGD and the potential neurobiological mechanisms underlying cognitive dysfunction., Materials and Methods: A total of 44 adolescent IGD subjects (male/female: 38/6) and 50 healthy controls (male/female: 40/10) were enrolled. Participants underwent demographic assessments, Young's Internet Addiction Scale, Barratt Impulsiveness Scale 11 Chinese Revised Version, the Chinese Adolescents' Maladaptive Cognitions Scale, exploratory eye movement tests, and functional magnetic resonance imaging (fMRI). FMRI data were analyzed using the GIFT software for independent component analysis, focusing on functional connectivity within and between resting-state brain networks., Results: In comparison to the control group, impulsivity in adolescent IGD subjects showed a positive correlation with the severity of IGD (r=0.6350, p < 0.001), linked to impairments in the Executive Control Network (ECN) and a decrease in functional connectivity between the Salience Network (SN) and ECN (r=0.4307, p=0.0021; r=-0.5147, p=0.0034). Decreased resting state activity of the dorsal attention network (DAN) was associated with attentional dysregulation of IGD in adolescents (r=0.4071, p=0.0017), and ECN increased functional connectivity with DAN. The degree of IGD was positively correlated with enhanced functional connectivity between the ECN and DAN (r=0.4283, p=0.0037)., Conclusions: This research demonstrates that changes in the ECN and DAN correlate with heightened impulsivity and attentional deficits in adolescents with IGD. The interaction between cognitive control disorders and resting-state brain networks in adolescent IGD is related., 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 Zhao, Zhang, Li, Wu, Wang, Lv, Li and Lang.)

Controversy still exists regarding how much the inflow arterial percutaneous transluminal angioplasty (PTA) contributed to maintaining fistula function for hemodialysis. We aimed to analyze patency and risk factors after inflow arterial PTA. Hemodialysis patients with inflow arterial primary stenosis who were admitted to our institution from January 2017 to December 2022 were examined. One group had arterial-venous fistula with inflow artery stenosis alone (AVF + iAS) and another group had AVF with inflow artery stenosis and any vein stenosis (AVF + iAS + VS). The characteristics of patients, stenotic lesions, and PTA procedures were recorded. Kaplan-Meier analysis was used to compare primary patency, assisted primary patency, and secondary patency in the two groups. Cox proportional hazard analysis was used to identify risk factors associated with patency. We examined 213 patients, 53 in the AVF + iAS group (51 radial arterial stenosis and 2 ulnar arterial stenosis) and 160 in the AVF + iAS + VS group (159 radial arterial stenosis and 1 ulnar arterial stenosis). Kaplan-Meier analysis indicated the AVF + iAS group had better primary patency and assisted primary patency (both P < 0.05), but the groups had similar secondary patency. Cox proportional hazard analysis indicated that none of the analyzed clinical and biochemical indexes had clinically meaningful effects on primary patency, assisted primary patency, or secondary patency in either group. The patency and safety after PTA for inflow arterial stenosis were satisfactory, and none of the examined risk factors had a major clinical impact on patency. We recommend PTA as treatment for inflow stenosis of an AVF., (© 2024. The Author(s).)

Background: Cognitive control involves flexibly configuring mental resources and adjusting behavior to achieve goal-directed actions. It is associated with the coordinated activity of brain networks, although it remains unclear how both structural and functional brain networks can predict cognitive control. Connectome-based predictive modeling (CPM) is a powerful tool for predicting cognitive control based on brain networks., Methods: The study used CPM to predict cognitive control in 102 healthy adults from the UCLA Consortium for Neuropsychiatric Phenomics dataset and further compared structural and functional connectome characteristics that support cognitive control., Results: Our results showed that both structural (r values 0.263-0.375) and functional (r values 0.336-0.503) connectomes can significantly predict individuals' cognitive control subcomponents. There is overlap between the functional and structural networks of all three cognitive control subcomponents, particularly in the frontoparietal (FP) and motor (Mot) networks, while each subcomponent also has its own unique weight prediction network. Overall, the functional and structural connectivity that supports different cognitive control subcomponents manifests overlapping and distinct spatial patterns., Conclusions: The structural and functional connectomes provide complementary information for predicting cognitive control ability. Integrating information from both connectomes offers a more comprehensive understanding of the neural underpinnings of cognitive control., 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.)

Background: Co-morbid hypertension is strong predictor of adverse cardiovascular (CV) outcomes in patients with atrial fibrillation (AF) but the optimal target for blood pressure (BP) control in this patient population has not been clearly defined., Methods: The Cardiovascular Risk reduction in patients with Atrial Fibrillation Trial (CRAFT) is an investigator-initiated and conducted, international, multicenter, open-label, parallel-group, blinded outcome assessed, randomized controlled trial of intensive BP control in patients with AF. The aim is to determine whether intensive BP control (target home systolic blood pressure [SBP] <120 mmHg) is superior to standard BP control (home SBP <135 mmHg) on the hierarchical composite outcome of time to CV death, number of stroke events, time to the first stroke, number of myocardial infarction (MI) events, time to the first MI, number of heart failure hospitalization (HFH) events, and time to the first HFH. A sample size of 1,675 patients is estimated to provide 80% power to detect a win-ratio of 1.50 for intensive versus standard BP control on the primary composite outcome. Study visits are conducted at 1, 2, 3, and 6 months postrandomization, and every 6 months thereafter during the study., Conclusions: This clinical trial aims to provide reliable evidence of the effects of intensive BP control in patients with AF., Trial Registration: The trial is registered at ClinicalTrials.gov (NCT04347330)., Competing Interests: Conflict of interest The principal Investigators of CRAFT study have no disclosures of financial and other competing interests. CSA reports receiving funding from the Medical Research Council (MRC) and Medical Research Foundation (MRF) of the UK, and the National Health and Medical Research (NHMRC) of Australia, and Penumbra and Takeda. AP is the nonremunerated Chair of the Board of George Medicines, a commercial spin-out of The George Institute that is aiming to bring a novel fixed-dose antihypertensive combination to market, and reports receiving funding from NHMRC., (Copyright © 2024. Published by Elsevier Inc.)

Background: Verbascoside, a compound classified as a phenylethanol glycoside in Dihuang, has been the subject of modern pharmacological investigations. These studies have revealed its noteworthy antioxidant, anti-inflammatory, memory-enhancing, neuroprotective, antitumor, and various other pharmacological properties. While verbascoside exhibits favorable antioxidant effects, its precise mechanism of action in ameliorating osteoporosis through the treatment of oxidative stress remains unclear., Methods: This study employed CCK8, ALP, ELISA, and ROS staining techniques to examine the osteoporotic effects of verbascoside on zebrafish and MC3T3-E1 cells. Additionally, this study aimed to investigate the molecular mechanism by which verbascoside improves osteoporosis by mitigating oxidative stress. To identify the common targets of verbascoside in relation to oxidative stress and osteoporosis, network pharmacology and molecular dynamics simulation were employed. The construction of the verbascoside - oxidative stress - osteoporosis - potential target gene network aimed to identify the core targets, while the mechanism of action was elucidated through KEGG analysis, and the accuracy was confirmed by assessing the mRNA expression of the targets., Results: In vivo experiments demonstrated that verbascoside exhibited therapeutic effects on osteoporosis and reduced ROS production in zebrafish. In vitro experiments further revealed that verbascoside enhanced the proliferation and differentiation of MC3T3-E1 cells, thereby improving the oxidative stress status of osteoblasts. Thirteen core targets and estrogen signaling pathways were identified through the application of network pharmacology. The pivotal role of the estrogen signaling pathway in facilitating the ability of verbascoside to mitigate oxidative stressinduced osteoporosis was substantiated by the modulation of target protein mRNA expression., Conclusion: The findings underscore the considerable therapeutic potential of verbascoside in ameliorating osteoporosis through the alleviation of oxidative stress, thus establishing it as a promising compound for the treatment of this condition., (Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.net.)

Introduction: The present study explores the effect of ginseng stem leaf (GSL) extract on the production performance, meat quality, antioxidant status, immune function, and lipid metabolism of white feathered broilers., Methods: There were 6 replicates in each group, with 10 broilers in each replicate. In the 42 day trial, 300 AA broilers were randomly divided into five groups: control group (CON), 1.25% GSL extract group (GSL-L), 2.5% GSL group (GSL-M), 5% GSL group (GSL-H), and 45 mg/kg chlortetracycline group (CTC)., Results: The results showed that different doses of GSL extract could improve the body weight, feed to gain ratio (F/G), average daily feed intake (ADFI), average daily gain (ADG), and meat quality of broilers. Compared with the control group, the addition of different doses of GSL improved the antioxidant and immune abilities of broilers to varying degrees, and the effect of GSL extract was significant in the GSL-H group ( p  < 0.05). In addition, medium and high doses of GSL extract significantly reduced the blood triglyceride (TG) and total cholesterol (TC) contents of broilers ( p  < 0.05)., Discussion: Adding GSL extract to the feed has a positive impact on the body weight, meat quality, antioxidant capacity, immunity, and blood lipids of broilers., Competing Interests: HY and QZ were employed by Liaoning Zhongqing Xinze Biotechnology 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 Zhang, Zhang, Ma, Lv, Yu and Zhang.)

Periodate (PI)-based advanced oxidation processes have gained increasing interest. This study for the first time elevates the light-activation capacity of PI by using far UVC at 222 nm (UV 222 /PI) without extra chemical inputs. The effectiveness and the underlying mechanisms of UV 222 /PI for the remediation of micropollutants were studied by selecting atenolol (ATL) as a representative. PI possessed a high molar absorption coefficient of 9480-6120 M -1 cm -1 at 222 nm in the pH range of 5.0-9.0, and it was rapidly decomposed by UV 222 with first-order rate constants of 0.0055 to 0.002 s -1 . ATL and the six other organic compounds were effectively degraded by the UV 222 /PI process under different conditions with the fluence-based rate constants generally two to hundred times higher than by UVA photolysis. Hydroxyl radical and ozone were confirmed as the major contributors to ATL degradation, while direct photolysis also played a role at higher pH or lower PI dosages. Degradation pathways of ATL were proposed including hydroxylation, demethylation, and oxidation. The high energy efficiency of the UV 222 /PI process was also confirmed. This study provides a cost-effective and convenient approach to enhance PI light-response activity for the treatment of micropollutants., 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.)

Bilirubin is widely recognized to possess antioxidant and anti-inflammatory characteristics. However, the relationship between bilirubin and coronary artery disease (CAD) remains controversial, particularly in individuals receiving Percutaneous Coronary Intervention (PCI). Given that statins may enhance the production of heme oxygenase-1 (HO-1) and bilirubin, we investigated the long-term cardiovascular prognostic role of bilirubin levels elevated by statin use in patients undergoing PCI. Data of 6945 subjects undergoing PCI were enrolled in this study. We divided the patients into two groups based on serum total bilirubin (TB) levels detected prior to PCI. The high TB group consisted of patients with serum TB values > 8.4 μmmol/L, while the low TB group consisted of patients with serum TB values ≤ 8.4 μmmol/L. The median follow-up time was 836 days. Cox proportional hazards models were performed to evaluate the hazard ratios (HRs) and 95% confidence interval (CI) for the incidence of major adverse cardiovascular event (MACE) associated with bilirubin levels. The association between TB levels and risk of MACE was significant [adjusted HR = 0.557, 95% CI (0.59-0.96), p = 0.020). Linear analysis was performed to determine the association between preadmission usage of statin and bilirubin level. The preadmission usage of statin independently linearly increases TB [adjusted-β = 0.371, 95% CI (0.134-0.608), p = 0.002] and direct bilirubin (DB) [adjusted-β = 0.411, 95% CI (0.300-0.522), p < 0.001). Mediation analysis demonstrated a direct protective role of preadmission statins treatment (β = - 0.024, p < 0.01), TB (β = - 0.003, p < 0.05) and DB (β = - 0.009, p < 0.05). Furthermore, it was found that TB (4.0%) and DB (12.0%) mediated the relationship between preadmission statins therapy and MACE. Bilirubin has a protective effect against MACE. In patients with normal bilirubin level undergoing elective PCI, preadmission statin use elevated bilirubin levels, which were independently associated with a lower incidence of MACE over the long-term follow-up period., (© 2024. The Author(s).)