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Performing arts education has been significantly affected by the COVID-19 pandemic crisis around the world since early 2020. Educators had to adapt the classes with remote learning when face-to-face instruction had been suspended during the pandemic. Although frustrations and confusion continued to abound with the implementation of new pedagogies, online teaching, and learning spurred new practices, innovative ideas, and breakthroughs. Some performing arts educators took this opportunity to explore new skills and strategies and provided performing arts students with more impactful learning experiences. Presently, with the COVID-19 pandemic gradually showing a sign of easing, many Hong Kong schools have returned to in-person instruction. Meanwhile, the impactful learning feedback from students triggered calls for redesigning the pedagogy of performing arts education. This study placed the impact of COVID-19 on performing arts education into context and drilled down into the delivery of performing arts education in the post-pandemic era. This study reviewed teaching and learning experiences of performing arts education, with the following three research questions addressed: (a) What is the correlation between performing arts students' academic traits and their proficiency in utilizing technology during the COVID-19 pandemic? (b) What are the influential factors impacting the hybrid learning experience and outcomes of performing arts students during the COVID-19 pandemic? (c) What are the anticipated expectations of performing arts students regarding future models of arts education? Furthermore, practical solutions and insights for performing arts educational delivery in the post-pandemic era are provided in this study.

Abstract Male infertility is one of the most common reproductive dysfunctions. Despite oligospermia being a cause of infertility, few studies have been conducted on it. This study aimed to investigate differences in semen metabolic patterns in patients with oligospermia and to identify potential biomarkers associated with oligospermia. Semen samples from oligospermia patients (20 cases) and healthy controls (20 cases) were detected by high performance liquid chromatography-tandem mass spectrometry (HPLC-MS/MS), and 72 and 89 metabolites were identified as potential markers in positive and negative ion modes, respectively. In addition, the results identified multiple metabolic pathways in patients with oligospermia, such as glycine serine and threonine metabolism, Synthesis and degradation of ketone bodies, Valine, leucine, and isoleucine degradation. These results described unique metabolic characteristics of semen in patients with oligospermia and provided novel insights into the mechanism of the semen disorder.

Abstract Glucagon-like peptide-1 (GLP-1) analogs are important therapeutics for type 2 diabetes and obesity. Ecnoglutide (XW003) is a novel, long-acting GLP-1 analog. We conducted a Phase 2, randomized, double-blind, placebo-controlled study enrolling 145 adults with T2DM. Participants were randomized to 0.4, 0.8, or 1.2 mg ecnoglutide or placebo as once-weekly injections for 20 weeks. The primary objective was to evaluate the efficacy of ecnoglutide, as measured by HbA1c change from baseline at Week 20. Secondary endpoints included body weight, glucose and lipid parameters, as well as safety. We show that, at end of treatment, the 0.4, 0.8, and 1.2 mg groups had statistically significant HbA1c reductions from baseline of −1.81%, −1.90%, and −2.39%, respectively, compared to −0.55% for placebo (P

Abstract Regulated cell death (RCD) plays a crucial role in the immune microenvironment, development, and progression of hepatocellular carcinoma (HCC). However, reliable immune-related cell death signatures have not been explored. In this study, we collected 12 RCD modes (e.g., apoptosis, ferroptosis, and cuproptosis), including 1078 regulators, to identify immune-related cell death genes based on HCC immune subgroups. Using a developed competitive machine learning framework, nine genes were screened to construct the immune-related cell death index (IRCDI), which is available for online application. Multi-omics data, along with clinical features, were analyzed to explore the HCC malignant heterogeneity. To validate the efficacy of this model, more than 18 independent cohorts, including survival and diverse treatment cohorts and datasets, were utilized. These findings were further validated using in-house samples and molecular biological experiments. Overall, the IRCDI may have a wide application in individual therapeutic decision-making and improving outcomes for HCC patients.

Abstract Background This study aimed to answer the research question: How reliable is ChatGPT in automated essay scoring (AES) for oral and maxillofacial surgery (OMS) examinations for dental undergraduate students compared to human assessors? Methods Sixty-nine undergraduate dental students participated in a closed-book examination comprising two essays at the National University of Singapore. Using pre-created assessment rubrics, three assessors independently performed manual essay scoring, while one separate assessor performed AES using ChatGPT (GPT-4). Data analyses were performed using the intraclass correlation coefficient and Cronbach's α to evaluate the reliability and inter-rater agreement of the test scores among all assessors. The mean scores of manual versus automated scoring were evaluated for similarity and correlations. Results A strong correlation was observed for Question 1 (r = 0.752–0.848, p 0.05), and there was a strong correlation between AES and manual scores (r = 0.829, p

Axolotls are known for their remarkable regeneration ability. Exploring their transcriptome provides insight into regenerative mechanisms. However, the current annotation of the axolotl transcriptome is limited, leaving the role of unannotated transcripts in regeneration unknown. To discourse this challenge, we exploited long-read sequencing technology, which enables direct observation of full-length RNA transcripts, greatly enhancing the coverage and accuracy of axolotl transcriptome annotation. By utilizing this method, we identified 222 novel gene loci and 4775 novel transcripts, which were quantified using short-read sequencing data. Through the inclusive analysis, we discovered novel homologs, potential functional proteins, noncoding RNAs, and alternative splicing events in key regeneration pathways. In particular, we identified novel transcripts with high protein-coding potential implicated in cell cycle regulation and musculoskeletal development, and regeneration were identified. Interestingly, alternative splice variants were also detected across diverse pathways critical to regeneration. This specifies that these novel transcripts potentially play vital roles underpinning the robust regenerative capacities of axolotls. Single-cell transcriptomic analysis further revealed these isoforms to predominantly exist in axolotl limb chondrocytes and mature tissue cell populations. Overall, the findings significantly advanced consideration of the axolotl transcriptome and provided a new perspective for understanding the mechanisms of regenerative abilities of axolotls.

Sugars will eventually be exported transporter (SWEET) is a novel class of sugars transporter families which mainly mediate either sucrose or hexose translocation bidirectional across the cellular membranesfollowinga concentrating gradient with a passive diffusion patten. In higher plants, SWEET proteins commonly have seven transmembrane domains that form a pore in the membrane to allow the passage of sugars, containing two MtN3/Saliva domains. Phylogenetically, plant SWEETs are divided into four clades. SWEET transporters play important roles in diverse physiological and biochemical processes including phloem loading, plant hormone transportand vegetative growth. In this review, based on the current advance of the plant SWEET transporters, we summarized their discovery, structure characteristicsand biological functions, and pointed out current research problems. Finally,put forward several better future research directions and potential solutions for SWEET sugar transporters in plant from the following three aspects: 1) exploring the molecular mechanism of substrate recognition and selectivity of SWEET proteins; 2) mining and utilizing of key SWEET genes increasing crop yield and improving quality; 3) using gene editing technology and phosphorylation of SWEET transporters to engineer high-yielding and high-quality crops.

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 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 Left ventricular assist device (LVAD) implantation is an effective alternative treatment to heart transplantation, especially for end‐stage heart failure patients who are ineligible for or unable to await a heart transplant. This report describes a complex and innovative surgery where LVAD implantation was performed alongside multiple concomitant cardiac and aortic procedures. A 62‐year‐old male patient with complicated comorbidities developed acute myocardial infarction and subsequent refractory advanced heart failure. Given his critically ill condition and intractable anatomical malformations, the CH‐VAD left ventricular assist system implantation was performed concomitantly with the Bentall procedure, coronary artery bypass grafting, tricuspid valvuloplasty, and foramen ovale closure. The patient was successfully discharged. This case details the medical decision‐making process and surgical strategy and demonstrates the feasibility of LVAD implantation combined with multiple additional cardiac and aortic procedures in expert cardiac centres. Success relies on experienced cardiac surgeons and a multidisciplinary LVAD Heart Team, ensuring excellence in surgical techniques, preoperative evaluation, post‐operative care, and rehabilitation.

The arthroconidial yeast-like species currently classified in the asexual genera Geotrichum and Saprochaete and the sexual genera Dipodascus, Galactomyces and Magnusiomyces are frequently associated with dairy and cosmetics production, fruit rot and human infection. However, the taxonomic system of these fungi has not been updated to accommodate the new nomenclature code adopting the “one fungus, one name” principle. Here, we performed phylogenetic analyses of these yeast-like species based on the sequences of the internal transcribed spacer (ITS) region and the D1/D2 domain of the large subunit of the rRNA gene. Two monophyletic groups were recognised from these species. One group contained Dipodascus, Galactomyces, and Geotrichum species and the other Magnusiomyces and Saprochaete species. We thus assigned the species in each group into one genus and selected the genus name Geotrichum for the first group and Magnusiomyces for the second one based on the principle of priority of publication. Five new Geotrichum species were identified from arthroconidial yeast strains recently isolated from various sources in China. The new species are described as Ge. dehoogii sp. nov., Ge. fujianense sp. nov., Ge. maricola sp. nov., Ge. smithiae sp. nov., and Ge. sinensis sp. nov.

Abstract The microreactor with two types of immobilized enzymes, exhibiting excellent orthogonal performance, represents an effective approach to counteract the reduced digestion efficiency resulting from the absence of a single enzyme cleavage site, thereby impacting protein identification. In this study, we developed a hydrophilic dual-enzyme microreactor characterized by rapid mass transfer and superior enzymatic activity. Initially, we selected KIT-6 molecular sieve as the carrier for the dual-IMER due to its three-dimensional network pore structure. Modification involved co-deposition of polyethyleneimine (PEI) and acrylamide (AM) as amine donors, along with dopamine to enhance material hydrophilicity. Remaining amino and double bond functional groups facilitated stepwise immobilization of trypsin and Glu-C. Digestion times for bovine serum albumin (BSA) and bovine hemoglobin (BHb) on the dual-IMER were significantly reduced compared to solution-based digestion (1 min vs. 36 h), resulting in improved sequence coverage (91.30% vs. 82.7% for BSA; 90.24% vs. 89.20% for BHb). Additionally, the dual-IMER demonstrated excellent durability, retaining 96.08% relative activity after 29 reuse cycles. Enhanced protein digestion efficiency can be attributed to several factors: (1) KIT-6’s large specific surface area, enabling higher enzyme loading capacity; (2) Its three-dimensional network pore structure, facilitating faster mass transfer and substance diffusion; (3) Orthogonality of trypsin and Glu-C enzyme cleavage sites; (4) The spatial effect introduced by the chain structure of PEI and glutaraldehyde’s spacing arm, reducing spatial hindrance and enhancing enzyme–substrate interactions; (5) Mild and stable enzyme immobilization. The KIT-6-based dual-IMER offers a promising technical tool for protein digestion, while the PDA/PEI/AM-KIT-6 platform holds potential for immobilizing other proteins or active substances.

Abstract Effective disinfection methods are crucial in the cold chain transportation process of food due to the specificity of temperature and the diversity of contaminated flora. The objective of this study was to investigate the sanitizing effect of different disinfectants on various fungi at – 20 °C to achieve accurate disinfection of diverse bacterial populations. Peracetic acid, hydrogen peroxide, and potassium bisulfate were selected as low-temperature disinfectants and were combined with antifreeze. The sanitizing effect of these cryogenic disinfectants on pathogens such as Bacillus subtilis black variant spores (ATCC9372), Staphylococcus aureus (ATCC 6538), Candida albicans (ATCC 10231), Escherichia coli (8099), and poliovirus (PV-1) was sequentially verified by bactericidal and virus inactivation experiments. After a specified time of disinfection, a neutralizing agent was used to halt the sanitizing process. The study demonstrates that different disinfectants exhibit selective effects during the low-temperature disinfection process. Peracetic acid, hydrogen peroxide, and potassium monopersulfate are suitable for the low-temperature environmental disinfection of bacterial propagules, viruses, and fungal contaminants. However, for microorganisms with strong resistance to spores, a low-temperature disinfectant based on peracetic acid should be chosen for effective disinfection treatment. Our results provide a valuable reference for selecting appropriate disinfectants to sanitize various potential pathogens in the future.

The title compound, tetraethylammonium triazidotri-μ3-sulfido-[μ3-(trimethylsilyl)azanediido][tris(3,5-dimethylpyrazol-1-yl)hydroborato]triiron(+2.33)molybdenum(IV), (C8H20N)[Fe3MoS3(C15H22BN6)(C3H9NSi)(N3)3] or (Et4N)[(Tp*)MoFe3S3(μ3-NSiMe3)(N3)3] [Tp* = tris(3,5-dimethylpyrazol-1-yl)hydroborate(1−)], crystallizes as needle-like black crystals in space group P\overline{1}. In this cluster, the Mo site is in a distorted octahedral coordination model, coordinating three N atoms on the Tp* ligand and three μ3-bridging S atoms in the core. The Fe sites are in a distorted tetrahedral coordination model, coordinating two μ3-bridging S atoms, one μ3-bridging N atom from Me3SiN2−, and another N atom on the terminal azide ligand. This type of heterometallic and heteroleptic single cubane cluster represents a typical example within the Mo–Fe–S cluster family, which may be a good reference for understanding the structure and function of the nitrogenase FeMo cofactor. The residual electron density of disordered solvent molecules in the void space could not be reasonably modeled, thus the SQUEEZE [Spek (2015). Acta Cryst. C71, 9–18] function was applied. The solvent contribution is not included in the reported molecular weight and density.

Abstract Incorporation of CO into substrates to construct high‐value carbonyl compounds is an intensive industrial carbonylation procedure, however, high toxicity and wide explosion limits (12.5–74.0 vol% in air) of CO limit its application in industrial production. The development of a CO‐free catalytic system for carbonylation is one of ideal methods, but full of challenge. Herein, this study reports the CO‐free aminocarbonylation conversion of terminal alkynes synergistically catalyzed by a unique Co(ІІ)/Ag(І) metal–organic framework (MOF), in which the combination of isocyanides and O2 is employed as safe and green source of aminocarbonyl. This reaction has broad substrate applicability in terminal alkyne and isocyanides components with 100% atom economy. The bimetal MOF catalyst can be recycled at least five times without substantial loss of catalytic activities. Mechanistic investigations demonstrate that the synergistic effect between Ag(I) and Co(II) sites can efficiently activate terminal alkyne and isocyanides, respectively. Free radical capture experiments, FT‐IR analysis and theoretical explorations further reveal that terminal alkynes and isocyanides can be catalytically transformed into an anionic intermediate through heterolysis pathways. This work provides secure and practical access to carbonylation as well as a new approach to aminocarbonylation of terminal alkynes.

Abstract A Pd‐catalyzed enantioselective aminosilylation of alkenes via tandem Aza‐Heck/silylation reaction under Pd/Sadphos catalysis is disclosed. A wide array of oxime esters and silicon reagents are tolerated, furnishing the chiral pyrrolines bearing one quaternary or two contiguous stereocenters in good yield with high enantioselectivity. Not only terminal alkenes but also tri‐substituented internal alkenes successfully participate in the reaction, delivering vicinal stereocenters in complete diastereoselectivity and high enantioselectivity. DFT study is conducted to probe the reaction pathway and the origin of the enantioselectivity, which revealed that the stereoinduction arises from the weak interaction between the aromatic ring of the substrate fragment and naphthyl group in the ligand.

Background: Sorafenib is approved for the targeted therapy of cancers such as liver cancer and renal cancer. Given its widespread use, drug-related adverse events have received attention, and the post-marketing regulatory link is crucial. Objective: By using the FAERS database to mine the adverse events (AEs) related to sorafenib, comparing the association intensity of key AEs, and exploring potential drug-related AEs, it provides a reference for clinical medication. Methods: Collect ADE data related to sorafenib in the FAERS database from 2006 to 2023. Standardize the data, and map adverse events to system organ classes and preferred terms. Analyze using various signal quantification techniques such as ROR, PRR, BCPNN, and MGPS. Results: Among 18,520 adverse event reports (AERs) where sorafenib was the primary suspected drug, a total of 390 preferred terms (PTs) of adverse reactions were identified, covering 24 different system organ classes (SOCs). Specifically, the adverse events of sorafenib mainly involve the digestive system, skin and subcutaneous tissue, as well as non-specific physical discomfort including infection and injury. Among them, digestive system symptoms and skin toxicity are typical adverse reactions of sorafenib. We also observed uncommon but clearly strong AE signals, such as chloracne (n = 3, ROR 1756.39, PRR 1756.32, IC 8.78, EBGM 439.83), low-differentiated thyroid cancer (n = 4, ROR 585.47, PRR 585.44, IC 8.2, EBGM 293.22). It is worth noting that palmar-plantar erythrodysaesthesia syndrome (n = 2109, ROR 73.98, PRR 72.03, IC 6.01, EBGM 64.25) and hepatic encephalopathy (n = 457, ROR 37.44, PRR 37.23, IC 5.13, EBGM 35.07) have a higher incidence and signal intensity. In addition, we also observed some adverse events not mentioned in the official drug instructions, such as vitamin K deficiency or increased protein induced by antagonist II (PIVKA-II), abnormal alpha-fetoprotein, tumor metastasis, and splenic atrophy. Conclusion: Sorafenib carries the risk of various adverse reactions while providing therapeutic effects. In clinical applications, physicians should closely monitor the occurrence of digestive system reactions, skin lesions, endocrine system lesions, as well as injuries, infections, and other events.

Abstract The enormous and widespread use of organoboronic acids has prompted the development of innovative synthetic methodologies to meet the demands on structural diversity and functional group tolerance. The existing photoinduced defunctionalization radical borylation, typically focused on the conversion of one C-X bond (X= Br, I, or other leaving group) into only one C-B bond. Herein, we disclose a divergent radical dechloroborylation reaction enabled by dinuclear gold catalysis with visible light irradiation. A wide range of structurally diverse alkyl boronic, α-chloroboronic, and gem-diboronic esters can be synthesized in moderate to good yields (up to 92%). Its synthetic robustness is further demonstrated on a preparative scale and applied to late-stage diversification of complex molecules. The process hinges on a C-Cl bond relay activation in readily available gem-dichloroalkanes through inner-sphere electron transfer, overcoming the redox potential limits of unreactive alkyl chlorides.

The development of a high-performance ferroelectric piezo-photocatalyst is an efficient strategy for advancing sustainability within the environmental and energy sectors. Yet, a major challenge lies in the creation of a strong polarized electric field that can effectively hinder charge recombination, both within the bulk and on the surface of catalysts. Herein, we synthesize a series of Nb-doped Bi4Ti3O12 nanosheets via a facile one-pot hydrothermal method to achieve synergistically enhanced piezo-photocatalytic performance in CO2 reduction and pollutant degradation. The optimized doped Bi4Ti3O12 demonstrates remarkable efficiency in the conversion of CO2 into CO, with a high production rate of 72.7 μmol∙g−1∙h−1 without using co-catalysts or any sacrificial agent, surpassing the performance of unmodified Bi4Ti3O12 by up to 4.69 folds. Additionally, our catalyst demonstrates ultra-fast piezo-photocatalytic degradation of organic pollutant Rhodamine B (RhB) at low concentrations and exceptional piezo-photocatalytic activity at high concentrations, outperforming most previously reported state-of-the-art catalysts. The systematic corroboration of catalyst characterization and experimental analysis reveals that the synergistic effect arises from the amplified macroscopic polarization induced by lattice distortion caused by the larger Nb ions, thereby improving piezo-photocatalytic efficiency. This research thus offers valuable insights into the direct design and fabrication of versatile catalytic systems, with applications spanning CO2 valorization and beyond.

Abstract Background TikTok is emerging as a vital platform for health information dissemination. Despite myopia being a global public health issue, the high-quality myopia information shared by health educators often fails to go viral. It is imperative to analyze the factors influencing video quality and popularity, especially from diverse perspectives of researchers, health educators, and audiences. Methods TikTok myopia-related videos were retrieved using TikTok’s default comprehensive search (DCS) and most liked search (MLS) strategies. Venn diagrams were employed to illustrate the relationships and commonalities between the two strategies across four sample sizes (top 200, 150, 100, and 50). Video metadata, including details such as creator information, production properties, upload time, video duration, and viewer engagement, were collected. Video quality was assessed using the DISCERN tool. Video content covering six aspects of myopia were evaluated. The impact of search strategies, video sample sizes, production properties, and myopia content on video quality and audience engagement was analyzed through single-factor or multi-factor analysis. Results DCS and MLS retrieval strategies, as well as varying sample sizes, resulted in differences in audience engagement for myopia videos (P 0.221). Videos published by healthcare professionals (HCPs) and non-profit organizations (NPOs) were associated with high-quality (P ≤ 0.014) but comparatively lower popularity (P 60s) exhibited the opposite trend (P

Abstract The local climate zones (LCZs) classification system has emerged as a more refined method for assessing the urban heat island (UHI) effect. However, few researchers have conducted systematic critical reviews and summaries of the research on LCZs, particularly regarding significant advancements of this field in recent years. This paper aims to bridge this gap in scientific research by systematically reviewing the evolution, current status, and future trends of LCZs framework research. Additionally, it critically assesses the impact of the LCZs classification system on climate-responsive urban planning and design. The findings of this study highlight several key points. First, the challenge of large-scale, efficient, and accurate LCZs mapping persists as a significant issue in LCZs research. Despite this challenge, the universality, simplicity, and objectivity of the LCZs framework make it a promising tool for a wide range of applications in the future, especially in the realm of climate-responsive urban planning and design. In conclusion, this study makes a substantial contribution to the advancement of LCZs research and advocates for the broader adoption of this framework to foster sustainable urban development. Furthermore, it offers valuable insights for researchers and practitioners engaged in this field.

Abstract Background Numerous studies highlight the genetic underpinnings of mental disorders comorbidity, particularly in anxiety, depression, and schizophrenia. However, their shared genetic loci are not well understood. Our study employs Mendelian randomization (MR) and colocalization analyses, alongside multi-omics data, to uncover potential genetic targets for these conditions, thereby informing therapeutic and drug development strategies. Methods We utilized the Consortium for Linkage Disequilibrium Score Regression (LDSC) and Mendelian Randomization (MR) analysis to investigate genetic correlations among anxiety, depression, and schizophrenia. Utilizing GTEx V8 eQTL and deCODE Genetics pQTL data, we performed a three-step summary-data-based Mendelian randomization (SMR) and protein–protein interaction analysis. This helped assess causal and comorbid loci for these disorders and determine if identified loci share coincidental variations with psychiatric diseases. Additionally, phenome-wide association studies, drug prediction, and molecular docking validated potential drug targets. Results We found genetic correlations between anxiety, depression, and schizophrenia, and under a meta-analysis of MR from multiple databases, the causal relationships among these disorders are supported. Based on this, three-step SMR and colocalization analyses identified ITIH3 and CCS as being related to the risk of developing depression, while CTSS and DNPH1 are related to the onset of schizophrenia. BTN3A1, PSMB4, and TIMP4 were identified as comorbidity loci for both disorders. Molecules that could not be determined through colocalization analysis were also presented. Drug prediction and molecular docking showed that some drugs and proteins have good binding affinity and available structural data. Conclusions Our study indicates genetic correlations and shared risk loci between anxiety, depression, and schizophrenia. These findings offer insights into the underlying mechanisms of their comorbidities and aid in drug development.

Abstract Left ventricular hypertrophy (LVH) is a hypertensive heart disease that significantly escalates the risk of clinical cardiovascular events. Its etiology potentially incorporates various clinical attributes such as gender, age, and renal function. From mechanistic perspective, the remodeling process of LVH can trigger increment in certain biomarkers, notably sST2 and NT‐proBNP. This multicenter, retrospective study aimed to construct an LVH risk assessment model and identify the risk factors. A total of 417 patients with essential hypertension (EH), including 214 males and 203 females aged 31–80 years, were enrolled in this study; of these, 161 (38.6%) were diagnosed with LVH. Based on variables demonstrating significant disparities between the LVH and Non‐LVH groups, three multivariate stepwise logistic regression models were constructed for risk assessment: the “Clinical characteristics” model, the “Biomarkers” model (each based on their respective variables), and the “Clinical characteristics + Biomarkers” model, which amalgamated both sets of variables. The results revealed that the “Clinical characteristics + Biomarkers” model surpassed the baseline models in performance (AUC values of the “Clinical characteristics + Biomarkers” model, the “Biomarkers” model, and the “Clinical characteristics” model were .83, .75, and .74, respectively; P

Background: Recently, the osteogenic potential of Adiponectin-labeled adipogenic lineage progenitors (Adipoq-lineage progenitors) in bone marrow has been observed to support bone maintenance and repair. However, little is known about the function of Schnurri-3 (SHN3, also known as HIVEP3) in other mesenchymal lineage cells, apart from its negative regulation of bone formation on osteoblasts. Method: In this study, we used single-cell RNA sequencing (scRNA-seq) profiling to demonstrate that Adipoq-lineage progenitors express higher levels of Shn3 compared to other mesenchymal cell populations in mice and humans. To investigate the role of SHN3 in Adipoq-lineage progenitors, we generated a murine model specifically harboring a Shn3-deficient allele in Adipoq-expressing cells. Information of mice body weight was collected weekly to generate body weight curve. Bone phenotype was analyzed using micro-CT and histomorphometric studies. To eliminate the role of peripheral adipose tissue on bone, we collected adipose wet weight, performed intraperitoneal glucose tolerance tests and intraperitoneal insulin tolerance tests, and conducted a fat-transplantation study. Osteoblast and osteoclast functions were assessed through toluidine blue staining and TRAP staining, respectively. We further investigated the effect of Shn3 depletion on the differentiation of Adipoq-lineage progenitors through immunostaining and in vitro differentiation assays. Finally, we evaluated whether Shn3 deficiency in Adipoq-lineage progenitors affects the fracture healing process by generating bi-cortical femoral fracture models. Results: Depletion of Shn3 in Adipoq-lineage progenitors resulted in a significant increase in trabecular bone mass and bone formation in vivo, without disrupting whole-body energy metabolism and skeletal development. Consistent with these findings, both cell-lineage tracing and functional assays revealed that Shn3 ablation effectively shifted the cell fate of Adipoq-lineage progenitors towards an osteogenic phenotype in the bone marrow. Furthermore, in vivo studies demonstrated that the lack of Shn3 in Adipoq-lineage progenitors also enhanced bone fracture healing under pathological conditions. Conclusion: Overall, our findings provide a novel strategy for targeting the osteoanabolic potential of bone marrow Adipoq-lineage progenitors as a potential treatment for bone loss-related disorders. Translational potential of this article: We have identified a novel gene target that directs the cell fate of a previously identified non-osteogenic cell population under physiological conditions. This study not only expands the therapeutic value of Shn3 ablation in treating osteoporotic or traumatic bone diseases but also provides new insights into the contribution of bone marrow Adipoq-lineage progenitors to osteogenesis. Thus, this article further supports Shn3 silencing as a valuable approach to treat osteopenia and accelerate fracture healing (see graphical abstract)

Abstract Background Hyperuricemia and low level of high-density lipoprotein cholesterol (HDL-C) are both risk factors for coronary artery disease (CAD). The uric acid to HDL-C ratio (UHR) has recently been identified as a new inflammatory and metabolic biomarker. However, the relationship between the UHR and coronary culprit plaques has not been fully investigated in patients with acute coronary syndrome (ACS). Methods A total of 346 patients with ACS were enrolled in this study. Culprit lesion characteristics were assessed by optical coherence tomography (OCT). Logistic regression and linear correlation analyses were performed to assess the association between the UHR and culprit plaques. The predictive value of the UHR was investigated by receiver operating characteristic (ROC) curve analysis. Results The percentages of typical culprit plaques, including ruptures, erosions and thrombi, were greater in the high-UHR subgroup than those in the low-UHR subgroup. A positive relationship was also found between the UHR and diameter stenosis (r = 0.160, P = 0.003) and between the UHR and area stenosis (r = 0.145, P = 0.007). The UHR was found to be independently associated with plaque rupture, erosion and thrombus. Furthermore, ROC analysis suggested that the UHR had a better predictive value than low-density lipoprotein cholesterol. Conclusions An elevated UHR level was independently related to the occurrence rate of culprit plaques. The UHR is a simple and easily acquired parameter for detecting culprit plaques in patients with ACS.

AbstractExosomes carry large cargo of proteins, lipids, and nucleic acids, serving as versatile biomarkers for disease diagnosis and vehicles for drug delivery. However, up to date, no well recognized standard procedures for exosome storage were available for clinical application. This study aimed to determine the optimal storage conditions and the anticoagulants for plasma-derived exosome isolation. Fresh whole blood samples were collected from healthy participants and preserved in four different anticoagulants including sodium citrate (SC1/4), sodium citrate (SC1/9), lithium heparin (LH), or Ethylenediamine tetraacetic acid (EDTA), respectively. Exosomes were extracted from the plasma by differential ultracentrifugation and stored at three different temperatures, 4°C, −20°C or − 80°C for a duration ranging from one week to six months. All plasma samples for storage conditions comparison were pretreated with LH anticoagulant. Exosome features including morphological characteristics, pariticles size diameter, and surface protein profiles (TSG101, CD63, CD81, CD9, CALNEXIN) were assessed by transmission electron microscopy, Nanoparticle Tracking Analysis, and Western Blotting, respectively. Exosomes preserved in LH and SC1/4 group tended to remain intact microstructure with highly abundant protein biomarkers. Exosomes stored at 4°C for short time were prone to be more stable compared to thos at −80°C. Exosomes stored in plasma were superior in terms of ultrastructure, size diameter and surface protein expression to those stored in PBS. In conclusion, plasma-dervied exosome characteristics strictly depend on the anticoagulants and storage temperature and duration.

Background Sedated colonoscopy has been increasingly selected. However, the effect of sedated colonoscopy on polyp/adenoma detection rate (PDR/ADR) remains controversial among studies. Methods In this retrospective study, the medical records of 11 504 consecutive patients who underwent colonoscopy at our department from July 1, 2021 to December 31, 2022 were collected. Patients were divided into sedated and unsedated groups according to the use of intravenous sedation during colonoscopy. Overall PDR/ADR, right-side, transverse, and left-side colon PDR/ADR, and single and multiple PDR/ADR were calculated. By adjusting for age, gender, body mass index, inpatient, screening/surveillance, cecal intubation time, colonoscopy withdrawal time ≥6 min, and an endoscopist’s experience ≥5 years, multivariate logistic regression analyses were performed to evaluate the association of sedated colonoscopy with overall PDR/ADR, right-side, transverse, and left-side colon PDR/ADR, and single and multiple PDR/ADR, where the absence of PDR/ADR was used as reference. Odds ratios (ORs) with their 95% confidence intervals (CIs) were calculated. Results Overall, 2275 patients were included, of whom 293 and 1982 underwent sedated and unsedated colonoscopy, respectively. Multivariate logistic regression analyses showed that sedated colonoscopy was independently associated with lower overall PDR/ADR (OR = 0.640, 95% CI = 0.460-0.889, P = 0.008), right-side colon PDR/ADR (OR = 0.591, 95% CI = 0.417-0.837, P = 0.003), single PDR/ADR (OR = 0.659, 95% CI = 0.436-0.996, P = 0.048), and multiple PDR/ADR (OR = 0.586, 95% CI = 0.402-0.855, P = 0.005), but not transverse or left-side colon PDR/ADR. Conclusion Sedated colonoscopy may not be beneficial in terms of overall PDR/ADR, right-side colon PDR/ADR, and number of polyps/adenomas. Thus, it should be selectively recommended. Additionally, it should be necessary to explore how to improve the quality of sedated colonoscopy.

Abstract Plasma protein‐induced aggregation of nanoparticles (NPs) is a crucial issue in many applications, such as drug delivery. Although great efforts have been made to investigate the protein adsorption kinetics or protein‐induced NPs coalescence in bulk solutions, limited evidence has been uncovered for interfacial circumstances. Diet, disease, medicine, or senility could thoroughly change interfacial physicochemical properties of the inner lining of blood vessels. Implants including stents and artificial heart valves also have varied and evolutionary interfaces. Hence, there is an urgent need to understand the mechanism behind the non‐specific protein adsorption and NP‐protein aggregation in such interfacial cases. Here, we use evanescent light scattering to observe polystyrene NPs‒fibrinogen aggregation at substrates with varying surface properties. A density‐fluctuation correlation function is utilized to reveal the relaxation dynamics of the aggregates. Both time‐resolved and spatial‐correlated evidence shows that the aging process of such soft materials is out‐of‐equilibrium, where the dynamics faster and slower than exponential can coexist in one single relaxation process. Besides, corona formation, inner stress, and interconnection together determine the microstructure, local adhesion, and structural relaxation of the aggregates, which can further correspond to the protein‐to‐NP ratio as well as the surface chemistry of NPs and substrates.

The optimized multi-head graph attention network (OPNet) uses the multi-head graph attention network to predict both the thermal decomposition temperature with a 5% mass loss (Td5%) and the glass transition temperature (Tg) of polymers as a machine learning model. The OPNet model provides reliable performance predictions for the Td5% and Tg datasets. The OPNet regression evaluation metrics R2 of Td5% is 0.76, which is the best, and the regression evaluation metrics R2 of Tg is 0.91, which is better than the current existing method models (the best model R2 ≈ 0.90). The OPNet model is an end-to-end network model, eliminating the need for manual data filtering or feature extraction. By analyzing the feature weights of the OPNet model, it is found that structures such as benzene rings play a more important role. At the same time, we have confirmed through other literature that such structures do have better stability and a higher thermal decomposition temperature and glass transition temperature. Therefore, the OPNet model exhibits interpretability and holds significant reference value for the field of materials science.

Objectives: This study aimed to summarize the existing literature on risk factors for arrhythmias after chemotherapy in cancer patients. To provide reliable evidence for treating arrhythmias after chemotherapy in oncology patients by assessing multiple biasing factors in the literature and quantifying the risk factors. Methods: The risk factors for arrhythmia following tumor chemotherapy were systematically collected from various reputable databases, including PubMed, Cochrane Library, MEDLINE, EMBASE, and multiple Chinese databases, covering the period from inception to May 2023. Two independent reviewers performed rigorous article screening, data extraction, and assessment of research quality. Data analysis was conducted using Review Manager 5.4 software, ensuring a standardized and robust approach to evaluate the gathered evidence. Results: The analysis of chemotherapy-induced arrhythmias included 16 articles, encompassing 14,785 cancer patients. Among the patients, 3295 belonged to the arrhythmia group, while 11,490 were in the non-arrhythmia group. These studies identified 12 significant risk factors associated with arrhythmias following chemotherapy in cancer patients. The findings of the analysis are as follows. General patient characteristics: The incidence of post-chemotherapy arrhythmias was 14.33 times higher in oncology patients aged ≥60 years compared to patients

The on-orbit radiometric calibration of spaceborne sensors is the foundation of quantitative remote sensing, and the calibration accuracy directly affects the quality of quantitative remote sensing products. The wide swath of the Chinese Ocean Color and Temperature Scanner (COCTS) onboard the HY-1C satellite makes it difficult to ignore errors caused by viewing angles during calibration. Thus, this article proposes a cross-calibration method based on the bottom-of-atmosphere (BOA) and top-of-atmosphere (TOA) spectral band adjustment factors (SBAFs). This method cross calibrates the COCTS sensor after correcting viewing geometry and radiometric differences. It is based on the Sentinel-3/ocean and land color instrument (OLCI) sensor. First, time-series data from the OLCI sensor were used to select calibration points in the Dunhuang area. Subsequently, the bidirectional reflectance distribution function (BRDF) for each corresponding spectral band of the OLCI sensor was constructed point by point. Next, the BOA and TOA SBAFs were calculated using the interpolated continuous spectra obtained from MOD09GA products. After correcting for the BRDF and SBAF, cross calibration between COCTS and OLCI was achieved. The results showed that the BOA SBAF model achieved higher precision calibration coefficients than the TOA SBAF model, with errors in each band below 5.76%. The proposed method can provide technical support for the cross calibration of wide-swath sensors.

Abstract Selective defluorinative functionalization of trifluoromethyl group (–CF3) is an attractive synthetic route to the pharmaceutically privileged fluorine-containing moiety. Herein, we report a strategy based on photoexcited copper catalysis to activate the C–F bond of di- or trifluoromethylated arenes for divergent radical C–N coupling with carbazoles and aromatic amines. The use of different ligands can tune the reaction products diversity. A range of substituted, structurally diverse α,α-difluoromethylamines can be obtained from trifluoromethylated arenes via defluorinative C-N coupling with carbazoles, while an interesting double defluorinative C-N coupling is ready for difluoromethylated arenes. Based on this success, a carbazole-centered PNP ligand is designed to be an optimal ligand, enabling a copper-catalyzed C–N coupling for the construction of imidoyl fluorides from aromatic amines through double C-F bond functionalization. Interestingly, a 1,2-difluoroalkylamination strategy of styrenes is also developed, delivering γ,γ-difluoroalkylamines, a bioisostere to β-aminoketones, in synthetically useful yields. The DFT studies reveal an inner-sphere electron transfer mechanism for Cu-catalyzed selective activation of C(sp3)–F bonds.

Remote sensing technology is widely used to obtain information on floating green tides, and thresholding methods based on indices such as the normalized difference vegetation index (NDVI) and the floating algae index (FAI) play an important role in such studies. However, as the methods are influenced by many factors, the threshold values vary greatly; in particular, the error of data extraction clearly increases in situations of high-turbidity water (HTW) (NDVI > 0). In this study, high spatial resolution, multispectral images from the Sentinel-2 MSI mission were used as the data source. It was found that the International Commission on Illumination (CIE) hue angle calculated using remotely sensed equivalent multispectral reflectance data and the RGB method is extremely effective in distinguishing floating green tides from areas of HTW. Statistical analysis of Sentinel-2 MSI images showed that the threshold value of the hue angle that can effectively eliminate the effect of HTW is 218.94°. A test demonstration of the method for identifying the floating green tide in HTW in a Sentinel-2 MSI image was carried out using the identified threshold values of NDVI > 0 and CIE hue angle < 218.94°. The demonstration showed that the method effectively eliminates misidentification caused by HTW pixels (NDVI > 0), resulting in better consistency of the identification of the floating green tide and its distribution in the true color image. The method enables rapid and accurate extraction of information on floating green tide in HTW, and offers a new solution for the monitoring and tracking of green tides in coastal areas.

Many traditional villages have been degraded to a certain extent due to urbanization and out-of-control management. In addition, due to the lack of recognition and continuation of spatial texture in some village conservation and planning that, in turn, resulting in the gradual disappearance of their distinctive landscape feature. Studying the spatial form of traditional villages helps preserve the authenticity of traditional villages as cultural landscape and inherits traditional historical characteristics. Using Puping Village in Zhangzhou City, Fujian Province as an example, this paper obtains the integrated information data of the village through UAV oblique photography, classifies and extracts the spatial constitution of the traditional village using digital technology, quantitatively analyses it from macroscopic to microscopic, and summarizes the spatial morphology analysis method of the traditional village. The results demonstrate that digital technology can effectively and accurately complete data collection and can provide an objective basis for zoning conservation of traditional villages based on the distinction between new and historic buildings. In addition, digital information collection on the traditional villages landscape features will prepare for the establishment of a database and comparative analysis in the future. We further suggest that digital technology analysis needs to be combined with traditional methods to have a deeper understanding of the formation process of village spatial morphology. The results of the practice in Puping Village show that the use of digital technology can provide a scientific basis for the protection and planning of traditional villages, and that this method is adaptable, which can help to efficiently collect and analyze data on landscape characteristics of other similar villages in China, and support innovative methodologies and technologies for China’s rural revitalization efforts.

Geo-mat system is considered as an alternative to a flexible or rigid pavement that can be used for fire lanes, parking areas, or roadway shoulders for cars, pickup trucks, utility/delivery trucks, and fire trucks. Also, it can be used to reduce the thickness of the base course in unpaved roads. In this investigation, six cyclic loading tests were conducted to assess the efficacy of the geo-mat system on weak to intermediate subgrade layers, characterized by California Bearing Ratios (CBR) of 2%, 3%, and 4%. Control sections, consisting of a 300-mm thick base course over subgrade layers with CBR values of 2% or 4%, were compared against the test sections comprising a geo-mat system placed atop aggregates of varied thickness (150 or 50 mm) on a geotextile layer over the same subgrade layers. Each test section underwent cyclic loading, progressively increasing from 17.8 to 71.2 kN using a 300-mm diameter steel plate. The results demonstrate that the geo-mat system, particularly when placed over a 150 mm-thick aggregate base, exhibited comparable or superior performance to the control sections with a 300 mm thickness, especially under substantial cyclic loading. This was evidenced by the reduced permanent deformations beneath the loading plate and a wider load distribution. The increase of the subgrade CBR value reduced the permanent deformation significantly. When the intermediate subgrade with a 4% CBR was used, the geo-mat system played a more important role than the aggregate base and the base thickness had a minor effect on the performance.

Abstract Loss of refreshment in nucleus pulposus (NP) cellularity leads to intervertebral disc (IVD) degeneration. Nevertheless, the cellular sequence of NP cell differentiation remains unclear, although an increasing body of literature has identified markers of NP progenitor cells (NPPCs). Notably, due to their fragility, the physical enrichment of NP‐derived cells has limited conventional transcriptomic approaches in multiple studies. To overcome this limitation, a spatially resolved transcriptional atlas of the mouse IVD is generated via the 10x Genomics Visium platform dividing NP spots into two clusters. Based on this, most reported NPPC‐markers, including Cathepsin K (Ctsk), are rare and predominantly located within the NP‐outer subset. Cell lineage tracing further evidence that a small number of Ctsk‐expressing cells generate the entire adult NP tissue. In contrast, Tie2, which has long suggested labeling NPPCs, is actually neither expressed in NP subsets nor labels NPPCs and their descendants in mouse models; consistent with this, an in situ sequencing (ISS) analysis validated the absence of Tie2 in NP tissue. Similarly, no Tie2‐cre‐mediated labeling of NPPCs is observed in an IVD degenerative mouse model. Altogether, in this study, the first spatial transcriptomic map of the IVD is established, thereby providing a public resource for bone biology.

Abstract Peripheral nerve injury (PNI) remains a challenging area in regenerative medicine. Nerve guide conduit (NGC) transplantation is a common treatment for PNI, but the prognosis of NGC treatment is unsatisfactory due to 1) neuromechanical unmatching and 2) the intra‐conduit inflammatory microenvironment (IME) resulting from Schwann cell pyroptosis and inflammatory‐polarized macrophages. A neuromechanically matched NGC composed of regenerated silk fibroin (RSF) loaded with poly(3,4‐ethylenedioxythiophene): poly(styrene sulfonate) (P:P) and dimethyl fumarate (DMF) are designed, which exhibits a matched elastic modulus (25.1 ± 3.5 MPa) for the peripheral nerve and the highest 80% elongation at break, better than most protein‐based conduits. Moreover, the NGC can gradually regulate the intra‐conduit IME by releasing DMF and monitoring sciatic nerve movements via piezoresistive sensing. The combination of NGC and electrical stimulation modulates the IME to support PNI regeneration by synergistically inhibiting Schwann cell pyroptosis and reducing inflammatory factor release, shifting macrophage polarization from the inflammatory M1 phenotype to the tissue regenerative M2 phenotype and resulting in functional recovery of neurons. In a rat sciatic nerve crush model, NGC promoted remyelination and functional and structural regeneration. Generally, the DMF/RSF/P:P conduit provides a new potential therapeutic approach to promote nerve repair in future clinical treatments.

Methylene blue (MB) was found to exert neuroprotective effect on different brain diseases, such as ischemic stroke. This study assessed the MB effects on ischemia induced brain edema and its role in the inhibition of aquaporin 4 (AQP4) and metabotropic glutamate receptor 5 (mGluR5) expression. Rats were exposed 1 h transient middle cerebral artery occlusion (tMCAO), and MB was injected intravenously following reperfusion (3 mg/kg). Magnetic resonance imaging (MRI) and 2,3,5-triphenyltetrazolium chloride (TTC) staining was performed 48 h after the onset of tMCAO to evaluate the brain infarction and edema. Brain tissues injuries as well as the glial fibrillary acidic protein (GFAP), AQP4 and mGluR5 expressions were detected. Oxygen and glucose deprivation/reoxygenation (OGD/R) was performed on primary astrocytes (ASTs) to induce cell swelling. MB was administered at the beginning of reoxygenation, and the perimeter of ASTs was measured by GFAP immunofluorescent staining. 3,5-dihydroxyphenylglycine (DHPG) and fenobam were given at 24 h before OGD to examine their effects on MB functions on AST swelling and AQP4 expression. MB remarkably decreased the volumes of T2WI and ADC lesions, as well as the cerebral swelling. Consistently, MB treatment significantly decreased GFAP, mGluR5 and AQP4 expression at 48 h after stroke. In the cultivated primary ASTs, OGD/R and DHPG significantly increased ASTs volume as well as AQP4 expression, which was reversed by MB and fenobam treatment. The obtained results highlight that MB decreases the post-ischemic brain swelling by regulating the activation of AQP4 and mGluR5, suggesting potential applications of MB on clinical ischemic stroke treatment.

Abstract Supramolecular chirality‐mediated selective interaction among native assemblies is essential for precise disease diagnosis and treatment. Herein, to fully understand the supramolecular chiral binding affinity‐achieved therapeutic efficiency, supramolecular chiral nanoparticles (WP5⊃D/L‐Arg+DOX+ICG) with the chirality transfer from chiral arginine (D/L‐Arg) to water‐soluble pillar[5]arene (WP5) are developed through non‐covalent interactions, in which an anticancer drug (DOX, doxorubicin hydrochloride) and a photothermal agent (ICG, indocyanine green) are successfully loaded. Interestingly, the WP5⊃D‐Arg nanoparticles show 107 folds stronger binding capability toward phospholipid‐composed liposomes compared with WP5⊃L‐Arg. The enantioselective interaction further triggers the supramolecular chirality‐specific drug accumulation in cancer cells. As a consequence, WP5⊃D‐Arg+DOX+ICG exhibits extremely enhanced chemo‐photothermal synergistic therapeutic efficacy (tumor inhibition rate of 99.4%) than that of WP5⊃L‐Arg+DOX+ICG (tumor inhibition rate of 56.4%) under the same condition. This work reveals the breakthrough that supramolecular chiral assemblies can induce surprisingly large difference in cancer therapy, providing strong support for the significance of supramolecular chirality in bio‐application.

Abstract Background Bexagliflozin and dapagliflozin are sodium‐glucose cotransporter‐2 (SGLT2) inhibitors. No direct comparison of SGLT2 inhibitors in a randomized controlled trial has been reported to date. Methods This was a multicenter, randomized, double‐blind, active‐controlled trial comparing bexagliflozin to dapagliflozin for the treatment of type 2 diabetes mellitus in adults with disease inadequately controlled by metformin. Subjects (n = 406) were randomized to receive bexagliflozin (20 mg) or dapagliflozin (10 mg) plus metformin. The primary endpoint was noninferiority of bexagliflozin to dapagliflozin for the change in glycated hemoglobin (HbA1c) from baseline to week 24. Secondary endpoints included intergroup differences in fasting plasma glucose (FPG), 2‐h‐postprandial glucose (PPG), body weight, and systolic blood pressure (SBP) from baseline to week 24. The trial also evaluated the safety profiles. Results The model‐adjusted mean change from baseline to week 24 HbA1c was −1.08% for bexagliflozin and −1.10% for dapagliflozin. The intergroup difference of 0.03% (95% confidence interval [CI] −0.14% to 0.19%) was below the prespecified margin of 0.4%, confirming the noninferiority of bexagliflozin. The changes from baseline in FPG, PPG, body weight, and SBP were −1.95 mmol/L, −3.24 mmol/L, −2.52 kg, and −6.4 mm Hg in the bexagliflozin arm and −1.87 mmol/L, −3.07 mmol/L, −2.22 kg, and −6.3 mm Hg in the dapagliflozin arm. Adverse events were experienced in 62.6% and 65.0% and serious adverse events affected 4.4% and 3.5% of subjects in the bexagliflozin and dapagliflozin arm, respectively. Conclusions Bexagliflozin showed nearly identical effects and a similar safety profile to dapagliflozin when used in Chinese patients on metformin.

The endophytic microbial community reassembles to participate in plant immune balance when the host plants are stressed by pathogens. However, it remains unclear whether this assembly is pathogen-specific and how regulatory pathways are coordinated in multi-pathogens. In order to investigate the effects of infection with Colletotrichum gloeosporioides (Cg treatment) and Fusarium proliferatum (Fp treatment) on walnut leaf endophytic microbiome in their assembly, co-occurrence pattern, and on comprehensive chemical function of the internal environment of leaf, an interaction system of the walnut–pathogenic fungi was constructed using seed embryo tissue culture technology. The study showed differences in the assembly of endophytic microbial communities in walnut trees across three groups (control group, Ck; Cg; Fp) after Cg and Fp treatments. Despite changes in relative abundances, the dominant communities in phyla and genera remained comparable during the infection of the two pathogens. Endophyte fungi were more sensitive to the pathogen challenge than endophyte bacteria. Both promoted the enrichment of beneficial bacteria such as Bacillus and Pseudomonas, changed the modularity of the community, and reduced the stability and complexity of the endophyte community. Pathogenic fungi infection mainly affects the metabolism of porphyrin and chlorophyll, purine metabolism, phenylpropane metabolism, and amino acid metabolism. However, there was no significant difference in the secondary metabolites for the different susceptible plants. By screening endogenous antagonistic bacteria, we further verified that Pseudomonas psychrotolerans and Bacillus subtilis had inhibitory effects on the two pathogenic fungi and participated in the interaction between the leaves and pathogenic fungi. The antibacterial substances may be 1-methylnaphthalene, 1,3-butadiene, 2,3-butanediol, and toluene aldehyde.

The investigation of ferroelectric materials is an important aspect of condensed matter physics. Compared to the traditional inorganic ferroelectric ones, organic ferroelectric materials possess unique advantages, including light weight, scalability, flexibility, and solvent treatability. However, the study of organic ferroelectric materials is still in its infancy, especially from the view of supramolecular chemistry; various mechanisms of forming self-assembly and thus diverse building blocks employed are not yet to be further developed. Herein, a pillararene-based charge transfer (CT) self-assembly was produced by utilizing pillar[5]quinone (P5Q) as the electron acceptor and phenothiazine (PTZ) as the electron donor. Compared to the intrinsic P5Q, our fabricated donor–acceptor complex displays particular intriguing features, such as the enhanced second-harmonic generation and ferroelectric responses, benefiting from the CT interaction between P5Q and PTZ. The current work provides a unique strategy for the successful construction of supramolecular ferroelectrics.

Background Myeloid-derived suppressor cells (MDSCs) have crucial immunosuppressive role in T cell dysfunction in various disease processes. However, the role of MDSCs and their impact on Tregs in COPD have not been fully understood. The aim of the present study is to investigate the immunomodulatory role of MDSCs and their potential impact on the expansion and function of Tregs in COPD patients. Methods Peripheral blood samples were collected to analyze circulating MDSCs, Tregs, PD-1/PD-L1 expression to assess the immunomodulatory role of MDSC and their potential impact on the expansion and function of Treg in COPD. A total of 54 COPD patients and 24 healthy individuals were enrolled in our study. Flow cytometric analyses were performed to identify granulocytic MDSCs (G-MDSCs), monocytic MDSCs (M-MDSCs), Tregs, and the expression of PD-1/PD-L1(L2) on MDSCs and Tregs in peripheral blood. Results Our results revealed a significantly higher percentage of G-MDSCs and M-MDSCs (p < 0.001) in COPD patients compared to the healthy controls. Additionally, a significantly higher proportion of peripheral blood Tregs was observed in COPD patients. Furthermore, an increased expression of cytotoxic T-lymphocyte-associated protein 4 (CTLA-4) on Tregs (p < 0.01) was detected in COPD patients. The expression of PD-1 on CD4+ Tcells and Tregs, but not CD8+Tcells, was found to be increased in patients with COPD compared to controls. Furthermore, an elevated expression of PD-L1 on M-MDSCs (p < 0.01) was also observed in COPD patients. A positive correlation was observed between the accumulation of M-MDSCs and Tregs in COPD patients. Additionally, the percentage of circulating M-MDSCs is positively associated with the level of PD-1 (r = 0.51, p < 0.0001) and CTLA-4 (r = 0.42, p = 0.0014) on Tregs in COPD. Conclusion The recruitment of MDSCs, accumulation of Tregs, and up-regulation of CTLA-4 on Treg in COPD, accompanied by an increased level of PD-1/PD-L1, suggest PD-1/PD-L1 axis may be potentially involved in MDSCs-induced the expansion and activation of Treg at least partially in COPD.