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Abstract Alternative promoter (AP) events, as a major pre-transcriptional mechanism, can initiate different transcription start sites to generate distinct mRNA isoforms and regulate their expression. At present, hundreds of thousands of APs have been identified across human tissues, and a considerable number of APs have been demonstrated to be associated with complex traits and diseases. Recent researches have also proven important effects of APs on animals. However, the landscape of APs in animals has not been fully recognized. In this study, 102,349 AP profiles from 23,077 samples across 12 species were systematically characterized. We further identified tissue-specific APs and investigated trait-related promoters among various species. In addition, we analyzed the associations between APs and enhancer RNAs (eRNA)/transcription factors (TF) as a means of identifying potential regulatory factors. Integrating these findings, we finally developed Animal-APdb, a database for the searching, browsing, and downloading of information related to Animal APs. Animal-APdb is expected to serve as a valuable resource for exploring the functions and mechanisms of APs in animals.

Abstract Objective The aim of this study was to investigate the effect of SARS-CoV-2 Omicron BA. 5.2 (hereafter referred to as Omicron BA. 5.2) infection on perioperative physiological indices and to provide clinical considerations for the precautions needed for patients who tested negative for SARS-CoV-2 infection perioperatively. Methods Patients who underwent time-limited surgery (surgery that must be performed within a certain time) at the Department of Orthopedics of our hospital from September 1, 2022, to March 31, 2023, were divided into an observation group (those with Omicron BA 5.2 and a negative nucleic acid test after December 7, 2022, n = 100) and a control group (those negative for SARS-CoV-2 infection before December 7, 2022, n = 100). Changes in the following factors were compared within and between the two groups: heart rate, mean arterial pressure, oxygenation index at the time of entry into the operating room, incision of the skin and exit from the operating room and the neutrophil‒lymphocyte ratio (NLR), platelet‒lymphocyte ratio (PLR), systemic immune inflammation index (SII), D-dimer level, and fibrinogen degradation product (FDP) level. Changes in interleukin-6 and calcitonin levels were assessed the day after surgery, and multivariate regression analysis of the meaningful results was conducted. Results Heart rate, mean arterial pressure, oxygenation index, NLR, PLR, SII, interleukin-6 and calcitonin were similar between the two groups (P > 0.05). The observation group had higher postoperative D-dimer and FDP levels (P

Introduction Necrotising enterocolitis (NEC) of the intestine of preterm infants leads to the risk of abdominal surgery, short bowel syndrome, neurodevelopmental disorders and death. Although the risks of NEC and its complications have been recognised in many countries, few countries have established NEC-specific registries to continuously monitor its aetiology and prognosis. In China, the understanding of risk factors and prognosis of NEC is incomplete, characterised by a lack of evidence from prospective and multicentre studies. Therefore, we designed a multicentre, prospective, open observational cohort study with the aim of investigating the risk factors and prognosis of NEC in a real-world setting in Shenzhen, Guangdong Province, by constructing an online registry of children with NEC and a bank of biospecimens.Methods This is a prospective, multicentre, open observational cohort study. From June 2024 to June 2028, more than 600 patients with NEC from 15 tertiary hospitals in Shenzhen, Guangdong Province, will be enrolled in the study. By constructing an online registry for NEC, clinical data will be collected during the prenatal and hospitalisation periods. Prospectively, biospecimens will be collected during the period of suspected NEC, at the time of confirmed NEC, and at the time of confirmed severe NEC, and filed in the online registry system. Follow-up data will include postdischarge healthcare needs, growth patterns measures, eye or vision examinations, cranial MRI findings, brainstem auditory evoked potentials or automated auditory brainstem responses, and the Chinese Griffith Developmental Scale at corrected age 18–24 months. Follow-up results were likewise recorded in an online registry system. Hospitalisation outcomes, including severe NEC, somatic growth and survival status, will be collected at discharge. Follow-up outcomes will include loss to visit, survival status, somatic growth measures and severe neurodevelopmental deficits at corrected age 18–24 months. This study will enhance our overall understanding of the risk factors and outcomes of NEC, ultimately helping to reduce the incidence of neonatal NEC and its poor prognosis.Ethics and dissemination Our programme has received approval from the Ethics Committee for Scientific Research Projects of the Longgang District Maternity & Child Healthcare Hospital in Shenzhen City (ethics approval number: LGFYKYXMLL-2024-47-01). We anticipate presenting our findings at various national conferences and submitting them to peer-reviewed paediatrics journals.Trial registration number ChiCTR2400085043.

This study investigates the effect of various structural parameters in plate-fin heat exchanger on the performance of a cascade refrigeration system (CRS). Focusing on five key factors—fin thickness, fin type, fin height, porosity, and element axial length—we analyze their contributions to COP, exergy destruction, and entropy production within the CRS. The results reveal that the fin type barely influences the CRS’ performance, the element axial length has the greatest impact, followed by fin height, porosity, and fin thickness, respectively. The COP of the CRS drops by 26.25 % as the element axial length increases from 124 mm to 136 mm, 23.67 % (23.08 %) as the fin height of perforated (straight) fin increases from 6.1 mm to 6.7 mm, and 10.27 % (10.38 %) as the fin thickness of perforated (straight) fin increases from 0.1 mm to 1.3 mm, and the exergy destruction increases by 42.42 %, 37 % (37 %), and 13 % (10.38 %), respectively. The effect of porosity on the CRS’ performance is opposite to that of other parameters. When the element axial length is 124 mm, the fin height is 6.1 mm, and the fin thickness is 0.1 mm, the COP of the CRS reaches the maximum value (0.689). The conclusion can provide data support for the performance optimization of CRS from the structure of the cascade heat exchanger.

Abstract This study presents a thermodynamic–dynamic model of a free‐piston Stirling engine (FPSE) with nonlinear coefficients of spring, load damping, and pressure for working spaces. The effects of the nonlinear coefficients of hardening and softening springs on the movement and operating frequency of a displacer and piston are investigated. Subsequently, the influences of the nonlinear pressure terms of the working space and buffer spaces, as well as the nonlinear coefficients of the load on the amplitudes of the two pistons, frequency, and output powers are discussed. The results indicate that the low nonlinear coefficients of the spring have a minor effect on the amplitudes and frequency. As the high nonlinear coefficients of the hardening spring increase, the amplitudes and output power decrease, while the frequency increases. As the nonlinear terms of the softening spring increase, the amplitudes and output power reach maximum values, but the frequency is reduced by 3.55%. The effects of the nonlinear pressure terms on the amplitudes and output power are not evident. However, an increase in the nonlinear load leads to a significant decrease in the FPSE's performance.

A thermodynamic analysis is proposed to improve the designing and operating parameters in an ultra-low temperature cascade refrigeration system (CRS). The expressions for predicted parameters of the CRS are obtained based on an artificial neural network (ANN) method. In the first part, a parametric analysis is carried out to analyze the influences of seven variables on the COP, total compressor input power, discharge temperature of two compressors, total exergy destruction, and exergy efficiency. The results show that the condensation temperature of the low-temperature circuit has an optimal value, which maximizes COP and exergy efficiency but minimizes the total compressor input power and exergy destruction. In the second part, the performance of CRS is predicted by the ANN model. Eighty sets of input-output parameters are applied as both the training and testing data. It is found that the correlation coefficients for training-testing data in the range of 0.9886–0.9994 are estimated. The mean absolute errors obtained in the prediction for COP, total compressor power, total exergy destruction, exergy efficiency, and discharge temperature of high and low-temperature cycles with the testing set are 0.0027, 0.9090, 1.0314, 0.1691, 1.1438, and 1.0230, respectively. The outcome indicates that the ANN model has good advantages in predicting the cascade refrigeration system's performance.

Objective. This study aims to develop and evaluate a nomogram for predicting the risk of chronic fatigue syndrome (CFS)-like symptoms in university students diagnosed with infectious mononucleosis (IM), using clinical characteristics and laboratory findings as predictive variables. The nomogram will be designed to assist healthcare providers in assessing the likelihood of CFS-like symptoms developing post-IM, rather than providing a definitive diagnosis of CFS. Methods. Clinical data and laboratory findings were collected from university students with IM. The variables included age, gender, smoking and drinking habits, relationship status, university grade, residence registration, number of symptoms and signs (NSS), body mass index (BMI), C-reactive protein (CRP) level, neutrophil–lymphocyte ratio (NLR), platelet–lymphocyte ratio (PLR), monocyte–lymphocyte ratio (MLR), aspartate aminotransferase to alanine aminotransferase ratio (AST/ALT, DeRitis), basophil percentage (Baso%), eosinophil percentage (Eos%), and albumin-to-globulin ratio (ALB/GLO). LASSO regression analysis was employed to identify significant predictors of CFS-like symptoms. A nomogram model was constructed based on these predictors and evaluated using performance metrics such as the concordance index (C-index), area under the curve (AUC), calibration curves, and decision curve analysis. Results. The LASSO regression analysis identified the NSS, CRP, NLR, and MLR as significant predictors of CFS-like symptoms in university students with IM. The nomogram demonstrated robust predictive performance, with a C-index of 0.846 (95% CI: 0.790–0.902) in the training set and 0.867 (95% CI: 0.8–0.954) in the validation set. High AUC values indicated excellent overall predictive accuracy. Calibration curves revealed a close match between predicted and observed probabilities. Additionally, decision curve analysis showed positive net benefits across a broad spectrum of threshold probabilities, underscoring the nomogram’s clinical applicability. Conclusion. The nomogram developed in this study serves as a valuable predictive tool for assessing the risk of CFS-like symptoms in university students with IM. The identified predictors, including NLR, the NSS, CRP, and MLR, can assist clinicians in evaluating individual risk profiles and inform decision-making processes. This nomogram model advances personalized risk assessment for the development of CFS-like symptoms in IM-affected university students.

Abstract Background Depression increases the risk of adverse clinical outcomes in patients with chronic kidney disease. Physical activity has been shown to improve depressive symptoms in this population, but the relationship of sedentary behavior with depression has not been studied. In this study, we examined the relationship between sedentary behavior and depression in patients with chronic kidney disease. Methods This cross-sectional study included 5,205 participants aged ≥ 18 years with chronic kidney disease participating in the 2007–2018 National Health and Nutrition Examination Survey. Depression was assessed using the Patient Health Questionnaire-9 (PHQ-9). Recreation activity, work activity, walking or cycling for transportation, and sedentary behavior were measured using the Global Physical Activity Questionnaire. A series of weighted logistic regression models were used to investigate the aforementioned relationship. Results The prevalence of depression among US adults with chronic kidney disease was 10.97% in our study. In addition, sedentary behavior was strongly associated with higher levels of depressive symptoms, as measured by the PHQ-9 (P

Background and aimsEvidence indicates that serum Klotho concentration is associated with mortality in patients with chronic kidney disease (CKD). However, evidence on this association among people with hypertension is scarce. Therefore, we aimed to examine the association between serum Klotho concentration and all-cause and cardiovascular mortality in American patients with hypertension.Methods and resultsWe included 6,778 participants with hypertension from the National Health and Nutrition Examination Survey (NHANES) 2007–2014. A Cox proportional hazard model was used to compute the hazard ratios (HRs) and 95% confidence intervals (CIs). The correlation between serum Klotho concentration and mortality was determined using restricted cubic spline and piecewise linear regression analyses. During 36,714 person-years of follow-up, 575 deaths were documented. Lower serum Klotho concentration was associated with increased all-cause mortality, but not cardiovascular mortality after multivariate adjustment. According to spline analysis, the correlation between serum Klotho concentration and all-cause mortality was non-linear (P < 0.001), and the threshold value was 574 pg/mL. The HR below the threshold point was 0.79 (95% CI: 0.67–0.93); no significant difference was found above the threshold point.ConclusionHigher serum Klotho concentration was associated with lower all-cause mortality, but not cardiovascular mortality in patients with hypertension with or without chronic renal impairment.

Background: Studies have demonstrated that cholesterol variability is an independent predictor of cerebrovascular and cardiovascular events. Objective: This study aimed to investigate the association of visit-to-visit variability in total cholesterol (TC) with kidney decline in a Chinese community-based population. Methods: We assessed intraindividual variability in TC among 6,465 hypertensive participants and correlated the results with endpoints. TC variability was measured using standard deviation (SD), average successive variability (ASV), coefficient of variation (CV), and variability independent of the mean (VIM). The endpoint of this study was progression of renal function decline defined as a decrease in estimated glomerular filtration rate (eGFR) ≥30% and to a level

Globally, educational psychology and theory have advanced the knowledge of various ways college students learn and retain information. Low academic performance in college education is directly attributed to learning disabilities. Using the underlying mechanism of mobile-assisted language learning, the present study explored how self-monitoring impacted self-management, as well as beliefs about language learning skills. The present study hypothesized that college students' beliefs about the problems associated with mobile phones to learn a language serve as a moderator in the relationship between self-management and beliefs about how their language skills are improving. Furthermore, this study investigated the role of self-management as a mediator in the relationship between self-monitoring and beliefs about mobile-assisted language skills. The data was gathered from 329 college students in the Chinese city of Shanghai. The PLS-based SEM results highlighted a direct relationship between self-monitoring and self-management, during mobile-assisted language learning in college English teaching. The findings also confirmed the underlying role of college students' beliefs on the issues associated with using mobile phones to learn a second language. Importantly, the findings highlighted the implications of the widely expanding mobile-assisted language learning in the education industry. [ABSTRACT FROM AUTHOR]

Microplastics (MPs) have been identified in various human tissues and organs. This study aims to evaluate the presence of MPs in human follicular fluid (hFF) and their potential impact on oocyte maturation. Laser direct infrared spectroscopy of 19 hFF samples identified 7956 particles, including 1739 microplastics (21.9 %) from 30 types. Of these, 923 particles had matching degrees > 0.8, and 7033 had matching degrees between 0.65 and 0.8. The most abundant MPs were Chlorinated Polyethylene (CPE), Fluorosilicone rubber, Polyvinyl chloride (PVC), Butadiene rubber (BR), and Styrene-butadiene-styrene (SBS), with diameters ranging from 20 to 100 μm. Five random samples were analyzed by pyrolysis-gas chromatography-mass spectrometry, which detected four types of microplastics—Polyethylene (PE), Polypropylene (PP), Polystyrene (PS), and PVC—at varying concentrations. PE was the most abundant (22.284 mg/kg), followed by PVC (1.061 mg/kg), PP (0.837 mg/kg), and PS (0.600 mg/kg). Based on the diameter and concentration ranges of MPs in hFF, we used seven types of fluorescence-labeled MP beads—PE, PVC, PP, PS, CPE, Polymethylmethacrylate (PMMA), and Polytetrafluoroethylene (PTFE)—to assess their impact on mouse oocyte in vitro maturation. The results showed that smaller MP beads (e.g., 50 μm PE) were more likely to penetrate the zona pellucida and enter the oocyte, while larger beads (e.g., 500 nm PMMA) tended to adhere to the zona and remain outside the oocyte. All seven types of MP beads hindered oocyte maturation, resulting in varying reductions in maturation rates compared to the control group. Our findings suggest that MPs contaminate hFF and may impair oocyte maturation.

Abstract Rheumatoid arthritis (RA) is a chronic autoimmune disease marked by synovitis and cartilage destruction. The active compound, icariin (ICA), derived from the herb Epimedium, exhibits potent anti-inflammatory properties. However, its clinical utility is limited by its water insolubility, poor permeability, and low bioavailability. To address these challenges, we developed a multifunctional drug delivery system—adipose-derived stem cells-exosomes (ADSCs-EXO)-ICA to target active macrophages in synovial tissue and modulate macrophage polarization from M1 to M2. High-performance liquid chromatography analysis confirmed a 92.4 ± 0.008% loading efficiency for ADSCs-EXO-ICA. In vitro studies utilizing cellular immunofluorescence (IF) and flow cytometry demonstrated significant inhibition of M1 macrophage proliferation by ADSCs-EXO-ICA. Enzyme-linked immunosorbent assay, cellular transcriptomics, and real-time quantitative PCR indicated that ADSCs-EXO-ICA promotes an M1-to-M2 phenotypic transition by reducing glycolysis through the inhibition of the ERK/HIF-1α/GLUT1 pathway. In vivo, ADSCs-EXO-ICA effectively accumulated in the joints. Pharmacodynamic assessments revealed that ADSCs-EXO-ICA decreased cytokine levels and mitigated arthritis symptoms in collagen-induced arthritis (CIA) rats. Histological analysis and micro computed tomography confirmed that ADSCs-EXO-ICA markedly ameliorated synovitis and preserved cartilage. Further in vivo studies indicated that ADSCs-EXO-ICA suppresses arthritis by promoting an M1-to-M2 switch and suppressing glycolysis. Western blotting supported the therapeutic efficacy of ADSCs-EXO-ICA in RA, confirming its role in modulating macrophage function through energy metabolism regulation. Thus, this study not only introduces a drug delivery system that significantly enhances the anti-RA efficacy of ADSCs-EXO-ICA but also elucidates its mechanism of action in macrophage function inhibition. Graphical abstract

This systematic review aims to offer a comprehensive analysis of recent empirical studies on technology-supported scaffoldings (TSS) within the education sector. A total of 31 TSS studies published between 2017 and 2022 were selected from the reputable databases. The analysis focuses on trends, research methods, intervention design, and student learning outcomes in TSS studies. The findings reveal that TSS applications encompass a diverse range of participants, subjects, pedagogical approaches, teaching strategies, and technological tools, impacting cognitive and affective domains. However, recent TSS research demonstrates a bias towards upper primary and junior secondary students, with a focus on science and language subjects. While established e-learning tools are commonly integrated into TSS designs, there is limited exploration of metacognitive and motivational scaffoldings. This study highlights the importance of dynamic scheduling and adjustment of TSS to cater to individual student needs and capabilities, laying the groundwork for future research to develop highly customized TSS that effectively support student learning.

This study examines the relationship between perceived social support and selfesteem and between perceived social support and social integration among adolescents with visual impairments. Adolescents with visual impairments (Ntime1 = 311, Ntime2 = 170) from four special education schools in eastern China participated in this study within a 1-year interval. The Child and Adolescent Social Support Scale, Rosenberg Self-esteem Questionnaire, and Interpersonal Adaptation Scale were used to collect data. The results from cross-lagged panel modeling showed reciprocal positive relationships between parental support and self-esteem. Self-esteem at T1 positively predicted three other sources of perceived social support at T2: teacher support, classmate support, and close-friend support. Social integration at T1 positively predicted closefriend support at T2. This study extends understanding of the relationships among perceived social support, self-esteem, and social integration, and provides practical implications for parents, schools, and communities to improve psychosocial outcomes in adolescents with visual impairment. [ABSTRACT FROM AUTHOR]

Background/Objectives: Hemerocallis citrina Baroni (HCB) is a traditional herb for the treatment of depression in China. However, the active constituents and the underlying mechanisms of its antidepressant effects remain unclear. The aim of this study was to identify the bioactive constituents of HCB and elucidate its underlying mechanism for the treatment of depression. Methods: The constituents of HCB were systematically analyzed using UHPLC-Q-Orbitrap HRMS. Its antidepressant effect was evaluated by chronic unpredictable mild stress (CUMS)-induced depression. The mechanism of HCB in treating depression was investigated through network pharmacology and molecular docking. Subsequently, its potential mechanism for the treatment of depression was carried out by RNA sequencing. Finally, the mechanism was further verified by Western blot. Results: A total of 62 chemical constituents were identified from HCB using UHPLC-Q-Orbitrap HRMS, including 17 flavonoids, 11 anthraquinones, 11 alkaloids, 10 caffeoylquinic acid derivatives, five phenolic acids, five triterpenoids, and three phenylethanosides, 13 of which were identified as potential active constituents targeting 49 depression-associated proteins. Furthermore, HCB was found to significantly reduce cognitive impairment, anxiety-like behavior, and anhedonia-like behavior. The expression levels of 5-hydroxytryptamine (5-HT), dopamine (DA), and brain-derived neurotrophic factor (BDNF) were elevated in the hippocampal CA3 region. Results from network pharmacology and transcriptomics indicated that the PI3K/Akt/CREB signaling pathway is essential for the therapeutic effects of HCB on depression. Research in the field of molecular biology has conclusively demonstrated that HCB is associated with an increase in the expression levels of several important proteins. Specifically, there was a notable upregulation of phosphorylated PI3K (p-PI3K) relative to its unphosphorylated form PI3K, as well as an elevation in the ratio of phosphorylated Akt (p-Akt) to total Akt. Additionally, the study observed increased levels of phosphorylated CREB (p-CREB) compared to its unphosphorylated CREB. Conclusions: This study provides compelling evidence that HCB possesses the ability to mitigate the symptoms of depression through its influence on the PI3K/Akt/CREB signaling pathway. HCB could be developed as a promising therapeutic intervention for individuals struggling with depression, offering new avenues for treatment strategies that target this particular signaling mechanism.

Collaborative programming is being increasingly used to overcome the difficulties of the individual programming process. In this study, we investigated the effect of collaborative perception on cognitive engagement and learning outcomes in collaborative programming. We used a quasi-experimental research to determine the differences in cognitive engagement and learning outcomes of three groups with different levels of collaborative perception. The findings highlight several important conclusions. First, there were significant differences in cognitive engagement and learning outcomes across collaborative perception groups. Students with high levels of collaborative perception demonstrate more comprehensive and diverse cognitive engagement, resulting in higher learning outcomes compared to those with lower perception. Second, students in the low collaborative perception group had more Clarification-Elaboration cognitive connections, and students in the high collaborative perception group had stronger Clarification-Positioning and Clarification-Verification cognitive connections. Third, collaborative perception positively moderated the relationship between cognitive engagement and learning outcomes. In particular, three cognitive engagement, Clarification, Elaboration, and Positioning, had a greater impact on performance when moderated by collaborative perceptions. These findings have practical implications for educators and course designers, emphasizing the importance of considering students' collaborative perception when forming groups and promoting effective collaborative programming.

Abstract Nanomaterials excel in mimicking the structure and function of natural enzymes while being far more interesting in terms of structural stability, functional versatility, recyclability, and large‐scale preparation. Herein, the story assembles hemin, histidine analogs, and G‐quadruplex DNA in a catalytically competent supramolecular assembly referred to as assembly‐activated hemin enzyme (AA‐heminzyme). The catalytic properties of AA‐heminzyme are investigated both in silico (by molecular docking and quantum chemical calculations) and in vitro (notably through a systematic comparison with its natural counterpart horseradish peroxidase, HRP). It is found that this artificial system is not only as efficient as HRP to oxidize various substrates (with a turnover number kcat of 115 s−1) but also more practically convenient (displaying better thermal stability, recoverability, and editability) and more economically viable, with a catalytic cost amounting to

Dark brown leaf spot on tea (Camellia sinensis (L.) O. Kuntze) caused by Epicoccum mackenziei Jayasiri, Camporesi & K. D. Hyde has caused a loss in the yield and quality of tea leaves in Guizhou Province, Southwest China. No research has been published on the gene expression profiles of tea leaves during infection by E. mackenziei. In this study, we report the high-quality transcriptome sequencing of tea genes during infection, using high-throughput next-generation sequencing on the Illumina Novaseq 6000 platform. The infection resulted in significantly up- or downregulated expression of the 960 or 397 differentially expressed mRNAs (DEmRNAs) from tea leaves, respectively. The DEmRNAs were annotated using the Gene Ontology and Kyoto Encyclopedia of Genes and Genomes databases. The expression of DEmRNA peroxidase 21 (TEA000222.1) was upregulated in response to infection by the pathogen and was enriched in terms of defense response to fungi at the biological process aspect. Expression of 26 or 13 of the tea DEmRNAs enriched in the pathways of plant-pathogen interaction were up- or downregulated, respectively, such as the genes WRKY transcription factor 1 (TEA028099.1), probable disease resistance protein At4g27220 (TEA018574.1), and serine/threonine-protein kinase CDL1 (TEA006388.1), which were downregulated. This comprehensive gene expression profiling study of tea leaves infected by this fungal pathogen will provide a valuable resource for future research on the identification of the host genes associated with the response to pathogen challenge and ultimately with disease resistance in the host. [Figure: see text] Copyright © 2023 The Author(s). This is an open access article distributed under the CC BY-NC-ND 4.0 International license.

Abstract Genomic abnormalities are strongly associated with cancer and infertility. In this study, we develop a simple and efficient method — multiple genetic abnormality sequencing (MGA-Seq) — to simultaneously detect structural variation, copy number variation, single-nucleotide polymorphism, homogeneously staining regions, and extrachromosomal DNA (ecDNA) from a single tube. MGA-Seq directly sequences proximity-ligated genomic fragments, yielding a dataset with concurrent genome three-dimensional and whole-genome sequencing information, enabling approximate localization of genomic structural variations and facilitating breakpoint identification. Additionally, by utilizing MGA-Seq, we map focal amplification and oncogene coamplification, thus facilitating the exploration of ecDNA’s transcriptional regulatory function.

Due to our lack of understanding of the host-pathogen epidemiology and the absence of effective control measures, tea leaf spot, caused by the fungus Epicoccum sorghinum, continues to reduce the productivity and quality of tea leaves in plantations in Guizhou Province, southwestern China. Here, samples of tea (Camellia sinensis [L.] O Kuntze) leaves either infected or uninfected by E. sorghinum were used as the study model. The mRNA and microRNA (miRNA) sequences in tea leaves from the two treatments were determined using the Illumina NovaSeq 6000 and the Illumina HiSeq 2500 platforms, respectively. In total, 33,932 genes or transcripts from tea leaves were annotated. In response to infection by E. sorghinum, 1,068 or 467 of the differentially expressed mRNAs (DEmRNAs) were up- or downregulated, respectively, and the DEmRNAs containing peroxidase 21 and LRR receptor-like serine/threonine-protein kinase ERECTA were enriched in terms of defense response. Meanwhile, 1,889 miRNAs were identified from infected or uninfected leaves. Nine or seven of the differentially expressed miRNAs (DEmiRNAs) were up- or downregulated, respectively. The DEmiRNAs MIR5303j-p5, MIR6173-p5, miR858-3p, and novel-miR0377-3p were predicted to bind to DEmRNAs. Fifteen DEmRNAs annotated into transcription factor proteins enriched with respect to the plant-pathogen interaction pathway were predicted to be bound by the DEmiRNA miR858-3p. The sequences and abundances of the mRNAs and miRNAs from tea leaves infected by E. nigrum, and the prediction of the interaction between DEmiRNAs and DEmRNAs could contribute to our understanding of this plant-pathogen interaction. [Figure: see text] Copyright © 2023 The Author(s). This is an open access article distributed under the CC BY-NC-ND 4.0 International license.

Gene editing contributes to enhancing food security through the creation of novel foods. However, public perception of gene-edited (GE) foods is crucial to their acceptance and adoption. This study expanded the knowledge–attitude–practice model and constructed an integrated framework comprising four dimensions: demographic factors, scientific literacy and beliefs, social trust, and perceptions of gene technology, aimed at explaining the public’s attitudes toward GE foods. A questionnaire survey was conducted (N = 649), revealing a positive attitude toward GE foods, with over 80% expressing a certain willingness to pay (WTP) for them. Factors such as income level, subjective knowledge, scientific beliefs, trust in scientists, trust in government, and trust in national technological capabilities and perceived benefits positively correlated with WTP. Conversely, objective knowledge, perceived risks, and perceived ethical concerns were negatively correlated with WTP. The impact of objective knowledge on attitudes toward GE foods demonstrated a significant, nonlinear relationship. Additionally, it is noteworthy that the Chinese public currently exhibits relatively low trust in national technological capabilities, necessitating vigilance against the emergence of conspiracy theories akin to those surrounding genetically modified foods. This research contributes theoretical insights into the public communication of GE foods.

Abstract Background Brain metastasis (BM) in triple‐negative breast cancer (TNBC) patients is associated with significant morbidity and mortality. In this research we aimed to develop a nomogram to predict the prognosis of TNBC patients with BMs (TNBC‐BM) and explore the potential risk factors. Methods We used data from the Surveillance, Epidemiology, and End Results (SEER) database. A prognostic nomogram was built and validated based on patients with BM at newly diagnosed TNBC (nTNBC‐BM). Its effect on TNBC patients with BM was also validated in an extended group. The prognostic effect of treatment and risk factors for nTNBC‐BM were further tested. Results A nomogram was constructed and validated to predict overall survival (OS) in TNBC‐BM patients. For patients with BM diagnosed at the initial treatment or later course, the C‐index (0.707, 0.801, and 0.685 in the training, validation, and extended groups, respectively) and calibration plots showed the acceptable prognostic accuracy and clinical applicability of the model. Surgery on the primary tumor and chemotherapy were found to confer significantly better OS (11 months vs. 4 months; 5 months vs. 3 months, respectively). In addition, advanced tumor/nodal stage and bilateral cancer were associated with a higher risk of nTNBC‐BM. Conclusion We developed a sensitive and discriminative nomogram to predict OS in TNBC‐BM patients, both at initial diagnosis and the latter course. nTNBC‐BM patients may benefit more from surgery and chemotherapy than from radiotherapy. In addition, in the predictive model, TNBC patients harboring advanced tumor/nodal stages and bilateral tumors were more likely to have BM at initial diagnosis.

Abstract Background Microsatellite instability‐high (MSI‐H) subgroup of gastric cancer (GC) is characterized by a high tumor mutational burden, increased lymphocytic infiltration, and enhanced inflammatory cytokines. GC patients with MSI‐H status have a good response to immune checkpoint blockade management. However, heterogeneity within the subtype and the underlying mechanisms of shaping tumor microenvironments remain poorly understood. Methods RNA expression levels and clinical parameters of GC were obtained from The Cancer Genome Atlas (TCGA) and Gene Expression Omnibus (GEO) databases. The data were analyzed using single‐sample Gene Set Enrichment Analysis (ssGSEA), univariate Cox regression, multivariate Cox regression, and Least Absolute Shrinkage Selection Operator (LASSO) regression. In addition, multiplex immunohistochemistry (mIHC) was used in our clinical cohort for the tumor microenvironment study. Results By ssGSEA and survival analysis, the EMT signaling pathway was identified as a representative pathway, which can stratify the patients with MSI‐H GC with significant survival predictive power. Then, a novel representative EMT‐related five‐gene signature (namely CALU, PCOLCE2, PLOD2, SGCD, and THBS2) was established from EMT signaling gene set, which sensitivity and specificity were further validated in the independent GEO database (GSE62254) cohort for disease outcome prediction. Based on public single‐cell data and in situ immunohistochemistry, we found that most of these five genes were abundantly expressed in cancer‐associated fibroblasts. Furthermore, patients with high or low risk divided by this five‐gene signature exhibited a strong correlation of the distinct patterns of tumor immune microenvironment. By mIHC staining of sections from 30 patients with MSI‐H status, we showed that the patients with better prognoses had the increased infiltration of CD8+ cells in the primary tumoral tissue. Conclusion Our study developed a simple five‐gene signature for stratifying MSI‐H GC patients with survival predictive power.

The proton-activated chloride (PAC) channel plays critical roles in ischemic neuron death, but its activation mechanisms remain elusive. Here, we investigated the gating of PAC channels using its novel bifunctional modulator C77304. C77304 acted as a weak activator of the PAC channel, causing moderate activation by acting on its proton gating. However, at higher concentrations, C77304 acted as a weak inhibitor, suppressing channel activity. This dual function was achieved by interacting with 2 modulatory sites of the channel, each with different affinities and dependencies on the channel's state. Moreover, we discovered a protonation-independent voltage activation of the PAC channel that appears to operate through an ion-flux gating mechanism. Through scanning-mutagenesis and molecular dynamics simulation, we confirmed that E181, E257, and E261 in the human PAC channel serve as primary proton sensors, as their alanine mutations eliminated the channel's proton gating while sparing the voltage-dependent gating. This proton-sensing mechanism was conserved among orthologous PAC channels from different species. Collectively, our data unveils the polymodal gating and proton-sensing mechanisms in the PAC channel that may inspire potential drug development.

The metabolic environment of tumours has wide-ranging effects on the anti-tumour immune response and the outcome of immune therapy. Authors show here that the purine metabolite inosine enhances tumour immunogenicity and thus immune checkpoint blockade therapy response by inhibiting the ubiquitin-activating enzyme UBA6 in tumour cells.

Abstract The activity of integrin-linked kinase (ILK) in cancerous cells is often oncogenic and associated with malignant properties, such as uncontrolled cell cycle progression and evasion from senescence. However, the role of ILK in cellular senescence in gastric cancer (GC) has not been previously examined. We generated single-cell clones of ILK knock-out using CRISPR-Cas9 in human GC lines with mesenchymal or epithelial histology. Cells with no residual ILK expression exhibited strong cellular senescence with diminished clathrin-mediated endocytosis, Surprisingly, ILK loss-induced cellular senescence appeared to be independent of its function in integrin signaling. The low dose of CPD22, a small molecule inhibitor of ILK activity-induced senescence in three GC cell lines with different histologies. Furthermore, senescent cells with ILK depletion transfected with N-terminal truncated ILK mutant remaining catalytic domains displayed the reduction of senescent phenotypes. RNA sequencing and cytokine array results revealed the enrichment of multiple pro-inflammatory signaling pathways in GC lines in the absence of ILK. Our study identified the important role and the potential mechanism of ILK in the cellular senescence of cancerous epithelial cells. The inhibition of ILK activity using small molecule compounds could have a pro-senescent effect as a therapeutic option for GC.

Activating transcription factors, ATFs, are a group of bZIP transcription factors that act as homodimers or heterodimers with a range of other bZIP factors. In general, ATFs respond to extracellular signals, indicating their important roles in maintaining homeostasis. The ATF family includes ATF1, ATF2, ATF3, ATF4, ATF5, ATF6, and ATF7. Consistent with the diversity of cellular processes reported to be regulated by ATFs, the functions of ATFs are also diverse. ATFs play an important role in cell proliferation, apoptosis, differentiation and inflammation-related pathological processes. The expression and phosphorylation status of ATFs are also related to neurodegenerative diseases and polycystic kidney disease. Various miRNAs target ATFs to regulate cancer proliferation, apoptosis, autophagy, sensitivity and resistance to radiotherapy and chemotherapy. Moreover, ATFs are necessary to maintain cell redox homeostasis. Therefore, deepening our understanding of the regulation and function of ATFs will provide insights into the basic regulatory mechanisms that influence how cells integrate extracellular and intracellular signals into genomic responses through transcription factors. Under pathological conditions, especially in cancer biology and response to treatment, the characterization of ATF dysfunction is important for understanding how to therapeutically utilize ATF2 or other pathways controlled by transcription factors. In this review, we will demonstrate how ATF1, ATF2, ATF3, ATF4, ATF5, ATF6, and ATF7 function in promoting or suppressing cancer development and identify their roles in tumour immunotherapy.

Abstract Over the last decade, there has been great research interest in the application of artificial intelligence (AI) in various fields, such as medicine, finance, and law. Recently, there has been a research focus on the application of AI in education, where it has great potential. Therefore, a systematic review of the literature on AI in education is therefore necessary. This article considers its usage and applications in Latin American higher education institutions. After identifying the studies dedicated to educational innovations brought about by the application of AI techniques, this review examines AI applications in three educational processes: learning, teaching, and administration. Each study is analyzed for the AI techniques used, such as machine learning, deep learning, and natural language processing, the AI tools and algorithms that are applied, and the main education topic. The results reveal that the main AI applications in education are: predictive modelling, intelligent analytics, assistive technology, automatic content analysis, and image analytics. It is further demonstrated that AI applications help to address important education issues (e.g., detecting students at risk of dropping out) and thereby contribute to ensuring quality education. Finally, the article presents the lessons learned from the review concerning the application of AI technologies in higher education in the Latin American context.

Abstract Background Oral administration of insulin (INS) could be absorbed into systemic circulation only if the carrier protected it from the hostile gastrointestinal conditions. However, traditional macromolecular carriers have not totally overcome challenges in addressing these biological barriers. Result In this study, inspired by small molecule natural products (SMNPs), we demonstrate the multi-functional self-assembly nanoparticles (BA-Al NPs) originating from baicalin (BA) and AlCl3 through coordination bonds and hydrogen bonds. As a novel carrier for oral insulin delivery (INS@BA-Al NPs), it displayed effective capacity in pH stimuli-responsive insulin release, intestinal mucoadhesion and transepithelial absorption enhance. Meanwhile, BA improved the paracellular permeability for insulin absorption, because of its downregulation at both mRNA and protein level on internal tight junction proteins. In vivo experiments exhibited remarkable bioavailability of INS and an ideal glucose homeostasis in the type I diabetic rat model. Conclusion This study offers a novel frontier of multi-functional carriers based on SMNPs with self-assembly character and bioactivity, which could be a promising strategy for diabetes therapy. Graphical Abstract

It is crucial to inhibit tumor growth and distant metastasis for breast cancer (BC) therapy. However, the treatment primarily dependent on surgery, chemotherapy, and radiotherapy is far from satisfactory. It had been demonstrated that the CXCL1/2-S100A8/9 axis played an essential role in BC therapy. Therefore, we constructed a natural product hydrogel for BC therapy by blocking CXCL1 signaling. The GK-GA (phytochemicals of Genkwa Flos-glycyrrhizic acid) hydrogel was designed in a one-step “green” approach. The pharmacodynamics study showed GK-GA exhibited significant anti-tumor and anti-lung metastasis activities, resulting in the inhibition rate of tumor growth (IRG) over 90 % at 6.25 mg·kg−1, and did not display any obvious toxicity. In addition, the potent antitumor efficiency was also attributed to aggregation/assembly-induced retention (AIR) property. RNA sequencing analysis revealed the gene expression was significantly down-regulated in the GK-GA group, which were BCL2, CASP3, CXCL1, CXCL2, CXCR2, S100A8, S100A9, and confirmed further by western blot (WB). Our findings indicated natural product GK-GA hydrogel inhibited tumor growth and lung metastasis via the BCL2-CASP3 mitochondrial apoptosis pathway as well as the CXCL1/2-S100A8/9 pathway. This study provides inspiration for the fabrication of new excipients-free nano-dispersion in a one-step, no‐carrier‐added, organic solvent-free, “green” approach, particularly for small molecular antitumor agents.