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Abstract Background Gastrointestinal (GI) cancers have heavily burdened public health. Few studies reported GI cancer burden among adolescents and young adults (AYA). To address this gap, we explored the burden of GI cancer among people aged 15–39. Methods We retrieved data from the Global Burden of Disease Study 2019 Data Resources. The average annual percent change (AAPC) of rates was calculated by linear regression analysis of the natural logarithm. Bayesian age-period-cohort model was applied to predict the future burden. Results In 2019, there were 171,857 (95% uncertain interval [95% UI]: 157,092–187,974) new GI cancer cases with a rate of 5.79/100,000 (95% UI: 5.29–6.33) and 91,033 (95% UI: 83,156–99,399) deaths at a rate of 3.07/100,000 (95% UI: 2.80–3.35) among AYA. The number of prevalent cases and disability-adjusted life years (DALYs) were 722,573 (95% UI: 660,806–789,476) and 5,151,294 (95% UI: 4,706,065–56,188,77), with rates of 24.35/100,000 (95% UI: 22.27–26.60) and 173.57/100,000 (95% UI: 158.57–189.32) respectively. The overall rates of mortality (AAPC = -1.281, p

Abstract. Background:. China is one of the countries with the largest burden of gastrointestinal and liver diseases (GILD) in the world. The GILD constitutes various causes of mortality and disability. The study aimed to investigate the trend of GILD in China using the Global Burden of Diseases Study 2019 (GBD 2019) data resources from 1990 to 2019. Methods:. The data on the age-standardized mortality rates (ASMR) and disability-adjusted life years (DALYs) for GILD in China from 1990 to 2019 were collected from the GBD 2019 data resources. Furthermore, the ranking of the main causes of deaths and DALYs, as well as the trends of ASMR, DALYs, years of life lost (YLLs), and years of life lost due to disability (YLDs) per 1,000,000 in GILD were reported. Results:. The ASMR and DALYs for stomach cancer, liver cancer, and esophageal cancer, which ranked top three among the GILDs from 1990 to 2019, were gradually decreasing. Significant decreases in the ASMR and DALYs were found in diarrheal diseases and acute hepatitis (A, E, and C). However, noteworthy increases were found in those of colon and rectum cancer (CRC) and pancreatic cancer. Trend of DALYs, mortality, and YLLs rates for most of GILD were decreasing from 1990 to 2019, except the burden of CRC and pancreatic cancer with an increasing trend. The DALYs, mortality and YLLs of most GILD diseases showed decreasing trends from 1990 to 2019, except the burden of CRC and pancreatic cancer with an increasing trends. Conclusions:. The result of the GBD 2019 showed that the rates of most GILDs decreased in China; however, gastrointestinal and liver cancer, such as stomach cancer still held the top ranking. Furthermore, the shift from infectious diseases to non-communicable causes among GILD burden is occurring.

The interfacial interaction between HMX molecules and coating materials is the key to the safety performance of explosives and has received extensive attention. However, screening suitable coating agents to enhance the interfacial effect to obtain high-energy and low-sensitivity explosives has long been a major challenge. In this work, HMX-PEI/rGO/g-C3N4 (HPrGC) composites were innovatively prepared by a multi-level coating strategy of two-dimensional graphite rGO and g-C3N4. The g-C3N4 used for desensitization has a rich π-conjugated system and shows outstanding ability in reducing friction sensitivity. The hierarchical structure of HPrGC formed by electrostatic self-assembly and π-π stacking can effectively dissipate energy accumulation under heat and mechanical stimulation through structural evolution, thus exhibiting a prominent synergistic desensitization effect on HMX. The results show that rGO/g-C3N4 coating has no effect on the crystal structure and chemical structure of HMX. More importantly, the perfect combination of g-C3N4 and rGO endows HPrGC with enhanced thermal stability and ideal mechanical sensitivity (IS: 21 J, FS: 216 N). Obviously, the new fabrication of HPrGC enriches the variety of desensitizer materials and helps to deepen the understanding of the interaction between explosives and coatings.

Abstract Due to low success rates and long cycles of traditional drug development, the clinical tendency is to apply omics techniques to reveal patient-level disease characteristics and individualized responses to treatment. However, the heterogeneous form of data and uneven distribution of targets make drug discovery and precision medicine a non-trivial task. This study takes pyroptosis therapy for triple-negative breast cancer (TNBC) as a paradigm and uses data mining of a large TNBC cohort and drug databases to establish a biofactor-regulated neural network for rapidly screening and optimizing compound pyroptosis drug pairs. Subsequently, biomimetic nanococrystals are prepared using the preferred combination of mitoxantrone and gambogic acid for rational drug delivery. The unique mechanism of obtained nanococrystals regulating pyroptosis genes through ribosomal stress and triggering pyroptosis cascade immune effects are revealed in TNBC models. In this work, a target omics-based intelligent compound drug discovery framework explores an innovative drug development paradigm, which repurposes existing drugs and enables precise treatment of refractory diseases.

Abstract Background Individuals with sensory processing sensitivity (SPS) tend to be overreactive in response to negative environmental stimuli. More is known about the positive relationship between SPS and quality of life (QoL); nevertheless, less is known regarding the roles of resilience and social determinants in this association. This research aimed to investigate the potential mediation effect of resilience and the moderation effect of social determinants on the relationship between SPS and QoL in a large sample of Chinese cancer patients. Methods We used the most recent datasets from an ongoing project conducted in southwest China. A two-stage random sampling strategy with a probability proportionate to sample size (PPS) design was adopted. The associations between resilience, SPS, and QoL were evaluated using a linear regression model. Path analysis was adopted to examine the mediation of resilience. Results Resilience was positively associated with quality of life, while increased sensory processing sensitivity was negatively associated with quality of life. The restricted cubic spline analysis revealed that as resilience increased, the coefficients of quality of life rapidly increased across all domains. Conversely, the coefficients for quality of life gradually decreased with the escalation of sensory processing sensitivity. Resilience was a significant mediator, accounting for 21.88% of the total SPS-QoL association. The mediation effect of resilience varied across ethnicity and sex. Conclusion Sensory processing sensitivity was significantly associated with quality of life in cancer patients, and promoting resilience could mitigate this negative impact. However, the effect of resilience varies across sex and ethnicity. Therefore, targeted resilience promotion interventions, especially those integrating social characteristics, should be considered for implementation.

Abstract Background The purpose of this in vitro study was to compare and evaluate the stress distribution of maxillary first premolar residual crowns restored with post-core crowns, endocrowns and inlay crowns after deep margin elevation, to explore the fitting restoration for residual crowns using finite element analysis. Methods A healthy complete right maxillary first premolar from a male adult was scanned by cone beam computed tomography (CBCT). The finite element model of the tooth was established by reverse engineering software such as Mimics, Geomagic and Hypermesh. On this basis, the residual crown model after deep margin elevation was made, and the experimental group models were divided into three groups, those restored with post core crowns, endocrowns and inlay crowns. Vertical and oblique static loads were applied to the experimental models to simulate the force on the tooth during mastication (the loading position was located in the central fossa of the occipital surface, and the load was 100 N) using Abaqus software. Results The peak value and distribution of von Mises stress in each part of the experimental model were observed. After deep margin elevation, the peak dentin von Mises stresses were lower than the tensile strength of normal dentin in the post-core crown, endocrown, and inlay crown groups; the lowest stress results were found in the post-core crown group for the dentin, restoration, enamel, and deep margin elevation (DME) layers under vertical and oblique loading. In terms of stress distribution clouds, the peak stresses in the dentin tissue were located in the apical 1/3 of the root after postcore crown restorations for both loads, while stress concentrations were evident in the cervical and root areas after endocrown and inlay crown restorations; regardless of the load and restoration method, the corresponding stress concentration areas appeared at the junction of the DME and dentin tissue at the loading site of the restorations; Conclusions Post-core crowns, endocrowns and inlay crowns can be used to restore residual crowns after deep margin elevation, and post-core crowns can better protect the residual tooth tissue.

Abstract Purpose In the past few years, there has been a notable rise in the incidence and prevalence of idiopathic pulmonary fibrosis (IPF) on a global scale. A considerable body of research has highlighted the ‘obesity paradox,’ suggesting that a higher body mass index (BMI) can confer a protective effect against numerous chronic diseases. However, the relationship between BMI and the risk of mortality in IPF patients remains underexplored in the existing literature. We aim to shed light on this relationship and potentially offer novel insights into prevention strategies for IPF. Methods We conducted a systematic search of the PubMed, Embase, and Web of Science databases to collect all published studies examining the correlation between Body Mass Index (BMI) and the mortality risk in patients with IPF, up until February 14, 2023. For the synthesis of the findings, we employed random-effects models. The statistical significance of the association between BMI and the mortality risk in IPF patients was evaluated using the hazard ratio (HR), with the 95% Confidence Interval (CI) serving as the metric for effect size. Results A total of 14 data sets involving 2080 patients with IPF were included in the meta-analysis. The combined results of the random-effects models were suggestive of a significant association between lower BMI and a higher risk of death (HR = 0.94, 95% CI = 0.91–0.97, P 100 groups: HR = 0.94, 95%CI = 0.91–0.97, P

The mitochondrial pyruvate dehydrogenase complex (PDC) plays a crucial role in linking the glycolysis pathway and the tricarboxylic acid (TCA) cycle. Previously, we reported that a mutation of MAB1, encoding an E1β subunit of PDC, affects the abundance of auxin efflux carriers PIN-FORMED proteins (PINs) via reduced recycling and enhanced degradation in vacuoles. Here, we further analyzed the effects of TCA cycle inhibition on vesicle trafficking using both the mab1-1 mutant and 3-BP, a TCA cycle inhibitor. Pharmacological and genetic impairment of the TCA cycle induced the aggregated components of ARA6, which is a plant-unique RAB5 GTPase that mediates endosomal trafficking to the plasma membrane. In addition, MAB4, which is an NPH3-like protein that inhibits PIN internalization from the plasma membrane, was severely reduced in 3-BP-treated roots and mab1-1. Furthermore, TCA cycle impairment led to the accumulation of reactive oxygen species in root tips, and treatment with H2O2 reduced MAB4 levels while increasing the internalization of PIN2 from the plasma membrane, and aggregated ARA6-positive compartments. These results suggest that TCA cycle impairment targets PIN proteins for degradation in the vacuole by disrupting both the MAB4-mediated block of internalization and the ARA6-mediated endocytic pathway.

IntroductionHyperuricemia (HUA) is a metabolic syndrome caused by purine metabolism disorders. Zanthoxyli Pericarpium (ZP) is a medicinal and food homologous plant, and its ripe peel is used to treat diseases and as a spice for cooking. Some studies have shown that ZP can inhibit the formation of xanthine oxidase and reduce the production of uric acid.MethodsThrough network pharmacology, ZP’s potential targets and mechanisms for HUA treatment were identified. Databases like TCMSP, UniProt, and Swiss Target Prediction were utilized for ZP’s active ingredients and targets. HUA-related targets were filtered using GeneCards, Drugbank, and Open Targets. Core targets for ZP’s HUA treatment were mapped in a PPI network and analyzed with Cytoscape. GO and KEGG pathway enrichments were conducted on intersected targets via DAVID. Molecular docking and virtual screening were performed to find optimal binding pockets, and ADMET screening assessed compound safety. Molecular dynamics simulations confirmed compound stability in binding sites.ResultsWe identified 81 ZP active ingredient targets, 140 HUA-related targets, and 6 drug targets, with xanthine dehydrogenase (XDH) as the top core target. Molecular docking revealed ZP’s active ingredients had strong binding to XDH. Virtual screening via Protein plus identified 48 compounds near the optimal binding pocket, with 2’-methylacetophenone, ledol, beta-sitosterol, and ethyl geranate as the most promising. Molecular dynamics simulations confirmed binding stability, suggesting ZP’s potential in HUA prevention and the need for further experimental validation.ConclusionOur study provides foundations for exploring the mechanism of the lowering of uric acid by ZP and developing new products of ZP. The role of ZP in the diet may provide a new dietary strategy for the prevention of HUA, and more experimental studies are needed to confirm our results in the future.

Gut microbiota/metabolites not only participate in the food and energy metabolism but also contribute to the host immune response and homeostasis. The alternation of gut microbiota/metabolites has been widely related to intestinal and extra-intestinal disorders such as intestinal bowel diseases (IBDs). Bactericidal substances from gut epithelial cells can regulate the composition of gut microbiota. However, the effects of regenerating protein 4 (REG4) (human)/(Reg4) (mice), a potentially bactericidal substance from gut epithelial cells, on the gut immune homeostasis maintain elusive. Here, we found that REG4/Reg4 is essential in maintaining gut immune homeostasis through REG4/Reg4 associated gut microbiota. Reg4 knockout (KO) mice were highly sensitive to DSS-mediated colitis, whereas human REG4 intestine epithelial cell transgenic (huREG4IECtg) mice exhibited more resistance to DSS-mediated colitis. Mechanistically, sequencing of gut microbiota and liquid chromatography-mass spectrometry showed that REG4/Reg4 could affect the composition of gut microbiota. REG4/Reg4 associated gut microbiota such as Lactobacillus could metabolize linoleic acid (LA) into conjugated linoleic acid (CLA). Immunoprecipitation and immunoblot showed that CLA could effectively promote the expression of IL-35 in macrophages through Gαq/11 mediated activation STAT1/4. Thus, our results demonstrate that REG4/Reg4 plays a critical role in maintaining gut immune homeostasis through CLA-mediated IL-35+ macrophages.

Bacteria-mediated antitumor therapy has gained widespread attention for its innate tumor-targeting capability and excellent immune activation properties. Nevertheless, the clinical approval of bacterial therapies remains elusive primarily due to the formidable challenge of balancing safety with enhancing in vivo efficacy. In this study, leveraging the probiotic Escherichia coli Nissle1917 (EcN) emerges as a promising approach for colon cancer therapy, offering a high level of safety attributed to its lack of virulence factors and its tumor-targeting potential owing to its obligate anaerobic nature. Specifically, we delineate the erythrocyte (RBC) membrane-camouflaged EcN, termed as Trojan horse EcN@RBC, which triggers apoptosis in tumor cells by mitigating mitochondrial membrane potential (MMP) and subsequently activating the PINK1/Parkin pathway associated with mitophagy. Concurrently, the decline in MMP induced by mitophagy disrupts the mitochondrial permeability transition pore (MPTP), leading to the release of Cytochrome C and subsequent apoptosis induction. Moreover, synergistic effects were observed through the combination of the autophagy activator rapamycin, bolstering the antitumor efficacy in vivo. These findings offer novel insights into probiotic-mediated antitumor mechanisms and underscore the therapeutic potential of EcN@RBC for colon cancer patients.

The global incidence and prevalence of inflammatory bowel disease (IBD) are gradually increasing. A high-fat diet (HFD) is known to disrupt intestinal homeostasis and aggravate IBD, yet the underlying mechanisms remain largely undefined. Here, a positive correlation between dietary fat intake and disease severity in both IBD patients and murine colitis models is observed. A HFD induces a significant decrease in indole-3-acetic acid (IAA) and leads to intestinal barrier damage. Furthermore, IAA supplementation enhances intestinal mucin sulfation and effectively alleviates colitis. Mechanistically, IAA upregulates key molecules involved in mucin sulfation, including 3’-phosphoadenosine 5’-phosphosulfate synthase 2 (Papss2) and solute carrier family 35 member B3 (Slc35b3), the synthesis enzyme and the transferase of 3’-phosphoadenosine-5’-phosphosulfate (PAPS), via the aryl hydrocarbon receptor (AHR). More importantly, AHR can directly bind to the transcription start site of Papss2. Oral administration of Lactobacillus reuteri, which can produce IAA, contributes to protecting against colitis and promoting mucin sulfation, while the modified L. reuteri strain lacking the iaaM gene (LactobacillusΔiaaM) and the ability to produce IAA fail to exhibit such effects. Overall, IAA enhances intestinal mucin sulfation through the AHR-Papss2-Slc35b3 pathway, contributing to the protection of intestinal homfeostasis.

Bioaerosols are ubiquitous and have a substantial impact on the atmosphere and human health. Despite the identification of numerous bioaerosol emission sources, the contribution of anthropogenic sources remains inadequately understood. In kitchens, oil stains accumulated at the vent may discharge microorganisms into the environment with airflow, potentially discharging bioaerosol pollution. This putative anthropogenic source of bioaerosols has been long ignored. To investigated whether kitchen chimneys can be a potential source for bioaerosols, air samples, oil stains from in/out chimneys, and surface sand samples were collected near several commercial restaurants. PCoA showed that sampling sites significantly impacted microbiomes, whereas SourceTracker analysis led to the finding that waste grease significantly contributed to bioaerosol composition. Both findings agree with the kitchen chimney as a source of microbes in bioaerosols in the surrounding environment. Furthermore, despite the low biodiversity, a high proportion of stress-tolerant and potential pathogenic bacteria and fungi were found in residual culinary grease, which may escape into the air causing potential risks to human beings. These results led to the proposal that airborne microbiota can originate from cooking waste grease. Immediate actions should be taken into account to enhance disinfection and sterilization aimed at fume vents.

Acute kidney injury (AKI) is primarily caused by renal ischemia-reperfusion injury (IRI), which is one of the most prevalent triggers. Currently, preventive and therapeutic measures remain limited. Ferroptosis plays a significant role in the pathophysiological process of IRI-induced AKI and is considered a key target for improving its outcomes. Silibinin, a polyphenolic flavonoid, possesses diverse pharmacological properties and is widely used as an effective therapeutic agent for liver diseases. Recent studies have reported that silibinin may improves kidney diseases, though the underlying mechanism remain unclear. In this study, we investigated whether silibinin protects against IRI-induced AKI and explored its mechanism of action. Our findings indicated that pretreatment with silibinin alleviated renal dysfunction, pathological damage, and inflammation in IRI-AKI mice. Furthermore, the results demonstrated that silibinin inhibited ferroptosis both in vivo and in vitro. Proteome microarrays were used to identify silibinin's target, and our results revealed that silibinin binds to FTH1. This binding affinity was confirmed through molecular docking, SPRi, CETSA, and DARTS. Additionally, co-IP assays demonstrated that silibinin disrupted the NCOA4-FTH1 interaction, inhibiting ferritinophagy. Finally, the inhibitory effects of silibinin on ferroptosis were reversed by knocking down FTH1 in vitro. In conclusion, our study shows that silibinin effectively alleviates AKI by targeting FTH1 to reduce ferroptosis, suggesting that silibinin could be developed as a potential therapeutic agent for managing and treating AKI.

PI3Kδ is a key signal transduction molecule in normal and malignant B cells, as well as in T-regulatory cells, making it a promising target for treatment of hematologic malignancies through both direct killing and anti-tumor immunity regulation. BGB-10188 is a highly selective inhibitor of PI3Kδ, showing more than 3000 folds selectivity over other PI3K isoforms and no significant inhibition across tested kinases. BGB-10188 potently inhibited PI3Kδ with IC50s ranging from 1.7-16 nM through various in vitro assays and showed a long-lasting and strong target inhibition in mouse B cells in vivo. BGB-10188 showed significant antitumor effects in human B cell lymphoma xenograft models as single agent or in combination with the BTK inhibitor zanubrutinib. BGB-10188 showed significant Treg inhibition in blood but not in colon, along with less drug accumulation in colon compared with idelalisib, which is an approved PI3Kdelta inhibitor with high incidence of gastrointestinal side effects in clinic. In summary, BGB-10188 is a novel PI3Kδ inhibitor with high selectivity, potency and improved safety profile shown in preclinical studies, which is showing the potential as a best-in-class PI3Kδ inhibitor.

Abstract Background Recently, the application of deep learning (DL) has made great progress in various fields, especially in cancer research. However, to date, the bibliometric analysis of the application of DL in cancer is scarce. Therefore, this study aimed to explore the research status and hotspots of the application of DL in cancer. Methods We retrieved all articles on the application of DL in cancer from the Web of Science database Core Collection database. Biblioshiny, VOSviewer and CiteSpace were used to perform the bibliometric analysis through analyzing the numbers, citations, countries, institutions, authors, journals, references, and keywords. Results We found 6,016 original articles on the application of DL in cancer. The number of annual publications and total citations were uptrend in general. China published the greatest number of articles, USA had the highest total citations, and Saudi Arabia had the highest centrality. Chinese Academy of Sciences was the most productive institution. Tian, Jie published the greatest number of articles, while He Kaiming was the most co-cited author. IEEE Access was the most popular journal. The analysis of references and keywords showed that DL was mainly used for the prediction, detection, classification and diagnosis of breast cancer, lung cancer, and skin cancer. Conclusions Overall, the number of articles on the application of DL in cancer is gradually increasing. In the future, further expanding and improving the application scope and accuracy of DL applications, and integrating DL with protein prediction, genomics and cancer research may be the research trends.

Abstract Diffuse light is produced by clouds and aerosols in the atmosphere. Exploring the effects of diffuse light on ecosystem productivity is important for understanding the terrestrial carbon (CO2) cycle. Here, 2 years of gross ecosystem primary productivity (GEP) from a (winter) wheat cropland in China was assessed using eddy covariance technology to explore the effects of diffuse photosynthetic active radiance (PAR) on wheat GEP. Wheat GEP increased significantly and positively along with diffuse PAR. In addition, wheat GEP was significantly affected by total PAR, air temperature, and vapor press deficit in different diffuse PAR fraction (fDIF) change stages. Because significant autocorrelations existed among the controlling factors, a path analysis was used to quantify the effects of diffuse light on GEP. Diffuse PAR was the primary and secondary importance factors affecting GEP with direct path coefficients of 0.54 and 0.48, respectively, in different fDIF change stages. A multilayer canopy model revealed that the middle and lower canopy levels intercepted more light when diffuse PAR increased. This resulted in the photosynthetic enhancement of middle and lower canopy levels, which contributed approximately 65% and 35%, respectively, to the increase in photosynthesis for the entire canopy (~ 30.5%). Overall, our study provided new evidence regarding the importance of diffuse light for CO2 uptake in agroecosystems, which is important for predicting the responses of ecosystem CO2 budgets to future climate-related light changes.

Abstract Background The adoption of digitization has emerged as a new trend in the advancement of healthcare systems. To ensure high-quality care, nurses should possess sufficient skills to assist in the digital transformation of healthcare practices. Suitable tools have seldom been developed to assess nurses’ skills in digital applications. This study aimed to develop the Nursing Digital Application Skill Scale (NDASS) and test its psychometric properties. Methods The Nursing Digital Application Skill Scale was developed in three phases. In Phase 1, an item pool was developed based on previous literature and the actual situation of nursing work. Phase 2 included 14 experts’ assessment of content validity and a focus group interview with 30 nurses to pretest the scale. In phase 3, 429 registered nurses were selected from March to June 2023, and item analysis, exploratory factor analysis, and confirmatory factor analysis were used to refine the number of items and explore the factor structure of the scale. Additionally, reliability was determined by internal consistency and test-retest reliability. Results The final version of the NDASS consisted of 12 items. The content validity index of NDASS reached 0.975 at an acceptable level. The convergent validity test showed that the average variance extracted value was 0.694 (> 0.5) and the composite reliability value was 0.964 (> 0.7), both of which met the requirements. The principal component analysis resulted in a single-factor structure explaining 74.794% of the total variance. All the fitting indices satisfied the standard based upon confirmatory factor analyses, indicating that the single-factor structure contributed to an ideal model fit. The internal consistency appeared high for the NDASS, reaching a Cronbach’s alpha value of 0.968. The test-retest reliability was 0.740, and the split-half coefficient was 0.935. Conclusion The final version of the NDASS, which possesses adequate psychometric properties, is a reliable and effective instrument for nurses to self-assess digital skills in nursing work and for nursing managers in designing nursing digital skill training.

Abstract This cross-sectional study aimed to explore the knowledge, attitude and practice (KAP) toward sleep disorders and sleep hygiene among perimenopausal women, who were enrolled in Dezhou region of Shandong Province between July and September 2023. A total of 720 valid questionnaires were collected (mean age: 51.28 ± 4.32 years old), and 344 (47.78%) reported experiencing insomnia. The mean scores for knowledge, attitude, practice, and Dysfunctional Beliefs and Attitudes about Sleep (DBAS) were 15.73 ± 7.60 (possible range: 0–36), 29.35 ± 3.15 (possible range: 10–50), 28.54 ± 4.03 (possible range: 10–50), and 6.79 ± 1.90 (possible range: 0–10), respectively. Path analysis showed that knowledge had direct effects on attitude (β = 0.04, 95% CI 0.01–0.07, P = 0.001), and DBAS (β = 0.04, 95% CI 0.02–0.05, P

Abstract Conductive cardiac patches can rebuild the electroactive microenvironment for the infarcted myocardium but their repair effects benefit by carried seed cells or drugs. The key to success is the effective integration of electrical stimulation with the microenvironment created by conductive cardiac patches. Besides, due to the concerns in a high re-admission ratio of heart patients, a remote medicine device will underpin the successful repair. Herein, we report a miniature self-powered biomimetic trinity triboelectric nanogenerator with a unique double-spacer structure that unifies energy harvesting, therapeutics, and diagnosis in one cardiac patch. Trinity triboelectric nanogenerator conductive cardiac patches improve the electroactivity of the infarcted heart and can also wirelessly monitor electrocardiosignal to a mobile device for diagnosis. RNA sequencing analysis from rat hearts reveals that this trinity cardiac patches mainly regulates cardiac muscle contraction-, energy metabolism-, and vascular regulation-related mRNA expressions in vivo. The research is spawning a device that truly integrates an electrical stimulation of a functional heart patch and self-powered e-care remote diagnostic sensor.

Abstract Background Colorectal cancer (CRC) incidence is increasing in recent years due to intestinal flora imbalance, making oral probiotics a hotspot for research. However, numerous studies related to intestinal flora regulation ignore its internal mechanisms without in-depth research. Results Here, we developed a probiotic microgel delivery system (L.r@(SA-CS)2) through the layer-by-layer encapsulation technology of alginate (SA) and chitosan (CS) to improve gut microbiota dysbiosis and enhance anti-tumor therapeutic effect. Short chain fatty acids (SCFAs) produced by L.r have direct anti-tumor effects. Additionally, it reduces harmful bacteria such as Proteobacteria and Fusobacteriota, and through bacteria mutualophy increases beneficial bacteria such as Bacteroidota and Firmicutes which produce butyric acid. By binding to the G protein-coupled receptor 109A (GPR109A) on the surface of colonic epithelial cells, butyric acid can induce apoptosis in abnormal cells. Due to the low expression of GPR109A in colon cancer cells, MK-6892 (MK) can be used to stimulate GPR109A. With increased production of butyrate, activated GPR109A is able to bind more butyrate, which further promotes apoptosis of cancer cells and triggers an antitumor response. Conclusion It appears that the oral administration of L.r@(SA-CS)2 microgels may provide a treatment option for CRC by modifying the gut microbiota.

IntroductionThis study aims to explore the mechanism by which community social capital influences pre-service teachers’ career calling, while also examining the mediating role of career exploration and the moderating effect of agreeableness.MethodsData were collected from 455 pre-service teachers at a local undergraduate normal college in Guangdong Province, and a structural equation model was employed for analysis.ResultsThe findings revealed a significant positive relationship between community social capital and career calling, with career exploration serving as a mediating variable between them. Additionally, agreeableness moderated the relationship between community social capital and career exploration.DiscussionThese results provide valuable theoretical and practical support for colleges and universities in developing community service-learning education programs that enhance pre-service teachers’ career exploration, address their individualized requirements, and cultivate their career calling.

IntroductionPlasmodium falciparum is the most damaging malaria pathogen and brings a heavy burden to global health. Host switching and morphological changes in P. falciparum are dependent on an effective gene expression regulatory system. C5 methylation of cytosines is a common RNA modification in eukaryotes, and the NSUN family are essential m5C modification executors. Currently, little is known about this family in Plasmodium spp. In this study, we focus on exploring the function of PfNSUN1 protein.MethodsAn efficient CRISPR/Cas9 gene editing technique was applied to construct the PfNSUN1 knockdown strain. The knockdown efficiency was confirmed by growth curves and western blot experiments. The knockdown transcriptome data was acquired to find differentially expressed genes, and target genes of PfNSUN1 protein were identified by RNA immunoprecipitation and high-throughput sequencing experiments.ResultsThe efficiency of PfNSUN1 protein down-regulated was about 34%. RNA-seq data revealed that differentially expressed genes were mainly down-regulated. And there were 224, 278, 556 genes that were down-regulated with more than 2-fold changes and p-adj

ObjectiveTo investigate the pivotal determinants contributing to the adverse prognosis in patients afflicted with traumatic lung injury (TLI), with an aim to mitigate the elevated mortality rate associated with this condition.MethodsA retrospective analysis was carried out on 106 TLI patients who were admitted to the intensive care unit of a comprehensive hospital from March 2018 to November 2022. The patients were categorized into two groups based on their 28-day outcome: the survival group (n = 88) and the death group (n = 18). Random forest model, least absolute shrinkage and selection operator (LASSO) regression and support vector machine recursive feature elimination (SVM-RFE) were utilized to pinpoint the primary factors linked to poor prognosis in TLI patients. The Receiver Operating Characteristic (ROC) curve analysis was utilized to ascertain the predictive value of INR in forecasting the prognosis of TLI patients. Based on the cut-off value of INR, patients were categorized into two groups: INR ≥ 1.36 group (n = 35) and INR

Abstract Mental disorders are the leading contributors to the globally nonfatal burden of disease. This study was aimed to estimate the burden of mental disorders in Asian countries. Based on GBD 2019, the prevalence and disability-adjusted life of years (DALYs) rates with 95% uncertainty intervals (UI) were estimated in Asian countries. Predictions for the future burden of 8 selected countries, ranks of the burden of mental disorders and correlations with Sociodemographic Index (SDI) were also estimated. During the past 3 decades, while the number of DALYs of mental disorders increased from 43.9 million (95% UI: 32.5–57.2) to 69.0 million (95% UI: 51.0–89.7), the age-standardized rates of DALYs of mental disorders remained largely consistent from 1452.2 (95% UI: 1080.16–1888.53) per 100,000 population in 1990 to 1434.82 (95% UI: 1065.02–1867.27) per 100,000 population in 2019, ranked as the eighth most significant disease burden in Asia in 2019. Depressive disorders (37.2%) were the leading contributors to the age-standardized DALY rates of mental disorders in Asia, followed by anxiety disorders (21.5%). The age-standardized DALY rates in females were higher than their male counterparts, both peaked at 30-34 years. The age-standardized DALY rates were predicted to remain stable, with the number of DALYs presented an upward trend in the future. There was no significant correlation between the burden of mental disorders and SDI. All mental disorders ranked higher in 2019, compared in 1990. To reduce this burden, urgent measures for prevention, treatment, and rehabilitation for mental disorders need to be taken by Asian governments.

High-entropy materials (HEMs) have attracted extensive attention in the field of electrochemical catalysis due to their unique properties. However, the preparation of high-entropy catalysts typically relies on high-temperature, energy-intensive, and time-consuming synthesis methods due to their compositional complexity. In this study, a facile low-temperature electrochemical reconstruction approach is adopted to synthesize Ag-decorated septenary Co-Cu-Fe-Mo-Zn-Ag-Ru high-entropy (oxy)hydroxide electrocatalysts for oxygen evolution reaction (OER). By introducing Ag and Ru elements and implanting Ag nanoparticles to co-regulate the electronic structure of the catalysts, the as-prepared catalyst achieves remarkable OER performance with a low overpotential of 298 mV at 100 mA/cm2 and a small Tafel slope of 30.1 mV/dec in 1 mol/L KOH. This work offers a valuable strategy for developing high-performance high-entropy OER electrocatalysts.

Abstract Major histocompatibility complex (MHC) allelic polymorphism is critically important for mediating antigen presentation in vertebrates. Presently, there are insufficient studies of MHC genetic diversity in domestic Anseriform birds. In this study, we analyzed the expression profile of MHC I genes and screened for MHC I exon 2 polymorphism in one domestic goose population from China using Illumina MiSeq sequencing. The results showed that four MHC I alleles (Ancy-IE2*09/*11/*13/*21) in one goose were identified based on cDNA cloning and sequencing using four primer combinations, and the varying number of cDNA clones implied that these four classical sequences showed differential expression patterns. Through next-generation sequencing, 27 alleles were obtained from 68 geese with 3-10 putative alleles per individual, indicating at least the existence of 5 MHC I loci in the goose. The marked excess of the non-synonymous over the synonymous substitution in the peptide-binding region (PBR) along 27 alleles and five positively selected sites (PSSs) detected around the PBR indicated that balancing selection might be the major force in shaping high MHC variation in the goose. Additionally, IA alleles displaying lower polymorphism were subject to less positive selection pressure than non-IA alleles with a higher level of polymorphism.

The electroplating industry is the main source of 6:2 chlorinated polyfluorinated ether sulfonate (6:2 Cl-PFESA) pollution, which presents risks to human health and the environment. It is therefore crucial to develop effective 6:2 Cl-PFESA degradation techniques. Persulfate oxidation is a potential treatment method for 6:2 Cl-PFESA due to its outstanding oxidative degradability following the generation of the sulfate radical (SO4•−) and hydroxyl radical (•OH). It has proven difficult to acquire a full understanding of the reaction mechanism and formation of intermediate (IM) products through conventional experimental studies because they are costly and time-consuming. Therefore, a theoretical analysis method based on density functional theory (DFT) calculations was applied. The DFT results showed that electron transfer for the degradation of 6:2 Cl-PFESA could be initiated by the protonated sulfate radical (HSO4•, ΔG≠SET = 9.16 kcal/mol), rather than SO4•− (ΔG≠SET = 41.60 kcal/mol). After desulfonation, the reaction underwent stepwise decarboxylation cycles under the action of •OH, leading to the elimination of the CF2 units until there was complete mineralization into HCl, HF, and CO2. Furthermore, the IMs and the end products of 6:2 Cl-PFESA were evaluated using ECOSAR and TEST software. The low bioaccumulation of the short-chain IMs meant that they could be considered safe in terms of ecotoxicity and health effects. This research determined the theoretical and mechanistic basis of the effects of persulfate in the treatment of water containing 6:2 Cl-PFESA, and its structural analogues.

IntroductionChina has experienced unprecedented transformations unseen in a century and is gradually progressing toward an emerging superpower. The epidemiological trends of digestive diseases in the United States (the US) have significant prescient effects on China.MethodsWe extracted data on 18 digestive diseases from the Global Burden of Diseases 2019 Data Resource. Linear regression analysis conducted by the JoinPoint software assessed the average annual percentage change of the burden. We performed subgroup analyses based on sex and age group.ResultsIn 2019, there were 836.01 and 180.91 million new cases of digestive diseases in China and the US, causing 1558.01 and 339.54 thousand deaths. The age-standardized incidence rates of digestive diseases in China and the US were 58417.87/100,000 and 55018.65/100,000 respectively, resulting in age-standardized mortality rates of 81.52/100,000 and 60.88/100,000. The rates in China annually decreased by 2.149% for mortality and 2.611% for disability-adjusted life of year (DALY). The mortality and DALY rates of the US, respectively, had average annual percentage changes of −0.219 and −0.251. Enteric infections and cirrhosis and other chronic liver diseases accounted for the highest incidence and prevalence in both counties, respectively. The burden of multiple digestive diseases exhibited notable sex disparities. The middle-old persons had higher age-standardized prevalence rates.ConclusionChina bore a greater burden of digestive diseases, and the evolving patterns were more noticeable. Targeted interventions and urgent measures should be taken in both countries to address the specific burden of digestive diseases based on their different epidemic degree.

Abstract Background The overgrowth of Desulfovibrio, an inflammation promoting flagellated bacteria, has been found in ulcerative colitis (UC) patients. However, the molecular mechanism in promoting colitis remains unestablished. Methods The relative abundance Desulfovibrio vulgaris (D. vulgaris) in stool samples of UC patients was detected. Mice were treated with dextran sulfate sodium to induce colitis with or without administration of D. vulgaris or D. vulgaris flagellin (DVF), and the severity of colitis and the leucine-rich repeat containing 19 (LRRC19) signaling were assessed. The interaction between DVF and LRRC19 was identified by surface plasmon resonance and intestinal organoid culture. Lrrc19 −/− and Tlr5 −/− mice were used to investigate the indispensable role of LRRC19. Finally, the blockade of DVF-LRRC19 interaction was selected through virtual screening and the efficacy in colitis was assessed. Results D. vulgaris was enriched in fecal samples of UC patients and was correlated with the disease severity. D. vulgaris or DVF treatment significantly exacerbated colitis in germ-free mice and conventional mice. Mechanistically, DVF could interact with LRRC19 (rather than TLR5) in colitis mice and organoids, and then induce the production of pro-inflammatory cytokines. Lrrc19 knockdown blunted the severity of colitis. Furthermore, typhaneoside, a blockade of binding interfaces, blocked DVF-LRRC19 interaction and dramatically ameliorated DVF-induced colitis. Conclusions D. vulgaris could promote colitis through DVF-LRRC19 interaction. Targeting DVF-LRRC19 interaction might be a new therapeutic strategy for UC therapy. Video Abstract

Abstract Background This study aimed to investigate the risks of all-cause and cardiovascular mortality associated with blood pressure (BP) levels of 130–139/80–89 mmHg in Chinese adults with different glucose metabolism, during a long-term follow-up of over 20 years. Methods A prospective population-based cohort of 2,132 adults in Shanghai was established in 2002 and followed for 21 years. The association between BP categories and mortality was assessed, and the risk was further analyzed using multiple Cox regression analysis by combining BP and blood glucose categories. Results The final analysis included 2,004 participants, with 397 all-cause and 166 cardiovascular mortality. The incidence of all-cause and cardiovascular mortality per 1,000 person-years for different BP categories were as follows: BP

The dry leaf of Turpinia arguta (Lindl.) Seem. is used in traditional Chinese medicine as a quick-acting product for sore throat and pharyngitis relief. Samples of T. arguta were collected from 40 different habitats mostly located in Jiangxi Province, and leaf appearance traits and dry matter yield were analyzed. HPLC was used to quantify ligustroflavone and rhoifolin, the pharmacological-quality markers for this species, according to the 2020 Edition of Chinese Pharmacopoeia. The correlations between leaf-measurable traits, ligustroflavone and rhoifolin contents, and climate factors were subsequently assessed using Pearson’s two-tailed correlation test and redundancy analysis. The highest dry matter yields were found in locations S(G-mt), Q(J-t), and A(X-t). Ligustroflavone and rhoifolin contents ranged from 0.023% to 1.336% and 0.008% to 0.962%, respectively; the highest levels of ligustroflavone and rhoifolin compounds were found in locations A(X-t) and Y(B-mt). Leaf morphology was influenced by the mean temperature of the warmest quarter, while leaf thickness was affected by the minimum temperature of the coldest month, precipitation seasonality, and solar radiation. Larger and thicker leaves predicted higher yields of ligustroflavone and rhoifolin compounds in T. arguta under Chinese southern conditions, such as those in Anyuan and Quannan counties. Our findings suggest that enhancing the mean diurnal temperature range and implementing appropriate shading during cultivation can enhance the ligustroflavone and rhoifolin compounds of T. arguta.

Human–machine interactions (HMIs) have penetrated into various academic and industrial fields, such as robotics, virtual reality, and wearable electronics. However, the practical application of most human–machine interfaces faces notable obstacles due to their complex structure and materials, high power consumption, limited effective skin adhesion, and high cost. Herein, we report a self-powered, skin adhesive, and flexible human–machine interface based on a triboelectric nanogenerator (SSFHMI). Characterized by its simple structure and low cost, the SSFHMI can easily convert touch stimuli into a stable electrical signal at the trigger pressure from a finger touch, without requiring an external power supply. A skeleton spacer has been specially designed in order to increase the stability and homogeneity of the output signals of each TENG unit and prevent crosstalk between them. Moreover, we constructed a hydrogel adhesive interface with skin-adhesive properties to adapt to easy wear on complex human body surfaces. By integrating the SSFHMI with a microcontroller, a programmable touch operation platform has been constructed that is capable of multiple interactions. These include medical calling, music media playback, security unlocking, and electronic piano playing. This self-powered, cost-effective SSFHMI holds potential relevance for the next generation of highly integrated and sustainable portable smart electronic products and applications.

Abstract Background Ferroptosis is related to the immunosuppression of tumors and plays a critical role in cancer progression. Fanconi anemia complementation group D2 (FANCD2) is a vital gene that regulates ferroptosis. However, the mechanism of action of FANCD2 in Hepatitis B-related hepatocellular carcinoma (HCC) remains unknown. In this study, we investigated the prognostic significance and mechanism of action of FANCD2 in Hepatitis B-related HCC. Methods The expression of FANCD2 in Hepatitis B-related HCC was explored using The Cancer Genome Atlas (TCGA) and validated using the Gene Expression Omnibus (GEO) database. Univariate and multivariate Cox regression analyses and Kaplan–Meier survival curves were used to analyze the relationship between FANCD2 expression and the overall survival of patients with Hepatitis B-related HCC. Protein–protein interaction networks for FANCD2 were built using the STRING website. In addition, correlations between FANCD2 expression and the dryness index, tumor mutational burden, microsatellite instability (MSI), immune pathways, genes involved in iron metabolism, and sorafenib chemotherapeutic response were analyzed. Results Our results indicated that FANCD2 was significantly overexpressed in Hepatitis B-related HCC and demonstrated a strong predictive ability for diagnosis (Area Under Curve, 0.903) and prognosis of the disease. High FANCD2 expression was associated with poor prognosis, high-grade tumors, high expression of PDL-1, high MSI scores, and low sorafenib IC50 in Hepatitis B-related HCC. BRCA1, BRCA2, FAN1, and FANCC were vital proteins interacting with FANCD2. The expression level of FANCD2 significantly correlated with the infiltration levels of Treg cells, B cells, CD8 + T cells, CD4 + T cells, neutrophils, macrophages, myeloid dendritic cells, and NK cells in Hepatitis B-related HCC. FANCD2 was positively correlated with the tumor proliferation signature pathway, DNA repair, and cellular response to hypoxia. Conclusion Our study indicated that FANCD2 was a potential novel biomarker and immunotherapeutic target against Hepatitis B-related HCC, which might be related to the chemotherapeutic response to sorafenib.

Abstract Objective To explore the effect of oral comprehensive nursing intervention on mechanically ventilated patients in ICU. Methods Select 76 cases of mechanically ventilated patients in severe ICU admitted to our hospital from January 2022 to October 2022 as the research objects, and divide them into the control group and the observation group according to the way the patients receive oral care. 38 cases each. The patients in the control group received routine nursing intervention, and the patients in the observation group received comprehensive oral nursing intervention on the basis of the nursing of the control group. The clinical index data, oropharyngeal hygiene, pH value, blood gas analysis index levels, and the occurrence and death of ventilator-associated pneumonia were compared between the two groups of patients. Results The hospitalization time of the two groups was compared (P > 0.05); the mechanical ventilation time and ICU stay time of the observation group were significantly lower than those of the control group (all, P

African swine fever virus (ASFV) is one of the most complex viruses. ASFV is a serious threat to the global swine industry because no commercial vaccines against this virus are currently available except in Vietnam. Moreover, ASFV is highly stable in the environment and can survive in water, feed, and aerosols for a long time. ASFV is transmitted through the digestive and respiratory tract. Mucosal immunity is the first line of defense against ASFV. Saccharomyces cerevisiae (SC), which has been certified by the U.S. Food and Drug Administration and has a generally recognized as safe status in the food industry, was used for oral immunization in this study. ASFV antigens were effectively expressed in recombinant SC strains with high DNA copy numbers and stable growth though surface display technology and chromosome engineering (δ-integration). The recombinant SC strains containing eight ASFV antigens—KP177R, E183L, E199L, CP204L, E248R, EP402R, B602L, and B646L— induced strong humoral and mucosal immune responses in mice. There was no antigenic competition, and these antigens induced Th1 and Th2 cellular immune responses. Therefore, the oral immunization strategy using recombinant SC strains containing multiple ASFV antigens demonstrate potential for future testing in swine, including challenge studies to evaluate its efficacy as a vaccine against ASFV.

Objectives This study aimed to assess the internal law and time trend of hospitalisation for oesophagogastric variceal bleeding (EGVB) in cirrhosis and develop an effective model to predict the trend of hospitalisation time.Design We used a time series covering 72 months to analyse the hospitalisation for EGVB in cirrhosis. The number of inpatients in the first 60 months was used as the training set to establish the autoregressive integrated moving average (ARIMA) model, and the number over the next 12 months was used as the test set to predict and observe their fitting effect.Setting and data Case data of patients with EGVB between January 2014 and December 2019 were collected from the Affiliated Hospital of Southwest Medical University.Outcome measures The number of monthly hospitalised patients with EGVB in our hospital.Results A total of 877 patients were included in the analysis. The proportion of EGVB in patients with cirrhosis was 73% among men and 27% among women. The peak age at hospitalisation was 40–60 years. The incidence of EGVB varied seasonally with two peaks from January to February and October to November, while the lowest number was observed between April and August. Time-series analysis showed that the number of inpatients with EGVB in our hospital increased annually. The sequence after the first-order difference was a stationary series (augmented Dickey-Fuller test p=0.02). ARIMA (0,1,0) (0,1,1)12 with a minimum Akaike Information Criterion value of 260.18 could fit the time trend of EGVB inpatients and had a good short-term prediction effect. The root mean square error and mean absolute error were 2.4347 and 1.9017, respectively.Conclusions The number of hospitalised patients with EGVB at our hospital is increasing annually, with seasonal changes. The ARIMA model has a good prediction effect on the number of hospitalised patients with EGVB in cirrhosis.

IntroductionHyperuricemia (HUA) is a metabolic disorder caused by purine metabolism dysfunction in which the increasing purine levels can be partially attributed to seafood consumption. Perillae Folium (PF), a widely used plant in functional food, has been historically used to mitigate seafood-induced diseases. However, its efficacy against HUA and the underlying mechanism remain unclear. MethodsA network pharmacology analysis was performed to identify candidate targets and potential mechanisms involved in PF treating HUA. The candidate targets were determined based on TCMSP, SwissTargetPrediction, Open Targets Platform, GeneCards, Comparative Toxicogenomics Database, and DrugBank. The potential mechanisms were predicted via Gene Ontology (GO) and Kyoto Gene and Genome Encyclopedia (KEGG) analyses. Molecular docking in AutoDock Vina and PyRx were performed to predict the binding affinity and pose between herbal compounds and HUA-related targets. A chemical structure analysis of PF compounds was performed using OSIRIS DataWarrior and ClassyFire. We then conducted virtual pharmacokinetic and toxicity screening to filter potential inhibitors. We further performed verifications of these inhibitors’ roles in HUA through molecular dynamics (MD) simulations, text-mining, and untargeted metabolomics analysis. ResultsWe obtained 8200 predicted binding results between 328 herbal compounds and 25 potential targets, and xanthine dehydrogenase (XDH) exhibited the highest average binding affinity. We screened out five promising ligands (scutellarein, benzyl alpha-D-mannopyranoside, elemol, diisobutyl phthalate, and (3R)-hydroxy-beta-ionone) and performed MD simulations up to 50 ns for XDH complexed to them. The scutellarein-XDH complex exhibited the most satisfactory stability. Furthermore, the text-mining study provided laboratory evidence of scutellarein’s function. The metabolomics approach identified 543 compounds and confirmed the presence of scutellarein. Extending MD simulations to 200 ns further indicated the sustained impact of scutellarein on XDH structure. ConclusionOur study provides a computational and biomedical basis for PF treating HUA and fully elucidates scutellarein's great potential as an XDH inhibitor at the molecular level, holding promise for future drug design and development.

The damage of corneal epithelium may lead to the formation of irreversible corneal opacities and even blindness. The migration rate of corneal epithelial cells directly affects corneal repair. Here, we explored ocu-microRNA 24-3p (miRNA 24-3p) that can promote rabbit corneal epithelial cells migration and cornea repair. Exosomes, an excellent transport carrier, were exacted from adipose derived mesenchymal stem cells for loading with miRNA 24-3p to prepare miRNA 24-3p-rich exosomes (Exos-miRNA 24-3p). It can accelerate corneal epithelial migration in vitro and in vivo. For application in cornea alkali burns, we further modified hyaluronic acid with di(ethylene glycol) monomethyl ether methacrylate (DEGMA) to obtain a thermosensitive hydrogel, also reported a thermosensitive DEGMA-modified hyaluronic acid hydrogel (THH) for the controlled release of Exos-miRNA 24-3p. It formed a highly uniform and clear thin layer on the ocular surface to resist clearance from blinking and extended the drug–ocular–epithelium contact time. The use of THH-3/Exos-miRNA 24-3p for 28 days after alkali burn injury accelerated corneal epithelial defect healing and epithelial maturation. It also reduced corneal stromal fibrosis and macrophage activation. MiRNA 24-3p-rich exosomes functionalized DEGMA-modified hyaluronic acid hydrogel as a multilevel delivery strategy has a potential use for cell-free therapy of corneal epithelial regeneration.

In this study, different concentrations of 17-β estradiol silk fibroin (SF)porous scaffolds (SFPS) were prepared using freeze-drying technique, with a hope for optimal concentration and apply it locally to the bone defect area. In this study, the porous scaffold morphology structure was characterized by SEM, FTIR and universal capacity testing machines, and the in vitro cytocompatibility and biological activity of scaffold materials were studied by cell adhesion, viability and proliferation experiments. The results showed that SFPS boasts better physicochemical properties, while 17-β estradiol SF scaffolds with low concentrations of 10−10 mol/L and 10−12 mol/L had more growth and proliferation of SF scaffolds with higher concentrations, and 10−10 mol/L was the optimal concentration of 17-β estradiol SFPS, which was more conducive to cell adhesion and proliferation. On the other hand, after osteogenesis induction of BMSCs inoculated on 17-β estradiol SFPS at different concentrations, it was found that the expression of alkaline phosphatase in BMSCs on different concentrations of 17-β estradiol porous scaffolds was not large. No conflict of interest exits in the submission of this manuscript.

Abstract Recasting phenomenological Lagrangians in terms of SM effective field theory (SMEFT) provides a valuable means of connecting potential BSM physics at momenta well above the electroweak scale to experimental signatures at lower energies. In this work we jointly fit the Wilson coefficients of SMEFT operators as well as the PDFs in an extension of the CT18 global analysis framework, obtaining self-consistent constraints to possible BSM physics effects. Global fits are boosted with machine-learning techniques in the form of neural networks to ensure efficient scans of the full PDF+SMEFT parameter space. We focus on several operators relevant for top-quark pair and jet production at hadron colliders and obtain constraints on the Wilson coefficients with Lagrange Multiplier scans. We find mild correlations between the extracted Wilson coefficients, PDFs, and other QCD parameters, and see indications that these correlations may become more prominent in future analyses based on data of higher precision. This work serves as a new platform for joint analyses of SM and BSM physics based on the CTEQ-TEA framework.

Surface soil moisture (SSM) plays an important role in agricultural and environmental systems. With the continuous improvement in the availability of remote sensing data, satellite technology has experienced widespread development in the monitoring of large-scale SSM. Synthetic Aperture Radar (SAR) and optical remote sensing data have been extensively utilized due to their complementary advantages in this field. However, the limited information from single-band SARs or single optical remote sensing data has restricted the accuracy of SSM retrieval, posing challenges for precise SSM monitoring. In contrast, multi-source and multi-band remote sensing data contain richer and more comprehensive surface information. Therefore, a method of combining multi-band SAR data and employing machine learning models for SSM inversion was proposed. C-band Sentinel-1 SAR data, X-band TerraSAR data, and Sentinel-2 optical data were used in this study. Six commonly used feature parameters were extracted from these data. Three machine learning methods suitable for small-sample training, including Genetic Algorithms Back Propagation (GA-BP), support vector regression (SVR), and Random Forest (RF), were employed to construct the SSM inversion models. The differences in SSM retrieval accuracy were compared when two different bands of SAR data were combined with optical data separately and when three types of data were used together. The results show that the best inversion performance was achieved when all three types of remote sensing data were used simultaneously. Additionally, compared to the C-band SAR data, the X-band SAR data exhibited superior performance. Ultimately, the RF model achieved the best accuracy, with a determinable coefficient of 0.9186, a root mean square error of 0.0153 cm3/cm3, and a mean absolute error of 0.0122 cm3/cm3. The results indicate that utilizing multi-band remote sensing data for SSM inversion offers significant advantages, providing a new perspective for the precise monitoring of SSM.

Tumor-associated macrophages (TAMs) are present in almost all solid tumor tissues. 16They play critical roles in immune regulation, tumor angiogenesis, tumor stem cell activation, tumor invasion and metastasis, and resistance to therapy. However, it is unclear how TAMs perform these functions. With the application of single-cell RNA sequencing (scRNA-seq), it has become possible to identify TAM subpopulations associated with distinct functions. In this review, we discuss four novel TAM subpopulations in distinct solid tumors based on core gene signatures by scRNA-seq, including FCN1+, SPP1+, C1Q+ and CCL18+ TAMs. Functional enrichment and gene expression in scRNA-seq data from different solid tumor tissues found that FCN1+ TAMs may induce inflammation; SPP1+ TAMs are potentially involved in metastasis, angiogenesis, and cancer cell stem cell activation, whereas C1Q+ TAMs participate in immune regulation and suppression; And CCL18+ cells are terminal immunosuppressive macrophages that not only have a stronger immunosuppressive function but also enhance tumor metastasis. SPP1+ and C1Q+ TAM subpopulations can be further divided into distinct populations with different functions. Meanwhile, we will also present emerging evidence highlighting the separating macrophage subpopulations associated with distinct functions. However, there exist the potential disconnects between cell types and subpopulations identified by scRNA-seq and their actual function.

Background: Mitochondria are dynamic organelles, and mitochondrial dynamics are important for the maintenance of mitochondrial inheritance and function. Recently, an increasing number of studies have shown that mitochondrial dynamics play an important role in the occurrence and development of hepatocellular carcinoma (HCC). However, bibliometric analyses of mitochondrial dynamics in HCC are scarce. Therefore, we conducted a bibliometric analysis to explore the current global research status and trends in mitochondrial dynamics and HCC. Methods: Global publications on mitochondrial dynamics and HCC published between 2007 and May 2023 were retrieved from the Web of Science Core Collection (WoSCC) database. Bibliometric analysis was performed using Bibliometrix, VOSviewer, and CiteSpace to analyze the numbers, citations, countries, institutions, authors, journals, references, and keywords. Results: A total of 518 publications were retrieved fromthe WoSCC database. China and The Fourth Military Medical University were the most productive countries and institutions. Zorzano, A published the most literature whereas Chen, HC was the author with the highest number of co-citations. Plos One was the most popular journal, whereas the Journal of Biological Chemistry had the highest number of co-citations. The most frequently used keyword was “mitochondria”. Further analysis of the references and keywords showed that the molecular mechanisms linking them to drug therapy targets should be the focus of future studies. Conclusions: Research on mitochondrial dynamics in HCC has received much attention, and many studies have been published. However, research on mitochondrial dynamics and HCC has been limited by insufficient regional development imbalances and global cooperation. Nevertheless, future research on mitochondrial dynamics and HCC is promising, especially regarding the molecular mechanisms of mitochondrial fission and fusion and how to link the currently known molecular mechanisms with drug therapy targets for HCC.

ABSTRACTAspartic acid (Asp) isomerization is a spontaneous non-enzymatic post-translation modification causing a change in the structure of the protein backbone, which is commonly observed in therapeutic antibodies during manufacturing and storage. The Asps in Asp–Gly (DG), Asp–Ser (DS), and Asp–Thr (DT) motifs in the structurally flexible regions, such as complementarity-determining regions (CDRs) in antibodies, are often found to have high rate of isomerization, and they are considered “hot spots” in antibodies. In contrast, the Asp-His (DH) motif is usually considered a silent spot with low isomerization propensity. However, in monoclonal antibody mAb-a, the isomerization rate of an Asp residue, Asp55, in the aspartic acid-histidine-lysine (DHK) motif present in CDRH2 was found to be unexpectedly high. By determining the conformation of DHK motif in the crystal structure of mAb-a, we found that the Cgamma of the Asp side chain carbonyl group and the back bone amide nitrogen of successor His were in proximal contact, which facilitates the formation of succinimide intermediate, and the +2 Lys played an important role in stabilizing such conformation. The contributing roles of the His and Lys residues in DHK motif were also verified using a series of synthetic peptides. This study identified a novel Asp isomerization hot spot, DHK, and the structural-based molecular mechanism was revealed. When 20% Asp55 isomerization in this DHK motif occurred in mAb-a, antigen binding activity reduced to 54%, but the pharmacokinetics in rat was not affected significantly. Although Asp isomerization of DHK motif in CDR does not appear to have a negative impact on PK, DHK motifs in the CDRs of antibody therapeutics should be removed, considering the high propensity of isomerization and impact on antibody activity and stability.

Background: IgA nephropathy (IgAN) is a major and growing public health problem. Renal fibrosis plays a vital role in the progression of IgAN. This study is to investigate the mechanisms of action underlying the therapeutic effects of Shenbing Decoction II (SBDII) in IgAN renal fibrosis treatment based on ultra-performance liquid chromatography-tandem mass spectrometry (UPLC-MS/MS), network pharmacology and experimental verification. Method: We first used UPLC-MS/MS to explore the main compounds of SBDII, and then used network pharmacology to predict the targets and key pathways of SBDII in the treatment of IgAN renal fibrosis. Next, bovine serum albumin (BSA), lipopolysaccharide (LPS), and carbon tetrachloride (CCL4) were used to induce IgAN in rats, and then biochemical indicators, renal tissue pathology, and renal fibrosis-related indicators were examined. At the same time, part of the results predicted by network pharmacology were also verified. Result: A total of 105 compounds were identified in SBDII by UPLC-MS/MS. Network pharmacology results showed that the active compounds such as acacetin, eupatilin, and galangin may mediate the therapeutic effects of SBDII in treating IgAN by targeting tumor protein p53 (TP53) and regulating phosphatidylinositol 3-kinase (PI3K)-Akt kinase (Akt) signaling pathway. Animal experiments showed that SBDII not only significantly improved renal function and fibrosis in IgAN rats, but also significantly downregulated the expressions of p53, p-PI3K and p-Akt. Conclusion: This UPLC-MS/MS, network pharmacological and experimental study highlights that the TP53 as a target, and PI3K-Akt signaling pathway are the potential mechanism by which SBDII is involved in IgAN renal fibrosis treatment. Acacetin, eupatilin, and galangin are probable active compounds in SBDII, these results might provide valuable guidance for further studies of IgAN renal fibrosis treatment.