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Abstract Semen Ziziphi Spinosae (SZS) is a traditional Chinese herbal medicine widely used to treat insomnia and anxiety in clinical practice. Currently, the demand for SZS is increasing every year, but the production of wild SZS is unstable due to environmental factors. Grafting sour jujube scions onto sour jujube or jujube tree stocks can achieve a high production rate within a short period of time. However, the effects of grafting on the quality of SZS have not been reported. This study investigated the differences between wild-type and grafted SZS from three aspects: phenotype, chemical composition, and molecular mechanism. The findings revealed that the grafted specimens were generally larger in morphology and lighter in color than the wild-type samples. The dimensions of both the grafted specimens were generally larger than those of the wild specimens. The HPLC-ELSD results revealed that the three main chemical components in the grafted SZS, namely, spinosin, jujuboside A, and jujuboside B, had higher contents than their wild-type counterparts. Comprehensive transcriptome sequencing analysis and KEGG annotation revealed that DEG enrichment between grafted and wild-type SZS occurred mainly during stress resistance and rootstock scion healing. There were 23 DEGs that may encode enzymes involved in the biosynthetic pathway of flavonoids and 21 genes encoding terpenoid saponins. Further investigation revealed that the expression of the genes C4H, CHS, CHI, and F3’5’H in the flavonoid biosynthesis pat.hway and HMGR, MVK, MVD, and FPPS in the saponin biosynthesis pathway accounted for the difference in quality between grafted and wild SZS. Furthermore, WGCNA identified 15 core genes related to medicinal ingredients between grafted and wild SZS. These results provide support for further research on the differences in the quality of medicinal ingredients between grafted and wild SZS.

Fengting Wang,1,* Limin Rong,1,* Linlin Luo,2 Fuqin Mu,1 Liju Qian,3 Yandan Qian,4 Xinyao Zhang,1 Yuying Lang,1 Weijia Wang,1 Yan Liu,5,6 Ying Zhang,7 Jianli Wang1,8 1School of Mental Health, Jining Medical University, Jining, Shandong, People’s Republic of China; 2Department of Hematology, Tai’an Central Hospital, Tai’an, Shandong, People’s Republic of China; 3Shandong Daizhuang Hospital, Jining, Shandong, People’s Republic of China; 4The Third People’s Hospital of Jiashan County, Jiashan, Zhejiang, People’s Republic of China; 5School of Public Health, Jining Medical University, Jining, Shandong, People’s Republic of China; 6Center of Evidence-Based Medicine, Jining Medical University, Jining, Shandong, People’s Republic of China; 7School of Public Health, University of Sydney, Sydney, NSW, Australia; 8Department of Community Health and Epidemiology, Dalhousie University, Halifax, Nova Scotia, Canada*These authors contributed equally to this workCorrespondence: Fengting Wang, School of Mental Health, Jining Medical University, Jining, Shandong, 272013, People’s Republic of China, Email wft.0810@163.com Yan Liu, School of Public Health, Jining Medical University, Jining, Shandong, 272013, People’s Republic of China, Email hakunaly@163.comBackground: Youth and young adults have a high prevalence of major depressive disorder (MDD). Limited longitudinal research has explored the relationship between different dimensions of psychological stress and MDD. This study aimed to estimate the effect of psychological stress on the risk of first onset MDD in a sample of Chinese freshmen.Methods: Using a longitudinal design, 8079 Chinese first-year students were recruited at baseline, and 6985 were followed up one year later. The Psychological Stress Scale for College Students was utilized to evaluate the levels of psychological stress. MDD was evaluated using the Chinese version of the Composite International Diagnostic Interview (CIDI-3.0). Logistic regression modeling was utilized to estimate the associations between dimensions of psychological stress and the risk of MDD.Results: Two dimensions of psychological stress, namely learning stress (OR=1.05, 95% CI:1.01– 1.09, P=0.017) and economic stress (OR=1.11, 95% CI:1.04– 1.19, P=0.001), were significantly associated with the risk of MDD. Other dimensions of psychological stress (specify family stress, interpersonal stress, intimate relationship stress, employment stress and appearance stress) were not associated with MDD.Conclusion: Psychological stress, especially learning and economic stresses, could increase the risk of MDD in university students. These factors should be incorporated into mental health prevention and intervention programs at universities to reduce the risks of MDD.Keywords: major depressive disorder, psychological stress, longitudinal study, freshmen

Dongdong Chen,1,2,* Surong Qian,3,* Wenjun Qian,3 Miao Wu,3 Xinlong Wang,3 Haitao Shen,1 Xianming Long,4 Ming Ye,1 Yan Gong,3 Gang Chen1 1Department of Neurosurgery& Brain and Nerve Research Laboratory, The First Affiliated Hospital of Soochow University, Suzhou, Jiangsu, 215006, People’s Republic of China; 2Department of Neurosurgery, The Affiliated Hospital of Jiang Nan University, Wuxi, Jiangsu, 214000, People’s Republic of China; 3Department of Rehabilitation Medicine, The Affiliated Suzhou Hospital of Nanjing Medical University, Suzhou Municipal Hospital Rehabilitation Medical Center, Gusu School, Suzhou, Jiangsu, 215000, People’s Republic of China; 4Department of Rheumatology, the First Affiliated Hospital of Soochow University, Suzhou, Jiangsu, 215006, People’s Republic of China*These authors contributed equally to this workCorrespondence: Yan Gong; Ming Ye, Email gongyan200605@126.com; yeming@suda.edu.cnBackground: Repetitive transcranial magnetic stimulation (rTMS) is a noninvasive neuromodulation technique that shows promise for the treatment of Parkinson’s disease (PD). However, there is still limited understanding of the optimal stimulation frequencies and whether rTMS can alleviate PD symptoms by regulating the CaMKII-CREB-BMAL1 pathway.Methods: A PD mouse model was induced intraperitoneally with 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) and treated with 1 Hz, 5 Hz, and 10 Hz rTMS. The neurological function, survival of dopaminergic neurons, and protein levels of Tyrosine hydroxylase (TH), α-synuclein(α-syn), and brain-derived neurotrophic factor (BDNF) in the striatum were measured to determine the optimal stimulation frequencies of rTMS treatment in PD mice. The levels of melatonin, cortisol, and the circadian rhythm of Brain and muscle ARNT-like 1 (BMAL1) in PD model mice were detected after optimal frequency rTMS treatment. Additionally, KN-93 and Bmal1siRNA interventions were used to verify that rTMS could alleviate PD symptoms by regulating the CaMKII-CREB-BMAL1 pathway.Results: Administration of 10 Hz rTMS significantly improved neurological function, increased the protein levels of TH and BDNF, and inhibited abnormal aggregation of a-syn. Furthermore, administration of 10 Hz rTMS regulated the secretion profile of cortisol and melatonin and reversed the circadian arrhythmia of BMAL1 expression. After the KN-93 intervention, the MPTP+rTMS+KN-93 group exhibited decreased levels of P- Ca2+/calmodulin-dependent protein kinase II (CaMKII)/CaMKII, P-cAMP-response-element-binding protein (CREB)/CREB, BMALI, and TH. After Bmal1siRNA intervention, the protein levels of BMAL1 and TH were significantly reduced in the MPTP+10 Hz+ Bmal1siRNA group. At the same time, there were no significant changes in the proportions of P-CaMKIIα/CaMKIIα and P-CREB/CREB expression levels. Finally, immunohistochemical analysis showed that the number of TH-positive neurons was high in the MPTP+10 Hz group, but decreased significantly after KN-93 and Bmal1siRNA interventions.Conclusion: Treatment with 10 Hz rTMS alleviated MPTP-induced PD symptoms by regulating the CaMKII-CREB-BMAL1 pathway. This study provides a comprehensive perspective of the therapeutic mechanisms of rTMS in PD.Keywords: Parkinson’s disease, transcranial magnetic stimulation, brain and muscle ARNT-like 1, Ca2+/calmodulin-dependent protein kinase II, cAMP-response-element-binding protein

Abstract Heat shock proteins are essential molecular chaperones that play crucial roles in stabilizing protein structures, facilitating the repair or degradation of damaged proteins, and maintaining proteostasis and cellular functions. Extensive research has demonstrated that heat shock proteins are highly expressed in cancers and closely associated with tumorigenesis and progression. The "Hallmarks of Cancer" are the core features of cancer biology that collectively define a series of functional characteristics acquired by cells as they transition from a normal state to a state of tumor growth, including sustained proliferative signaling, evasion of growth suppressors, resistance to cell death, enabled replicative immortality, the induction of angiogenesis, and the activation of invasion and metastasis. The pivotal roles of heat shock proteins in modulating the hallmarks of cancer through the activation or inhibition of various signaling pathways has been well documented. Therefore, this review provides an overview of the roles of heat shock proteins in vital biological processes from the perspective of the hallmarks of cancer and summarizes the small-molecule inhibitors that target heat shock proteins to regulate various cancer hallmarks. Moreover, we further discuss combination therapy strategies involving heat shock proteins and promising dual-target inhibitors to highlight the potential of targeting heat shock proteins for cancer treatment. In summary, this review highlights how targeting heat shock proteins could regulate the hallmarks of cancer, which will provide valuable information to better elucidate and understand the roles of heat shock proteins in oncology and the mechanisms of cancer occurrence and development and aid in the development of more efficacious and less toxic novel anticancer agents. Graphic abstract

AIM: To investigate whether retinal nerve fiber layer defects (RNFLDs) is a potential risk factor for chronic kidney disease (CKD) in Chinese adults. METHODS: The Kailuan Eye Study was a population-based study that included 14 440 participants. All participants underwent detailed assessments, RNFLDs were diagnosed using color fundus photographs. RESULTS: Overall, 12 507 participants [8533 males (68.23%)] had complete systemic examination data and at least one evaluable fundus photograph. RNFLDs were found in 621 participants [5.0%; 95% confidence interval (CI): 4.6%-5.34%], and 70 cases of multiple RNFLDs were found (11.27%). After adjusting multiple factors, RNFLDs was significantly associated with CKD severity, the ORs of CKD stage 3, stage 4 and stage 5 were 1.698, 4.167, and 9.512, respectively. Multiple RNFLDs were also associated with CKD severity after adjusting multiple factors, the ORs of CKD stage 3 and stage 5 were 4.465 and 11.833 respectively. Furthermore, 2294 participants had CKD (18.34%, 95%CI: 17.68%-18.99%). After adjusting for other factors, CKD presence was significantly correlated with the presence of RNFLDs. CONCLUSION: The strongest risk factors for RNFLDs are CKD and hypertension. Conversely, RNFLDs can be an ocular feature in patients with CKD. Fundoscopy can help detect systemic diseases, and assessment for RNFLDs should be considered in CKD patients.

Abstract Tandem repeats (TRs) are genomic regions that tandemly change in repeat number, which are often multiallelic. Their characteristics and contributions to gene expression and quantitative traits in rice are largely unknown. Here, we survey rice TR variations based on 231 genome assemblies and the rice pan-genome graph. We identify 227,391 multiallelic TR loci, including 54,416 TR variations that are absent from the Nipponbare reference genome. Only 1/3 TR variations show strong linkage with nearby bi-allelic variants (SNPs, Indels and PAVs). Using 193 panicle and 202 leaf transcriptomic data, we reveal 485 and 511 TRs act as QTLs independently of other bi-allelic variations to nearby gene expression, respectively. Using plant height and grain width as examples, we identify and validate TRs contributions to rice agronomic trait variations. These findings would enhance our understanding of the functions of multiallelic variants and facilitate rice molecular breeding.

Abstract Acute pancreatitis, a common exocrine inflammatory disease affecting the pancreas, is characterized by intense abdominal pain and multiple organ dysfunction. However, the alterations in retinal blood vessels among individuals with acute pancreatitis remain poorly understood. This study employed optical coherence tomography angiography (OCTA) to examine the superficial and deep retinal blood vessels in patients with pancreatitis. Sixteen patients diagnosed with pancreatitis (32 eyes) and 16 healthy controls (32 eyes) were recruited from the First Affiliated Hospital of Nanchang University for participation in the study. Various ophthalmic parameters, such as visual acuity, intraocular pressure, and OCTA image for retina consisting of the superficial retinal layer (SRL) and the deep retinal layer (DRL), were recorded for each eye. The study observed the superficial and deep retinal microvascular ring (MIR), macrovascular ring (MAR), and total microvessels (TMI) were observed. Changes in retinal vascular density in the macula through annular partitioning (C1–C6), hemispheric quadrant partitioning (SR, SL, IL, and IR), and early diabetic retinopathy treatment studies (ETDRS) partitioning methods (R, S, L, and I). Correlation analysis was employed to investigate the relationship between retinal capillary density and clinical indicators. Our study revealed that in the superficial retinal layer, the vascular density of TMI, MIR, MAR, SR, IR, S, C2, C3 regions were significantly decreased in patients group compared with the normal group. For the deep retinal layer, the vascular density of MIR, SR, S, C1, C2 regions also reduced in patient group. The ROC analysis demonstrated that OCTA possesses significant diagnostic performance for pancreatitis. In conclusion, patients with pancreatitis may have retinal microvascular dysfunction, and OCTA can be a valuable tool for detecting alterations in ocular microcirculation in pancreatitis patients in clinical practice.

Abstract Ketamine has recently become an anesthetic drug used in human and veterinary clinical medicine for illicit abuse worldwide, but the detection of illicit abuse and inference of time intervals following ketamine abuse are challenging issues in forensic toxicological investigations. Here, we developed methods to estimate time intervals since ketamine use is based on significant metabolite changes in rat serum over time after a single intraperitoneal injection of ketamine, and global metabolomics was quantified by ultra-performance liquid chromatography-quadrupole-time-of-flight mass spectrometry (UPLC-Q-TOF–MS). Thirty-five rats were treated with saline (control) or ketamine at 3 doses (30, 60, and 90 mg/kg), and the serum was collected at 21 time points (0 h to 29 d). Time-dependent rather than dose-dependent features were observed. Thirty-nine potential biomarkers were identified, including ketamine and its metabolites, lipids, serotonin and other molecules, which were used for building a random forest model to estimate time intervals up to 29 days after ketamine treatment. The accuracy of the model was 85.37% in the cross-validation set and 58.33% in the validation set. This study provides further understanding of the time-dependent changes in metabolites induced by ketamine abuse.

The effects of the addition of curdlan gel with two different forms, thermal reversible curdlan gum (TRC) and thermal irreversible curdlan gum (TIRC) on the gelling properties and in vitro digestibility of myofibrillar proteins (MP) gel were investigated. The results showed that the gel strength and water holding capacity of MP gel significantly increased with increasing TRC or TIRC concentration (P0.05). Therefore, this study provides a theoretical basis for the effect of TRC or TIRC on the formation and in vitro digestion of MP gel, and lays a technical support for the application of curdlan gum in meat industry.

Abstract Background Primary electrical disorders (PEDs) are a group of cardiac rhythm abnormalities that occur in the absence of detectable structural heart disease and are a significant cause of sudden cardiac death (SCD). The initiation of cardiac muscle contraction and relaxation is orchestrated by the action potential (AP), generated through ionic changes across the membrane. Mutations in the AP-related gene CACNA2D1 have been identified as a causative factor for PED. Methods We recruited a Chinese family with a history of arrhythmia. The proband has experienced palpitations and chest tightness for over 40 years, with symptoms worsening over the past year. Whole exome sequencing (WES) was used to determine the genetic etiologies in this family. Results A novel heterozygous missense mutation (NM_000722.3: c.1685G > C;p.G562A) of CACNA2D1 gene was detected. Genotyping of the proband’s parents indicated that the arrhythmia phenotype in the proband was caused by a de novo mutation. Conclusions WES was utilized to explore the genetic etiology in a family with arrhythmia, leading to the identification of a novel mutation in the CACNA2D1 gene. This study not only expands the mutation spectrum of the CACNA2D1 gene but also contributes to genetic counseling and clinical diagnosis for this family.

Abstract Background The transplantation of periodontal ligament stem cells (PDLSCs) has been shown to enhance periodontal regeneration in animal models and clinical trials. However, it is not known whether PDLSCs are antibacterial and whether this affects oral microbiota and periodontal regeneration. Methods We isolated human PDLSCs from periodontal ligament of extracted teeth. Rats’ periodontal fenestration defects were prepared, and treated with PDLSC injections (Cell group), using saline injections (Saline group) as the control. The oral microbiota was explored by 16 S rDNA sequencing and compared with that before surgery (PRE group). The antibacterial property of PDLSCs and its underlying mechanism were tested in vitro. Results Microbiome analyses reveal a decreased biodiversity, a changed community structure, and downregulated community functions of the oral microbiome in the Saline group. PDLSCs injections enhance periodontal regeneration, reverse the decrease in diversity, and increase the abundance of non-pathogenic bacterial Bifidobacterium sp. and Lactobacillus sp., making the oral microbiome similar to that of the PRE group. In vitro, PDLSCs inhibit the growth of Staphylococcus aureus, Escherichia coli, and Fusobacterium nucleatum. The main mechanism of action is postulated to involve production of the cationic antimicrobial peptide LL-37. Conclusions Our findings reveal that PDLSC injections enhance periodontal regeneration and regulate the oral microbiome to foster an oral cavity microenvironment conducive to symbiotic microbiota associated with health.

Abstract Objective To establish a practical risk stratification system (RSS) based on ultrasonography (US) and clinical characteristics for predicting soft tissue masses (STMs) malignancy. Methods This retrospective multicenter study included patients with STMs who underwent US and pathological examinations between April 2018 and April 2023. Chi-square tests and multivariable logistic regression analyses were performed to assess the association of US and clinical characteristics with the malignancy of STMs in the training set. The RSS was constructed based on the scores of risk factors and validated externally. Results The training and validation sets included 1027 STMs (mean age, 50.90 ± 16.64, 442 benign and 585 malignant) and 120 STMs (mean age, 51.93 ± 17.90, 69 benign and 51 malignant), respectively. The RSS was constructed based on three clinical characteristics (age, duration, and history of malignancy) and six US characteristics (size, shape, margin, echogenicity, bone invasion, and vascularity). STMs were assigned to six categories in the RSS, including no abnormal findings, benign, probably benign (fitted probabilities [FP] for malignancy: 0.001–0.008), low suspicion (FP: 0.008–0.365), moderate suspicion (FP: 0.189–0.911), and high suspicion (FP: 0.798–0.999) for malignancy. The RSS displayed good diagnostic performance in the training and validation sets with area under the receiver operating characteristic curve (AUC) values of 0.883 and 0.849, respectively. Conclusion The practical RSS based on US and clinical characteristics could be useful for predicting STM malignancy, thereby providing the benefit of timely treatment strategy management to STM patients. Critical relevance statement With the help of the RSS, better communication between radiologists and clinicians can be realized, thus facilitating tumor management. Key Points There is no recognized grading system for STM management. A stratification system based on US and clinical features was built. The system realized great communication between radiologists and clinicians in tumor management. Graphical Abstract

Background Endothelin-1 (ET-1) is an endogenous vasoconstrictor implicated in coronary artery disease (CAD) and diabetes. This study aimed to determine the prognostic value of ET-1 in the patients with stable CAD under different glucose metabolism states. Methods In this prospective, large-cohort study, we consecutively enrolled 7,947 participants with angiography-diagnosed stable CAD from April 2011 to April 2017. Patients were categorized by baseline glycemic status into three groups (normoglycemia, prediabetes, and diabetes) and further divided into nine groups by circulating ET-1 levels. Patients were followed for the occurrence of cardiovascular events (CVEs), including nonfatal myocardial infarction, stroke, and cardiovascular mortality. Results Of the 7,947 subjects, 3,352, 1,653, and 2,942 had normoglycemia, prediabetes, and diabetes, respectively. Over a median follow-up of 37.5 months, 381 (5.1%) CVEs occurred. The risk for CVEs was significantly higher in patients with elevated ET-1 levels after adjustment for potential confounders. When patients were categorized by both status of glucose metabolism and plasma ET-1 levels, the high ET-1 levels were associated with higher risk of CVEs in prediabetes (adjusted hazard ratio [HR], 2.089; 95% confidence interval [CI], 1.151 to 3.793) and diabetes (adjusted HR, 2.729; 95% CI, 1.623 to 4.588; both P

Abstract Background Liver cancer (LC) screening, such as AFP test and abdominal ultrasound, is an effective way to prevent LC, one of the most common cancers worldwide. Despite the proven screening benefits, screening participation among high-risk populations for LC remains low. This suggests that targeted, systematic, and effective interventions should be provided to improve knowledge and awareness related to LC screening, enhance screening intentions, and thereby promote screening behaviors. Telephone is people’s main medium of daily communication and mHealth-based programs offer a potential and effective solution for promoting health behaviors. The purpose of this study is to develop and implement a mHealth (WeChat app) based intervention guided by Fogg’s Behavior Model (FBM) to augment the knowledge of LC prevention among people at risk of LC and enhance their motivation for screening, and to validate its effectiveness in improving LC screening. Methods We propose a two-arm, single-blind randomized controlled trial with 82 at-risk individuals of LC, delivering a 6-month mHealth-based intervention program with optional health counseling. Recruitment will be through tertiary hospitals and community organizations in 4 districts in Heng Yang. In total, 82 individuals at high risk for HCC will be randomized 1:1 to intervention or control (usual care) groups. The intervention group will receive intervention, whose contents are based on the FBM model, via multiple forms of media including PowerPoint presentation, multimedia video, health information booklet and screening message, which is delivered in the WeChat Applet. Control dyads will be provided with usual health education. Outcomes will be assessed at baseline and post-intervention. Discussion The findings of this study will provide evidence of the benefits of utilizing mHealth-based approaches in intervention development to enhance the effectiveness of screening adherence for high-risk people of LC. Further, the findings would provide reference to the potential incorporation of the targeted intervention in local community organizations. Trial registration Chinese Clinical Trial Registry (ChiCTR2400080530) Date registered: 31/1/2024.

Abstract Depression, a widespread and highly heritable mental health condition, profoundly affects millions of individuals worldwide. Neuroimaging studies have consistently revealed volumetric abnormalities in subcortical structures associated with depression. However, the genetic underpinnings shared between depression and subcortical volumes remain inadequately understood. Here, we investigate the extent of polygenic overlap using the bivariate causal mixture model (MiXeR), leveraging summary statistics from the largest genome-wide association studies for depression (N = 674,452) and 14 subcortical volumetric phenotypes (N = 33,224). Additionally, we identify shared genomic loci through conditional/conjunctional FDR analyses. MiXeR shows that subcortical volumetric traits share a substantial proportion of genetic variants with depression, with 44 distinct shared loci identified by subsequent conjunctional FDR analysis. These shared loci are predominantly located in intronic regions (58.7%) and non-coding RNA intronic regions (25.4%). The 269 protein-coding genes mapped by these shared loci exhibit specific developmental trajectories, with the expression level of 55 genes linked to both depression and subcortical volumes, and 30 genes linked to cognitive abilities and behavioral symptoms. These findings highlight a shared genetic architecture between depression and subcortical volumetric phenotypes, enriching our understanding of the neurobiological underpinnings of depression.

Understanding the temporal and spatial variation of hydrochemical components in large freshwater lakes is crucial for effective management and conversation. In this study, we identify the temporal-spatial characteristics and driving factors of the hydrochemical components in Baiyangdian Lake using geochemical methods (Gibbs diagram, Piper diagram and End-element diagram of ion ratio) and multivariate statistical techniques (Principal component analysis and Correlation analysis). 16 sets of samples were collected from Baiyangdian Lake in May (normal season), July (flood season), and December (dry season) of 2022. Results indicate significant spatial variation in Na+, Cl−, SO42− and NO3− , suggesting a strong influence of human activities. Cation concentrations exhibit greater seasonal variation in the dry season compared to the flood season, while the concentrations of the four anions show inconsistent seasonal changes due to the combined effects of river water chemical composition and human activities. The hydrochemical type of Baiyangdian Lake is primarily HCO3·Cl-Na·Ca2+, Mg2+ and HCO3− originate mainly from silicate and carbonate rock dissolution, while K+, Na+ and Cl− originate mainly from sewage and salt dissolution in sediments. SO42− may mainly stem from industrial wastewater, while NO3− primarily originates from animal feces and domestic sewage. Through the use of Principal Component Analysis, it is identified that water-rock interaction (silicate and carbonate rocks dissolution, and dissolution of salt in sediments), carbonate sedimentation, sewage, agricultural fertilizer and manure, and nitrification are the main driving factors of the variation of hydrochemical components of Baiyangdian Lake across three hydrological seasons. These findings suggest the need for effective control of substandard domestic sewage discharge, optimization of agricultural fertilization strategies, and proper management of animal manure to comprehensively improve the water environment in Baiyangdian Lake.

[Objective] To delve deeper into the spatiotemporal characteristics and pivotal driving factors underlying the hardness of black soil in eroded sloping farmlands. [Methods] Based on the dynamic monitoring of soil penetration resistance across 110 sample points in typical water erosion sloping farmlands, coupled with measurements of pertinent factors, the factors affecting soil penetration resistance were analyzed by multivariate linear regression (MLR) and random forest (RFR) models, and its transfer function was further construct. [Results] The spatiotemporal variability of soil penetration resistance was influenced by a combination of soil depth, moisture conditions, and agricultural practices. Notably, the spatial heterogeneity was significantly lower in the topsoil layer compared to the sub-surface layer, with coefficients of variation of 17.4% and 26.3%, respectively. As the soil dried out and the duration since the last tillage increases, spatial heterogeneity tended to intensify. Soil erosion played a significant role, with higher soil penetration resistance observed in areas of intense erosion compared to deposition zones, particularly under wet conditions where the difference is most pronounced (p

Abstract Background The relationship between human gut microbiota and high-altitude hypoxia acclimatization remains highly controversial. This stems primarily from uncertainties regarding both the potential temporal changes in the microbiota under such conditions and the existence of any dominant or core bacteria that may assist in host acclimatization. Results To address these issues, and to control for variables commonly present in previous studies which significantly impact the results obtained, namely genetic background, ethnicity, lifestyle, and diet, we conducted a 108-day longitudinal study on the same cohort comprising 45 healthy Han adults who traveled from lowland Chongqing, 243 masl, to high-altitude plateau Lhasa, Xizang, 3658 masl, and back. Using shotgun metagenomic profiling, we study temporal changes in gut microbiota composition at different timepoints. The results show a significant reduction in the species and functional diversity of the gut microbiota, along with a marked increase in functional redundancy. These changes are primarily driven by the overgrowth of Blautia A, a genus that is also abundant in six independent Han cohorts with long-term duration in lower hypoxia environment in Shigatse, Xizang, at 4700 masl. Further animal experiments indicate that Blautia A-fed mice exhibit enhanced intestinal health and a better acclimatization phenotype to sustained hypoxic stress. Conclusions Our study underscores the importance of Blautia A species in the gut microbiota’s rapid response to high-altitude hypoxia and its potential role in maintaining intestinal health and aiding host adaptation to extreme environments, likely via anti-inflammation and intestinal barrier protection.

Abstract Background Coarctation of the aorta (CoA) is the most common undiagnosed congenital heart defect during prenatal screening. High false positive and false negative rates seriously affect prenatal consultation and postnatal management. The objective of the study was to assess the utility of various measurements to predict prenatal CoA and to derive a diagnostic algorithm. Methods One hundred and fifty-four fetuses with suspected CoA who presented at Fuwai Hospital between December 2017 and August 2021 were enrolled and divided into confirmed CoA cases (n = 47) and false positive cases (n = 107), according to their postnatal outcomes. The transverse aortic arch, isthmus, and descending aorta were measured in the long-axis view of the aortic arch. The angle between the transverse aortic arch (TAO) and the descending aortic arch (DAO) was defined as the TAO-DAO angle and measured in the long axis or sagittal view. Based on the database in GE Voluson E10 and the formula (Z = $$\frac{\text{x}-{\mu }}{\alpha }$$ ), the standard score (Z-score) of the dimensions of the aorta were calculated in relation to the gestational age. The main echocardiographic indices were combined to design a 3-step diagnostic protocol. The TAO-DAO angle was used as the first step in the diagnostic model. The diameter of the transverse arch and the Z-score of the isthmus were the second step. The third-step indices included a Z-score of the transverse arch, diameter of the isthmus, distance from the left subclavian artery (LSA) to left common carotid artery (LCCA), the ratio of isthmus diameter and LSA diameter and ratio of the distances (the distance between the LSA and LCCA to the distance between the right innominate artery and LCCA). The receiver operating characteristic (ROC) curve determined the predictive capability of each diagnostic parameter, and the kappa test determined the diagnostic accuracy of the proposed model. Results The cases with confirmed CoA had thinner transverse arches (1.92 ± 0.32 mm vs. 3.06 ± 0.67 mm, P = 0.0001), lower Z-scores of the isthmus (-8.97 ± 1.45 vs. -5.65 ± 1.60, P = 0.0001), smaller TAO-DAO angles (105.54 ± 11.51° vs. 125.29 ± 8.97°, P = 0.0001) and larger distance between the LSA and LCCA (4.45 ± 1.75 mm vs. 2.74 ± 1.07 mm, P = 0.0001) than the false positive cases. The area under the curve (AUC) was 0.947 (95% CI 0.91–0.98) for the TAO-DAO angle ≤ 115.75°, 0.942 (95% CI 0.91–0.98) for the transverse arch diameter ≤ 2.31 mm, 0.937 (95% CI 0.90–0.98) for the Z-score of the isthmus ≤ -7.5, and 0.975 (95% CI 0.95–1.00) for the 3-step diagnostic protocol with 97.8% sensitivity and 97.2% specificity. The kappa test showed that the model’s diagnostic accuracy was consistent with postnatal outcomes (kappa value 0.936, P = 0.0001). Conclusions The 3-step diagnostic protocol included the three most useful measurements and the additional indices with appropriate cut-off values. The algorithm is useful for the detection of aortic coarctation in fetuses with a high degree of accuracy. Trial registration Retrospectively registered.

Abstract Background R2R3-MYB transcription factors belong to one of the largest gene subfamilies in plants, and they are involved in diverse biological processes. However, the role of R2R3-MYB transcription factor subfamily genes in the response of rice (Oryza sativa L.) to salt stress has been rarely reported. Results In this study, we performed a genome-wide characterization and expression identification of rice R2R3-MYB transcription factor subfamily genes. We identified a total of 117 R2R3-MYB genes in rice and characterized their gene structure, chromosomal location, and cis-regulatory elements. According to the phylogenetic relationships and amino acid sequence homologies, the R2R3-MYB genes were divided into four groups. qRT-PCR of the R2R3-MYB genes showed that the expression levels of 10 genes significantly increased after 3 days of 0.8% NaCl treatment. We selected a high expression gene OsMYB2-115 for further analysis. OsMYB2-115 was highly expressed in the roots, stem, leaf, and leaf sheath. OsMYB2-115 was found to be localized in the nucleus, and the yeast hybrid assay showed that OsMYB2-115 has transcriptional activation activity. Conclusion This result provides important information for the functional analyses of rice R2R3-MYB transcription factor subfamily genes related to the salt stress response and reveals that OsMYB2-115 may be an important gene associated with salt tolerance in rice.

Abstract Recent advances in imaging sensors and digital light projection technology have facilitated rapid progress in 3D optical sensing, enabling 3D surfaces of complex-shaped objects to be captured with high resolution and accuracy. Nevertheless, due to the inherent synchronous pattern projection and image acquisition mechanism, the temporal resolution of conventional structured light or fringe projection profilometry (FPP) based 3D imaging methods is still limited to the native detector frame rates. In this work, we demonstrate a new 3D imaging method, termed deep-learning-enabled multiplexed FPP (DLMFPP), that allows to achieve high-resolution and high-speed 3D imaging at near-one-order of magnitude-higher 3D frame rate with conventional low-speed cameras. By encoding temporal information in one multiplexed fringe pattern, DLMFPP harnesses deep neural networks embedded with Fourier transform, phase-shifting and ensemble learning to decompose the pattern and analyze separate fringes, furnishing a high signal-to-noise ratio and a ready-to-implement solution over conventional computational imaging techniques. We demonstrate this method by measuring different types of transient scenes, including rotating fan blades and bullet fired from a toy gun, at kHz using cameras of around 100 Hz. Experiential results establish that DLMFPP allows slow-scan cameras with their known advantages in terms of cost and spatial resolution to be used for high-speed 3D imaging tasks.

Abstract Background The identification of spotted leaf 50 (spl50), a novel lesion mimic mutant (LMM) in rice, provides critical insights into the mechanisms underlying programmed cell death (PCD) and innate immunity in plants. Results Based on ethyl methane sulfonate (EMS)-induced mutagenesis, the spl50 mutant mimics hypersensitive responses in the absence of pathogen by displaying spontaneous necrotic lesions after the tillering phase. SPL50, an ARM repeat protein essential for controlling reactive oxygen species (ROS) metabolism and boosting resistance to blast disease, was identified by map-based cloning techniques. This work also demonstrates the detrimental effects of spl50 on photosynthetic efficiency and chloroplast development. The crucial significance of SPL50 in cellular signaling and stress response is shown by its localization to the cytoplasm and constitutive expression in various plant tissues. In light of growing concerns regarding global food security, this study highlights the pivotal role of SPL50 in regulating programmed cell death (PCD) and enhancing the immune response in plants, contributing to strategies for improving crop disease resistance. Conclusions The novel identification of the SPL50 gene in rice, encoding an ARM repeat protein, reveals its pivotal role in regulating PCD and innate immune responses independently of pathogen attack.

Abstract Anaplastic thyroid cancer (ATC) is among the most aggressive and metastatic malignancies, often resulting in fatal outcomes due to the lack of effective treatments. Prosapogenin A (PA), a bioactive compound prevalent in traditional Chinese herbs, has shown potential as an antineoplastic agent against various human tumors. However, its effects on ATC and the underlying mechanism remain unclear. Here, we demonstrate that PA exhibits significant anti-ATC activity both in vitro and in vivo by inducing GSDME-dependent pyroptosis in ATC cells. Mechanistically, PA promotes lysosomal membrane permeabilization (LMP), leading to the release of cathepsins that activate caspase 8/3 to cleave GSDME. Remarkably, PA significantly upregulates three key functional subunits of V-ATPase—ATP6V1A, ATP6V1B2, and ATP6V0C—resulting in lysosomal over-acidification. This over-acidification exacerbates LMP and subsequent lysosomal damage. Neutralization of lysosomal lumen acidification or inhibition/knockdown of these V-ATPase subunits attenuates PA-induced lysosomal damage, pyroptosis and growth inhibition of ATC cells, highlighting the critical role for lysosomal acidification and LMP in PA’s anticancer effects. In summary, our findings uncover a novel link between PA and lysosomal damage-dependent pyroptosis in cancer cells. PA may act as a V-ATPase agonist targeting lysosomal acidification, presenting a new potential therapeutic option for ATC treatment.

Typha angustifolia, commonly known as narrowleaf cattail, is a marginal, semi-aquatic, herbaceous perennial species with both ecological and edible values. In this study, the complete chloroplast (cp) genome of T. angustifolia was assembled using the next-generation sequencing technology. The whole cp genome was 161,597 bp in length, consisting of a large single copy (LSC, 89,119 bp) and a small single copy (SSC, 18,550 bp) separated by two copies of inverted region (IR, 26,964 bp). The genome encoded 113 unique genes, including 79 protein-coding genes, 30 tRNA genes, four rRNA genes, with 19 duplicated genes in the IR regions. Phylogenetic analysis showed that T. angustifolia is sister to Typha orientalis in the family Typhaceae. The cp genome of T. angustifolia is reported for the first time, which will provide essential and important genetic resources for future phylogenetic investigation within the genus Typha.

As a natural immune cell and antigen presenting cell, macrophages have been studied and engineered to treat human diseases. Macrophages are well-suited for use as drug carriers because of their biological characteristics, such as excellent biocompatibility, long circulation, intrinsic inflammatory homing and phagocytosis. Meanwhile, macrophages’ uniquely high plasticity and easy re-education polarization facilitates their use as part of efficacious therapeutics for the treatment of inflammatory diseases or tumors. Although recent studies have demonstrated promising advances in macrophage-based drug delivery, several challenges currently hinder further improvement of therapeutic effect and clinical application. This article focuses on the main challenges of utilizing macrophage-based drug delivery, from the selection of macrophage sources, drug loading, and maintenance of macrophage phenotypes, to drug migration and release at target sites. In addition, corresponding strategies and insights related to these challenges are described. Finally, we also provide perspective on shortcomings on the road to clinical translation and production.

Abstract Despite the broad potential applications of C-glycosides, facile synthetic methods remain scarce. Transforming glycosyltransferases with promiscuous or natural O-specific chemoselectivity to C-glycosyltransferases is challenging. Here, we employ rational directed evolution of the glycosyltransferase MiCGT to generate MiCGT-QDP and MiCGT-ATD mutants which either enhance C-glycosylation or switch to O-glycosylation, respectively. Structural analysis and computational simulations reveal that substrate binding mode govern C-/O-glycosylation selectivity. Notably, directed evolution and mechanism analysis pinpoint the crucial residues dictating the binding mode, enabling the rational design of four enzymes with superior non-inherent chemoselectivity, despite limited sequence homology. Moreover, our best mutants undergo testing with 34 substrates, demonstrating superb chemoselectivities, regioselectivities, and activities. Remarkably, three C-glycosides and an O-glycoside are produced on a gram scale, demonstrating practical utility. This work establishes a highly selective platform for diverse glycosides, and offers a practical strategy for creating various types of glycosylation platforms to access pharmaceutically and medicinally interesting products.

Abstract Understanding the distribution of cutting force provides a foundation for the design and optimization of cutterhead layout. The simulation of rotary cutting with a large cutting radius remains a challenge for laboratory tests. In this study, taking the driving condition of the Mawan Tunnel located in the Guangdong-Hong Kong-Macao Greater Bay Area as a case study, a full-scale rotary cutting platform with large cutting radius was used to investigate the rock-breaking effects. Rotary cutting with cutting depths of 1–8 mm and cutting radii of 200–1400 mm were carried out on the granite testing platform using a 19-in disc cutter. The normal force, rolling force, and side force during the cutting process were systematically monitored. Moreover, the time–frequency characteristics of the rock breaking process and the effects of cutting depth, cutting radius and stress state on the average and peak loads were investigated. The results show that the average normal force and rolling force increased with increasing cutting depth, while the side force was less affected by cutting depth through the Boltzman model analysis. The average normal force and rolling force were not significantly affected by the cutting radius, but the average side force decreased as a power function with increasing cutting radius, and showed a stable side force when the installation radius exceeded 1000 mm. The dominant frequency of the cutting force was 0–1.2 Hz, exhibiting notable low-frequency characteristics. Additionally, the ratio of peak to average (RPA) with respect to triaxial cutting force demonstrated an increase with the growth of cutting depth, while RPA in terms of side force exhibited a corresponding growth with the increasing cutting radius. In particular, the cutting force characteristics of the cutterhead obtained in this study can inform the layout of disc cutters and real-life TBM operations, thereby avoiding severe overloading of internal disc cutters.

Some core designs integrate high-enriched fuel and moderator materials to enhance neutron utilization. This combination results in a broad spectrum within the system, posing challenges in resonance calculation. This paper introduces a general framework to realize resonance self-shielding treatment in broad-spectrum fuel lattice problems. The framework consists of three components. First, a new energy group structure is devised to support resonance calculation in the entire energy range and capture spectral transition and thermalization effects during eigenvalue calculation. Second, the subgroup method based on narrow approximation is selected as a universal method to perform resonance calculation. Finally, transport equations for each fissionable region are solved for neutron flux to collapse the fission spectrum. The proposed method is verified against fast, intermediate, and thermal spectrum pin cell problems and an assembly problem featuring a fast-thermal coupled spectrum. Numerical results affirm the accuracy of the proposed method in handling these scenarios, with eigenvalue errors below 154 pcm for pin cell problems and 106 pcm for the assembly problem. The verification results revealed that the proposed method enables accurate resonance self-shielding treatment for broad-spectrum problems.

Abstract Purpose This study utilizes a meta-analytic approach to investigate the effects of cryoablation and robot-assisted partial nephrectomy on perioperative outcomes, postoperative renal function, and oncological results in patients. Methods This study followed the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) statement. Four electronic databases (PubMed, Embase, Web of Science, and the Cochrane Library database) were systematically searched to identify relevant studies published in English up to November 2023. The primary outcomes were perioperative results, complications, postoperative renal function and oncologic outcomes. Review Manager 5.4 was used for this analysis. Results This study included a total of 10 studies comprising 2,011 patients. Compared to RAPN (Robot-Assisted Partial Nephrectomy), the CA (Cryoablation) group had a shorter hospital stay [MD -1.76 days; 95% CI -3.12 to -0.41; p = 0.01], less blood loss [MD -104.60 ml; 95% CI -152.58 to -56.62; p

Abstract Background After a 920-day hiatus, COVID-19 resurged in the Tibet Autonomous Region of China in August 2022. This study compares the characteristics of COVID-19 between high-altitude residents and newcomers, as well as between newcomers and lowlanders. Methods This multi-center cohort study conducted at the Third People’s Hospital of Tibet Autonomous Region and Beijing University Shenzhen Hospital, included 520 high-altitude resident patients, 53 high-altitude newcomer patients, and 265 lowlander patients infected with the Omicron variant. Initially, we documented epidemiological, clinical, and treatment data across varying residency at admission. We compared the severity of COVID-19 and various laboratory indicators, including hemoglobin concentration and SpO2%, over a 14-day period from the date of the first positive nucleic acid test, as well as the differences in treatment methods and disease outcomes between highlanders and high-altitude newcomers. We also compared several characteristics of COVID-19 between high-altitude newcomers and lowlanders. Univariate analysis, multivariable logistic regression, and the generalized linear mixed model were utilized for the analysis. Results No fatalities were observed. The study found no significant differences in COVID-19 severity or in the physiological measures of hemoglobin concentration and SpO2% between high-altitude and lowland residents. Similarly, there were no statistically significant differences in the values or trends of hemoglobin and SpO2% between high-altitude residents and newcomers throughout the 14-day observation period. However, compared to age- and sex-matched lowlander patients (1:5 ratio), high-altitude newcomers exhibited higher heart rates, respiratory rates, and average hemoglobin concentrations, along with lower platelet counts. There were no significant differences in hospital stays between the two groups. Conclusions High-altitude residents and newcomer patients exhibit clinical similarities. However, the clinical characteristics of high-altitude newcomers and lowlander patients differ due to the impact of the high-altitude environment. These results highlight potential considerations for public health strategies in high-altitude regions such as Tibet.

Abstract Background Previous studies indicated that excessive engagement in digital devices could lead to negative psychological impacts in general population. We aimed to determine the association of electronic screen exposure with depression among women in early pregnancy. Methods A cross-sectional study was conducted from June 2021 to June 2022. A total of 665 women in early pregnancy were recruited and the information included socio-demographic characteristics, screen exposure and Patient Health Questionnaire − 9 depression scale. Results Among the women in early pregnancy, the total daily smartphone viewing time was the longest (median [P25-P75], 5 [3–6] hours/day) in the three types of electronic screen exposure. The total daily smartphone viewing time (P = 0.015, OR[95%CI] = 1.09[1.11–1.18]), smartphone (P = 0.016, OR[95%CI] = 1.24[1.04–1.47]) and television viewing time (P = 0.006, OR[95%CI] = 1.35[1.09–1.67]) before nocturnal sleep were significantly associated with depression among women in early pregnancy. The thresholds calculated by receiver operator characteristic curves were 7.5 h/day, 1.5 h/day and 1.5 h/day, respectively. In addition, women with higher scores of smartphone addiction were more susceptible to depression (P

Abstract Background People with epilepsy (PWE) frequently experience sleep disturbances that can severely affect their quality of life. Depression is also a common symptom in the PWE population and can aggravate sleep problems. However, the interplay between epilepsy, depression, and sleep disturbances is not yet fully understood. Our study was designed to investigate the association between epilepsy and sleep disturbances in US adults and to determine whether depressive symptoms play a mediating role in this relationship. Methods We examined data from the National Health and Nutrition Examination Survey (NHANES) spanning January 1, 2015, to March 2020, before the pandemic.A total of 10,093 participants aged ≥ 20 years with complete data on epilepsy and sleep disturbance were included. Weighted multiple logistic regression and mediation analysis were used to explore the associations among depression, epilepsy, and sleep disturbance. Interaction effects of epilepsy with various covariates were also investigated. Results Epilepsy was associated with depression and sleep disturbances. Weighted logistic regression analysis revealed a significant association between epilepsy and sleep disturbances (OR = 3.67, 95% CI = 1.68–8.04). Depression partially mediated this relationship, demonstrating a mediation effect of 23.0% (indirect effect = 0.037, P

Abstract Background In China, retail pharmacies are critical sources for obtaining medications and play a vital role in residents’ daily access to drugs and treatment of common illnesses. Effectively guiding the placement of these pharmacies in areas of need through government regulation is crucial for enhancing medication access. In this study, we used population and retail pharmacy spatial distribution data from Shanghai to design guidance and supplementary methods for optimizing the spatial layout of retail pharmacies and medical insurance designated pharmacies based on regional characteristics. Methods Population distribution, road traffic network, administrative division and retail pharmacy data from Shanghai in 2018 were collected from relevant government departments. ArcGIS 10.3 was used to map the retail pharmacies and population distribution. Based on the spatial distribution of population and the service standards of pharmacies, service circles with insufficient pharmacies were identified, and supplementary methods for retail pharmacies and medical insurance designated pharmacies were developed. Results In 2018, Shanghai had 3009 retail pharmacies, each serving an average of 6412 residents. The city was divided into 2188 basic pharmaceutical service circles, each within a 15-minute walking distance. The results indicated that there were 1387 service circles without any pharmacies, 151 of which had populations exceeding 5000. Additionally, 356 service circles had pharmacies but lacked medical insurance designated ones. After supplementation, 841 retail pharmacies were planned to be added in residential areas. Compared with before, the coverage area and population served of the pharmacies increased significantly. Conclusions This study mapped the spatial distribution of population and retail pharmacies in Shanghai, and designed government guidance and supplementary methods for optimizing the layout of retail pharmacies. The findings offer valuable insights for government agencies in low- and middle-income countries to improve the spatial distribution of retail pharmacies.

Abstract Background Early detection of colorectal cancer (CRC) significantly enhances patient outcomes. Conventional CRC screening tools, like endoscopy and stool-based tests, have constraints due to their invasiveness or suboptimal patient adherence. Recently, liquid biopsy employing plasma cell-free DNA (cfDNA) has emerged as a potential noninvasive screening technique for various malignancies. Methods In this research, we harnessed the Mutation Capsule Plus (MCP) technology to profile an array of genomic characteristics from cfDNA procured from a single blood draw. This profiling encompassed DNA methylation, the 5’ end motif, copy number variation (CNV), and genetic mutations. An integrated model built upon selected multiomics biomarkers was trained using a cohort of 93 CRC patients and 96 healthy controls. Results This model was subsequently validated in another cohort comprising 89 CRC patients and 95 healthy controls. Remarkably, the model achieved an area under the curve (AUC) of 0.981 (95% confidence interval (CI), 0.965–0.998) in the validation set, boasting a sensitivity of 92.1% (95% CI, 84.5%-96.8%) and a specificity of 94.7% (95% CI, 88.1%-98.3%). These numbers surpassed the performance of any single genomic feature. Importantly, the sensitivities reached 80% for stage I, 89.2% for stage II, and were 100% for stages III and IV. Conclusion Our findings underscore the clinical potential of our multiomics liquid biopsy test, indicating its prospective role as a noninvasive method for early-stage CRC detection. This multiomics approach holds promise for further refinement and broader clinical application.

Abstract Background ST-elevation myocardial infarction (STEMI) is a common acute ischemia heart disease that causes serious damage to human health worldwide. Even though morbidity and mortality have significantly decreased by percutaneous coronary intervention (PCI), an additional cardiac protection strategy is still required. Acupuncture therapy has presented a dominant cardiac protection in many studies lately. Thus, we aim to evaluate the effect and safety of acupuncture as an adjunctive therapy in STEMI patients after PCI through a randomized controlled trial. Methods/Design This study describes a protocol of multicenter, double-blinded, parallel-controlled, randomized controlled trial. Ninety-six patients with STEMI aged 18–85 years who undergoing PCI will be recruited from the Affiliated Hospital of Chengdu University of Traditional Chinese Medicine, The Affiliated Third Hospital of Chengdu Traditional Chinese Medicine University/Chengdu Pidu District Hospital of Traditional Chinese Medicine, and Zhaotong Municipal Hospital of Traditional Chinese Medicine. Participants will be randomly assigned (1:1 ratio) to the verum acupuncture plus basic therapy (i.e., treatment) group or the sham acupuncture plus basic therapy (i.e., control) group. These participants will be treated for 5 days and then will be followed up for 24 weeks. Any adverse events will be recorded throughout the study to evaluate safety. Discussion The present study aims to investigate the effect and safety of acupuncture for patients with STEMI after PCI and set up standardized treatment programs for acupuncture of these patients. Trial registration This study was registered in the Chinese Clinical Trial Registry (Registration ID: [ChiCTR2400081117]), on February 22, 2024.

Abstract A novel approach is proposed to probe the nature of the double charm tetraquark through the prompt production asymmetry between $$T_{\bar{c}\bar{c}}^-$$ T c ¯ c ¯ - and $$T_{cc}^+$$ T cc + in pp collisions. When comparing two theoretical pictures, i.e. the compact tetraquark and hadronic molecular pictures, we find that the former one exhibits a significantly larger production asymmetry, enabling the unambiguous determination of the tetraquark’s internal structure. Additionally, distinctive differences in the transverse momentum and rapidity distributions of $$T_{\bar{c}\bar{c}}^-$$ T c ¯ c ¯ - and $$T_{cc}^+$$ T cc + cross sections emerge, particularly at $$p_\textrm{T}\approx 2~\textrm{GeV}$$ p T ≈ 2 GeV and $$y\approx \pm 6$$ y ≈ ± 6 at a center-of-mass energy of 14 $$~\textrm{TeV}$$ TeV . The insignificant asymmetry in hadronic molecular picture is because that hadronic molecules are produced in hadronic phase, where the phase space of their constituents needs to be taken into account rigorously. Our work can be extended to the exploration of other double heavy tetraquark candidates, offering a versatile approach to advance our understanding of exotic hadrons.

Abstract Objective The underlying mechanisms of Overactive Bladder (OAB) remain unclear. This research is designed to investigate the correlation between the intake of dietary live microorganisms and OAB. Methods This analysis encompasses a cross-sectional study of broad population information gathered from the National Health and Nutrition Examination Surveys (NHANES) spanning the years 2007 to 2018. Participants were categorized into three groups—low, medium, and high—according to their consumption of dietary live microorganisms, as per the Sanders Dietary Active Microbiota Classification System. We utilized a weighted logistic regression model, restricted cubic spline (RCS), and subgroup analyses to investigate the relationship between dietary live microorganism intake and OAB. Results This research encompassed 16,795 subjects. The incidence of OAB was reduced in the group consuming a high amount of live dietary microbes compared to the groups with low and medium intake of such microbes. After detailed adjustments for covariates, analysis revealed that participants in the high live dietary microbe group had notably reduced odds of OAB compared to those in the low live dietary microbe group (OR: 0.84, 95% CI: 0.71–0.99, p = 0.03). RCS analysis indicated a nonlinear correlation between high dietary active microbiota intake and the incidence of OAB. Conclusion This research emphasizes the potential advantages of a high dietary intake of active microbiota for preventing OAB. These findings support incorporating active microbiota into dietary guidelines, demonstrating their connection with a decreased incidence of OAB.

Abstract Many disease resistance genes have been introgressed into wheat from its wild relatives. However, reduced recombination within the introgressed segments hinders the cloning of the introgressed genes. Here, we have cloned the powdery mildew resistance gene Pm13, which is introgressed into wheat from Aegilops longissima, using a method that combines physical mapping with radiation-induced chromosomal aberrations and transcriptome sequencing analysis of ethyl methanesulfonate (EMS)-induced loss-of-function mutants. Pm13 encodes a kinase fusion protein, designated MLKL-K, with an N-terminal domain of mixed lineage kinase domain-like protein (MLKL_NTD domain) and a C-terminal serine/threonine kinase domain bridged by a brace. The resistance function of Pm13 is validated through transient and stable transgenic complementation assays. Transient over-expression analyses in Nicotiana benthamiana leaves and wheat protoplasts reveal that the fragment Brace-Kinase122-476 of MLKL-K is capable of inducing cell death, which is dependent on a functional kinase domain and the three α-helices in the brace region close to the N-terminus of the kinase domain.

Hejia Wan,1,* Bingqi Wei,2,* Wenli Qian,3 Jing Zhang1 1School of Nursing, Henan University of Chinese Medicine, Zhengzhou, People’s Republic of China; 2School of Traditional Chinese Medicine, Henan University of Chinese Medicine, Zhengzhou, People’s Republic of China; 3School of Management, Henan University of Chinese Medicine, Zhengzhou, People’s Republic of China*These authors contributed equally to this workCorrespondence: Jing Zhang, Email 1839640376@qq.comObjective: To explore the research trends and hotspots of health economics evaluations of patients with chronic fatigue syndrome.Methods: To explore the research trends and hotspots of health economics evaluations of chronic fatigue syndrome, 180 articles published between 1991 and 2024 were visualized and analyzed via CiteSpace 6.3 software. R3 and VOSviewer1.6.20 and R4.3.3. The content includes annual publication volume, journal distribution, author country, publishing organization, author collaboration, citation analysis, and keyword analysis in 7 aspects.Results: Fewer studies have evaluated the health economics of individuals with chronic fatigue syndrome in China and abroad, Chinese studies are especially rare, and research results in the UK are mostly found in other countries. Moreover, cooperation and linkages between institutions, as well as between authors, are not yet strong.Conclusion: The hotspot of health economics evaluation methods in this field is cost-effectiveness analysis, and the hotspot of diagnosis and treatment methods is cognitive‒behavioral therapy. We also found that chronic fatigue syndrome may also have a strong potential association with depression from the perspective of health economics. Health economic evaluations of multiple treatments should be conducted simultaneously to increase attention to this field and provide a reference basis for low-cost and high-quality diagnostic and treatment programs.Keywords: chronic fatigue syndrome, myalgic encephalomyelitis, health economics, CiteSpace, visual analysis, bibliometrics

Quirui Nie,1 Hui Qian,2,3 Shenjian Chen,3 Wenwen Xiang,3 Yu Shen3,4 1Department of Gerontology, Nanchang First Hospital, Nanchang, People’s Republic of China; 2Department of Neurology, Fengxin County People’s Hospital, Fengxin, People’s Republic of China; 3Department of Neurology, The Second Affiliated Hospital, Jiangxi Medical College, Nanchang University, Nanchang, People’s Republic of China; 4Department of Neurology, The First Affiliated Hospital, Jiangxi Medical College, Nanchang University, Nanchang, People’s Republic of ChinaCorrespondence: Yu Shen, Department of Neurology, The First Affiliated Hospital, Jiangxi Medical College, Nanchang University, Nanchang, 330006, People’s Republic of China, Email shenyu19950712@sina.comObjective: To compare the differences in risk factors and etiological classification between cerebral infarction in young patients and elderly patients, and explore the correlation between cerebral infarction in young patients and white matter lesions (WMLs).Methods: Sixty young patients with cerebral infarction and 142 elderly patients with cerebral infarction were included. The distributions of risk factors such as hypertension, diabetes, heart disease, smoking status, alcohol consumption status, migraine status, and WMLs in the two groups were carefully investigated and statistically analyzed.Results: According to the univariate analysis, the proportions of males, obese patients, patients with migraine, and patients with obstructive sleep apnea-hypopnea syndrome (OSAHS) in the young group were significantly greater than those in the elderly group. Hypertension, heart disease, and hyperhomocysteinemia were significantly more common in the elderly group than in the young group. According to the TOAST classification, the incidence of stroke of undetermined etiology in the young group was greater than that in the elderly group, whereas the incidence of large-artery atherosclerosis (LAA) in the elderly group was greater than that in the young group. Binary logistic regression analysis revealed that male sex, migraine status, and obstructive sleep apnea-hypopnea syndrome were independently associated with cerebral infarction in young adults, whereas hypertension, heart disease, and hyperhomocysteinemia were independently related to cerebral infarction in elderly individuals. In addition, the incidence of WMLs in the migraine group of young cerebral infarction patients was significantly greater than that in the nonmigraine group.Conclusion: Compared with those in elderly patients with cerebral infarction, the risk factors for cerebral infarction in young patients are relatively controllable. Furthermore, more methods are needed to determine the etiology of unexplained cerebral infarction in young patients. WMLs are thought to have a relatively high incidence in young patients with cerebral infarction and are significantly associated with migraine.Keywords: cerebral infarction, white matter lesions, young people, risk factors, migraine

Abstract Background Chronic osteomyelitis is a highly prevalent and severe orthopaedic complication, representing a critical unresolved issue. The clinical symptoms of osteomyelitis are influenced by various factors, including geography, lifestyle, and pre-existing medical conditions.This study aims to provide theoretical basis for treatment and prevention of osteomyelitis by investigating and analyzing clinical features and pathogen distribution among 282 patients with chronic tibial osteomyelitis in xinjiang. Methods A total of 282 patients with chronic tibial osteomyelitis from January 1, 2012 to January 1, 2022 in the First Affiliated Hospital of Xinjiang Medical University were retrospectively analyzed. All data were collected from electronic medical record (EMR) system including demographics, etiology, risk factors, osteomyelitis location and clinical classification. Results Farmers, students, unemployed and retirees accounted for a relatively large proportion of the 282 patients. There were 233 males and 49 females with a gender ratio of 4.75:1. The average age was 40.21 ± 15.68 years and was mainly concentrated in 41–50 years, specifically, the mean age of females was slightly older than that of males. Education level was mostly primary and secondary school education, and illiteracy. Risk factors of chronic tibial osteomyelitis included history of smoking and drinking, history of multiple repeated surgeries, and impaired immunity. Frequent clinical symptoms were in the order of pain, local swelling, pus discharge and skin ulceration. Among all inflammatory markers, proportion of positive results were 30.85%, 59.93% and 53.90% for white blood cell (WBC), erythrocyte sedimentation rate (ESR) and C-reactive protein (CRP), respectively. Positive rate of pathogenic microorganism culture was low and the three most common bacteria were Staphylococcus aureus (S. aureus), Pseudomonas aeruginosa (P. aeruginosa) and Escherichia coli (E. coli). The most frequent site of infection was middle tibia. According to Cierny-Mader osteomyelitis classification, the most common types were type IIIA, IVA and IIA. Conclusion Number of visits due to chronic osteomyelitis increased year by year, with young and middle-aged male farmers and low education level as the main groups. Smoking and drinking were two considerable risk factors that should be attached to a great importance. No significant increase was found in inflammatory markers and lower positive rate of pathogenic microorganism culture was observed. Multi-drug resistant bacteria were common and S. aureus remained the most frequent pathogen. Elevated ESR had certain diagnostic value for osteomyelitis. Type III and type IV osteomyelitis accounted for a large proportion which posed great challenges for clinical diagnosis and treatment.

Abstract This research aimed to investigate the effects of dietary fructooligosaccharides (FOS) on attenuating the Aeromonas hydrophila (A. hydrophila)-induced oxidative stress and apoptosis in blunt snout bream Megalobrama amblycephala. Fish were divided into three groups as follows: C1 (Control), T1 (A. hydrophila), and T2 (A. hydrophila + 4 g/kg FOS). The results showed that the activities of antioxidant enzymes increased, the liver morphology had disorderly arrangement, and extensive cell necrosis occurred because of A. hydrophila-infection. While the dietary FOS improved the above-mentioned liver damage. Additionaly, FOS elevated mRNA levels of pro-apoptotic molecules, including caspase-8 and 9, and down-regulated mRNA levels of the anti-apoptotic molecule Bcl-2, which is triggered by A. hydrophila-infection. The transcriptome analysis showed that the oxidative stress-related DEGs pathways were activated in intestine of blunt snout bream by A. hydrophila-infection. The FOS-added group led to the enrichment of more pathways to health. Further WGCNA co-expression network analysis showed that the screened single genes were clustered into 49 modules. The two modules with the highest association to the five traits (10 hub genes) were chosen to build the network by combining the physiological and biochemical characteristic. In summary, this research offers a foundation for the exploring of A. hydrophila-restoration genes in dietary FOS, and also lays a theoretical foundation for aquaculture in the future.

Abstract Background Although peritoneal dialysis (PD) is an efficient therapy for renal replacement, the long-term survival rate of patients undergoing PD remains low. The platelet-to-albumin ratio (PAR), recently identified as a parameter of inflammatory and nutritional status, is associated with an adverse prognosis for various diseases. However, the association between the serum PAR and prognosis of patients undergoing PD is poorly understood. This study aimed to evaluate whether the PAR is a reliable predictor of cardiovascular disease (CVD) and all-cause mortality in patients undergoing PD. Methods This multicenter cohort study enrolled patients undergoing PD from January 1, 2009, to September 30, 2018. The patients were divided into four groups according to the quartiles of their baseline PAR. The primary endpoint was all-cause and CVD-related mortality. Cox proportional hazard models were used to determine the association between the PAR and all-cause or CVD-related mortality. The receiver operating characteristic (ROC) curve was utilized to compare the performance among PAR and other inflammatory indicators. C-statistic, net reclassification improvement (NRI), and integrated discrimination improvement (IDI) were applied to examine the incremental prognostic value of PAR compared with baseline model for predicting all-cause and CVD mortality. Results A total of 2825 patients were included. During the follow-up period of 47.5 ± 28.3 months, 747 (26.4%) mortality cases were observed, of which 415 (55.6%) were CVD-related. Compared with the Q1 (PAR 7.27) was associated with an increased risk of all-cause mortality and CVD mortality (p

Abstract Migratory cells exist in the heart, such as immune cells, fibroblasts, endothelial cells, etc. During myocardium injury, such as ischemia–reperfusion (MIRI), cells migrate to the site of injury to perform repair functions. However, excessive aggregation of these cells may exacerbate damage to the structure and function of the heart, such as acute myocarditis and myocardial fibrosis. Myocardial injury releases exosomes, which are a type of vesicle with signal transduction function and the miRNA carried by exosomes can control cell migration function. Therefore, regulating this migratory cell population through cardiac-derived exosomal miRNA is crucial for protecting and maintaining cardiac function. Through whole transcriptome RNA sequencing, exosomal miRNA sequencing and single-cell dataset analysis, we (1) determined the potential molecular regulatory role of the lncRNA‒miRNA‒mRNA axis in MIRI, (2) screened four important exosomal miRNAs that could be released by cardiac tissue, and (3) screened seven genes related to cell locomotion that are regulated by four miRNAs, among which Tradd and Ephb6 may be specific for promoting migration of different cells of myocardial tissue in myocardial infarct. We generated a core miRNA‒mRNA network based on the functions of the target genes, which may be not only a target for cardiac repair but also a potential diagnostic marker for interactions between the heart and other tissues or organs. In conclusion, we elucidated the potential mechanism of MIRI in cardiac remodeling from the perspective of cell migration, and inhibition of cellular overmigration based on this network may provide new therapeutic targets for MIRI and to prevent MIRI from developing into other diseases.

Abstract This quantitative study examines the influence of innovative pedagogical approaches (IPA) on enhancing student critical thinking (SCT) and student learning outcomes (SLO) in higher education, with an emphasis on the mediating role of inclusive leadership(IL). Using a sample of 321 students from public and private universities in Pakistan, the research reveals that methods such as problem-based learning, flipped classrooms, and interactive teaching significantly boost academic performance and cultivate critical thinking skills. The findings indicate that innovative pedagogical approaches positively and significantly impact student critical thinking (β = 0.536, t = 6.539, p

Abstract Shiga toxin-producing Escherichia coli (STEC) can cause mild diarrhea even severe hemolytic uremic syndrome (HUS). Shiga toxin (Stx) is the primary virulence factor. Two Stx types and several subtypes have been identified. STEC strains encoding stx2f (Stx2f-STECs) are frequently identified from pigeons. Stx2f was initially considered to be associated with mild symptoms, more recently Stx2f-STECs have been isolated from HUS cases, indicating their pathogenic potential. Here, we investigated the prevalence of Stx2f-STECs among domestic pigeons in two regions in China, characterized the strains using whole-genome sequencing (WGS), and assessed the Stx2f transcriptions. Thirty-two Stx2f-STECs (4.36%) were culture-positive out of 734 fecal samples (one strain per sample). No other stx subtype-containing strain was isolated. Four serotypes and two sequence types were determined, and a novel sequence type ST15057 was identified. All strains harbored the E. coli attaching and effacing gene eae. Two types of Stx2f prophages were assigned. Stx2f-STECs showed variable Stx transcription levels induced by mitomycin C. Whole genome single-nucleotide polymorphism (wgSNP) analysis revealed different genetic backgrounds between pigeon-derived strains and those from diarrheal or HUS patients. In contrast, pigeon-derived Stx2f-STECs from diverse regions exhibited genetic similarity. Our study reports the prevalence and characteristics of Stx2f-STECs from pigeons in China. The pigeon-derived strains might pose low public health risk.

Abstract Combing macroscopic experimental method and mesoscopic numerical method, this study analyses the strain-softening behaviours of granite and sandstone. From the macroscopic perspective, the stress–strain curves of granite and sandstone under different confining pressures are studied by laboratory triaxial compression test. Variations of post-peak reduction modulus and critical plastic shear strain versus confining stress are obtained. Evolution of strength parameters at peak, residual and strain-softening stage are proposed. Then a method to develop the strain-softening model of hard and soft rocks is presented. From the mesoscopic perspective, based on the laboratory test results, the parameters of discrete element method PFC for the samples of the granite and sandstone are calibrated. Comparing the basically consistent results of laboratory experiment and numerical simulation, the feasibility of discrete element method is verified. Evolutions of mesoscopic crack propagation and mesoscopic particle displacement field in the complete failure process are analysed. Typical stresses of granite sample and sandstone sample in the failure stage are investigated. Above combined macroscopic experimental method and mesoscopic numerical method systematically analyse the characteristics of hard rock and soft rock in the strain-softening stage. Failure process and mechanical property of hard rock and soft rock are revealed at the macroscopic and mesoscopic levels. The initiation and propagation process of micro-cracks in rock are thoroughly investigated. The research results provide a scientific foundation for the analyse of strain-softening behaviour of hard rock and soft rock. The result shows that both the mesoscopic numerical method and macroscopic experimental method indicate that the failure pattern of sandstone is influenced by both confining pressure and axial stress, while granite is mainly affected by axial stress.