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Background: Recent research showed that cross-notation magnitude knowledge of fractions and decimals was related to better performance in fraction arithmetic, but it remains unclear whether it made an independent contribution to fraction arithmetic longitudinally when other cognitive variables are considered. Aims: To examine the extent to which children's earlier knowledge of cross-notation magnitude predicted subsequent performance in fraction addition and subtraction as well as fraction multiplication and division longitudinally. Sample: Three hundred and fifty-four Chinese children (Mage = 112.1 months). Methods: During the first wave of assessment, a range of cognitive abilities of children were measured, including within-notation fraction and decimal magnitude comparisons, whole-number arithmetic fluency, non-verbal intelligence, attentive behaviours, counting recall, word-level reading, and phonological awareness. Twelve months later, the same children were assessed again with two tasks of fraction arithmetic: fraction addition and subtraction as well as fraction multiplication and division. Results and Conclusions: Multiple linear regressions showed that within-notation fraction and decimal magnitude knowledge predicted fraction addition and subtraction longitudinally, after the effects of working memory, nonverbal intelligence, language skills, attentive behaviour, and whole-number arithmetic were controlled. Cross-notation magnitude knowledge made independent contributions to fraction addition and subtraction longitudinally beyond the influence of within-notation fraction and decimal magnitude knowledge and other covariates. However, within-notation fraction and decimal magnitude knowledge were not associated with fraction multiplication and division, whereas cross-notation magnitude knowledge remained a unique predictor. These findings suggest that it may be useful to incorporate cross-notation knowledge in the assessments of children's mathematics abilities and teaching.

The rapid evolution of AI technologies has reshaped our daily lives. As AI systems become increasingly prevalent, AI literacy, the ability to comprehend and engage with these technologies, becomes paramount in modern society. However, existing research has yet to establish a comprehensive framework for AI literacy. This study aims to fill this gap by developing a holistic AI literacy scale. Three levels of dimensions are considered: individual, interactive, and sociocultural. The scale includes cognitive, behavioral, and normative competencies. After rigorous reliability and validity assessments, the final AI literacy scale comprises six dimensions: AI features, AI processing, algorithm influences, user efficacy, ethical consideration, and threat appraisal. Detailed scale development, validation, and dimension-specific items are thoroughly explained. This comprehensive scale equips individuals with the competencies needed to navigate and critically engage with AI in today's multifaceted AI landscape.

With the growing popularity of Virtual Reality (VR), the integration of the Community of Inquiry (CoI) framework provides insights into its role in facilitating student learning in VR environments. VR offers immersive experiences and visualization of abstract concepts. However, the abundance of information in VR can be overwhelming without proper guidance, hindering students' knowledge acquisition and organization. To address this issue, a concept map-based community of inquiry (CM-CoI) framework VR system was developed for a ninth-grade Earth Science course. A quasi-experiment was conducted to investigate its impact on learning achievement, reflection tendencies, and perceptions. The experimental group used the CM-CoI-based VR system, while the control group used a conventional CoI-based VR system. The results showed that the experimental group outperformed the control group in learning achievement and reflection tendencies. Interviews revealed that students in the experimental group found the method helpful for clarifying confusing knowledge. This study demonstrates the potential of CM-CoI-based VR systems to enhance learning achievement and reflection tendencies. It informs educators on integrating VR technology and concept mapping into Earth Science education, and on enhancing students' learning experiences and outcomes.

Creative writing is a valuable skill that enables learners to become proficient writers. One reason students often struggle with creative writing is their lack of contextual experiences. Spherical video-based virtual reality (SVVR) has been argued to support students' writing through immersive virtual experiences. However, what specific pedagogical practices can be developed and integrated with emerging technologies like SVVR to improve their effectiveness to support elementary school students' creative writing needs further work. This study proposes an innovative approach that integrated the generative learning strategy (GLS) of imagining with SVVR to enhance elementary school students' creative writing performance. To test the effectiveness of the proposed approach, a quasi-experiment was conducted in an elementary school writing class. The experimental group (N = 56) used the generative learning-based SVVR approach (GSVVR), while the control group (N = 55) used the generative learning-based conventional approach (GC). The results showed that the GSVVR group outperformed the GC group in terms of creative writing (F = 10.953, p < 0.01) with a medium effect size. Furthermore, we found a significant impact on students' behavioural and emotional engagement as well as their learning persistence, particularly if they had engagement values below 4.3 before the intervention. These findings indicates that while the approach may have limited benefits for students who are already highly engaged (engagement values exceeding 4.3) with SVVR. It can also notably enhance the performance of relatively less engaged (engagement values below 4.3) students. There was a positive correlation between learning persistence and creative writing in the GSVVR group, with learning persistence being one of the significant predictors of student creative writing performance. The study is concluded with a discussion on the pedagogical and theoretical implications of the findings to support elementary school students' creative writing.

Abstract With the development of urbanization, the spatial and temporal distribution characteristics of the urban landscape pattern play a decisive role in the intensity of the urban heat island (UHI) effect. A panel data model was constructed to study the relationship between the UHI effect and landscape pattern in Kunming from 1995 to 2020 at four different scales. The results indicate: (1) The landscape pattern of Kunming changed obviously with time, the artificial patch increased, the natural patch decreased, and the UHI effect became more and more obvious; (2) With an increase in scale, the number of influencing variables continues to grow, and the impact of artificial patches gradually intensifies; (3) The normalized difference water index (NDWI) has the greatest influence on the UHI, and the cooling effect is more obvious with the increase in scale. Unlike previous studies, the spatial configuration of the landscape in Kunming City had a stronger effect on the UHI effect than the landscape grouping and vegetation index; (4) This paper introduces the panel data model into the discussion of the UHI for the first time, providing a new method for better understanding the changing patterns of the urban thermal environment.

Fluconazole-resistant clade 4 Candida tropicalis causing candidemia in humans has been detected in tropical/subtropical areas, including those in China, Singapore, and Australia. We analyzed 704 individual yeasts isolated from fruits, soil, water, and farmers at 80 orchards in Taiwan. The most common pathogenic yeast species among 251 isolates recovered from farmers were Candida albicans (14.7%) and C. parapsilosis (11.6%). In contrast, C. tropicalis (13.0%), C. palmioleophila (6.6%), and Pichia kudriavzevii (6.0%) were prevalent among 453 environmental isolates. Approximately 18.6% (11/59) of C. tropicalis from the environment were resistant to fluconazole, and 81.8% (9/11) of those belonged to the clade 4 genotype. C. tropicalis susceptibility to fluconazole correlated with susceptibilities to the agricultural azole fungicides, difenoconazole, tebuconazole, and triadimenol. Tandem gene duplications of mutated ERG11 contributed to azole resistance. Agriculture environments are a reservoir for azole-resistant C. tropicalis; discontinuing agricultural use of azoles might reduce emergence of azole-resistant Candida spp. strains in humans.

Abstracts The interactions between myogenic cells and adipocytes play an important role in improving carcass traits and the efficiency of energy utilization. However, there are few reports about the interaction between them mediated by small extracellular vesicles (sEV). In this study, sEV derived from porcine primary skeletal muscle stem cells (MuSCs) was found to be involved in the inhibition of porcine primary adipocyte viability, triglyceride content, Oil Red O enrichment and the expression of adipogenic genes. When the MuSCs were treated with insulin (INS) and oleic acid (OA), the effects of their secreted sEVs on adipose precursor cells were reversed, suggesting that the signaling effects of sEV are related to their own heterogeneity. Further by component heterogeneity analysis, miR-146a-5p was found to be enriched in sEVs of MuSCs and to regulate and suppress adipogenesis through its heterogeneity. This study provides an important mechanism and molecular target for small extracellular vesicles to regulate the interaction between muscle and adipose tissue and improve carcass traits at the intercellular level.

Abstract Hydrogel-based tissue expansion combined with mass spectrometry (MS) offers an emerging spatial proteomics approach. Here, we present a filter-aided expansion proteomics (FAXP) strategy for spatial proteomics analysis of archived formalin-fixed paraffin-embedded (FFPE) specimens. Compared to our previous ProteomEx method, FAXP employed a customized tip device to enhance both the stability and throughput of sample preparation, thus guaranteeing the reproducibility and robustness of the workflow. FAXP achieved a 14.5-fold increase in volumetric resolution. It generated over 8 times higher peptide yield and a 255% rise in protein identifications while reducing sample preparation time by 50%. We also demonstrated the applicability of FAXP using human colorectal FFPE tissue samples. Furthermore, for the first time, we achieved bona fide single-subcellular proteomics under image guidance by integrating FAXP with laser capture microdissection.

Abstract Small extracellular vesicles (sEV) have emerged as a novel mode of intercellular material transport and information transmission. It has been suggested hormones may regulate the production and function of sEV. However, the specific impact of growth hormone-releasing hormone (GHRH) on pituitary sEV production and the role of sEV in the regulation of the GHRH-GH-IGF axis has not been previously reported. The results of the present study demonstrated that GHRH increased the production of pituitary sEV by promoting the expression of Rab27a. More importantly, GHRH induced alterations in protein and miRNA levels within GH3-sEV components. Notably, GH3-sEV with GHRH treatment exhibited the enhanced ability to impede BRL 3A cell proliferation and the expression of IGF-1. Conclusively, for the first time, we corroborate the influence of GHRH on pituitary sEV, thereby presenting novel evidence for how sEV participates in the balance of the GHRH-GH-IGF axis. Importantly, this study provides new insight into a novel balance mechanism mediated by sEV within the endocrine system. Graphical Abstract

Abstract Background The direct anterior approach (DAA) for total hip arthroplasty (THA) has gained popularity due to perceived advantages in achieving better early outcomes. However, the theoretical benefits such as precise implant positioning and accurate leg length restoration are still inconsistent. In this study, we compared implant position and leg length discrepancy (LLD) of the DAA and posterolateral approach (PLA) conducted by a single surgeon who had mastered both approaches. Methods This study retrospectively reviewed the medical records and radiographic images of 244 patients who underwent THA between 2012 and 2021 by a single experienced surgeon using either the DAA (n = 120) or PLA (n = 124). Postoperative pelvic anteroposterior radiographs at 6 months follow-up were used to assess acetabular component inclination and anteversion, as well as LLD. Mann-Whitney U tests and Chi-squared test were performed to compare outcomes between the two approaches. Results No significant differences were observed in patient demographics between the two groups. The DAA group demonstrated significantly lower postoperative LLD (0.00 mm) compared to the PLA group (5.00 mm, p

Abstract Background The aim of this study is to assess the feasibility and safety of monitored anesthesia care (MAC) versus intubated general anesthesia (IGA) for patients undergoing elective cardiac surgery with cardiopulmonary bypass (CPB). Methods This prospective observational study included patients scheduled for cardiac surgery involving CPB at our institution between April 2012 and February 2017. The enrolled patients were categorized into MAC and IGA groups. MAC involved local anesthesia at the sternotomy site, sedation with dexmedetomidine, analgesia with remifentanil/sufentanil, and electroacupuncture (EA). Eleven patients underwent MAC, and 13 patients received IGA. There were no instances of conversion from MAC to IGA, and both groups exhibited no major complications. The demographic characteristics, baseline parameters, and operative variables were comparable between the two groups. Results Intraoperative opioid consumption was significantly lower in the MAC group compared to the IGA group (P

Abstract Sea cucumbers are predominant deposit feeders in benthic ecosystems, providing protective benefits to coral reefs by reducing disease prevalence. However, how they receive sufficient nutrition from seabed sediments remains poorly understood. Here, we investigate Holothuria leucospilota, an ecologically significant tropical sea cucumber, to elucidate digestive mechanisms underlying marine deposit-feeding. Genomic analysis reveals intriguing evolutionary adaptation characterized by an expansion of digestive carbohydrase genes and a contraction of digestive protease genes, suggesting specialization in digesting microalgae. Developmentally, two pivotal dietary shifts, namely, from endogenous nutrition to planktonic feeding, and from planktonic feeding to deposit feeding, induce changes in digestive tract enzyme profiles, with adults mainly expressing carbohydrases and lipases. A nuanced symbiotic relationship exists between gut microbiota and the host, namely, specific resident bacteria supply crucial enzymes for food digestion, while other bacteria are digested and provide assimilable nutrients. Our study further identifies Holothuroidea lineage-specific lysozymes that are restrictedly expressed in the intestines to support bacterial digestion. Overall, this work advances our knowledge of the evolutionary innovations in the sea cucumber digestive system which enable them to efficiently utilize nutrients from seabed sediments and promote food recycling within marine ecosystems.

Abstract Background Pre-cluster symptoms (PCSs) are symptoms preceding cluster bouts and might have implications for the treatment of cluster headache (CH). This study investigated the prevalence of PCSs, and their utility in predicting upcoming bouts as well as the associations with therapeutic efficacy. Methods We prospectively collected data from patients with CH. Each patient received a structured interview and completed questionnaire surveys during CH bouts. In sub-study 1, we cross-sectionally analyzed the prevalence, symptomatology, and predictability of upcoming bouts. Overall, 34 PCSs, divided into seven categories, were queried, including head and neck pain, cranial autonomic symptoms, restlessness, fatigue or mood changes, sleep alterations, constitutional symptoms, and generalized pain. In sub-study 2, we recorded the weekly frequency of CH attacks after the initiation of verapamil concurrently with a 14-day transitional therapy based on the patients’ headache diary. A responder to verapamil was defined as a patient who have a reduction from baseline of at least 50% in the weekly frequency of CH attacks 4 weeks after the initiation of verapamil. Results A total of 168 CH patients (women/men: 39/129) completed the study. In sub-study 1, we found 149 (88.7%) experienced PCSs, with a median of 24 (IQR 18 to 72) hours before the bouts. Up to 57.7% of patients with PCS reported that they could predict upcoming bouts. Among the seven categories of PCSs, head and neck pain was the most common (81.0%) and was associated with a higher predictability of upcoming bouts (odds ratio [OR] = 4.0; 95% confidence interval [CI] 1.7–9.6). In sub-study 2, we found two categories of PCSs were associated with the response to verapamil: sleep alteration (OR = 2.5 [95% CI = 1.3–4.8], p = 0.004) and ≥ 1 cranial autonomic symptoms (OR = 2.7 [95% CI = 1.4–5.1], p = 0.003). Conclusion PCSs were very common in CH and could be used to predict upcoming bouts. Different symptom categories of PCSs may have different clinical implications.

Abstract The electroreduction of nitrate offers a promising, sustainable, and decentralized route to generate valuable ammonia. However, a key challenge in the nitrate reduction reaction is the energy efficiency of the reaction, which requires both a high ammonia yield rate and a high Faradaic efficiency of ammonia at a low working potential (≥−0.2 V versus reversible hydrogen electrode). We propose a bimetallic Co–B/Ru12 electrocatalyst which utilizes complementary effects of Co–B and Ru to modulate the quantity of adsorbed hydrogen and to favor the specific hydrogenation for initiating nitrate reduction reaction at a low overpotential. This effect enables the catalyst to achieve a Faradaic efficiency for ammonia of 90.4 ± 9.2% and a remarkable half-cell energy efficiency of 40.9 ± 4% at 0 V versus reversible hydrogen electrode. The in-situ electrochemical reconstruction of the catalyst contributes to boosting the ammonia yield rate to a high level of 15.0 ± 0.7 mg h−1 cm−2 at −0.2 V versus reversible hydrogen electrode. More importantly, by employing single-entity electrochemistry coupled with identical location transmission electron microscopy, we gain systematic insights into the correlation between the increase in the catalyst’s active sites and its structural transformations during the nitrate reduction reaction.

Abstract Background Migraine-related perfusion changes are documented but inconsistent across studies due to limited sample size and insufficient phenotyping. The phasic and spatial dynamics across migraine subtypes remains poorly characterized. This study aimed to determine spatiotemporal dynamics of gray matter (GM) perfusion in migraine. Methods We prospectively recruited episodic (EM) and chronic migraine (CM) patients, diagnosed with the International Headache Society criteria and healthy controls (HCs) between 2021 and 2023 from the headache center in a tertiary medical center, and adjacent communities. Magnetic resonance (3-tesla) arterial spin labeling (ASL) was conducted for whole brain cerebral blood flow (CBF) in all participants. The voxel-wise and whole brain gray matter (GM) CBF were compared between subgroups. Spatial pattern analysis of CBF and its correlations with headache frequency were investigated regarding different migraine phases and subtypes. Sex- and age-adjusted voxel-wise and whole brain GM comparisons were performed between HCs and different EM and CM phases. Spatial pattern analysis was conducted by CBF clusters with phasic differences and spin permutation test. Correlations between headache frequency and CBF were investigated regarding different EM and CM phases. Results Totally 344 subjects (172 EM, 120 CM, and 52 HCs) were enrolled. Higher CBF in different anatomical locations was identified in ictal EM and CM. The combined panels of the specific locations with altered CBF in ictal EM on receiver operating characteristic curve analysis demonstrated areas under curve of 0.780 (vs. HCs) and 0.811 (vs. preictal EM). The spatial distribution of ictal-interictal CBF alteration of EM and CM were not correlated with each other (p = 0.665; r = − 0.018). Positive correlations between headache frequency and CBF were noted in ictal EM and CM regarding whole GM and specific anatomical locations. Conclusions Patients with migraine exhibited unique spatiotemporal CBF dynamics across different phases and distinct between subtypes. The findings provide neurobiological insights into how selected anatomical structures engage in a migraine attack and adapt to plastic change of repeated attacks along with chronicity.

Abstract Ovarian cancer (OC) is one of the most prevalent and lethal gynecological malignancies, with high mortality primarily due to its aggressive nature, frequent metastasis, and resistance to standard therapies. Recent research has highlighted the critical role of extracellular vesicles (EVs) in these processes. EVs, secreted by living organisms and carrying versatile and bioactive cargoes, play a vital role in intercellular communication. Functionally, the transfer of cargoes orchestrates multiple processes that actively affect not only the primary tumor but also local and distant pre-metastatic niche. Furthermore, their unique biological properties position EVs as novel therapeutic targets and promising drug delivery systems, with potential profound implications for cancer patients. This review summarizes recent progress in EV biology, delving into the intricate mechanisms by which EVs contribute to OC metastasis and drug resistance. It also explores the latest advances and therapeutic potential of EVs in the clinical context of OC. Despite the progress made, EV research in OC remains in its nascent stages. Consequently, this review presents existing research limitations and suggests avenues for future investigation. Altogether, the review aims to elucidate the critical roles of EVs in OC and spotlight their promising potential in this field.

Abstract Background Ailanthone (Ail) extracted from medicinal plants has played an anticancer role in multiple cancers, while there is no research about Ail in renal cell carcinoma (RCC). Methods In the present study, we performed CCK-8 and flow cytometry to assess the effect of Ail on cell viability, apoptosis and cycle. We also performed tandem mass tags (TMT)-labeled quantitative proteomic technology and bioinformatic analysis to identify the functional pathway and proteins of Ail in RCC. Results The results showed Ail could inhibit cell viability and induce cell apoptosis. Proteomic profiling identified 1732 differentially expressed proteins in cells treated with Ail, compared to the negative control group. Gene ontology function annotation and Gene Set Enrichment Analysis (GSEA) were performed to identified the involved biological processes, molecular function and pathway. Results of GSEA proved the enrichment of Deps in EZH2 targets. The comparison between Deps and EZH2 co-expressed genes revealed 44 overlapped genes and we identified 4 hub genes (CDC20, CEP55, TOP2A, and UBE2C) associated with RCC progression. The molecular docking study revealed a moderate to tight binding potential of Ail and EZH2, and western blotting showed EZH2 was suppressed after cells treated with Ail. Conclusion Altogether, we identified the anticancer role of Ail in RCC, including inhibition of cell proliferation and induction of apoptosis. The results also screened the key proteins mediate the function of Ail, which have laid a theoretical foundation for elucidating the applications of Ail in clinical research.

Abstract Anaerobic digestion (AD) is an efficient technology for treating organic solid wastes, and the volatile fatty acids (VFAs) produced during AD have significant value due to their wide range of applications and higher added value compared to methane. This study investigated the long-term effects of high solid content and straw proportion in mixed substrates (straw, sludge, and food wastes) on VFAs production through semi-continuous reactors under thermophilic and mesophilic conditions. Results showed that both reactors achieved a maximum VFAs concentration of ~ 22 g/L as the straw proportion increased to 50%. Acetate (48.3 – 64.5%) was the main component of produced VFAs in both reactors, while butyrate and propionate production in thermophilic temperature were superior compared to mesophilic conditions. Microbial community analysis revealed that Defluviitoga plays a pivotal role in acidogenesis within both reactors; besides, unclassified Hungateiclostridiaceae and Caproiciproducen were found to be dominant in thermophilic reactor, while Lachnospiraceae_NK3A20_group and Rikenellaceae_RC9_gut_group were essential for VFAs production under mesophilic conditions. These findings provide valuable insights for the biotechnological exploration of acidogenic fermentation for large-scale mechanized production of VFAs from agricultural wastes.

Abstract Knee osteoarthritis (KOA) is a common chronic joint disease globally. Synovial inflammation plays a pivotal role in its pathogenesis, preceding cartilage damage. Identifying biomarkers in osteoarthritic synovial tissues holds promise for early diagnosis and targeted interventions. Gene expression profiles were obtained from the Gene Expression Omnibus database. Subsequent analyses included differential expression gene (DEG) analysis and weighted gene co-expression network analysis (WGCNA) on the combined datasets. We performed functional enrichment analysis on the overlapping genes between DEGs and module genes and constructed a protein–protein interaction network. Using Cytoscape software, we identified hub genes related to the disease and conducted gene set enrichment analysis on these hub genes. The CIBERSORT algorithm was employed to evaluate the correlation between hub genes and the abundance of immune cells within tissues. Finally, Mendelian randomization analysis was utilized to assess the potential of these hub genes as biomarkers. We identified 46 differentially expressed genes (DEGs), comprising 20 upregulated and 26 downregulated genes. Using WGCNA, we constructed a gene co-expression network and selected the most relevant modules, resulting in 24 intersecting genes with the DEGs. KEGG enrichment analysis of the intersecting genes identified the IL-17 signaling pathway, associated with inflammation, as the most significant pathway. Cytoscape software was utilized to rank the candidate genes, with JUN, ATF3, FOSB, NR4A2, and IL6 emerging as the top five based on the Degree algorithm. A nomogram model incorporating these five genes, supported by ROC curve analysis, validated their diagnostic efficacy. Immune infiltration and correlation analysis revealed that macrophages were significantly associated with JUN (p

Abstract Zingiber striolatum Diels is a unique medicine food homology plant native to China. In recent years, due to severe habitat destruction, studying the impact of climate change on the distribution of wild resources is of great significance for the ecological conservation and artificial cultivation of Z. striolatum. This study collected 141 valid species distribution records, and 37 environmental variables, and projected two future climate scenarios (SSP126 and SSP585) for two periods (2050s and 2090s). By employing Pearson analysis, Maximum Entropy Model (MaxEnt), and Geographic Information System (ArcGIS), we predicted the potential suitable habitats for Z. striolatum under present and future climates, as well as identified the dominant environmental variables influencing its distribution. The results indicated that the MaxEnt model performed well (AUC > 0.9) with high accuracy and reliability. The dominant environmental factors included Precipitation of driest quarter (39.0 ~ 473.8 mm), Precipitation of wettest quarter (593.2 ~ 1269.4 mm), Temperature annual range (9.8 ~ 28.6℃), and Mean diurnal range (6.5 ~ 9.6℃). The highly suitable areas for Z. striolatum were mainly distributed in western and southern Yunnan, northern and western Guangxi, Guangdong, Fujian, and central Hainan. Under future climate change, the centroid of the total suitable area for Z. striolatum is projected to shift towards the southwest (Yungui Plateau) at higher elevations.

Abstract With the emergence of new variant strains resulting from high mutation rates and genome recombination, avian infectious bronchitis virus (IBV) has caused significant economic losses to the poultry industry worldwide. Little is known about the underlying mechanisms of IBV-host interactions, particularly how IBV utilizes host metabolic pathways for efficient viral replication and transmission. In the present study, the effects of the cell membrane, viral envelope membrane, and viperin-mediated cholesterol synthesis on IBV replication were explored. Our results revealed significant increase in cholesterol levels and the expression of viperin after IBV infection. Acute cholesterol depletion in the cell membrane and viral envelope membrane by treating cells with methyl-β-cyclodextrin (MβCD) obviously inhibited IBV replication; thereafter, replenishment of the cell membrane with cholesterol successfully restored viral replication, and direct addition of exogenous cholesterol to the cell membrane significantly promoted IBV infection during the early stages of infection. In addition, overexpression of viperin effectively suppressed cholesterol synthesis, as well as IBV replication, whereas knockdown of viperin (gene silencing with siRNA targeting viperin, siViperin) significantly increased IBV replication and cholesterol levels, whereas supplementation with exogenous cholesterol to viperin-transfected cells markedly restored viral replication. In conclusion, the increase in viperin induced by IBV infection plays an important role in IBV replication by affecting cholesterol production, providing a theoretical basis for understanding the pathogenesis of IBV and discovering new potential antiviral targets.

The success of messenger RNA (mRNA) vaccines in controlling COVID-19 has warranted further developments in new technology. Currently, their quality control process largely relies on low-resolution electrophoresis for detecting chain breaks. Here, we present an approach using multi-primer reverse transcription sequencing (MPRT-seq) to identify degradation fragments in mRNA products. Using this in-house-made mRNA containing two antigens and untranslated regions (UTRs), we analyzed the mRNA completeness and degradation pattern at a nucleotide resolution. We then analyzed the sensitive base sequence and its correlation with the secondary structure. Our MPRT-seq mapping shows that certain sequences on the 5′ of bulge–stem–loop structures can result in preferential chain breaks. Our results agree with commonly used capillary electrophoresis (CE) integrity analysis but at a much higher resolution, and can improve mRNA stability by providing information to remove sensitive structures or sequences in the mRNA sequence design.

Abstract Globally, poverty and illness are linked, attracting widespread attention. In China, illness contributes to about 40% of rural poverty. This study sought to investigate how healthcare-seeking behavior differs between impoverished and non-impoverished populations within the same Chinese healthcare delivery system. It also sought to understand how differences should be considered when assessing spatial accessibility to provide more accurate recommendations for healthcare resource optimization and promote village revitalization and health equity in China. Methodologically, a survey conducted in May 2019 in Enshi Prefecture (a national impoverished region in Hubei Province, China) collected data on healthcare resource utilization regarding the inpatient and outpatient needs of both impoverished and non-impoverished populations. A Chi-square test compared their respective healthcare-seeking behaviors in three respects (e.g., preference for healthcare institution type, transportation mode, and travel time). Baidu Map data with healthcare institution locations and real-life travel times were then incorporated to assess spatial access to different types of healthcare institutions. Results showed that in Enshi, the most widespread village clinics (low-level) were generally the most utilized healthcare institutions for outpatient visits, with patients usually walking for about 30 min. The middle-level Township Health Centers (THCs) and high-level public hospitals were the most used for inpatient visits, with patients willing to drive up to 30 min to THCs and 60 min to hospitals. Comparatively, the impoverished have more frequent service demands but tend to choose lower-level healthcare institutions, with longer travel times and limited transportation modes. Although 75% of Enshi’s area was covered within 30 min by village clinics and 51% of the villages were within 60 min’ drive to hospitals, considerable areas remain under-served compared with the shortest travel time targets in China. In conclusion, spatial access to healthcare resources in Enshi must be further improved, especially by strengthening the service capacity of primary healthcare institutions to address the healthcare needs of Enshi’s impoverished population. The disparity in healthcare-seeking behavior between different population groups should be fully considered to effectively allocate limited healthcare resources to promote health equity for vulnerable populations as proposed in international and domestic policies.

Purpose: To investigate the relationship between prostatic urethral angle (PUA) and the development of surgical capsule calculi (SCC) within the prostate, and to examine the presence and impact of intravesical prostatic protrusion (IPP). Materials and Methods: A retrospective analysis was conducted on 90 patients who underwent radical prostatectomy, with preoperative assessments using both transrectal ultrasound of the prostate (TRUS) and magnetic resonance imaging. Patients were divided into groups with and without SCC and further categorized into type 1 and type 2 stones based on the location and severity of the calculi. Statistical analysis included chi-square and independent sample t-tests, with p

Writing is a fundamental skill linked closely with academic achievement, day-to-day communication, formal negotiations, and more. However, due to their lack of contextual experience, learning to write has been a demanding and complex cognitive process for most learners. As a result, learners struggle to exhibit positive learning behaviours and cognitive engagement in writing, let alone embrace deep and autonomous learning. To solve these problems, in the present study, a spherical video-based virtual reality (SVVR) learning environment is developed to provide students with a contextual learning experience. Moreover, a peer feedback strategy is used to guide students in deep learning in writing. A quasi-experimental study was conducted to verify the effectiveness of the proposed approach. A total of 79 students from one primary school in southeast China were recruited. The students were assigned to either the experimental group (EG) exposed to the peer-feedback-based SVVR (PF-SVVR) approach or the control group (CG) exposed to the conventional SVVR (C-SVVR) approach. The results show that PF-SVVR had more positive effects than C-SVVR in terms of students' writing performance, cognitive engagement and autonomous learning tendency. In addition, the PF-SVVR approach was found to be more beneficial for triggering deep learning in writing than the C-SVVR approach. This study further found that students in the PF-SVVR group tended to exhibit less disorderly behaviours than those in the C-SVVR group. Our study contributes to the prior literature by exploring the educational potential of the PF approach in the context of SVVR-enabled writing learning.

This research followed a qualitative design to identify preschool teachers' mindsets about workload-related stress. Twenty in-service Chinese preschool teachers were invited to delineate their perceived workload-related stress consequences. Directed by a hybrid of inductive and conductive approaches, we conducted thematic content analyses on two rounds of in-depth teacher interviews. Findings suggested that workload-related stress was like a two-edged sword for preschool teachers. On the one hand, teachers regard workload-related stress as enhancing in the aspects of motivating them to shift working strategies, to refine professional learning, to issue teacher leadership, and to mobilize colleague teachers' teamwork. On the other hand, some teachers' mindsets focus on the downsides of their workload-related stress, emphasizing its deleterious influences on working efficiencies, emotional wellbeing, as well as its spillover effects on family life. Teachers' individual-, preschool- and sociocultural-level elements were discussed to explain the patterns of Chinese preschool teachers' workload-related stress mindset.

本研究採協同行動研究法，探討卡那卡那富族藝術文化融入幼兒園美感課程之教學實踐與成效。研究者帶領教保員規劃文化本位的原住民族美感課程、實施教學、進行觀察與省思、評估課程成效。研究參與者主要為 12 位三至五歲混齡班原住民族幼兒。資料蒐集包括：課程週誌、課程討論記錄、訪談、美感能力評量前後測、族群認同訪談前後測、教學省思札記等。質性資料以編碼與範疇分析，量化資料以描述性統計、無母數檢定進行分析。研究發現：一、教保員將卡那卡那富族藝術文化融入學習區及老幼共學活動，引導幼兒探索部落自然環境，創作相關藝術作品，並欣賞幼兒自己的作品。二、本課程有助於幼兒提升美感能力以及族群認同。三、透過協同行動研究，教保員在美感教學專業有所成長。 This study used collaborative action research to investigate the pedagogical practices and effects of incorporating Kanakanavu arts and culture into a preschool aesthetic curriculum. The researcher guided the educare giver in implementing a cultural-based indigenous aesthetic curriculum within a Kanakanavu language immersion class. This process involved designing, teaching, observing, and reflecting on the new curriculum. The main participants were 12 indigenous children aged 3-5 in a mixed-age class. Data were collected through weekly curriculum journals, curriculum discussion notes, interviews, pre- and post-tests of aesthetic ability, pre- and post-interviews on ethnic identity, and teaching reflection notes. Qualitative data were analyzed through coding and categorizing, while quantitative data were examined using descriptive statistics and non-parametric tests. The findings are as follows. First, the educare giver integrated Kanakanavu arts and culture into learning areas and intergenerational learning activities. She guided the children to explore the natural environment in the tribe, create related artworks, and appreciate their own artworks. Secondly, the curriculum positively impacted the children, enhancing both their aesthetic abilities and ethnic identity. Thirdly, through collaborative action research, the educare giver advanced her professional skills in aesthetic teaching.

Abstract Hyperlipidemia and hypertension might play a role in cardiac fibrosis, in which a heterogeneous population of fibroblasts seems important. However, it is unknown whether CD34+ progenitor cells are involved in the pathogenesis of heart fibrosis. This study aimed to explore the mechanism of CD34+ cell differentiation in cardiac fibrosis during hyperlipidemia. Through the analysis of transcriptomes from 50,870 single cells extracted from mouse hearts and 76,851 single cells from human hearts, we have effectively demonstrated the evolving cellular landscape throughout cardiac fibrosis. Disturbances in lipid metabolism can accelerate the development of fibrosis. Through the integration of bone marrow transplantation models and lineage tracing, our study showed that hyperlipidemia can expedite the differentiation of non-bone marrow-derived CD34+ cells into fibroblasts, particularly FABP4+ fibroblasts, in response to angiotensin II. Interestingly, the partial depletion of CD34+ cells led to a notable reduction in triglycerides in the heart, mitigated fibrosis, and improved cardiac function. Furthermore, immunostaining of human heart tissue revealed colocalization of CD34+ cells and fibroblasts. Mechanistically, our investigation of single-cell RNA sequencing data through pseudotime analysis combined with in vitro cellular studies revealed the crucial role of the PPARγ/Akt/Gsk3β pathway in orchestrating the differentiation of CD34+ cells into FABP4+ fibroblasts. Through our study, we generated valuable insights into the cellular landscape of CD34+ cell-derived cells in the hypertrophic heart with hyperlipidemia, indicating that the differentiation of non-bone marrow-derived CD34+ cells into FABP4+ fibroblasts during this process accelerates lipid accumulation and promotes heart failure via the PPARγ/Akt/Gsk3β pathway.

Abstract Most cancer cells reprogram their glucose metabolic pathway from oxidative phosphorylation to aerobic glycolysis for energy production. By reducing enzyme activity of pyruvate kinase M2 (PKM2), cancer cells attain a greater fraction of glycolytic metabolites for macromolecule synthesis needed for rapid proliferation. Here we demonstrate that hydrogen sulfide (H2S) destabilizes the PKM2 tetramer into monomer/dimer through sulfhydration at cysteines, notably at C326, leading to reduced PKM2 enzyme activity and increased PKM2-mediated transcriptional activation. Blocking PKM2 sulfhydration at C326 through amino acid mutation stabilizes the PKM2 tetramer and crystal structure further revealing the tetramer organization of PKM2-C326S. The PKM2-C326S mutant in cancer cells rewires glucose metabolism to mitochondrial respiration, significantly inhibiting tumor growth. In this work, we demonstrate that PKM2 sulfhydration by H2S inactivates PKM2 activity to promote tumorigenesis and inhibiting this process could be a potential therapeutic approach for targeting cancer metabolism.

Adipose-derived stem cells (ADSCs) comprise a promising therapy for osteoarthritis (OA). The therapeutic potential of ELIXCYTE®, an allogeneic human ADSC (hADSC) product, was demonstrated in a phase I/II OA clinical trial. However, the exact mechanism underlying such effects is not clear. Moreover, studies suggest that interleukin-11 (IL-11) has anti-inflammatory, tissue-regenerative, and immune-regulatory functions. Our aim was to unravel the mechanism associated with the therapeutic effects of ELIXCYTE® on OA and its relationship with IL-11. We cocultured ELIXCYTE® with normal human articular chondrocytes (NHACs) in synovial fluid obtained from individuals with OA (OA-SF) to investigate its effect on chondrocyte matrix synthesis and degradation and inflammation by assessing gene expression and cytokine levels. NHACs exposed to OA-SF exhibited increased MMP13 expression. However, coculturing ELIXCYTE® with chondrocytes in OA-SF reduced MMP13 expression in chondrocytes and downregulated PTGS2 and FGF2 expression in ELIXCYTE®. ELIXCYTE® treatment elevated anti-inflammatory cytokine (IL-1RA, IL-10, and IL-13) levels, and the reduction in MMP13 was positively correlated with IL-11 concentrations in OA-SF. These findings indicate that IL-11 in OA-SF might serve as a predictive biomarker for the ELIXCYTE® treatment response in OA, emphasizing the therapeutic potential of ELIXCYTE® to mitigate OA progression and provide insights into its immunomodulatory effects.

Abstract Background Ensuring that the scale and hierarchical structure of health human resources are rational, and that medical services are efficient and fair, is an important task of practical significance. On this basis, examining the impact of health human resources on the level of medical services presents a new and formidable challenge. This study aims to delve into how the scale and hierarchical structure of health human resources in China’s four major economic regions affect the fairness and efficiency of medical services, and to identify optimization strategies. Methods This study utilizes provincial panel data from China’s four major economic regions spanning the years 2009 to 2021. Initially, it provides a statistical description of the current state of health human resources and the level of medical services. Subsequently, it employs a fixed-effects model to analyze the impact of the scale and hierarchical structure of health human resources, as well as their interactive effects, on the fairness and efficiency of medical services, and discusses the interactive mechanisms between medical service fairness and medical service efficiency. Furthermore, after conducting a comprehensive evaluation of the level of medical services using the entropy weight method, it explores the regional heterogeneity and temporal dynamics in the influence of the scale and hierarchical structure of health human resources on the level of medical services. Finally, the study examines the scientific validity and rationality of the research findings through various robustness checks, including the substitution of research variables and models. Results The study found that the scale of health human resources has a promoting effect on the equity of medical services (β ≤ 0.643, p ≤ 0.01), but exhibits an inhibitory effect on the efficiency of medical services (β ≥ -0.079, p ≤ 0.1); the hierarchical structure of health human resources shows a positive impact on both the equity and efficiency of medical services (βequity ≤ 0.160, p ≤ 0.01; βefficiency ≤ 0.341, p ≤ 0.05); at the same time, the results indicate that the interactive effect of the scale and hierarchical structure of health human resources promotes equity in medical services (β = 0.067, p ≤ 0.01), but restricts the efficiency of medical services (β ≥ -0.039, p ≤ 0.01); the mechanism by which health human resources affect the level of medical services in China’s western and northeastern regions is more pronounced than in the central and eastern regions; after the implementation of the “Healthy China 2030” Planning Outline, the role of health human resources in the level of medical services has been strengthened; in the robustness tests, the model remains robust after replacing the core explanatory variables, with R2 maintained between 0.869 and 0.972, and the dynamic GMM model test shows a significant second-order lag in the level of medical services (βequity ≤ 0.149, p ≤ 0.01; βefficiency ≤ 0.461, p ≤ 0.01); the channel test results prove that managerial personnel and other technical personnel are key pathways in regulating the impact of medical staff on the level of medical services. Conclusion This study provides an in-depth analysis of the impact of health human resources on the level of medical services, revealing that both the scale and hierarchical structure of health human resources significantly affect the equity and efficiency of medical services. Furthermore, the influence of health human resources on the level of medical services exhibits regional heterogeneity and temporal characteristics. Robustness tests ensure the scientific validity and robustness of the research conclusions. This provides effective references for optimizing the allocation of health human resources and improving the level of medical services.

Abstract Background This study conducted in-depth interviews to explore the factors that influence the adoption of fall detection technology among older adults and their families, providing a valuable evaluation framework for healthcare providers in the field of fall detection, with the ultimate goal of assisting older adults immediately and effectively when falls occur. Methods The method employed a qualitative approach, utilizing semi-structured interviews with 30 older adults and 29 families, focusing on their perspectives and expectations of fall detection technology. Purposive sampling ensured representation from older adults with conditions such as Parkinson's, dementia, and stroke. Results The results reveal key considerations influencing the adoption of fall-detection devices, including health factors, reliance on human care, personal comfort, awareness of market alternatives, attitude towards technology, financial concerns, and expectations for fall detection technology. Conclusions This study identifies seven key factors influencing the adoption of fall detection technology among older adults and their families. The conclusion highlights the need to address these factors to encourage adoption, advocating for user-centered, safe, and affordable technology. This research provides valuable insights for the development of fall detection technology, aiming to enhance the safety of older adults and reduce the caregiving burden.

Abstract Background Dietary diversity has been suggested as a potential preventive measure against frailty in older adults, but the effect of changes in dietary diversity on frailty is unclear. This study was conducted to examine the association between the dietary diversity score (DDS) and frailty among older Chinese adults. Methods A total of 12,457 adults aged 65 years or older were enrolled from three consecutive and nonoverlapping cohorts from the Chinese Longitudinal Healthy Longevity Survey (the 2002 cohort, the 2005 cohort, and the 2008 cohort). DDS was calculated based on nine predefined food groups, and DDS changes were assessed by comparing scores at baseline and the first follow-up survey. We used 39 self-reported health items to assess frailty. Cox proportional hazard models were performed to examine the association between DDS change patterns and frailty. Results Participants with low-to-low DDS had the highest frailty incidence (111.1/1000 person-years), while high-to-high DDS had the lowest (41.1/1000 person-years). Compared to the high-to-high group of overall DDS pattern, participants in other DDS change patterns had a higher risk of frailty (HRs ranged from 1.25 to 2.15). Similar associations were observed for plant-based and animal-based DDS. Compared to stable DDS changes, participants with an extreme decline in DDS had an increased risk of frailty, with HRs of 1.38 (1.24, 1.53), 1.31 (1.19, 1.44), and 1.29 (1.16, 1.43) for overall, plant-based, and animal-based DDS, respectively. Conclusions Maintaining a lower DDS or having a large reduction in DDS was associated with a higher risk of frailty among Chinese older adults. These findings highlight the importance of improving a diverse diet across old age for preventing frailty in later life.

Abstract Background There has long been clinical disagreement over the resumption of antiplatelet therapy in patients with primary intracranial hemorrhage (ICH). This meta-analysis aimed to systematically evaluate the efficacy and safety of restarting antiplatelet therapy after ICH among different races and ethnicities. Methods All relevant medical studies involving adults with antiplatelet-associated ICH published in PubMed, The Cochrane Library and Chinese National Knowledge Infrastructure from inception to March 2024 were sourced. Outcome measures were thromboembolic events (stroke and myocardial infarction) and recurrence of ICH. After assessing study heterogeneity and publication bias, we performed a meta-analysis using random-effects model to assess the strength of association between resumption of antiplatelet therapy and our outcomes.The review was not registered and the review protocol was not prepared. Results Thirty-five studies were included, with 9758 ICH patients. Subgroup analysis revealed that restarting antiplatelet therapy was associated with a significantly higher risk of recurrence or aggravation of cerebral hemorrhage in Asians[OR = 1.48, 95% CI (1.13–1.94), P = 0.004]; in Caucasians, on the contrary, reinitiation of antiplatelet therapy was not associated with a significantly higher risk of recurrence or aggravation of cerebral hemorrhage [OR = 0.85, 95% CI (0.67–1.06), P = 0.149]. Reinitiation of antiplatelet therapy was associated with a significantly lower risk of cerebral infarction [OR = 0.61, 95% CI (0.39–0.96), P = 0.033]. Restarting antiplatelet therapy after cerebral hemorrhage was not associated with a higher incidence rate of mortality [OR = 0.79, 95% CI (0.57, 1.08), P = 0.138], myocardial infarction [OR = 2.40, 95%CI (0.53,10.79), P = 0.253], hemiparesis [OR = 0.38, 95%CI (0.03,4.81), P = 0.451], neurological deficit [OR = 0.86,95%CI(0.32,2.33),P = 0.766]. Conclusion Reinstitution of antiplatelet therapy after ICH was associated with a lower risk of thromboembolic complications.Resumption of antiplatelet therapy was not associated with a higher incidence of cerebral hemorrhage in Caucasians, but may be associated with a higher risk of cerebral hemorrhage recurrence in Asian populations.

Abstract Thrombotic cardiovascular diseases are a prevalent factor contributing to both physical impairment and mortality. Thrombolysis and ischemic mitigation have emerged as leading contemporary therapeutic approaches for addressing the consequences of ischemic injury and reperfusion damage. Herein, an innovative cellular-cloaked spermatozoon-driven microcellular submarine (SPCS), comprised of multimodal motifs, was designed to integrate nano-assembly thrombolytics with an immunomodulatory ability derived from innate magnetic hyperthermia. Rheotaxis-based navigation was utilized to home to and cross the clot barrier, and finally accumulate in ischemic vascular organs, where the thrombolytic motif was “switched-on” by the action of thrombus magnetic red blood cell-driven magnetic hyperthermia. In a murine model, the SPCS system combining innate magnetic hyperthermia demonstrated the capacity to augment delivery efficacy, produce nanotherapeutic outcomes, exhibit potent thrombolytic activity, and ameliorate ischemic tissue damage. These findings underscore the multifaceted potential of our designed approach, offering both thrombolytic and ischemia-mitigating effects. Given its extended therapeutic effects and thrombus-targeting capability, this biocompatible SPCS system holds promise as an innovative therapeutic agent for enhancing efficacy and preventing risks after managing thrombosis. Graphical abstract

Abstract In the continental margin of the northeastern South China Sea, the sea level fluctuations since the Last Glacial Maximum have profoundly impacted the sedimentary environment. Our sub-bottom profiler data show a sedimentation process change from deposition to erosion during the Last Glacial Maximum. After the widespread erosion, the sedimentation process returned depositional throughout the Holocene, probably due to the rise of the sea level. This sedimentary process results in a widespread sedimentary unconformity in the continental slope, providing a benchmark for the end of the Last Glacial Maximum. Analyzing the sediment cores, we affirm that the change in current intensity is the primary factor controlling the sedimentary environments. The current intensities strengthened during the eustatic lowstand and weakened during the highstand periods, leading to alternating erosional and depositional processes. The widespread distribution of the erosive surface represents a regional-scale change in the sedimentary environment instead of a local event.

Background: Real-world vaccine effectiveness following the third dose of vaccination against SARS-CoV-2 remains less investigated among people with HIV (PWH). Methods: PWH receiving the third dose of BNT162b2 and mRNA-1273 (either 50- or 100-μg) were enrolled. Participants were followed for 180 days until the fourth dose of COVID-19 vaccination, SARS-CoV-2 infection, seroconversion of anti-nucleocapsid IgG, death, or loss to follow-up. Anti-spike IgG was determined every 1–3 months. Results: Of 1427 participants undergoing the third-dose COVID-19 vaccination, 632 (44.3%) received 100-μg mRNA-1273, 467 (32.8%) 50-μg mRNA-1273, and 328 (23.0%) BNT162b2 vaccine and the respective rate of SARS-CoV-2 infection or seroconversion of anti-nucleocapsid IgG was 246.1, 280.8 and 245.2 per 1000 person-months of follow-up (log-rank test, p = 0.28). Factors associated with achieving anti-S IgG titers >1047 BAU/mL included CD4 count 200 copies/mL (aOR, 0.27; 95% CI, 0.09–0.80), having achieved anti-spike IgG >141 BAU/mL within 3 months after primary vaccination (aOR, 3.69; 95% CI, 2.68–5.07), receiving BNT162b2 vaccine as the third dose (aOR, 0.20; 95% CI, 0.10–0.41; reference, 100-μg mRNA-1273), and having previously received two doses of mRNA vaccine in primary vaccination (aOR, 2.46; 95% CI, 1,75-3.45; reference, no exposure to mRNA vaccine). Conclusions: PWH receiving different types of the third dose of COVID-19 vaccine showed similar vaccine effectiveness against SARS-CoV-2 infection. An additional dose with 100-μg mRNA-1273 could generate a higher antibody response than with 50-μg mRNA-1273 and BNT162b2 vaccine.

Abstract Three-dimensional (3D) imaging of individual atoms is a critical tool for discovering new physical phenomena and developing new technologies in microscopic systems. However, the current single-atom-resolved 3D imaging methods are limited to static circumstances or a shallow detection range. Here, we demonstrate a generic dynamic 3D imaging method to track the extensive motion of single ions by exploiting the engineered point-spread function (PSF). We show that the image of a single ion can be engineered into a helical PSF, thus enabling single-snapshot acquisition of the position information of the ion in the trap. A preliminary application of this technique is demonstrated by recording the 3D motion trajectory of a single trapped ion and reconstructing the 3D dynamical configuration transition between the zig and zag structures of a 5-ion crystal. This work opens the path for studies on single-atom-resolved dynamics in both trapped-ion and neutral-atom systems.

Abstract Background There are no effective pharmacological treatments for sarcopenia. We aim to identify potential therapeutic targets for sarcopenia by integrating various publicly available datasets. Methods We integrated druggable genome data, cis‐eQTL/cis‐pQTL from human blood and skeletal muscle tissue, and GWAS summary data of sarcopenia‐related traits to analyse the potential causal relationships between drug target genes and sarcopenia using the Mendelian Randomization (MR) method. Sensitivity analyses and Bayesian colocalization were employed to validate the causal relationships. We also assessed the side effects or additional indications of the identified drug targets using a phenome‐wide MR (Phe‐MR) approach and investigated actionable drugs for target genes using available databases. Results MR analysis identified 17 druggable genes with potential causation to sarcopenia in human blood or skeletal muscle tissue. Six of them (HP, HLA‐DRA, MAP 3K3, MFGE8, COL15A1, and AURKA) were further confirmed by Bayesian colocalization (PPH4 > 90%). The up‐regulation of HP [higher ALM (beta: 0.012, 95% CI: 0.007–0.018, P = 1.2*10−5) and higher grip strength (OR: 0.96, 95% CI: 0.94–0.98, P = 4.2*10−5)], MAP 3K3 [higher ALM (beta: 0.24, 95% CI: 0.21–0.26, P = 1.8*10−94), higher grip strength (OR: 0.82, 95% CI: 0.75–0.90, P = 2.1*10−5), and faster walking pace (beta: 0.03, 95% CI: 0.02–0.05, P = 8.5*10−6)], and MFGE8 [higher ALM (muscle eQTL, beta: 0.09, 95% CI: 0.06–0.11, P = 6.1*10−13; blood pQTL, beta: 0.05, 95% CI: 0.03–0.07, P = 3.8*10−09)], as well as the down‐regulation of HLA‐DRA [lower ALM (beta: ‐0.09, 95% CI: −0.11 to −0.08, P = 5.4*10−36) and lower grip strength (OR: 1.13, 95% CI: 1.07–1.20, P = 1.8*10−5)] and COL15A1 [higher ALM (muscle eQTL, beta: ‐0.07, 95% CI: −0.10 to −0.04, P = 3.4*10−07; blood pQTL, beta: ‐0.05, 95% CI: −0.06 to −0.03, P = 1.6*10−07)], decreased the risk of sarcopenia. AURKA in blood (beta: ‐0.16, 95% CI: −0.22 to −0.09, P = 2.1*10−06) and skeletal muscle (beta: 0.03, 95% CI: 0.02 to 0.05, P = 5.3*10−05) tissues showed an inverse relationship with sarcopenia risk. The Phe‐MR indicated that the six potential therapeutic targets for sarcopenia had no significant adverse effects. Drug repurposing analysis supported zinc supplementation and collagenase clostridium histolyticum might be potential therapeutics for sarcopenia by activating HP and inhibiting COL15A1, respectively. Conclusions Our research indicated MAP 3K3, MFGE8, COL15A1, HP, and HLA‐DRA may serve as promising targets for sarcopenia, while the effectiveness of zinc supplementation and collagenase clostridium histolyticum for sarcopenia requires further validation.

The paper analyses the spatial and temporal characteristics of extreme precipitation in the upper reaches of the Yangtze River through extreme precipitation indicators based on the trend method, the Mann–Kendall trend test, and the rescaled extreme deviation extreme deviation using daily precipitation data from 1961 to 2021. The following conclusions were obtained: The overall precipitation in the upper reaches of the Yangtze River is reduced, and the number of rainy days is reduced. The frequency of extreme precipitation is generally reduced, but the spatial difference in the intensity of extreme precipitation is greater, which makes the occurrence of extreme precipitation more concentrated and more destructive. Extreme precipitation indicators showed relatively large fluctuations after 2000, especially in terms of extreme precipitation intensity. The frequency of extreme precipitation in the upper reaches of the Yangtze River is the highest in the main stream of the Yangtze River Basin and the Wujiang River Basin, the intensity of extreme precipitation is in the Jialing River and the Wujiang River Basin, and the accumulation of extreme precipitation is the highest in the Jialing River and the Wujiang River Basin, whereas the maximum value of the station extreme precipitation intensity and frequency is in the Minjiang River Basin. HIGHLIGHTS The overall extreme precipitation characteristics of the upper reaches of the Yangtze River under climate change were analysed.; Differences in extreme precipitation characteristics of the first-tier tributaries of the upper Yangtze River were analysed.; Changes in water resources in the upper reaches of the Yangtze River have a major impact on China's economy, food security, and energy resources.;

Abstract Background Isolated methylmalonic acidemia, an autosomal recessive disorder of propionate metabolism, is usually caused by mutations in the methylmalonyl-CoA mutase gene (mut-type). Because no universal consensus was made on whether mut-type methylmalonic acidemia should be included in newborn screening (NBS), we aimed to compare the outcome of this disorder detected by NBS with that detected clinically and investigate the influence of NBS on the disease course. Design & methods In this study, 168 patients with mut-type methylmalonic acidemia diagnosed by NBS were compared to 210 patients diagnosed after disease onset while NBS was not performed. Clinical data of these patients from 7 metabolic centers in China were analyzed retrospectively, including initial manifestations, biochemical metabolites, the responsiveness of vitamin B12 therapy, and gene variation, to explore different factors on the long-term outcome. Results By comparison of the clinically-diagnosed patients, NBS-detected patients showed younger age at diagnosis, less incidence of disease onset, better responsiveness of vitamin B12, younger age at start of treatment, lower levels of biochemical features before and after treatment, and better long-term prognosis (P

Abstract Steroids are cholesterol-derived biomolecules that play an essential role in biological processes. These substances used as growth promoters in animals are strictly regulated worldwide. Targeted assays are the conventional methods of monitoring steroid abuse, with limitations: only detect known metabolites. Metabolism leads to many potential compounds (isomers), which complicates the analysis. Thus, to overcome these limitations, non-targeted analysis offers new opportunities for a deeper understanding of metabolites related to steroid metabolism. Molecular networking (MN) appears to be an innovative strategy combining high-resolution mass spectrometry and specific data processing to study metabolic pathways. In the present study, two databases and networks of steroids were constructed to lay the foundations for the implementation of the GNPS-MN approach. Steroids of the same family were grouped together, nandrolone and testosterone were linked to other analogues. This network and associated database were then applied to a few urine samples in order to demonstrate the annotation capacity in steroidome study. The results show that MN strategy could be used to study steroid metabolism and highlight biomarkers.

Abstract Background Non-syndromic tooth agenesis (NSTA) is a type of ectodermal dysplasia (ED) in which patients with non-syndromic oligodontia may only affect teeth. No pathological findings were found in other tissues of the ectodermal. Herein, we report a case of a NSTA patient with severe dental anxiety and poor oral health. Case presentation A 5-year-old boy without systemic diseases presented as a patient with oligodontia, extensive caries, and periapical periodontitis. Molecular genetic analysis found a mutation in the Ectodysplasin A (EDA) gene, confirming the diagnosis of NSTA. Conclusion Tooth agenesis (TA) is the most common ectodermal developmental abnormality in humans. Non-syndromic oligodontia patients often seek treatment in the department of stomatology. Because of their complex oral conditions, these patients should be provided with a systematic and personalized treatment plan.

Abstract The small Extracellular vesicles (sEV) has been recognized to be significant for intercellular communication due to their ability to transfer important cellular cargoes like miRNAs through circulation. The pituitary gland has not been clearly known about the role of its secreted sEV under normal physiological conditions. And Liver disease is a global public health burden. The present study is the first to investigate the effect of pituitary sEV on the liver. Sequencing and qRT-PCR revealed miR-143-3p is one of the richest in the pituitary sEV. MiR-143 Knockout (KO) mice resulted in a remarkable decrease in insulin-like growth factor 1 (IGF-1) levels and a significant increase in insulin-like growth factor binding protein 5 (IGFBP5) levels along with a reduction in liver primary cell growth. More importantly, compared with miR-143-KO-sEV, WT-sEV possesses a more robust capacity to improve miR-143 KO mice liver repair through the Wnt/β-catenin pathway after an acute injury caused by carbon tetrachloride (CCl4). Our results indicate that pituitary-derived sEV promotes hepatocyte proliferation and liver repair by its cargo miR-143-3p and provides new insight into the regulation mechanism of the pituitary-liver axis, and open a new window for endocrine regulation by using sEV.

Abstract Lead-free Cs3Bi2I9 single crystals have been demonstrated to be promising materials for direct X-ray detectors with remarkable performance. However, their application for 2D X-ray imaging is hindered by their time-consuming preparation and limited crystal size. In this paper, a thick Cs3Bi2I9 perovskite film fabricated via facile spray coating at a low processing temperature, which increases the area of the photoactive film, reduces the processing time, decreases the energy budget and the production cost, and enhances the production yield due to high material utilization, has great potential for commercial applications. Careful control of the processing temperature and intervals during spray coating results in a dense and thick perovskite film with well-stacked perovskite domains. The compact perovskite film enhances the charge transport capability of the Cs3Bi2I9 perovskite film and reduces the dark current density of the X-ray detector. The resultant X-ray detector, prepared through a two-step spray coating process, exhibited a sensitivity of 127.23 μC Gyair −1 cm−2 and a detection limit of 7.4 μGyair s−1. In addition, the device delivers long-term stability with a consistent photoresponse when exposed to consecutive X-ray pulse irradiation.