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Transnational online education has become an emerging trend in promoting academic collaboration and exchange in higher education during and after the pandemic. Guided by the learning ecology framework, we conducted concurrent mixed methods research by distributing an online survey to Chinese students (N=51) to collect quantitative and qualitative data. This helped us deeply understand their experiences and perceptions of a cross-cultural online learning environment in the United States. We applied multiple regression and thematic analysis to analyze the data. The merging of both types of data analysis indicated the confirmation of the importance of discipline-based English learning environments, the transformation of online learning practices, the insufficiency of student-to-instructor interactions, discordance of technological self-efficacy and the disadvantages of technology-assisted instruction, and discordance between the usefulness and difficulties of learning activities and assessments. We further discussed appropriate strategies and techniques to promote online teaching and learning excellence in transnational distance education.

Aims: To determine the associations between COVID-19 school closures and school readiness skills for Chinese kindergarteners. Design: We utilized the natural experimental condition created by local COVID-19 outbreaks in 2022 (Study 1) to compare school readiness skills of children whose kindergartens were closed for 5 months (Group 1) with children whose kindergartens stayed open (Group 2). We further compared the school readiness skills of one pre-COVID-19 cohort (Cohort 2019) with one COVID-19 cohort (Cohort 2021) from a fifth kindergarten (Study 2). Samples: For Study 1, Group 1 included 445 children and Group 2 included 584 children aged 4-6 years. For Study 2, Cohort 2019 included 156 children and Cohort 2021 included 228 children aged 3-6 years. Measures: For both studies, survey data on four school readiness skills were collected from parents. Additionally, Study 1 collected parental locus of control data from parents. Results: Controlling for covariates, Study 1 revealed that Group 1 and Group 2 did not differ in terms of language and emergent literacy or approaches to learning. However, Group 1 scored lower than Group 2 on health and well-being and arts and imagination. Study 2 revealed that Cohort 2021 scored higher than Cohort 2019 on language and emergent literacy but lower on the other three skills. Conclusions: The associations of COVID-19 school closures with Chinese children's school readiness skills were not uniform, with a positive relation with language and emergent literacy and negative associations with health and well-being, approaches to learning, as well as arts and imagination.

Abstract Background Healthcare workers in dental hospitals frequently experience repeated occupational exposures (ROEs). In our study, we aim to analyze these repeated exposures among dental healthcare workers (DHWs), assess the risk levels of different risk factors, and explore the significance of ROE data for infection control in dental hospitals. Methods Based on hospital statistical data, we categorized the occupational exposure incidents at West China Hospital of Stomatology over the past seven years into initial and repeated exposures. We analyzed the association of various risk factors, including personnel types, gender, treatment locations, timing of occupational exposure, and pathways of occupational exposure, with the occurrence of repeated exposures. The Statistical Package for Social Sciences (SPSS) 21 was used to conduct chi-square analysis and binary logistic regression analysis, with the significance level set at p

Abstract Oncostatin M (OSM) is a unique Interleukin 6 (IL-6) family cytokine that plays pivotal roles in numerous biological events by signaling via two types of receptor complexes. While type I OSM receptor complex is formed by glycoprotein 130 (gp130) heterodimerization with Leukemia Inhibitory Factor receptor (LIFR), type II OSM receptor complex is composed of gp130 and OSM receptor (OSMR). OSM is an important contributor to multiple inflammatory diseases and cancers while OSM inhibition has been shown to be effective at reducing symptoms, making OSM an attractive therapeutic target. Using cryogenic electron microscopy (cryo-EM), we characterize full extracellular assemblies of human type I OSM receptor complex and mouse type II OSM receptor complex. The juxtamembrane domains of both complexes are situated in close proximity due to acute bends of the receptors. The rigid N-terminal extension of OSM contributes to gp130 binding and OSM signaling. Neither glycosylation nor pro-domain cleavage of OSM affects its activity. Mutagenesis identifies multiple OSM and OSMR residues crucial for complex formation and signaling. Our data reveal the structural basis for the assemblies of both type I and type II OSM receptor complexes and provide insights for modulation of OSM signaling in therapeutics.

Abstract Pro-death Bax family member, Bax∆2, forms protein aggregates in Alzheimer’s disease neurons and causes stress granule-mediated neuronal death. Production of Bax∆2 originated from two events: alternative splicing of Bax exon 2 and a microsatellite mutation (a deletion from poly guanines, G8 to G7). Each event alone leads to a reading frameshift and premature termination. While Bax exon 2 alternative splicing is common in Alzheimer’s brains, the G7 mutation is not, which is inconsistent with the high Bax∆2 protein levels detected in clinical samples. Here, we report an alternative mechanism to produce Bax∆2 protein in the absence of the G7 mutation. Using dual-tag systems, we showed that a ribosomal frameshift (RFS) can compensate the lack of G7 mutation in translating Bax∆2 protein. Intriguingly, the microsatellite poly G repeat is neither essential nor the site for the RFS. However, disruption of the poly G sequence impaired the RFS, potentially due to alteration of the local RNA structure. Using immunoprecipitation-mass spectrometry, we pinpointed the RFS site at 15 base pairs upstream of the microsatellite. These results uncover an alternative mechanism for generating functional Bax∆2-subfamily isoforms, highlighting the production plasticity of Bax family isoforms and unveiling potential new therapeutic targets for Alzheimer’s disease.

Non-small cell lung cancer (NSCLC) is a major disease with high incidence, low survival rate and prone to develop drug resistance to chemotherapy. The mechanism of secondary drug resistance in NSCLC chemotherapy is very complex, and studies have shown that the abnormal activation of STAT3 (Signal Transducer and Activator of Transcription 3) plays an important role in it. In this study, the pGPU6/GFP/Neo STAT3-shRNA recombinant plasmid was constructed with STAT3 as the precise target. By modifying hydrophilic and hydrophobic blocks onto chitosan, a multifunctional vitamin E succinate-chitosan-polyethylene glycol monomethyl ether histidine (VES-CTS-mPEG-His) micelles were synthesized. The micelles could encapsulate hydrophobic drug doxorubicin through self-assembly, and load the recombinant pGPU6/GFP/Neo STAT3-shRNA (pDNA) through positive and negative charges to form dual-loaded nanoparticles DOX/VCPH/pDNA. The co-delivery and synergistic effect of DOX and pDNA could up-regulate the expression of PTEN (Phosphatase and Tensin Homolog), down-regulate the expression of CD31, and induce apoptosis of tumor cells. The results of precision targeted therapy showed that DOX/VCPH/pDNA could significantly down-regulate the expression level of STAT3 protein, further enhancing the efficacy of chemotherapy. Through this study, precision personalized treatment of NSCLC could be effectively achieved, reversing its resistance to chemotherapy drugs, and providing new strategies for the treatment of drug-resistant NSCLC.

Emerging contaminants (ECs) are widely present in aquatic environments, posing potential risks to both ecosystems and human health. The ultrasound-assisted persulfate oxidation process has attracted considerable attention in the degradation of ECs due to its ability to generate both sulfate radicals and cavitation effects, enhancing degradation effects. In this paper, the principle of ultrasonic synergistic Fenton-like oxidation system for degrading organic pollutants was reviewed, divided into homogeneous system, non-homogeneous system, and single-atom system to explore the synergistic effect of ultrasound-enhanced persulfate technology in three aspects, and the effects of environmental factors such as ultrasonic frequency and power, system pH, temperature, and initial oxidant concentration on the system's decontamination performance were discussed. Finally, future research on ultrasonically activated persulfate technology is summarized and prospected.

The assessment of male fertility has traditionally depended on the evaluation of conventional semen parameters. Recent advances have identified sperm DNA fragmentation as a valuable biomarker for the assessment of male infertility. This study recruited 121 men from an andrology clinic to evaluate the diagnostic efficiency of the sperm DNA fragmentation index (DFI), utilizing the sperm chromatin structure assay (SCSA) through both flow cytometry and fluorescence microscopy. The study also explored the relationship between sperm DFI and standard semen parameters such as concentration, motility and morphology. The results showed that men with abnormal semen parameters were found to have significantly reduced sperm progressive motility (p < 0.001), total motility (p < 0.001) and normal morphology (p < 0.001), as well as higher sperm DFI, as determined by both fluorescence microscopy and flow cytometry (both p < 0.001), compared to those with normal semen parameters. A negative correlation was observed between sperm progressive motility, total motility, sperm normal morphology and sperm DFI, regardless of whether the DFI evaluation was conducted using fluorescence microscopy or flow cytometry (all p < 0.001). In conclusion, the application of the SCSA assay via both fluorescence microscopy and flow cytometry reveals that sperm DFI is closely associated with seminal parameters, reinforcing its utility in the clinical evaluation of male fertility.

Abstract Spatial transcriptomics technologies have been widely applied to decode cellular distribution by resolving gene expression profiles in tissue. However, sequencing techniques still limit the ability to create a fine-resolved spatial cell-type map. To this end, we develop a novel deep-learning-based approach, STASCAN, to predict the spatial cellular distribution of captured or uncharted areas where only histology images are available by cell feature learning integrating gene expression profiles and histology images. STASCAN is successfully applied across diverse datasets from different spatial transcriptomics technologies and displays significant advantages in deciphering higher-resolution cellular distribution and resolving enhanced organizational structures.

Abstract Background Prenatal ultrasound is the preferred modality for diagnosing fetal congenital heart disease. Given issues of physician proficiency and hospital distribution, we propose a dynamic sequential cross-sectional scanning (SCS) to explore the feasibility of cardiac screening by sonographers with less than 5 years of experience in ultrasound. Materials and methods Twenty residents were randomly divided into two groups, receiving training in the American Institute of Ultrasound in Medicine (AIUM) fetal echocardiography and the SCS method. According to the needs of training, the professional staff developed the theoretical knowledge question bank, the CHD ultrasonic video disease bank, and the assessment scale. Trainees completed the pre-training examination, theory and skill operation training, and post-training assessment. For the two groups, the theoretical knowledge, skill operation and disease diagnosis were analyzed statistically before and after training. Results After training, the trainees in both groups had significantly improved knowledge and diagnostic abilities, their diagnostic thinking about CHD was clear, and they could identify major or even all structural abnormalities and make a definite diagnosis. In terms of skill operation, both groups could complete all required scanning within the specified time. The scanning time of the SCS group was significantly lower than that of the AIUM group, and the effect of the receptor site in the AIUM group was significantly higher than that in the SCS group. Conclusion SCS can be used as a new rapid fetal cardiac scanning method and try to popularize among echocardiographer.

Abstract Background Resilience is a protective feature against anxiety and depression disorders. However, the precise relationship and structure of resilience and anxiety and depression remain poorly understood. This study sought to investigate the link among resilience’ components and anxiety as well as depression. Methods 1,279 clinical nurses were recruited. 10-item Connor-Davidson Resilience Scale, Generalized Anxiety Disorder 7, and Patient Health Questionnaire 9 were employed to evaluate resilience, anxiety, and depression, respectively. The regularized partial-correlation network was generated utilizing data from cross-sectional survey and the bridge expected influence index was utilized to quantify bridge components. Results The rates of anxiety and depression within clinical nurses were 67.3% and 67.2%, accordingly. Four strongest bridge edges appeared in the resilience-anxiety network, like “Adapt to change”- “Fear that something might happen”, and “Stay focused under pressure”- “Uncontrollable worry”. Two strongest bridge edges appeared in the resilience-depression network, like “Adapt to change”- “Concentration difficulties” and “Stay focused under pressure”- “Fatigue”. “Adapt to change” was recognized as bridging nodes in both the resilience-anxiety network and the resilience-depression network. Conclusions Interventions targeting the bridge component “Adapt to change” within resilience, may mitigate the intensity of anxiety and depression symptoms among clinical nurses.

Abstract Background Microsatellites are increasingly realized to have biological significance in human genome and health in past decades, the assembled complete reference sequence of human genome T2T-CHM13 brought great help for a comprehensive study of short tandem repeats in the human genome. Results Microsatellites density landscapes of all 24 chromosomes were built here for the first complete reference sequence of human genome T2T-CHM13. These landscapes showed that short tandem repeats (STRs) are prone to aggregate characteristically to form a large number of STRs density peaks. We classified 8,823 High Microsatellites Density Peaks (HMDPs), 35,257 Middle Microsatellites Density Peaks (MMDPs) and 199, 649 Low Microsatellites Density Peaks (LMDPs) on the 24 chromosomes; and also classified the motif types of every microsatellites density peak. These STRs density aggregation peaks are mainly composing of a single motif, and AT is the most dominant motif, followed by AATGG and CCATT motifs. And 514 genomic regions were characterized by microsatellite density feature in the full T2T-CHM13 genome. Conclusions These landscape maps exhibited that microsatellites aggregate in many genomic positions to form a large number of microsatellite density peaks with composing of mainly single motif type in the complete reference genome, indicating that the local microsatellites density varies enormously along the every chromosome of T2T-CHM13.

Abstract This study aimed to identify predictive factors for the prognosis of acute-on-chronic liver disease (AoCLD) due to both hepatitis B virus (HBV) and alcohol and to develop prognostic models to improve treatment management. AoCLD patients with HBV and alcohol as etiological factors were selected from two multicenter prospective cohorts (NCT02457637,NCT03641872) and included in separate training and validation cohorts (n = 180 and n = 148). In the training cohort, the CATCH-LIFE A nomogram (based on age, bilirubin, international normalized ratio, serum sodium, and hepatic encephalopathy score) and CATCH-LIFE B nomogram (based on age, bilirubin, international normalized ratio, serum albumin, white blood cell, platelet count, and hepatic encephalopathy score) had discriminatory ability for predicting 28-day (c-indexes of 0.910 and 0.899) and 90-day mortality (c-indexes of 0.878 and 0.887, respectively). The area under the curve values for 28-day and 90-day mortality prediction by the CATCH-LIFE A nomogram were 0.922 (95% CI : 0.874, 0.971) and 0.905 (0.856, 0.956), respectively, while those for the CATCH-LIFE B nomogram were 0.916(0.861,0.972) and 0.915 (0.866,0.964), respectively. Similar performance results were observed in the validation cohort. Optimal cut-off scores for each nomogram could be used for patient stratification in high- and low-risk groups, and the high-risk groups showed shorter survival times than the low-risk groups in both the training and validation cohorts. Two nomograms constructed from the first short-term follow-up data from patients with AoCLD due to combined HBV infection and alcohol exposure showed good predictive performance for 28-day and 90-day mortality and might be used to guide clinical management.

Abstract Atopic dermatitis (AD) is a common chronic inflammatory skin disorder characterized by disrupted epidermal barrier function and aberrant immune responses. Despite recent developments in new therapeutics for AD, there is still a large unmet medical need for disease management due to the complex and multifactorial nature of AD. Recent genome-wide association studies (GWAS) have identified NLRP10 as a susceptible gene for AD but the physiological role of NLRP10 in skin homeostasis and AD remains unknown. Here we show that NLRP10 is downregulated in AD skin samples. Using an air-lift human skin equivalent culture, we demonstrate that NLRP10 promotes keratinocyte survival and is required for epidermal differentiation and barrier function. Mechanistically, NLRP10 limits cell death by preventing the recruitment of caspase-8 to the death inducing signaling complex (DISC) and by inhibiting its subsequent activation. NLRP10 also stabilizes p63, the master regulator of keratinocyte differentiation, to drive proper keratinocyte differentiation and to reinforce the barrier function. Our findings underscore NLRP10 as a key player in atopic dermatitis pathogenesis, highlighting NLRP10 as a potential target for therapeutic intervention to restore skin barrier function and homeostasis in AD.

Abstract The quest for reliable vehicle navigation in urban environments has led the integration of Light Detection and Ranging (LiDAR) Odometry (LO) with Global Navigation Satellite Systems (GNSS) and Inertial Measurement Units (IMU). However, the performance of the integrated system is limited by a lack of accurate LO error modeling. In this paper, we propose a weighted GNSS/IMU/LO integration-based navigation system with a novel LO error model. The Squared Exponential Gaussian Progress Regression (SE-GPR) based LO error model is developed by considering the vehicle velocity and number of point cloud features. Based on error prediction for GNSS positioning and LO, a weighting strategy is designed for integration in an Extended Kalman Filter (EKF). Furthermore, error accumulation of the navigation state, especially in GNSS-challenging scenarios, is restrained by the LiDAR-Aided Lateral Constraint (LALC) and Non-Holonomic Constraint (NHC). An experiment was conducted in a deep urban area to test the proposed algorithm. The results show that the proposed algorithm delivers horizontal and three-dimensional (3D) positioning Root Mean Square Errors (RMSEs) of 3.669 m and 5.216 m, respectively. The corresponding accuracy improvements are 35.9% and 50.0% compared to the basic EKF based GNSS/IMU/LO integration.

Abstract Objective To investigate the structural abnormalities, genetic results, and postnatal clinical outcomes of fetuses with bovine aortic arch (Bovine Aortic Arch, BAA) to provide a basis for prenatal counseling and management. Methods A retrospective analysis was conducted on 216 fetuses diagnosed with bovine aortic arch through prenatal ultrasound screening at the First Affiliated Hospital of Anhui Medical University and the No.901 Hospital of the Joint Service of the People’s Liberation Army from January 2019 to February 2023. Their family history of genetic diseases, prenatal screening results, and postnatal follow-up data were collected. The fetuses were divided into an isolated BAA group (n = 192) and a non-isolated BAA group (n = 24). Chromosomal karyotyping and copy number variation (CNV) testing were conducted, and statistical analysis was performed using SPSS 22.0 software. Results Of the 216 fetuses with BAA, 192 were isolated BAA (88.89%), and 24 were non-isolated BAA (11.11%). Among the isolated BAA fetuses, only 1 case (0.52%) had chromosomal karyotype and pathogenic CNV abnormalities. Among the non-isolated BAA fetuses, 4 cases (16.67%) had chromosomal or CNV abnormalities, but the overall risk was low. The postnatal outcomes of isolated BAA fetuses were good (99.48%), while 79.17% of non-isolated BAA fetuses had good postnatal outcomes. Conclusion Most BAA fetuses are isolated, with a very low incidence of chromosomal abnormalities and pathogenic CNVs, and have good postnatal outcomes. The clinical value of isolated BAA is limited, and invasive prenatal diagnosis is not recommended for low-risk populations. Prenatal screening should focus on the risk of concurrent severe structural anomalies and chromosomal abnormalities.

Abstract Objectives MicroRNAs are considered as a class of potential biomarkers for HF. This study aimed to retrospectively evaluate the diagnostic and prognostic value of microRNA423-5p in patients with HF. Methods The observational group comprised 98 patients diagnosed with HF due to coronary atherosclerotic heart disease (n = 45), hypertension (n = 26), or cardiac valve insufficiency (n = 27). Conversely, the control group consisted of 30 healthy volunteers without any history of HF. These patients were further classified into heart function class II (n = 33), class III (n = 32), and class IV (n = 33) according to the NYHA classification. Of these patients, 33 were diagnosed with HF with mid-range ejection fraction (HFmrEF) and the remaining 65 with HF with reduced ejection fraction (HFrEF). The diagnostic and prognostic significance of microRNA423-5p in patients with HF was assessed through laboratory parameter assessments (microRNA423-5p and B-type natriuretic peptide test, BNP), cardiac ultrasound evaluations (left ventricular ejection fraction, LVEF), and subsequent follow-up assessments. Results In this study, we found that patients with HF exhibited notably elevated levels of microRNA423-5p and BNP, as well as significantly lower LVEF values. A significant positive correlation between microRNA423-5p and BNP indicators was validated. In addition, our study also revealed an elevation in the level of microRNA423-5p correlating with the progression of the HF. The combined evaluation of LEVF, BNP, and microRNA423-5p demonstrated superior diagnostic efficacy in comparison to the solitary use of BNP. Conclusions Elevated levels of microRNA423-5p in the serum of patients with HF suggest its potential utility as a novel biomarker for both the diagnosis and prognosis of this condition.

Abstract Malaria is one of the major health threats in Africa, and the risk of transmission is projected to be exacerbated by global warming. Rwanda experienced an 11-fold increase in malaria incidence from 2011 to 2015 despite extensive funding and implementation of control measures. Here, we focus on Rwanda as a case study and simulate monthly malaria incidence between 2010 and 2015, employing an ensemble learning method. Next, we project future malaria prevalence using shared socio-economic pathways (SSP2-4.5 and SSP5-8.5). We find that the projected increases in temperature and precipitation may shift malaria transmission risk to the highlands of western and northern Rwanda. These two regions that currently experience low malaria transmission. The seasonal effects of malaria incidence may be less apparent from January to June, and the peak season for malaria transmission in the highlands could occur one month earlier. Our findings highlight the impacts of climate change on malaria epidemics in Rwanda, which have implications for other world regions.

Objective To analyze the epidemiological characteristics and spatial clustering of severe fever with thrombocytopenia syndrome (SFTS) in Dalian from 2011 to 2023, and provide evidence for the prevention and control of SFTS. Method The incidence data of SFTS wer obtained from the National Disease Reporting Information System of Chinese Center for Disease Control and Prevention and referral tracking of all SFTS confirmed cases by CDC in all districts, cities and counties under the jurisdiction of Dalian Municipality. The epidemiological charac-teristics and spatial aggregation of SFTS were analyzed by descriptive analysis, Joinpoint regression analysis, and spatial autocorrelation analysis. Result From 2011 to 2023, a total of 701 laboratory confirmed cases of SFTS, including 166 deaths. The annual average morbidity rate was 0.77/100 000 (0.15/100 000 – 1.93/100 000), and the CFR was 23.68%. The overall morbidity rate of SFTS in Dalian had an increasing trend from 2011 to 2023 was in increase with an average annual percentage change (AAPC) of 24.00% (P < 0.05). And the mortality rate had a increasing trend from 2011 to 2023 with an average annual percentage change (AAPC) of 20.95% (P < 0.05). The cases mainly occurred from Apirl to October and the incidence peak was in summer. The middle-aged and elderly farmers were the main SFTS population.The top three areas of incidence number were 228 cases of Zhuanghe city, 194 cases of Pulandian city, 156 cases of Wafangdian city. Global spatial autocorrelation analysis showed that the spatial aggeration occurred in the incidence of SFTS from 2017 to 2023 (P < 0.05). Local spatial autocorrelation analysis showed that "High-high clustering" areas were mainly concentrated in the mountainous areas of northern Dalian such as Zhuanghe, Pulandian and Wafangdian. Conclution From 2011 – 2023, the incidence of SFTS increased in Dalian, and the spread and obvious spatially cluesterd were observed. The morbidity and mortality risk were high in the elderly. The incidence of SFTS was seasonal.

Abstract Background To assess the effects of inactivated Lactobacillus rhamnosus (ILR) on growth performance, serum biochemical indices, colonic microbiota, and metabolomics in weaned piglets, 120 piglets were randomly divided into five groups. Samples in the control group were fed a basal diet, while the experimental ILR1, ILR2, ILR3, and ILR4 groups were fed basal diets supplemented with 0.1%, 0.2%, 0.3%, and 0.4% ILR, respectively. The prefeeding period lasted for 5 days and was followed by a formal period of 28 days. Results Compared to the control, the average daily gain increased by 4.38%, 7.98%, 19.32%, and 18.80% for ILR1, ILR2, ILR3, and ILR4, respectively, and the ratio of feed to gain decreased by 0.63%, 3.80%, 12.66%, and 10.76%, respectively. Serum IgA, IgG, IgM, total antioxidant capacity, and glutathione peroxidase levels increased significantly in weaned piglets in the treatment groups. Addition of 0.3% ILR significantly increased the Shannon and Simpson indices of the colonic microbiota in weaned piglets and altered the microbiota composition. Changes in metabolic profiles were observed and were primarily related to the urea cycle, amino acid metabolism, and lipid metabolism. Conclusion ILR improved growth performance and serum immunological and biochemical indices and optimized the colonic microbiota structure and metabolism of weaned piglets.

Abstract Background The existing predictive models for metabolic-associated fatty liver disease (MAFLD) possess certain limitations that render them unsuitable for extensive population-wide screening. This study is founded upon population health examination data and employs a comparison of eight distinct machine learning (ML) algorithms to construct the optimal screening model for identifying high-risk individuals with MAFLD in China. Methods We collected physical examination data from 5,171,392 adults residing in the northwestern region of China, during the year 2021. Feature selection was conducted through the utilization of the Least Absolute Shrinkage and Selection Operator (LASSO) regression. Additionally, class balancing parameters were incorporated into the models, accompanied by hyperparameter tuning, to effectively address the challenges posed by imbalanced datasets. This study encompassed the development of both tree-based ML models (including Classification and Regression Trees, Random Forest, Adaptive Boosting, Light Gradient Boosting Machine, Extreme Gradient Boosting, and Categorical Boosting) and alternative ML models (specifically, k-Nearest Neighbors and Artificial Neural Network) for the purpose of identifying individuals with MAFLD. Furthermore, we visualized the importance scores of each feature on the selected model. Results The average age (standard deviation) of the 5,171,392 participants was 51.12 (15.00) years, with 52.47% of the participants being females. MAFLD was diagnosed by specialized physicians. 20 variables were finally included for analyses after LASSO regression model. Following ten rounds of cross-validation and parameter optimization for each algorithm, the CatBoost algorithm exhibited the best performance, achieving an Area Under the Receiver Operating Characteristic Curve (AUC) of 0.862. The ranking of feature importance indicates that age, BMI, triglyceride, fasting plasma glucose, waist circumference, occupation, high density lipoprotein cholesterol, low density lipoprotein cholesterol, total cholesterol, systolic blood pressure, diastolic blood pressure, ethnicity and cardiovascular diseases are the top 13 crucial factors for MAFLD screening. Conclusion This study utilized a large-scale, multi-ethnic physical examination data from the northwestern region of China to establish a more accurate and effective MAFLD risk screening model, offering a new perspective for the prediction and prevention of MAFLD.

Abstract Medullary thyroid carcinoma (MTC) is a rare type of thyroid malignancy that accounts for approximately 1–2% of all thyroid cancers (TCs). MTC include hereditary and sporadic cases, the former derived from a germline mutation of rearrangement during transfection (RET) proto-oncogene, whereas somatic RET mutations are frequently present in the latter. Surgery is the standard treatment for early stage MTC, and the 10-year survival rate of early MTC is over 80%. While for metastatic MTC, chemotherapy showing low response rate, and there was a lack of effective systemic therapies in the past. Due to the high risk (ca. 15–20%) of distant metastasis and limited systemic therapies, the 10-year survival rate of patients with advanced MTC was only 10–40% from the time of first metastasis. Over the past decade, targeted therapy for RET has developed rapidly, bringing hopes to patients with advanced and progressive MTC. Two multi-kinase inhibitors (MKIs) including Cabozantinib and Vandetanib have been shown to increase progression-free survival (PFS) for patients with metastatic MTC and have been approved as choices of first-line treatment. However, these MKIs have not prolonged overall survival (OS) and their utility is limited due to high rates of off-target toxicities. Recently, new generation TKIs, including Selpercatinib and Pralsetinib, have demonstrated highly selective efficacy against RET and more favorable side effect profiles, and gained approval as second-line treatment options. Despite the ongoing development of RET inhibitors, the management of advanced and progressive MTC remains challenging, drug resistance remains the main reason for treatment failure, and the mechanisms are still unclear. Besides, new promising therapeutic approaches, such as novel drug combinations and next generation RET inhibitors are under development. Herein, we overview the pathogenesis, molecular genetics and current management approaches of MTC, and focus on the recent advances of RET inhibitors, summarize the current situation and unmet needs of these RET inhibitors in MTC, and provide an overview of novel strategies for optimizing therapeutic effects.

Abstract Period-doubling bifurcation, as an intermediate state between order and chaos, is ubiquitous in all disciplines of nonlinear science. However, previous experimental observations of period doubling in ultrafast fiber lasers are mainly restricted to self-sustained steady state, controllable manipulation and dynamic switching between period doubling and other intriguing dynamical states are still largely unexplored. Here, we propose to expand the vision of dissipative soliton periodic doubling, which we illustrate experimentally by reporting original spontaneous, collisional, and controllable spectral period doubling in a polarization-maintaining ultrafast fiber laser. Specifically, the spontaneous period doubling can be observed in both single- and double-pulses. The mechanism of the switchable state and periodic doubling was revealed by numerical simulation. Moreover, state transformation of individual solitons can be resolved during the collision of triple solitons involving stationary, oscillating, and period doubling. Further, controllable deterministic switching between period doubling and other dynamical states, as well as exemplifying the application of period-doubling-based digital encoding, is achieved under programmable pump modulation. Our results open a new window for unveiling complex Hopf bifurcation in dissipative systems and bring useful insights into nonlinear science and applications.

Abstract Background The roles of the transcriptional factor SIX2 have been identified in several tumors. However, its roles in gastric cancer (GC) progression have not yet been revealed. Our objective is to explore the impact and underlying mechanisms of SIX2 on the stemness of GC cells. Methods Lentivirus infection was employed to establish stable expression SIX2 or PFN2 in GC cells. Gain- and loss-of-function experiments were conducted to detect changes of stemness markers, flow cytometry profiles, tumor spheroid formation, and tumor-initiating ability. ChIP, RNA-sequencing, tissue microarray, and bioinformatics analysis were performed to reveal the correlation between SIX2 and PFN2. The mechanisms underlying the SIX2/PFN2 loop-mediated effects were elucidated through tissue microarray analysis, RNA stability assay, IP-MS, Co-Immunoprecipitation, and inhibition of the JNK signaling pathway. Results The stemness of GC cells was enhanced by SIX2. Mechanistically, SIX2 directly bound to PFN2’s promoter and promoted PFN2 activity. PFN2, in turn, promoted the mRNA stability of SIX2 by recruiting RNA binding protein YBX-1, subsequently activating the downstream MAPK/JNK pathway. Conclusion This study unveils the roles of SIX2 in governing GC cell stemness, defining a novel SIX2/PFN2 regulatory loop responsible for this regulation. This suggests the potential of targeting the SIX2/PFN2 loop for GC treatment (Graphical Abstracts). Graphical Abstract

Abstract Radiomics offers a noninvasive avenue for predicting clinicopathological factors. However, thorough investigations into a robust breast cancer outcome-predicting model and its biological significance remain limited. This study develops a robust radiomic model for prognosis prediction, and further excavates its biological foundation and transferring prediction performance. We retrospectively collected preoperative dynamic contrast-enhanced MRI data from three distinct breast cancer patient cohorts. In FUSCC cohort (n = 466), Lasso was used to select features correlated with patient prognosis and multivariate Cox regression was utilized to integrate these features and build the radiomic risk model, while multiomic analysis was conducted to investigate the model’s biological implications. DUKE cohort (n = 619) and I-SPY1 cohort (n = 128) were used to test the performance of the radiomic signature in outcome prediction. A thirteen-feature radiomic signature was identified in the FUSCC cohort training set and validated in the FUSCC cohort testing set, DUKE cohort and I-SPY1 cohort for predicting relapse-free survival (RFS) and overall survival (OS) (RFS: p = 0.013, p = 0.024 and p = 0.035; OS: p = 0.036, p = 0.005 and p = 0.027 in the three cohorts). Multiomic analysis uncovered metabolic dysregulation underlying the radiomic signature (ATP metabolic process: NES = 1.84, p-adjust = 0.02; cholesterol biosynthesis: NES = 1.79, p-adjust = 0.01). Regarding the therapeutic implications, the radiomic signature exhibited value when combining clinical factors for predicting the pathological complete response to neoadjuvant chemotherapy (DUKE cohort, AUC = 0.72; I-SPY1 cohort, AUC = 0.73). In conclusion, our study identified a breast cancer outcome-predicting radiomic signature in a multicenter radio-multiomic study, along with its correlations with multiomic features in prognostic risk assessment, laying the groundwork for future prospective clinical trials in personalized risk stratification and precision therapy.

Salvia Miltiorrhiza, extensively distributed and commonly employed as a traditional Chinese medicinal herb, has garnered significant attention. In this study, the Salvia Miltiorrhiza extract (SME) was prepared by one-step water extraction method, and was firstly used as a novel corrosion inhibitor for Q235 steel in 1 mol/L HCl solution. As identified via liquid chromatography-mass spectrometry, the findings reveal that Salvianic acid A, tanshinone II A, danshenxinkun D, dihydrotanshinone, and methylene tanshinquinone are the primary constituents of SME. The optimum corrosion inhibition efficiency reached 92.8 % at 200 mg/L and maintained at 90.4 % after 72 h. Based on in-situ scanning vibration electrode technology (SVET) monitoring, the adsorption of inhibitor molecules on metal surface greatly retarded the propagation of localized corrosion. AFM examination of the corroded surface reveals that the samples supplemented with SME exhibit a smoother surface compared to the blank group. The force curve graph for the SME-added group demonstrates a more evenly distributed point array and an elevated average adhesion force, indicating that the addition of SME improves the corrosion resistance of the metal surface. XPS characterization illustrated that SME interacted with iron ions to form insoluble precipitate. This work investigated the application of SME as an eco-friendly corrosion inhibitor for carbon steel in acidic medium, providing a new approach for the high value-added utilization of Salvia Milliorrhiza.

Rare actinomycete genera are highly recognized as a promising source of structurally diverse and bioactive natural products. Among these genera, Allokutzneria and Kibdelosporangium are two phylogenetically closely related and have been reported to encode some valuable biosynthetic enzymes and secondary metabolites. However, there is currently no relevant systematic research available to outline the linkage of genomic and metabolomics for specific secondary metabolites in these two promising genera. In this study, we first investigated the genus-specific secondary metabolic potential in Allokutzneria and Kibdelosporangium by comparing the diversity and novelty of their secondary metabolite biosynthetic gene clusters (BGCs). The specific secondary metabolites produced by two representative strains of these genera were comprehensively investigated using untargeted metabolomics techniques. The findings unveiled that the majority (95.4%) of the gene cluster families (GCFs) encoded by Allokutzneria and Kibdelosporangium were genus-specific, including NRPS GCFs encoding siderophores. The untargeted metabolomics analysis revealed that the metabolic profiles of two representative strains exhibit extensive specificity, with the culture medium having a big impact on the metabolic profiles. Besides, an MS-cluster featuring a series of hydroxamate-type siderophores was identified from Allokutzneria albata JCM 9917, with two of them, including a novel one (N-deoxy arthrobactin A), being experimentally validated. The present study offers valuable insights for the targeted discovery of genus-specific natural products from microorganisms.

Our study examined young children's pre-academic and social skills in relation to parental locus of control and children's behaviours of ADHD. The participants were parents of 1,502 children from four Chinese kindergartens (M[subscript age] = 4.59, SD = 0.93; Girls: 51.40%). Data on six domains of children's pre-academic and social skills, parental external and internal locus of control, and children's inattention and hyperactivity/impulsivity were obtained with the Early Learning and Development for Children Aged 3 to 6 years, the Parental Locus of Control scale, and the ADHD Rating Scale-IV Preschool Home Version respectively. Hierarchical regression results showed that controlling for other variables, higher scores in parental external locus of control and child inattention behaviours significantly predicted lower scores in all six domains, while higher scores in internal locus of control and child hyperactivity/impulsivity behaviours predicted higher scores in all six domains (R[superscript 2] ranged from 18.0% to 47.0%). Noticeably, parental locus of control explained a smaller amount of the variance (1.0-5.0%) than behaviours of ADHD (5.0-11.0%) in the children's outcomes.

Abnormal hyperphosphorylation of tau protein is a principal pathological hallmark in the onset of neurodegenerative disorders, such as Alzheimer's disease (AD), which can be induced by an excess of reactive oxygen species (ROS). As an antioxidant, hydrogen gas (H2) has the potential to mitigate AD by scavenging highly harmful ROS such as •OH. However, conventional administration methods of H2 face significant challenges in controlling H2 release on demand and fail to achieve effective accumulation at lesion sites. Herein, we report artificial nanoreactors that mimic natural photosynthesis to realize near-infrared (NIR) light-driven photocatalytic H2 evolution in situ. The nanoreactors are constructed by biocompatible crosslinked vesicles (CVs) encapsulating ascorbic acid and two photosensitizers, chlorophyll a (Chla) and indoline dye (Ind). In addition, platinum nanoparticles (Pt NPs) serve as photocatalysts and upconversion nanoparticles (UCNP) act as light-harvesting antennas in the nanoreacting system, and both attach to the surface of CVs. Under NIR irradiation, the nanoreactors release H2 in situ to scavenge local excess ROS and attenuate tau hyperphosphorylation in the AD mice model. Such NIR-triggered nanoreactors provide a proof-of-concept design for the great potential of hydrogen therapy against AD.

Cryopreservation of sperm is an effective method for conserving germplasm resources in fish genetic breeding. The high-quality hybrid fish (WR) derived from white crucian carp (Carassius cuvieri, WCC, ♀) and red crucian carp (C. auratus red var., RCC, ♂), possesses valuable traits such as high survival rates, strong resistance, and rapid growth, representing an important germplasm resources of crucian carp. This study compared the effects of different antifreeze solutions on sperm viability among three varieties (WR, WCC, and RCC) and examined changes in enzyme activity, fertilization rates, and hatching rates after cryopreservation, aiming to enhance the cryogenic sperm cryopreservation technique in hybrid fish and investigate the mechanisms underlying spermatozoa damage caused by cryopreservation. The results showed that the antifreeze combination of D14 with 15 % dimethyl sulfoxide (DMSO) had the best effect in preserving the sperm of WR and WCC, while D20 with 10 % DMSO was the optimal combination for RCC sperm. After ultra-low temperature preservation, the longevity, fertilization, and hatching rates of frozen sperm were significantly lower (P