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The purpose of this research study was to examine the overall effect of adaptive learning systems deployed using artificial intelligence technology across a range of relevant variables (e.g., duration, student level, etc.). Following a systematic procedure, this meta-analysis examined literature from 18 academic databases and identified N = 45 independent studies utilizing AI-enabled adaptive learning. This meta-analysis examined the overall effect of AI-enabled adaptive learning systems on students' cognitive learning outcomes when compared with non-adaptive learning interventions and found that they have a medium to large positive effect size (g = 0.70). The effect was significantly moderated by publication type, origin of study, student classification level, student discipline, duration, and research design. In addition, all three adaptive sources (cognitive, affective, and behavioral) and adaptive targets (navigation and assessment) were significant moderators. The type of AI used in the adaptive engine did not moderate the effects. Implications for both practice and research are provided.

We report findings from an eDelphi study that aimed to explore 16 expert panelists' perspectives regarding the key attributes of learning experience design (LXD) as it relates to the following: design, disciplines, methods, and theory. Findings suggest consensus was reached regarding LXD's focus on learner-centrism and incorporating human-centered design practices to design learning environments. LXD practitioners adapt methods and theories from fields such as human--computer interaction and user experience. Implications suggest a need to develop specific methods and theories within our own field.

Abstract Flaviviruses strategically utilize the endoplasmic reticulum (ER) in their replication cycles. However, the role of ER autophagy (ER-phagy) in viral replication process remains poorly understood. Here, we reveal that prolonged Zika virus (ZIKV) infection results from the degradation of ER-phagy receptor FAM134B, facilitated by viral NS2A protein. Mechanistically, ER-localized NS2A undergoes K48-linked polyubiquitination at lysine (K) 56 by E3 ligase AMFR. Ubiquitinated NS2A binds to FAM134B and AMFR orchestrates the degradation of NS2A-FAM134B complexes. AMFR-catalyzed NS2A ubiquitination not only targets FAM134B degradation but also hinders the FAM134B-AMFR axis. Notably, a recombinant ZIKV mutant (ZIKV-NS2AK56R), lacking ubiquitination and ER-phagy inhibition, exhibits attenuation in ZIKV-induced microcephalic phenotypes in human brain organoids and replicates less efficiently, resulting in weakened pathogenesis in mouse models. In this work, our mechanistic insights propose that flaviviruses manipulate ER-phagy to modulate ER turnover, driving viral infection. Furthermore, AMFR-mediated flavivirus NS2A ubiquitination emerges as a potential determinant of viral pathogenecity.

Abstract Ambient-condition acetylene hydrogenation to ethylene (AC-AHE) is a promising process for ethylene production with minimal additional energy input, yet remains a great challenge due to the difficulty in the coactivation of acetylene and H2 at room temperature. Herein, we report a highly efficient AC-AHE process over robust sulfur-confined atomic Pd species on tungsten sulfide surface. The catalyst exhibits over 99% acetylene conversion with a high ethylene selectivity of 70% at 25 oC, and a record space-time yield of ethylene of 1123 molC2H4 molPd −1 h−1 under ambient conditions, which is nearly four times that of the typical Pd1Ag3/Al2O3 catalyst, and exhibiting superior stability of over 500 h. We demonstrate that the confinement of Pd-S coordination induces positively-charged atomic Pdδ+, which not only facilitates C2H2 hydrogenation but also promotes C2H4 desorption, thereby enabling a high conversion of C2H2 to C2H4 at room temperature while suppressing over-hydrogenation to C2H6.

Abstract Spatial distribution orientations of blocks can cause significant errors in the discrete element model (DEM) calculation of soil-rock mixture (SRM). To avoid this error, spherical harmonic (SH) series whose harmonization degrees fixed at 15 were proposed for block reconstruction. This research refers to the case-history of a deep excavation rift valley spanning from the Mabian to Zhaojue section of the Leshan-Xichang Expressway, mainly containing moderately-weathered silty mudstone, in the Leshan City, Sichuan Province, China. The appropriate degree of finite-term SH series is selected by the volume, surface area. 100 blocks were scanned on site, and sphericity and angularity of the blocks were calculated. The sphericity and angularity of 50 reconstructed blocks were considered for the error analysis of SH method. Moreover, stochastic polyhedron method was considered for comparing different block reconstructions. The maximum block placement angle was defined to control the spatial distribution orientations of the blocks. Large scale direct tests were carried. Numerical simulations of large-scale direct shear tests were conducted to study the influence of the spatial distribution orientations of the blocks on the mechanical properties of the SRMs. The results revealed that the finite-term SH series fixed at 15 accurately reflected the shape characteristics and mechanical behaviors of actual blocks. The spatial distribution orientations of the blocks had a minimal impact on the friction angle and cohesion of SRM constructed through the SH method. The SRMs developed via the SH method exhibited marginal variations in contact force and anisotropy index of contact across diverse block placement strategies. The evolution of coordination number was closer when employing the SH method under varied block placement methods. Blocks reconstructed by the SH method, could mitigate errors in DEM calculation caused by the spatial distribution orientations of the blocks.

Abstract Numerous clinical trials for myasthenia gravis (MG) treatment have been conducted recently, with satisfactory cognitive and clinical results. However, due to the limited evidence for direct comparison of the safety and effectiveness of various drugs, there is a need for further exploration of the advantages and disadvantages of different monoclonal antibodies and immunosuppressants. Thus, in the present network meta-analysis (NMA), we aimed to compare the efficacy and safety of immunosuppressants and monoclonal antibodies in treating MG. We systematically searched for randomized controlled trials published in PubMed, Embase, Web of Science, and the Cochrane Library between January 1, 2000 and March 6, 2024. Statistical analyses were performed using R software (version 4.2.3), JAGS, and STATA (version 15.0). The surface under the cumulative ranking curve (SUCRA) value was calculated to assess the potential efficacy of each drug and the likelihood of adverse events (AEs), with higher SUCRA values indicating better efficacy or a lower likelihood of AEs. This NMA included 21 randomized controlled trials involving 13 drugs and 1,657 patients. Based on changes in Quantitative MG and MG Composite scores, batoclimab was most likely to exert the best therapeutic effects, with SUCRA values of 99% and 92%, respectively. Rozanolixzumab performed better than the other drugs in terms of the MG Activities of Daily Living score (85%). Eculizumab exhibited the highest potential in reducing the 15-item revised version of the MG Quality of Life score (96%). Regarding safety, belimumab had the highest SUCRA value (85%), demonstrating the lowest likelihood of AEs. In conclusion, all immunosuppressants and monoclonal antibodies analyzed in this study were more effective than the placebo in treating MG, with rozanolixzumab and batoclimab potentially being the most effective. Regarding safety, rozanolixzumab exhibited a higher likelihood of AEs than did placebo. The conclusions guide the clinical selection of effective drugs and offer insights for future drug experiments.

Extended reality (XR) such as Virtual Reality (VR) and Augmented Reality (AR) has been heralded as a particularly promising technology for autistic people. However, prior studies have centered around curing or ameliorating deficits and impairments and are typically conducted by non-disabled and non-autistic researchers. Using co-design and a variety of learning experience design methods and processes, Project PHoENIX (Participatory, Human-centered, Equitable, Neurodiverse, and Inclusive XR) speaks to the need for research that applies a social-ecological perspective to the design and evaluation of VR experiences for autistic users, with the goal of decreasing environmental barriers and promoting a more inclusive society. In this study, we describe a multi-cycle process of educational design research (EDR), consisting of iterative human-centered formative design, development, implementation, and evaluation of Project PHoENIX from Spring 2021 to Spring 2022. A framework for conducting co-design and collaborative educational design research with autistic individuals in a VR environment is provided along with design principles that support this framework. Findings from 3 meso-cycles illustrate the dual outcomes of educational design research, namely, (1) a consistently maturing intervention and (2) improving theoretical understanding. Findings underscore the feasibility of our approach, and demonstrate potential to scale.

Abstract A time domain rock mass parameter identification method considering the Rayleigh damping is proposed in this paper. Starting with a set of initial parameter values, the algorithm solves the finite-element (FE) equations updating the parameters in each iterative step until the result converges to a local optimum. Numerical FE analysis, displacement sensitivity analysis, and the truncated singular value decomposition method are integrated into the solution algorithm for parameter identification. The technique introduced is verified in numerical studies with in-situ experiments of rock mass structures. Our results show that the approach, compared with conventional methods, can reduce ambiguities caused by inadequate data and provide more accurate insights into the subsurface for rock mass quality evaluation.

Abstract Background To explore the application value of syndecan-1 (SDC-1) in the diagnosis of coronary artery lesions (CALs) in Kawasaki disease (KD) patients and the correlation of multiple laboratory indicators in KD patients. Methods 86 pediatric Kawasaki disease (KD) patients and 52 healthy controls admitted from January 2018 to December 2023 were retrospectively analyzed. Venous blood samples from KD patients were analyzed for white blood cells (WBC), platelets (PLT), C-reactive protein (CRP), interleukin-6 (IL-6), syndecan-1 (SDC-1), coagulation parameters, and lipid profiles. Correlations between these laboratory indicators were assessed. Receiver operating characteristic (ROC) curve analysis determined the diagnostic value of SDC-1 for coronary artery lesions (CALs) in KD patients. SDC-1 levels were further compared across different CAL severity groups. Results The levels of ALT, AST, WBC, PLT, CRP, IL-6, and SDC-1 in the KD group were significantly higher than those in the control group (P

Objective: To analyze the hotspots, patterns, and distribution of research on the safety and risk of antibody preparations in the past 20 years. It also seeks to summarize the current status and trends of research on the safety and risk control of antibody preparations. Methods: Taking “antibody preparation”, “safety” and “risk” as keywords, relevant articles were searched in the databases Web of Science. CiteSpace was utilized to analyze the annual number of publications, countries, authors, institutions, highly cited literature and keywords of the screened literature, and the relevant maps were drawn and the results were analyzed. Results: A total of 1693 articles were included. The annual number of publications in the field of antibody preparation safety has shown stable growth followed by a rapid increase between 2002 and 2022. Among the countries, the United States accounted for 36.7% of the total publications, ranking first in the world. Large foreign pharmaceutical companies, research institutions, comprehensive university and their affiliated hospitals were the most high-yield institutions. Current hot topics in the field of antibody preparation safety research include “ADC”, “monoclonal antibody”, “anti-tumor activity”, “immunotherapy”, etc. Conclusion: Over the past 20 years, research on antibody formulations has garnered increasing attention both domestically and internationally, with a focus mainly on efficacy and safety. There has been relatively little research on risk control. In the future, more in-depth research is needed on the mechanisms of adverse reactions in antibody formulations to provide more effective strategies for risk control.

Abstract Podocalyxin-like protein (PODXL) is known to originate from tumor cells in several cancers; however, which cell type it is expressed in, whether and how it may contribute to tumor progression after radiotherapy or chemoradiotherapy in cervical cancer (CC) remain unknown. In this study, we investigated these issues using a cohort of 180 immune stain data, single-cell RNA sequencing (scRNA-seq) data of 29,453 cells, and bulk RNA sequencing data from 187 cervical cancer samples treated with radiotherapy or chemoradiotherapy. ScRNA-seq analysis revealed that PODXL was predominantly expressed in tumor endothelial cells (TECs) of CC, which was corroborated by tumor section staining. Moreover, the PODXL expression level was negatively associated with progression-free survival and overall survival of 180 CC patients receiving radiotherapy or chemoradiotherapy (both p

Abstract Background Concerns have been raised regarding changes in lipid profiles among patients with chronic hepatitis B (CHB) during tenofovir alafenamide fumarate (TAF) treatment. We aimed to evaluate the effect of TAF treatment on the lipid profiles of patients with CHB. Methods A total of 430 patients with CHB from three hospitals were retrospectively included, including 158 patients treated with TAF and 272 patients treated with tenofovir disoproxil fumarate (TDF). Results In this multicenter cohort, the cumulative incidence of dyslipidemia was notably higher in the TAF group than in the TDF group (P

Contribution: This article proposes a task-driven ADDIE-Twist design model with a double-helix structure, which introduces intelligent teaching tools and lightweight collaboration platforms to design a knowledge-sharing and group collaboration model with two layers of teaching task driven and learning task driven, providing inspiration for the construction of new engineering courses and teaching reforms. Background: The ADDIE model is a classic instructional design model, but it still faces issues, such as a lack of flexibility, feedback mechanism, and emphasis on learners. The goal of new engineering education is to cultivate students' future-oriented professional literacy, knowledge structure, innovation, entrepreneurship capabilities, and teamwork spirit to meet the needs of society and industry development. In order to address these issues, this article proposes the ADDIE-Twist model. Research Questions: Can the use of the ADDIE-Twist model solve the problems of the traditional ADDIE model mentioned above? Can the use of the ADDIE-Twist model in engineering education improve the issues of lack of interaction and slow feedback between teachers and students? Methodology: Taking the experiment and implementation of the "Programmable Logic Circuit Design" course at Jinan University as an example, this article presents a design scheme for engineering education courses based on the ADDIE-Twist model. The application effect of the model is analyzed through three aspects: 1) a questionnaire survey; 2) semi-structured interviews; and 3) student awards. Results: 1) The ADDIE-Twist model can effectively enhance the frequency of teacher--student interaction. 2) The teaching reform of the ADDIE-Twist model helps to improve students' learning motivation, participation, self-learning, and active exploration capabilities.

Fracture/fault instability induced by fluid injection in deep geothermal reservoirs could not only vary the reservoir permeability but also trigger hazardous seismicity. To address this, we conducted triaxial shear experiments on granite fractures with different architected roughnesses reactivated under fluid injection, to investigate the controls on permeability evolution linked to reactivation. Our results indicate that the fracture roughness and injection strategies are two main factors affecting permeability evolution. For fractures with different roughnesses, a rougher fracture leads to a lower peak reactivated permeability (kmax), and varying the fluid injection strategy (including the confining pressure and injection rate) has a less impact on kmax, indicating that the evolution of permeability during fluid pressurization is likely to be determined by the fracture roughness along the shear direction. Both the fracture roughness and injection strategies affect the average rates of permeability change and this parameter also reflects the long-term reservoir recovery. Our results have important implications for understanding the permeability evolution and the injection-induced fracture/fault slips in granite reservoirs during the deep geothermal energy extraction.

Simultaneous nitrification and denitrification (SND) is an efficient method to remove nitrogen in municipal wastewater treatment. However, low dissolved oxygen (DO) concentrations are generally required, leading to serious membrane fouling in membrane bioreactors (MBRs). This study aimed to clarify the synergistic effect of biomass and DO on nitrogen removal and membrane fouling. To achieve this goal, four submerged MBRs equipped with ceramic membranes were operated with different biomass (mixed liquor suspended solids (MLSS)) concentrations (3 000 mg/L, 5 000 mg/L, 7 500 mg/L, and 12 000 mg/L) under various DO concentrations (2.0 mg/L, 1.0 mg/L, and 0.5 mg/L). As a result, increasing biomass in the MBRs enhanced total nitrogen (TN) removal via SND, and excellent TN removal efficiencies of 60.7% and 75.8% were obtained using the MBR with an MLSS concentration of 12 000 mg/L and DO concentrations of 2.0 mg/L and 1.0 mg/L. However, a further decrease in DO deteriorated TN removal due to the inhibition of nitrification. Moreover, high MLSS concentrations were beneficial to membrane fouling control for ceramic membranes in MBRs. The lowest transmembrane pressure development rate was observed for the MBR with an MLSS concentration of 12 000 mg/L. High biomass offset the adverse effect of DO decrease on membrane fouling to some extent, and improved the stability of the reactor. Therefore, biomass might be an important parameter for membrane fouling reduction in ceramic MBRs. Overall, optimal biomass and DO concentrations for TN removal were identified, providing useful information for the successful operation of MBRs with efficient TN removal and membrane fouling control.

When tunnel boring machines (TBMs) excavate through jointed rock masses, the cutting efficiency is strongly affected by the shear strength of joints, the mechanism of which, however, remains poorly understood. In this study, a series of disc-cutter indentation tests were conducted on granite rock mass specimens with different joint shear strengths. During the indentation, the cracking process was recorded by a digital image correlation (DIC) system. The deformation and strength of specimens, cracking behavior, rock breakage mode and cutting efficiency were quantitatively investigated. In addition, to investigate the combined effects of joint shear strength, orientation and spacing on the rock breakage mechanism, numerical rock mass models were established based on a particle flow code PFC2D. Experimental results reveal that the cracking of primary and secondary cracks changes from the mixed shear-tensile to tensile mode in the initial stage, while the joint shear strength does not affect the cracking mode in the subsequent propagation process. The rock breakage mode is classified to an internal block breakage mode, a cross-joint breakage mode and a cutters-dependent breakage mode. The cross-joint breakage mode is optimal for improving the cutting efficiency. Numerical simulation results reveal that the increase in the joint shear strength changes the internal block breakage mode to cross-joint breakage mode for rock masses of particular ranges of joint orientation and spacing. These findings provide basis for improving the TBM cutting efficiency through jointed rock masses.

Abstract Osteogenesis imperfecta (OI) is a disorder of low bone mass and increased fracture risk due to a range of genetic variants that prominently include mutations in genes encoding type I collagen. While it is well known that OI reflects defects in the activity of bone-forming osteoblasts, it is currently unclear whether OI also reflects defects in the many other cell types comprising bone, including defects in skeletal vascular endothelium or the skeletal stem cell populations that give rise to osteoblasts and whether correcting these broader defects could have therapeutic utility. Here, we find that numbers of skeletal stem cells (SSCs) and skeletal arterial endothelial cells (AECs) are augmented in Col1a2 oim/oim mice, a well-studied animal model of moderate to severe OI, suggesting that disruption of a vascular SSC niche is a feature of OI pathogenesis. Moreover, crossing Col1a2 oim/oim mice to mice lacking a negative regulator of skeletal angiogenesis and bone formation, Schnurri 3 (SHN3), not only corrected the SSC and AEC phenotypes but moreover robustly corrected the bone mass and spontaneous fracture phenotypes. As this finding suggested a strong therapeutic utility of SHN3 inhibition for the treatment of OI, a bone-targeting AAV was used to mediate Shn3 knockdown, rescuing the Col1a2 oim/oim phenotype and providing therapeutic proof-of-concept for targeting SHN3 for the treatment of OI. Overall, this work both provides proof-of-concept for inhibition of the SHN3 pathway and more broadly addressing defects in the stem/osteoprogenitor niche as is a strategy to treat OI.

Abstract Replacement of expensive and rare platinum with metal–nitrogen–carbon catalysts for oxygen reduction reactions in proton exchange membrane fuel cells is hindered by their inferior activity. Herein, we report a highly active iron-nitrogen-carbon catalyst by optimizing the carbon structure and coordination environments of Fe-N4 sites. A critical high-temperature treatment with ammonium chloride and ammonium bromide not only enhances the intrinsic activity and density of Fe-N4 sites, but also introduces numerous defects, trace Br ions and creates mesopores in the carbon framework. Notably, surface Br ions significantly improve the interaction between the ionomer and catalyst particles, promoting ionomer infiltration and optimizing the O2 transport and charge transfer at triple-phase boundary. This catalyst delivers a high peak power density of 1.86 W cm−2 and 54 mA cm−2 at 0.9 ViR-free in a H2-O2 fuel cells at 80 °C. Our findings highlight the critical role of interface microenvironment regulation.

Abstract The field of nickel catalysis has witnessed remarkable growth in recent years. However, the use of nickel catalysts in enantioselective C–H activation remains a daunting challenge because of their variable oxidation states, intricate coordination chemistry, and unpredictable reactivity patterns. Herein, we report an enantioselective C–H activation reaction catalyzed by commercially available and air-stable nickel(II) catalyst. Readily available and simple (S)-BINOL is used as a chiral ligand. This operationally simple protocol enables the synthesis of planar chiral metallocenes in high yields with excellent enantioselectivity through desymmetrization and kinetic resolution. Air-stable planar chiral nickelacycle intermediates are first synthesized via enantioselective C–H nickelation and shown to be possible intermediates of the reaction. Deuterium-labeling studies, alongside the characterization and transformation of chiral nickel(II) species, suggest that C–H cleavage is the enantio-determining step. Moreover, the large-scale synthesis and diverse synthetic transformations underscore the practicality of this protocol.

Abstract Cancer is measured as a major threat to human life and is a leading cause of death. Millions of cancer patients die every year, although a burgeoning number of researchers have been making tremendous efforts to develop cancer medicine to fight against cancer. Owing to the complexity and heterogeneity of cancer, lack of ability to treat deep tumor tissues, and high toxicity to the normal cells, it complicates the therapy of cancer. However, bacterial derivative-mediated drug delivery has raised the interest of researchers in overcoming the restrictions of conventional cancer chemotherapy. In this review, we show various examples of tumor-targeting bacteria and bacterial derivatives for the delivery of anticancer drugs. This review also describes the advantages and limitations of delivering anticancer treatment drugs under regulated conditions employing these tumor-targeting bacteria and their membrane vesicles. This study highlights the substantial potential for clinical translation of bacterial-based drug carriers, improve their ability to work with other treatment modalities, and provide a more powerful, dependable, and distinctive tumor therapy. Graphical Abstract

Abstract Very‐low‐frequency (VLF) transmitting antennas have a crucial influence on the nearby electromagnetic environment. Commercial software packages, such as CST Studio Suite (CST) or Altair FEKO (FEKO), are always utilised to calculate the electric fields of VLF antennas, which consume considerable computing resources and time. The classical method of electric field calculation, the charge simulation method (CSM), is first applied to the calculation of electric field near the VLF transmitting antenna. The distribution characteristics of three‐dimensional electric fields were analysed. The electric field surrounding the antenna exhibited axial symmetry. The highest electric field strength was at the top of the antenna, and as the distance from the antenna increased, the electric field strength exponentially decreased. The comparisons are performed between the results of the CSM and those of commercial software, the average relative errors of CSM on two observation paths are very small, 2.20% and 2.21%, respectively. Meanwhile, the CSM shows considerable advantages in saving calculation resources and improving efficiency. Additionally, the comparison between CSM calculation and the measured data is carried out. The results show that this method can accurately calculate the electric field near VLF transmitting antenna and offer valuable insights and a new solution.

Abstract Glioblastoma (GBM) is associated with a median survival rate of less than 15 months, necessitating innovative treatment approaches. This study investigates the safety and efficacy of the low-frequency magnetic field (LFMF) OM-100 instrument in GBM therapy. In vitro experiments utilized normal astrocyte and GBM cell lines, determining that OM-100 at 100 kHz for 72 h selectively targeted GBM cells without harming normal cells. Subsequent analyses revealed OM-100’s impact on cell viability, apoptosis, migration, invasion, reactive oxide species levels, and PD-L1 expression. In vivo studies on mice with U87-induced GBM demonstrated OM-100's synergy with anti-PD-1 therapy, leading to significant tumor volume reduction and increased apoptosis. Notably, OM-100 exhibited safety in healthy mice. Overall, OM-100 could enhance anti-PD-1 immunotherapy effectiveness probably by directly inhibiting tumor proliferation and migration as well as promoting PD-L1 expression, offering a promising therapeutic strategy for GBM treatment.

Abstract This study investigated the association between serum albumin concentration and 12-weeks mortality of HIV/AIDS with late diagnosis in China. This retrospective cohort study included, 1079 inpatients diagnosis with late HIV/AIDS between January 2018 and December 2021. Disease progression was estimated based on the 12-weeks mortality rate. Cox proportional hazards regression models were used to evaluate the relationship between serum albumin levels and disease progression. The effects of serum albumin levels on mortality was estimated via Kaplan–Meier curves. The mortality risk decreased by 7% with every 1 g/L increase in serum albumin after adjustment ([HR] = 0.93, 95% CI: 0.88–0.97). Compared with that of the low (< 28 g/L) serum albumin group, the middle (28–34 g/L) group’s mortality risk decreased by 70% (HR = 0.30, 95% CI: 0.15–0.59), and that of the high (≥ 34 g/L) group decreased by 40% (HR = 0.6, 95% CI: 0.29–1.23) after adjustment. Our findings suggest a positive correlation between the increase in serum albumin levels upon admission and a decrease in mortality at 12 weeks post-discharge among patients with late AIDS/HIV diagnosis. Further research is needed to characterize the role of serum albumin in 12-weeks mortality prevention in patients with a late diagnosis.

Abstract The skeleton has been suggested to function as an endocrine organ controlling whole organism energy balance, however the mediators of this effect and their molecular links remain unclear. Here, utilizing Schnurri-3−/− (Shn3 −/− ) mice with augmented osteoblast activity, we show Shn3 −/− mice display resistance against diet-induced obesity and enhanced white adipose tissue (WAT) browning. Conditional deletion of Shn3 in osteoblasts but not adipocytes recapitulates lean phenotype of Shn3 −/− mice, indicating this phenotype is driven by skeleton. We further demonstrate osteoblasts lacking Shn3 can secrete cytokines to promote WAT browning. Among them, we identify a C-terminal fragment of SLIT2 (SLIT2-C), primarily secreted by osteoblasts, as a Shn3-regulated osteokine that mediates WAT browning. Lastly, AAV-mediated Shn3 silencing phenocopies the lean phenotype and augmented glucose metabolism. Altogether, our findings establish a novel bone-fat signaling axis via SHN3 regulated SLIT2-C production in osteoblasts, offering a potential therapeutic target to address both osteoporosis and metabolic syndrome.

Abstract In pursuing cheap and effective oxygen reduction catalysts, the Fe/N/C system emerges as a promising candidate. Nevertheless, the structural transformations of starting materials into Fe- and N-doped carbon catalysts remains poorly characterized under pyrolytic conditions. Here, we explore the evolution of Fe species and track the formation of Fe–N4 site development by employing diverse in-situ diagnostic techniques. In-situ heating microscopy reveals the initial formation of FeOx nanoparticles and subsequent internal migration within the carbon matrix, which stops once FeOx is fully reduced. The migration and decomposition of nanoparticles then leads to carbon layer reconstruction. Experimental and theoretical analysis reveals size-dependent behavior of FeOx where nanoparticles below 7 nm readily release Fe atoms to form Fe–N4 while nanoparticles with sizes >10 nm tend to coalesce and impede Fe–N4 site formation. The work visualizes the pyrolysis process of Fe/N/C materials, providing theoretical guidance for the rational design of catalysts.

Abstract Background Microbial infection and colonization are frequently associated with disease progression and poor clinical outcomes in bronchiectasis. Identification of pathogen spectrum is crucial for precision treatment at exacerbation of bronchiectasis. Methods We conducted a prospective cohort study in patients with bronchiectasis exacerbation onset and stable state. Bronchoalveolar lavage fluid (BALF) was collected for conventional microbiological tests (CMTs) and metagenomic Next-Generation Sequencing (mNGS). Bronchiectasis patients were monitored for documenting the time to the next exacerbation during longitudinal follow-up. Results We recruited 168 eligible participants in the exacerbation cohorts, and 38 bronchiectasis patients at stable state at longitudinal follow-up. 141 bronchiectasis patients at exacerbation onset had definite or probable pathogens via combining CMTs with mNGS reports. We identified that Pseudomonas aeruginosa, non-tuberculous mycobacteria, Haemophilus influenzae, Nocardia spp, and Staphylococcus aureus were the top 5 pathogens with a higher detection rate in our cohorts via combination of CMTs and mNGS analysis. We also observed strong correlations of Pseudomonas aeruginosa, Haemophilus influenzae, non-tuberculous mycobacteria with disease severity, including the disease duration, Bronchiectasis Severity Index, and lung function. Moreover, the adjusted pathogenic index of potential pathogenic microorganism negatively correlated (r = -0.7280, p

Abstract Background With the increasing incidence of obesity and the childbearing-age delay among women, a debate over obesity’s impacts on pregnancy and neonatal outcomes becomes hot. The potential negative effects of obesity and aging on fertility lead to an idea, whether an obese female pursuing IVF treatment can benefit from an ideal BMI achieved over a long-time weight loss process at the cost of aging? We aimed to assess the association between body mass index (BMI) and clinical or neonatal outcomes in patients undergoing in vitro fertilization (IVF) treatment, for answering whether it is necessary to lose weight first for obese patients, particularly those at advanced age. Methods A retrospective cohort study was performed using multicentered data from China. The women were stratified into 5 groups in terms of pre-gravid BMI (kg/m2) with the WHO obesity standard (group 1: BMI

Abstract Background Soybean (Glycine max) is a vital oil-producing crop. Augmenting oleic acid (OA) levels in soybean oil enhances its oxidative stability and health benefits, representing a key objective in soybean breeding. Pongamia (Pongamia pinnata), known for its abundant oil, OA, and flavonoid in the seeds, holds promise as a biofuel and medicinal plant. A comparative analysis of the lipid and flavonoid biosynthesis pathways in Pongamia and soybean seeds would facilitate the assessment of the potential value of Pongamia seeds and advance the genetic improvements of seed traits in both species. Results The study employed multi-omics analysis to systematically compare differences in metabolite accumulation and associated biosynthetic genes between Pongamia seeds and soybean seeds at the transcriptional, metabolic, and genomic levels. The results revealed that OA is the predominant free fatty acid in Pongamia seeds, being 8.3 times more abundant than in soybean seeds. Lipidomics unveiled a notably higher accumulation of triacylglycerols (TAGs) in Pongamia seeds compared to soybean seeds, with 23 TAG species containing OA. Subsequently, we identified orthologous groups (OGs) involved in lipid biosynthesis across 25 gene families in the genomes of Pongamia and soybean, and compared the expression levels of these OGs in the seeds of the two species. Among the OGs with expression levels in Pongamia seeds more than twice as high as in soybean seeds, we identified one fatty acyl-ACP thioesterase A (FATA) and two stearoyl-ACP desaturases (SADs), responsible for OA biosynthesis, along with two phospholipid:diacylglycerol acyltransferases (PDATs) and three acyl-CoA:diacylglycerol acyltransferases (DGATs), responsible for TAG biosynthesis. Furthermore, we observed a significantly higher content of the flavonoid formononetin in Pongamia seeds compared to soybean seeds, by over 2000-fold. This difference may be attributed to the tandem duplication expansions of 2,7,4ʹ-trihydroxyisoflavanone 4ʹ-O-methyltransferases (HI4ʹOMTs) in the Pongamia genome, which are responsible for the final step of formononetin biosynthesis, combined with their high expression levels in Pongamia seeds. Conclusions This study extends beyond observations made in single-species research by offering novel insights into the molecular basis of differences in lipid and flavonoid biosynthetic pathways between Pongamia and soybean, from a cross-species comparative perspective.

Abstract Background The association of hepatitis B virus (HBV) DNA levels and liver fibrosis in chronic hepatitis B (CHB) patients with immune-tolerant phase remains unclear. We explored the association between liver fibrosis and HBV DNA levels in HBeAg-positive CHB patients with normal alanine transaminase (ALT) with relatively high HBV DNA. Methods Six hundred and twenty-two HBeAg-positive CHB patients with normal ALT were included. Patients were divided into three categories: low (6 log10 IU/mL ≤ HBV DNA

Background: Acute myocardial ischemia/reperfusion injury (MIRI) with complicated mechanisms contributes to a high risk of ventricular arrhythmia, high lethality, and even sudden death. In vitro, Fraxinellone (FRA) exhibits an array of biologic activities and may possess cardioprotective effects. However, no relevant studies have examined FRA's protective potential against MIRI and related ventricular arrhythmias. The present study was undertaken to determine the effectiveness of FRA on MIRI and ventricular fibrillation (VF) susceptibility in rats and to elucidate the underlying mechanisms. Methods: 48 healthy male Sprague-Dawley (SD) rats were randomly divided into the following four groups: Sham+vehicle(n=12), Sham+FRA(n=12), I/R+vehicle(n=12) and I/R+FRA(n=12). Histopathology, electrophysiological examination, HRV analysis in combination with molecular biology were used to investigate the therapeutic benefits of FRA on cardiac injury and VF susceptibility during myocardial IR. Finally, the potential mechanism by which FRA protects myocardium from MIRI was explored. Results: Pretreatment with FRA ameliorated myocardial fibrosis after MIRI in vivo, alleviated myocardial injury, inflammation, oxidative stress and apoptosis in vivo and in vitro, thereby protecting myocardium from MIRI injury. In addition, FRA administration could improve HRV, prolong ventricular effective refractory period (ERP) and action potential duration (APD), attenuate VF induction rate, and contribute to improving ventricular sympathetic nerve remodeling and ion channel remodeling. Mechanistically, FRA may reduce MIRI via the PI3K/AKT pathway. Conclusion: FRA may exert cardioprotective effects during MIRI by inhibiting myocardial inflammation, oxidative stress and apoptosis, and decrease VF susceptibility by improving sympathetic remodeling and ion channel remodeling, which might represent a potential therapeutic strategy for attenuation of MIRI.

Background The aim of this study was to compare differences in shot placement and accuracy between national and international level squash players. Squash is a technically demanding sport and understanding the biomechanical characteristics of athletes at different levels is important for developing effective training strategies. Methods The study used a three-dimensional motion analysis system, a high-speed video camera, and a professional tee for biomechanical testing. Participants included national and international level squash players. The kinematic characteristics of the shoulder, elbow, and wrist joints of the upper extremity for backhand strokes, as well as the accuracy of the strokes, were analyzed to compare the differences between the two groups of athletes in terms of stroke posture and accuracy. Results The kinematic analysis of the backward backhand stroke revealed that national squash players showed significant differences compared to international players in several key parameters. Specifically, national players had significantly greater trunk flexion (P = 0.018) and less shoulder medial rotation (P = 0.027). They also had lower racket velocity in the X-direction (P = 0.043). However, there were no significant differences in trunk lateral flexion (P = 0.487), trunk rotation (P = 0.293), shoulder extension/flexion (P = 0.396), elbow flexion/extension (P = 0.818), wrist flexion/extension (P = 0.177), wrist rotation (P = 0.476), racket pitch (P = 0.112), racket velocity in the Y-direction (P = 0.587), or racket velocity in the Z-direction (P = 0.327). Additionally, data for racket yaw, racket roll, and racket Vx were not provided with significant values, indicating that these parameters do not show significant differences. Conclusion International level players outperformed national level players in squash stroke accuracy and control. Key kinematic factors influencing accuracy include trunk forward flexion, shoulder abduction, shoulder internal rotation, and racket angles. The study recommends that coaches design training to enhance technical details and positional control to improve squash performance.

ABSTRACT Although the Omicron variant has been associated with greater transmissibility and tropism of the upper respiratory tract, the clinical and pathogenic features of patients infected with the Omicron variant during an outbreak in China have been unclear. Adults with COVID-19 were retrospectively enrolled from seven medical centers in Guangzhou, China, and clinical information and specimens ( BALF, sputum, and throat swabs) from participants were collected. Conventional detection methods, metagenomics next-generation sequencing (mNGS), and other methods were used to detect pathogens in lower respiratory tract samples. From December 2022 to January 2023, we enrolled 836 patients with COVID-19, among which 56.7% patients had severe/critical illness. About 91.4% of patients were infected with the Omicron strain (BA.5.2). The detection rate of possible co-infection pathogens was 53.4% by mNGS, including Klebsiella pneumoniae (16.3%), Aspergillus fumigatus (12.2%), and Pseudomonas aeruginosa (11.8%). The co-infection rate was 19.5%, with common pathogens being Streptococcus pneumoniae (11.5%), Haemophilus influenzae (9.2%), and Adenovirus (6.9%). The superinfection rate was 75.4%, with common pathogens such as Klebsiella pneumoniae (26.1%) and Pseudomonas aeruginosa (19.4%). Klebsiella pneumoniae (27.1%% vs 6.1%, P < 0.001), Aspergillus fumigatus (19.6% vs 5.3%, P = 0.001), Acinetobacter baumannii (18.7% vs 4.4%, P = 0.001), Pseudomonas aeruginosa (16.8% vs 7.0%, P = 0.024), Staphylococcus aureus (14.0% vs 5.3%, P = 0.027), and Streptococcus pneumoniae (0.9% vs 10.5%, P = 0.002) were more common in severe cases. Co-infection and superinfection of bacteria and fungi are common in patients with severe pneumonia associated with Omicron variant infection. Sequencing methods may aid in the diagnosis and differential diagnosis of pathogens.IMPORTANCEOur study has analyzed the clinical characteristics and pathogen spectrum of the lower respiratory tract associated with co-infection or superinfection in Guangzhou during the outbreak of the Omicron strain, particularly after the relaxation of the epidemic prevention and control strategy in China. This study will likely prompt further research into the specific issue, which will benefit clinical practice.

The Chinese medicine residue (CMR) is composed of wet substances, so using hydrothermal carbonization (HTC) to recover renewable energy from the residue is a suitable treatment method. Chromium (Cr), a kind of heavy metal element, is enriched in hydrochar and severely restricts its effective utilization. An in-depth analysis of the migration path and mechanism of Cr in hydrochar is helpful in promoting energy utilization for CMR. Here, licorice, a significant Chinese medicine, was selected as the example to analyze the evolutions of its pore and chemical structures and their effects on the migration mechanism of Cr during the HTC process. The products obtained under various HTC conditions were analyzed using nitrogen adsorption, FTIR, and 13C NMR. The results show that, considering reaction time and relevant reactions as the primary factors during the HTC process, the migration pathway of Cr in hydrochar undergoes two stages, and they are the accompanying migration stage and the recovery aggregation stage. Active adsorption sites for Cr may exist within the pore structure of hydrochar. In the HTC process, hydrolysis, decarboxylation, and decarbonylation reactions are the direct drivers of Cr migration, while aromatization is the underlying cause of Cr recovery and aggregation. It is hypothesized that Cr catalyzes the acetylene cyclotrimerization reaction, thereby promoting the formation of aromatic structures in hydrochar and integrating into the hydrochar carbon skeleton.

Background: Infectious diseases remain a major global health concern, including in China, with an estimated >10 million cases of infectious disease in 2019. We describe the burden of site-specific infectious diseases among Chinese adults. Methods: From 2004 to 2008, the prospective China Kadoorie Biobank enrolled 512,726 adults aged 30-79 years from 10 diverse areas (5 rural, 5 urban) of China. During the 12 years of follow-up, 101,673 participants were hospitalized for any infectious disease. Descriptive analyses examined standardized incidence, mortality and case fatality of infections. Findings: The incidence of any infectious disease was 1856 per 100,000 person-years; respiratory tract infections (1069) were most common. The infectious disease mortality rate was 31.8 per 100,000 person-years (20.3 and 9.4 for respiratory and non-respiratory infections, respectively) and case fatality was 2.2% (2.6% and 1.6% for respiratory and non-respiratory infections, respectively). Infectious disease incidence and mortality rates were higher at older ages and in rural areas. There were no clear sex differences in infectious disease incidence rates, but mortality and case fatality rates were twice as high in men as in women. Interpretation: Infectious diseases were common in Chinese adults. The observed burden of, and disparities in, site-specific infections can inform targeted prevention efforts. Funding: Kadoorie Foundation, Wellcome Trust, MRC, BHF, CR-UK, MoST, NNSF.

Background: The clinical significance of gastrointestinal (GI) symptoms in patients with severe fever and thrombocytopenia syndrome (SFTS) is poorly characterized. This study aimed to determine the prevalence and effect of GI symptoms on the prognosis of patients with SFTS. Methods: This was a retrospective multi-center cohort study that included hospitalized patients with SFTS from three institutions between October 2010 and August 2022. The risk factors for mortality and intensive care unit (ICU) admission were identified by Cox and logistic regression analyses, respectively. Kaplan-Meier curves were used to analyze the cumulative mortality risk. Results: Among 304 patients, the median age was 62.0 years and 51.0 % of the patients were male. A total of 202 patients (66.4 %) had at least one GI symptom on admission. Diarrhea (69.8 %) and nausea (57.4 %) were the most common symptoms. Patients with GI symptoms had lower male proportion (46.0 % vs. 60.8 %, P = 0.015), higher aspartate aminotransferase (177.5 U/L vs. 118.0 U/L, P = 0.010) and lactic dehydrogenase (771.0 U/L vs. 666.5 U/L, P = 0.017) levels than that of patients without GI symptoms. However, there was no significant difference in mortality rates (23.8 % vs. 21.6 %, P = 0.668) and ICU admission (14.4 % vs. 12.7 %, P = 0.701) between SFTS patients with and without GI symptoms. Multivariate analysis suggested that GI symptoms at admission were not associated with mortality and ICU admission. Conclusions: GI symptoms are common in patients with SFTS. However, the presence of GI symptoms was not an independent risk factor for poor prognosis.

Evaluating the health of river surface water is essential, as rivers support significant biological resources and serve as vital drinking water sources. While the Water Quality Index (WQI) is commonly employed to evaluate surface water quality, it fails to consider biodiversity and does not fully capture the ecological health of rivers. Here we show a comprehensive assessment of the ecological health of surface water in the lower Yangtze River (LYR), integrating chemical and biological metrics. According to traditional WQI metrics, the LYR's surface water generally meets China's Class II standards. However, it also contains 43 high-risk emerging contaminants; nitrobenzenes are found at the highest concentrations, representing 25–90% of total detections, while polycyclic aromatic hydrocarbons present the most substantial environmental risks, accounting for 81–93% of the total risk quotient. Notably, the plankton-based index of biological integrity (P-IBI) rates the ecological health of the majority of LYR water samples (59.7%) as ‘fair’, with significantly better health observed in autumn compared to other seasons (p

IntroductionThe aim of research was to study the feasibility and safety of surgery providing specimen extraction through natural orifices in patients with colorectal cancer.Materials and methodsThis study is a comparative retrospective analysis of findings obtained from 265 patients who underwent surgical treatment using NOSES technique and 275 patients who underwent laparoscopic-assisted (LA) resection. Data included preoperative patients’ information, intraoperative findings, results of postoperative pathological examination of surgical specimens, early postoperative period analysis, and follow-up.ResultsBoth groups were comparable in terms of gender, age and BMI. The duration of surgery was similar in both groups (p = 0.94). Intraoperative blood loss under NOSES interventions was slightly lower than in laparoscopic-assisted surgeries (p 0.05). It was revealed that in the NOSES group, the function of the gastrointestinal tract normalized at an earlier time, slightly the time to start liquid food intake and the duration of postoperative hospital stay were reduced (p 0.05).ConclusionThe results of this study demonstrate that NOSES technique is a relatively safe and effective surgical option in patients with colorectal cancer. It has high surgical efficiency providing no increased risk of surgical intervention, reducing total number of postoperative complications, reducing duration of postoperative hospital stay, reducing the time for gastrointestinal function recovery and the start of food intake. This study supports that NOSES has clear advantages over conventional laparoscopic-assisted surgery.

BackgroundThe gut microbiota (GM) plays a pivotal role in influencing various health outcomes, including immune-mediated conditions, but its potential association with autoimmune thyroid disease (AITD) remains underexplored. We aimed to investigate the potentially pathogenic or protective causal impacts of specific GM on two types of AITD, namely Graves’ disease and Hashimoto’s thyroiditis, and analyzed the mediating effect of 731 immune cell phenotypes.MethodsLeveraging pooled genome-wide association study (GWAS) data of 211 gut microbiota traits, 731 immune cell phenotypes, and two types of AITD (Hashimoto’s thyroiditis and Graves’ disease), we performed bidirectional Mendelian randomization (MR) analyses to explore the causal relationships between the GM and AITD. Subsequently, we employed a multivariable MR analysis to discover potential mediating immune cell traits. Additionally, sensitivity analyses were utilized to ensure the reliability of the outcomes.ResultsOur analysis revealed that a total of 7 GM taxa were positively associated with AITD, and other 14 taxa showed a negative correlation with AITD. Furthermore, we identified several immune cell traits that mediated the effects of GM on AITD. Most notably, Actinobacteria (p) presented protective effects on Hashimoto’s thyroiditis via CCR2 on myeloid Dendritic Cell (5.0%), and Bifidobacterium (g) showed facilitating effects on Graves’ disease through CD39+ CD4+ T cell %CD4+ T cell (5.0%) and CD14 on CD33+ HLA DR+ CD14dim (12.2%).ConclusionThe current MR study provides evidence supporting the causal relationships between several specific GM taxa and AITD, and further identified potential mediating immunophenotypes.