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This article introduces the use of Internet-mediated joint construction (JC) to engage second language (L2) writers to participate in virtual classroom activities in an online teaching environment. Affected by the ongoing COVID-19 pandemic, schools and universities in the People's Republic of China were required to rapidly transit to remote teaching. The switch from the traditional classroom-based scenarios to the online environment was challenging for teachers. One of the extreme difficulties is to engage students in virtual-class activities. To address this issue, the authors designed an Internet-mediated JC teaching practice and implemented it on ClassIn, an online teaching platform for one semester. Analysis of students' after-class online surveys and interviews suggested that the Internet-mediated JC practice helped students to build a connected network and thus engaged them in actively interacting with both the teacher and peers in the online environment. Pedagogical implications are discussed to contribute to the teaching practice of L2 online writing instruction.

Recurrent event analyses have found a wide range of applications in biomedicine, public health, and engineering, among others, where study subjects may experience a sequence of event of interest during follow-up. The R package reReg offers a comprehensive collection of practical and easy-to-use tools for regression analysis of recurrent events, possibly with the presence of an informative terminal event. The regression framework is a general scale-change model which encompasses the popular Cox-type model, the accelerated rate model, and the accelerated mean model as special cases. Informative censoring is accommodated through a subject-specific frailty without any need for parametric specification. Different regression models are allowed for the recurrent event process and the terminal event. Also included are visualization and simulation tools.

Multidimensional theory of mind assessments should include items assessing both explicit theory of mind (theory of mind knowledge) and applied theory of mind (application of theory of mind knowledge in real-life contexts). However, the two theory of mind scores cannot be interpreted collectively to identify children having mismatched explicit and applied theory of mind due to the lack of links between the two scores. To map the information between two theory of mind scores, data of 221 autistic children aged 3-12 years were extracted. Items of the Theory of Mind Task Battery and Theory of Mind Inventory-2 were used to respectively assess the explicit and applied theory of mind. Rasch analysis and correlation coefficients were used to examine the model fits/dimensionality and relationships. After the removal of misfit items, the remaining 45 items showed satisfactory model fits (infit and outfit mean squares < 1.35). Large correlation (r = 0.63) was found between the Rasch scores of the two theory of mind constructs. The scatter plots highlighted that each applied theory of mind score could reflect multiple explicit ToM scores. Accordingly, the information from each theory of mind measure is unique and irreplaceable. Moreover, cutoff scores for identifying children with mismatched explicit and applied theory of mind were proposed to determine the priority of interventions.

To retrospectively explore the characteristics of plasma amino acids (PAAs) in children with autism spectrum disorder and their clinical association via case-control study. A total of 110 autistic and 55 healthy children were recruited from 2014 to 2018. The clinical phenotypes included severity of autism, cognition, adaptability, and regression. Compared with the control group, autistic children had significantly elevated glutamate, [gamma]-Amino-n-butyric acid, glutamine, sarcosine, [delta]-aminolevulinic acid, glycine and citrulline. In contrast, their plasma level of ethanolamine, phenylalanine, tryptophan, homocysteine, pyroglutamic acid, hydroxyproline, ornithine, histidine, lysine, and glutathione were significantly lower. Elevated neuroactive amino acids (glutamate) and decreased essential amino acids were mostly distinct characteristics of PAAs of autistic children. Increased level of tryptophan might be associated with severity of autism.

Abstract Background As a currently incurable but preventable disease, the prevention and early diagnosis of Alzheimer’s disease (AD) has long been a research hotspot. Amyloid deposition has been shown to be a major pathological feature of AD. Notably, not all the people with amyloid-beta (Aβ) pathology will have significant cognitive declines and eventually develop AD. Therefore, the aim of this study was to explore the risk factors for cognitive decline in Aβ-positive participants. Methods We included 650 non-demented participants who were Aβ-positive at baseline from the Alzheimer’s Disease Neuroimaging Initiative (ADNI) database. Mixed effects and COX regression models were applied to assess 37 potential risk factors. Mixed effects models were employed to assess the temporal associations between potential risk factors and four cognitive assessment scales. COX regression models were used to assess the impact of potential risk factors on cognitive diagnosis conversion. Univariate and multivariate analyses were applied to the above models. Additionally, we used the Cochran-Armitage trend test to examine whether the incidence of cognitive decline increased with the number concurrent of risk factors. Results Six factors (low diastolic pressure, low body mass index, retired status, a history of drug abuse, Parkinsonism, and depression) were the identified risk factors and four factors (a history of urinary disease, musculoskeletal diseases, no major surgical history, and no prior dermatologic-connective tissue diseases) were found to be suggestive risk factors. The incidence of cognitive decline in the Aβ-positive participants gradually increased as the number of concurrent risk factors increased (p for trend = 0.0005). Conclusions Our study may facilitate the understanding of the potential pathological processes in AD and provide novel targets for the prevention of cognitive decline among participants with Aβ positivity.

Abstract Background Transposition of the great arteries (TGA) is the most common cyanotic congenital heart defect in neonates but with low prenatal detection rate. This study sought to review the prenatal diagnosis, associated abnormalities, and mid-term postnatal outcomes of fetuses with TGA and investigate the integrated prenatal and postnatal management for TGA neonates. Methods A total of 134 infants prenatally diagnosed with TGA in Guangdong Provincial People’s Hospital, China, from January 2009 to December 2022 were included in the study. The prenatal ultrasound data and neonatal records were reviewed to assess the accuracy of prenatal diagnosis. Univariate and multivariate logistic and Cox analyses were used to identify risk factors associated with prognosis in such individuals. Results The population originated from 40 cities in 10 provinces in China, with integrated antenatal and postnatal management rate reaching 94.0% (126/134) and a high accuracy rate (99.3%) of prenatal primary diagnosis. The median period of follow-up was 1.6 [interquartile range (IQR) 0.1–4.3] years. There were 3 (2.2%) postnatal deaths, 118 (88.1%) patients undergoing arterial switch operation (ASO), 3 (2.2%) undergoing Rastelli operations and 5 (3.7%) doing stage operations. Of 118 patients receiving ASO, the major morbidity occurred in 64 patients (54.2%), and right ventricular outflow tract obstruction (RVOTO) in 31 (26.3%). In the multivariate logistic analysis, gestational ages at birth (OR = 0.953, 95% CI 0.910–0.991; p = 0.025) and cardiopulmonary bypass (CPB) time (OR = 1.010, 95% CI 1.000–1.030; p = 0.038) were identified as independent risk factors associated with major morbidity. In the Cox multivariate analysis, aortic cross-clamping time (HR = 1.030, 95% CI 1.000–1.050; p = 0.017) was identified as independent risk factor associated with RVOTO. Conclusion Earlier gestational ages at birth and longer CPB time are significantly associated with increased morbidity. Integrated prenatal and postnatal management is recommended for patients with prenatal diagnosis of TGA.

Abstract Tuberculosis (TB), caused by Mycobacterium tuberculosis, remains a serious threat to global public health. Fluoroquinolones (FQs) are effective against M. tuberculosis; however, resistant strains have limited their efficacy. M ycobacterium fluoroquinolone resistance protein A (MfpA) confers intrinsic resistance to FQs; however, its regulatory mechanisms remain largely unknown. Using M. smegmatis as a model, we investigated whether MfpC is necessary for FQ susceptibility. MfpC mutants were sensitive to moxifloxacin, indicating that MfpC is involved in FQ susceptibility. By testing the mfpC inactivation phenotype in different mutants and using mycobacterial protein fragment complementation, we demonstrated that the function of MfpC depends on its interactions with MfpB. Guanine nucleotide exchange assays and site-directed mutagenesis confirmed that MfpC acts as a guanine nucleotide exchange factor to regulate MfpB. We propose that MfpB influences MfpA at the translational level. In summary, we reveal the role of MfpC in regulating the function of MfpA in FQ resistance.

Abstract Single nucleotide polymorphism (SNP) interactions are the key to improving polygenic risk scores. Previous studies reported several significant SNP–SNP interaction pairs that shared a common SNP to form a cluster, but some identified pairs might be false positives. This study aims to identify factors associated with the cluster effect of false positivity and develop strategies to enhance the accuracy of SNP–SNP interactions. The results showed the cluster effect is a major cause of false-positive findings of SNP–SNP interactions. This cluster effect is due to high correlations between a causal pair and null pairs in a cluster. The clusters with a hub SNP with a significant main effect and a large minor allele frequency (MAF) tended to have a higher false-positive rate. In addition, peripheral null SNPs in a cluster with a small MAF tended to enhance false positivity. We also demonstrated that using the modified significance criterion based on the 3 p-value rules and the bootstrap approach (3pRule + bootstrap) can reduce false positivity and maintain high true positivity. In addition, our results also showed that a pair without a significant main effect tends to have weak or no interaction. This study identified the cluster effect and suggested using the 3pRule + bootstrap approach to enhance SNP–SNP interaction detection accuracy.

Abstract Background Microglial activation has been suggested to be involved in the pathogenesis of depression and Alzheimer’s disease (AD). Soluble triggering receptor expressed on myeloid cells 2 (sTREM2) is a marker of microglial activation. The purpose of this study was to investigate the interrelationships of cerebrospinal fluid (CSF) sTREM2, AD pathology, as well as minimal depressive symptoms (MDSs), and cognition. Methods A total of 545 non-demented individuals from the Alzheimer’s Disease Neuroimaging Initiative cohort were included in our study. The average age of the total population was 72.6 years and the percentage of females was 42.6%. Linear regression models were conducted to investigate the linear relationships of MDSs with CSF sTREM2, AD pathology, cognition, and brain structure. Mediation models and structural equation models (SEM) were conducted to examine whether CSF sTREM2 mediated the relationships of MDSs with AD pathology and cognition. Results Results revealed that individuals with MDSs had lower CSF sTREM2 levels than normal controls. Linear regression showed that MDSs were linearly associated with CSF sTREM2 (P FDR = 0.012) and amyloid biomarkers (P FDR < 0.05), as well as cognitive scores (P FDR < 0.05) and hippocampal volume (P FDR = 0.003). Mediation analyses revealed that CSF sTREM2 mediated the association between MDSs and amyloid pathology, with the mediating proportions ranging from 6.030 to 18.894%. However, SEM failed to reveal that MDS affected cognition through CSF amyloid pathology and CSF sTREM2. Conclusions MDSs are associated with amyloid pathology and cognition. CSF sTREM2 may potentially be an intervenable target between depression and AD pathology.

Abstract Background Hepatocellular carcinoma (HCC) constitutes an important contributor to fatalities. Coronavirus disease 2019 (COVID-19) frequently presents with complications such as respiratory distress, systemic inflammatory responses, and damage to various organs. Several studies have investigated the relationship between COVID-19 and mortality in patients with liver cancer, but there are few research on the relationship between them. This study is to explore the correlation between the two diseases and drugs treating them. Methods The Gene Expression Omnibus (GEO) database provides gene datasets of COVID-19 patients and HCC patients. Through differential gene analysis and weighted gene co-expression network analysis, we determined 223 genes represented in HCC and COVID-19. We then used functional annotation, protein–protein interaction network construction, predictive model development and verification, prognostic value analysis, and miRNA–gene network construction. Besides, we created a drug–hub–gene network by predicting possible medications that interact with hub genes using the Drug–Gene Interaction Database (DGIdb). Ultimately, we applied immunohistochemistry to ascertain the hub genes expression. Results This study revealed that eight core genes (RRM2, TPX2, DTL, CDT1, TYMS, CDCA5, CDC25C, and HJURP) co-existed in both HCC and COVID-19 and were differentially expressed in both HCC and normal tissues.CDC25C, RRM2, CDCA5, and HJURP had diagnostic value (AUC > 0.8) and prognostic value (adjusted P-value

Abstract Background A comprehensive understanding of the genetic basis of rare diseases and their regulatory mechanisms is essential for human molecular genetics. However, the genetic mutant spectrum of pathogenic genes within the Chinese population remains underrepresented. Here, we reported previously unreported functional ABHD12 variants in two Chinese families and explored the correlation between genetic polymorphisms and phenotypes linked to PHARC syndrome. Methods Participants with biallelic pathogenic ABHD12 variants were recruited from the Chinese Deafness Genetics Cohort. These participants underwent whole-genome sequencing. Subsequently, a comprehensive literature review was conducted. Results Two Han Chinese families were identified, one with a compound heterozygous variant and the other with a novel homozygous variant in ABHD12. Among 65 PHARC patients, including 62 from the literature and 3 from this study, approximately 90% (57 out of 63) exhibited hearing loss, 82% (50 out of 61) had cataracts, 82% (46 out of 56) presented with retinitis pigmentosa, 79% (42 out of 53) experienced polyneuropathy, and 63% (36 out of 57) displayed ataxia. Seventeen different patterns were observed in the five main phenotypes of PHARC syndrome. A total of 33 pathogenic variants were identified in the ABHD12. Compared with other genotypes, individuals with biallelic truncating variants showed a higher incidence of polyneuropathy (p = 0.006), but no statistically significant differences were observed in the incidence of hearing loss, ataxia, retinitis pigmentosa and cataracts. Conclusions The diagnosis of PHARC syndrome is challenging because of its genetic heterogeneity. Therefore, exploring novel variants and establishing genotype-phenotype correlations can significantly enhance gene diagnosis and genetic counseling for this complex disease.

Background/purpose: Limited studies have addressed the exacerbation of symptoms and long COVID in inflammatory bowel disease (IBD) patients following non-severe COVID-19 infection, particularly with post-COVID-19 vaccination. We aim to investigate factors associated with exacerbated gastrointestinal symptoms (EGS) and long COVID in IBD patients with non-severe COVID-19, which is most common situation in daily practice. Methods: This is an observational study by multiple centers in Taiwan from May 2020 to March 2023. We collected clinical manifestation, data, and medication information from IBD patients with non-severe COVID-19. EGS was defined as increased frequency of diarrhea, bloody stool, and abdomen pain within 14 days after SARS-COV-2 infection. Long COVID was defined following the guidelines of the World Health Organization. Results: Out of 90 patients, most of them (88.9%) received at least standard two doses of COVID-19 vaccination and the majority (87.8%) were mild diseases of COVID-19.30% of patients experienced EGS during COVID-19 with higher ESR levels serving as a predictive factor (Odds ratio: 3.6, 95% confidence interval: 1.2–10.5, P = 0.02). 38.1% of those patients developed long COVID. The patients who experienced EGS during COVID-19 and with a history of longer IBD duration showed a significant association with long COVID (p = 0.03 and p = 0.02). Conclusion: Our study revealed that EGS and long COVID occurred in one third of IBD patients with non-severe COVID-19, even though most of them had received the standard plus booster vaccination. We identified associated factors for EGS and long COVID, emphasizing the importance of post-COVID-19 follow-up in IBD patients.

Abstract Understanding protein function is pivotal in comprehending the intricate mechanisms that underlie many crucial biological activities, with far-reaching implications in the fields of medicine, biotechnology, and drug development. However, more than 200 million proteins remain uncharacterized, and computational efforts heavily rely on protein structural information to predict annotations of varying quality. Here, we present a method that utilizes statistics-informed graph networks to predict protein functions solely from its sequence. Our method inherently characterizes evolutionary signatures, allowing for a quantitative assessment of the significance of residues that carry out specific functions. PhiGnet not only demonstrates superior performance compared to alternative approaches but also narrows the sequence-function gap, even in the absence of structural information. Our findings indicate that applying deep learning to evolutionary data can highlight functional sites at the residue level, providing valuable support for interpreting both existing properties and new functionalities of proteins in research and biomedicine.

Ulcerative colitis (UC) is a chronic inflammation of the gastrointestinal tract and is characterized by alternating periods of inflammation and remission. Although UC incidence is lower in Taiwan than in Western countries, its impact remains considerable, demanding updated guidelines for addressing local healthcare challenges and patient needs. The revised guidelines employ international standards and recent research, emphasizing practical implementation within the Taiwanese healthcare system. Since the inception of the guidelines in 2017, the Taiwan Society of Inflammatory Bowel Disease has acknowledged the need for ongoing revisions to incorporate emerging therapeutic options and evolving disease management practices. This updated guideline aims to align UC management with local contexts, ensuring comprehensive and context-specific recommendations, thereby raising the standard of care for UC patients in Taiwan. By adapting and optimizing international protocols for local relevance, these efforts seek to enhance health outcomes for patients with UC.

Crohn’s disease (CD) is a chronic, fluctuating inflammatory condition that primarily affects the gastrointestinal tract. Although the incidence of CD in Taiwan is lower than that in Western countries, the severity of CD presentation appears to be similar between Asia and the West. This observation indicates the urgency for devising revised guidelines tailored to the unique reimbursement system, and patient requirements in Taiwan. The core objectives of these updated guidelines include the updated treatment choices and the integration of the treat-to-target strategy into CD management, promoting the achievement of deep remission to mitigate complications and enhance the overall quality of life. Given the diversity in disease prevalence, severity, insurance policies, and access to medical treatments in Taiwan, a customized approach is imperative for formulating these guidelines. Such tailored strategies ensure that international standards are not only adapted but also optimized to local contexts. Since the inception of its initial guidelines in 2017, the Taiwan Society of Inflammatory Bowel Disease (TSIBD) has acknowledged the importance of continuous revisions for incorporating new therapeutic options and evolving disease management practices. The latest update leverages international standards and recent research findings focused on practical implementation within the Taiwanese healthcare system.

Abstract Circulating cell-free DNA (cfDNA) in the peripheral blood is a promising biomarker for cancer diagnosis and prognosis. Somatic mutations identified in cancers have been used to detect therapeutic targets for clinical transformation and individualize drug selection, while germline variants can predict a patient’s risk of developing cancer and drug sensitivity. However, no platform has been developed to analyze, calculate, integrate, and friendly visualize these pan-cancer cfDNA mutations deeply. In this work, we performed panel sequencing encompassing 1,115 cancer-related genes across 16,659 cancer patients, spanning 27 cancer types. We detected 496 germline variants in leukocytes and 11,232 somatic mutations in the cfDNA of all patients. CPGV (Cancer Peripheral blood Gene Variations), a database constructed from this dataset, is the first pan-cancer cfDNA database that encompasses somatic mutations, germline variants, and further comparative analyses of mutations across different cancer types. It bears great promise to serve as a valuable resource for cancer research.

Abstract The metabolic profile predating the onset of Parkinson’s disease (PD) remains unclear. We aim to investigate the metabolites associated with incident and prevalent PD and their predictive values in the UK Biobank participants with metabolomics and genetic data at the baseline. A panel of 249 metabolites was quantified using a nuclear magnetic resonance analytical platform. PD was ascertained by self-reported history, hospital admission records and death registers. Cox proportional hazard models and logistic regression models were used to investigate the associations between metabolites and incident and prevalent PD, respectively. Area under receiver operating characteristics curves (AUC) were used to estimate the predictive values of models for future PD. Among 109,790 participants without PD at the baseline, 639 (0.58%) individuals developed PD after one year from the baseline during a median follow-up period of 12.2 years. Sixty-eight metabolites were associated with incident PD at nominal significance (P

Abstract The comprehensive understanding of propagation patterns of extreme precipitation events (EPEs) is essential for early warning of associated hazards such as floods and landslides. In this study, we utilize climate networks based on an event synchronization measure to investigate the propagation patterns of EPEs over the global land masses, and identify 16 major propagation pathways. We explain them in association with regional weather systems, topographic effects, and travelling Rossby wave patterns. We also demonstrate that the revealed propagation pathways carry substantial EPE predictability in certain areas, such as in the Appalachian, the Andes mountains. Our results help to improve the understanding of key propagation patterns of EPEs, where the global diversity of the propagated patterns of EPEs and corresponding potential predictability provide prior knowledge for predicting EPEs, and demonstrate the power of climate network approaches to study the spatiotemporal connectivity of extreme events in the climate system.

Abstract Hepatocellular carcinoma (HCC) is characterized by a notable sex disparity in incidence and tumor aggressiveness. Revealing differences in genetic landscapes between male and female HCCs may expand the understanding of sexual disparities mechanisms and assist the development of precision medicine. Although reports on the sex disparity of HCC are accumulated, studies focusing on sex-related biomarkers among Asian populations remain limited. Here, we conducted a comprehensive genomic profiling analysis to explore differences between male and female patients within a cohort of 195 Taiwanese HCC patients. We did not detect any sex-biased genomic alterations. However, when our investigation extended to the TCGA dataset, we found higher frequencies of gene copy gains in CCNE2 and mutations in CTNNB1 and TP53 among male patients. Besides, we further evaluated the associations between genomic alterations and patients’ prognosis by sex. The results showed that female patients harboring tumors with STAT3 gain and alterations in the JAK–STAT pathway displayed a poor prognosis. These two factors remained independently associated with unfavorable prognosis even after adjusting for the patient’s age and stage characteristics (Hazard ratio = 10.434, 95% CI 3.331–32.677, P

Abstract Bcr-Abl transformation leads to chronic myeloid leukemia (CML). The acquirement of T315I mutation causes tyrosine kinase inhibitors (TKI) resistance. This study develops a compound, JMF4073, inhibiting thymidylate (TMP) and cytidylate (CMP) kinases, aiming for a new therapy against TKI-resistant CML. In vitro and in vivo treatment of JMF4073 eliminates WT-Bcr-Abl-32D CML cells. However, T315I-Bcr-Abl-32D cells are less vulnerable to JMF4073. Evidence is presented that ATF4-mediated upregulation of GSH causes T315I-Bcr-Abl-32D cells to be less sensitive to JMF4073. Reducing GSH biosynthesis generates replication stress in T315I-Bcr-Abl-32D cells that require dTTP/dCTP synthesis for survival, thus enabling JMF4073 susceptibility. It further shows that the levels of ATF4 and GSH in several human CML blast-crisis cell lines are inversely correlated with JMF4073 sensitivity, and the combinatory treatment of JMF4073 with GSH reducing agent leads to synthetic lethality in these CML blast-crisis lines. Altogether, the investigation indicates an alternative option in CML therapy.

Abstract This paper utilizes the theory of quantum diffusion to analyze the electron probability and spreading width of a wavepacket on each layer in a two-dimensional (2D) coupled system with edge disorder, aiming to clarify the effects of edge disorder on the stability of the electron periodic oscillations in 2D coupled systems. Using coupled 2D square lattices with edge disorder as an example, we show that, the electron probability and wavepacket spreading width exhibit periodic oscillations and damped oscillations, respectively, before and after the wavepacket reaches the boundary. Furthermore, these electron oscillations exhibit strong resistance against disorder perturbation with a longer decay time in the regime of large disorder, due to the combined influences of ordered and disordered site energies in the central and edge regions. Finally, we numerically verified the universality of the results through bilayer graphene, demonstrating that this anomalous quantum oscillatory behavior is independent of lattice geometry. Our findings are helpful in designing relevant quantum devices and understanding the influence of edge disorder on the stability of electron periodic oscillations in 2D coupled systems.

Topical atropine has been widely used for controlling myopia progression in children, yet its long-term efficacy and safety, including potential intraocular pressure (IOP) elevation, are still being studied. The mydriasis and cyclopegia induced by atropine may reduce traction on the trabecular meshwork, together with pigment released into anterior chamber due to the friction between the iris and lens during pupil dilation, may obstruct and reduce the trabecular outflow. This review first explores postdilation IOP changes across different groups – healthy individuals, glaucoma patients, and children. The response to pupil dilation varies widely, with IOP potentially increasing or decreasing. Glaucoma patients, whether with open or closed-angle glaucoma, may experience more significant IOP rises postdilation. The second section examines IOP effects in children using topical atropine for myopia, where most of the 25 reviewed studies showed nonsignificant IOP changes, although slight increases were observed in a few. In addition, no alterations in the retinal nerve fiber layer thickness were found. However, the research on children’s IOP under topical atropine is constrained by small sample sizes, cross-sectional studies, brief follow-ups, and often lacks control groups or pretreatment IOP measurements. Given the extended atropine use for myopia and the significant individual variation in IOP response, we recommend routine IOP monitoring for children receiving topical atropine.

【Objective】The study aims to screen the formula of vacuum freeze-drying protective agent for Vibrio alginolyticus, optimize the freeze-drying process conditions, and explore the influence of freeze-drying on the virulence and drug sensitivity of the strains, with a view to providing a theoretical basis for the application of freeze-drying in the preservation of the strains.【Method】With Vibrio alginolyticus HY9901 as the research object, the vacuum freeze-drying technology was used to freeze-dry the strains. Through single factor test and orthogonal test, the effects of six single cryoprotectants (L-glutamate sodium, trehalose, skim milk, glucose, mannitol and glycine) on the activity of the strains were investigated, and the optimal formula of cryoprotectants was selected. The influences of four factors, namely, concentration of bacterial solution, pre-freezing time, pre-freezing temperature and rehydration medium, on the freeze-drying process of strains were studied, and the freeze-drying process conditions for Vibrio alginolyticus were optimized. At the same time, storage test, LD50 test and antimicrobial susceptibility test were used to investigate the changes in the activity of lyophilized strains and their of biological characteristics.【Result】There were significant differences in the protective effects of 6 cryoprotectants on lyophilized Vibrio alginolyticus, and the effects from strongest to weakest showed as: L-glutamate sodium, trehalose, skim milk, glucose, mannitol and glycine. The optimum freeze-drying compound formula of cryoprotectants was trehalose 50 g/L+ L-glutamate sodium 50 g/L+ skim milk 50 g/L, with a survival rate of 62.12%, which was significantly different from that of single cryoprotectant. The optimal conditions of freeze-drying process were as follows: bacterial solution concentration 1×108-109 CFU/mL, pre-freezing time 3 h, pre-freezing temperature -80 ℃, rehydration medium PBS or 50 g/L skim milk, under which the activity of the strains could reach the maximum of 63.72%. There was no significant difference in the activity of the strains during 60 days of storage under optimal freeze-drying conditions. The LD50 values of the strains before and after freeze-drying were 1.22×108 CFU/mL and 1.20×108 CFU/mL, respectively, with no significant difference in LD50. There was no significant difference in the diameter of the antimicrobial inhibition zone before and after freeze-drying, and the strains were sensitive to florfenicol, chloramphenicol, ciprofloxacin and other drugs. They were moderately sensitive to neomycin and kanamycin, and resistant to drugs like amimcana and piperacillin.【Conclusion】The freeze-drying formula for Vibrio alginolyticus HY9901 is trehalose 50 g/L+ L-glutamate sodium 50 g/L+ skim milk 50 g/L, and the freeze-drying process conditions are: bacterial solution concentration 1×108-109 CFU/mL, pre-freezing time 3 h, pre-freezing temperature -80 ℃, rehydration medium PBS or 50 g/L skim milk. The fomula and process for this strain are reasonable and feasible, with good storage and stability of biological characteristics.

Abstract Background Dysregulation of enhancer transcription occurs in multiple cancers. Enhancer RNAs (eRNAs) are transcribed products from enhancers that play critical roles in transcriptional control. Characterizing the genetic basis of eRNA expression may elucidate the molecular mechanisms underlying cancers. Methods Initially, a comprehensive analysis of eRNA quantitative trait loci (eRNAQTLs) was performed in The Cancer Genome Atlas (TCGA), and functional features were characterized using multi-omics data. To establish the first eRNAQTL profiles for colorectal cancer (CRC) in China, epigenomic data were used to define active enhancers, which were subsequently integrated with transcription and genotyping data from 154 paired CRC samples. Finally, large-scale case-control studies (34,585 cases and 69,544 controls) were conducted along with multipronged experiments to investigate the potential mechanisms by which candidate eRNAQTLs affect CRC risk. Results A total of 300,112 eRNAQTLs were identified across 30 different cancer types, which exert their influence on eRNA transcription by modulating chromatin status, binding affinity to transcription factors and RNA-binding proteins. These eRNAQTLs were found to be significantly enriched in cancer risk loci, explaining a substantial proportion of cancer heritability. Additionally, tumor-specific eRNAQTLs exhibited high responsiveness to the development of cancer. Moreover, the target genes of these eRNAs were associated with dysregulated signaling pathways and immune cell infiltration in cancer, highlighting their potential as therapeutic targets. Furthermore, multiple ethnic population studies have confirmed that an eRNAQTL rs3094296-T variant decreases the risk of CRC in populations from China (OR = 0.91, 95%CI 0.88–0.95, P = 2.92 × 10−7) and Europe (OR = 0.92, 95%CI 0.88–0.95, P = 4.61 × 10−6). Mechanistically, rs3094296 had an allele-specific effect on the transcription of the eRNA ENSR00000155786, which functioned as a transcriptional activator promoting the expression of its target gene SENP7. These two genes synergistically suppressed tumor cell proliferation. Our curated list of variants, genes, and drugs has been made available in CancereRNAQTL ( http://canernaqtl.whu.edu.cn/#/ ) to serve as an informative resource for advancing this field. Conclusion Our findings underscore the significance of eRNAQTLs in transcriptional regulation and disease heritability, pinpointing the potential of eRNA-based therapeutic strategies in cancers.

Abstract Lime is widely used for soft ground treatment, rendering the compressibility of lime-treated soil a crucial factor in deformation analysis in engineering applications. This study investigated the compressibility of three remoulded lime-treated slurries with high water content in Southeast China. Sixty groups of oedometer tests were conducted on lime-treated soils with an initial water content of 1 to 3 times the liquid limit and lime contents between 1 and 3%. The oedometer test results were discussed to examine the remoulded yield stress $${\upsigma }_{y}^{\prime}$$ σ y ′ of lime-treated slurry. Considering the relationships between $${\upsigma }_{y}^{\prime}$$ σ y ′ , the void ratio, lime content, and initial water content were preliminarily discussed and quantitatively established. Research on the normalised compression curve of lime-treated soil revealed that for soil samples containing a lime content of 0–%, the normalised compression curve at $${\upsigma }_{p}^{\prime}$$ σ p ′ > $${\upsigma }_{y}^{\prime}$$ σ y ′ can be represented by a unique line. Furthermore, the log(1 + e) − log $${\sigma }_{\text{v}}^{\prime}$$ σ v ′ compression curve of lime-treated slurry at pre-yield state is analysed, and a prediction method for the modified compression index is proposed.

Abstract Background Sleep health and obesity may affect the risk of female infertility. However, few studies focused on the interaction of obesity and sleep health on the female infertility risk. This study aimed to evaluate the combined impact of trouble sleeping / sleep duration and overweight/obesity/ abdominal obesity on the risk of female infertility. Methods The data for this cross-sectional study was obtained from National Health and Nutritional Examination Survey, which provided information on trouble sleeping, sleep duration, overweight/obesity, abdominal obesity, and confounding factors. Adopted weighted univariate and multivariate logistic regression models to explore the relationship between trouble sleeping, sleep duration, overweight/obesity, abdominal obesity, and the risk of infertility, respectively, and the combined effect of trouble sleeping and overweight/obesity, trouble sleeping and abdominal obesity, sleep duration and overweight/obesity, sleep duration and abdominal obesity, on the female infertility risk. Results This study included a total of 1,577 women, and 191 were diagnosed with infertility. Women with infertility had a higher proportion of people with overweight/obesity, abdominal obesity, sleep duration ≤ 7 h and trouble sleeping than those with non-infertility. The result indicated that trouble sleeping [odds ratio (OR) = 2.25, 95% confidence intervals (CI): 1.49–3.39], sleep duration ≤ 7 h (OR = 1.59, 95% CI: 1.03–2.48), and the combined impact of abdominal obesity and trouble sleeping (OR = 2.18, 95% CI: 1.28–3.72), abdominal obesity and sleep duration ≤ 7 h (OR = 2.00, 95% CI: 1.17–3.40), overweight/obesity and trouble sleeping (OR = 2.29, 95% CI: 1.24–4.26), and overweight/obesity and sleep duration ≤ 7 h (OR = 1.88, 95% CI: 1.01–3.49) were associated with increased odds of infertility, respectively. Conclusion There was combined effects of trouble sleeping/sleep duration ≤ 7 h and overweight/obesity/ abdominal obesity on increased odds of female infertility.

Background: The association between Chinese herbal medicine (CHM) and the risk of developing major adverse cardiovascular events (MACEs) in patients with dialysis hypotension is unclear and has not yet been investigated. This study aimed to determine whether CMH intervention could reduce the risk of MACEs in patients with dialysis hypotension. Methods: The study data from the Taiwan National Health Insurance Research Database were analyzed to clarify this association. For this study, a case-control design with a cohort of patients who received hemodialysis (HD) from 2008 to 2018, 20 295 HD patients who had received blood pressure (BP) raising drugs were identified. After 1:1 frequency-matching, 730 patients were identified as CHM users and CHM non-users. Vascular access revision/reconstruction and MACEs were observed as the main outcomes during the follow-up period. Results: The occurrence of vascular access revision/reconstruction in HD patients receiving BP raising drugs was associated with a 0.34-fold lower risk in CHM users than in CHM non-users [adjusted hazard ratio (aHR) = 0.34, 95% confidence interval (CI) = 0.26, 0.45]. The occurrences of MACEs in HD patients receiving BP raising drugs was associated with a 0.41-fold lower risk in CHM users than in CHM non-users (aHR = 0.41, 95% CI = 0.33, 0.51). A markedly predominant effect was observed in those receiving CHM for more than 180 days (aHR = 0.32; 95% CI = 0.22, 0.45). Conclusion: The findings revealed lower vascular access dysfunction and MACEs risk correlated with the use of CHM treatment among HD patients who received BP raising drugs.

Objective To explore the risk factors of arteriovenous fistula (AVF) dysfunction in hemodialysis (HD) patients and validate a risk warning model based upon synthetic minority oversampling technique (SMOTE). Methods From January 1, 2019 to December 31, 2021, 400 HD patients with AVF as dialysis access were selected as study subjects. According to AVF function of HD, they were assigned into two groups of poor AVF function (n=81) and normal AVF function (n=319). The relevant clinical data of selected HD patients were reviewed and the risk factors of poor AVF function screened by univariate and multivariate Logistic regression. Then the above risk factors were reconstructed by SMOTE algorithm for established an early warning model of poor AVF function. The prediction efficiency of two models was compared.Results Females, diabetes mellitus (DM), albumin 2 mmol/L and AVF stenosis were the risk factors for AVF dysfunction in HD patients (P