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Abstract Background Tar is the main toxic of cigarettes, and its effect on atherosclerosis progression and the underlying mechanisms remain largely unknown. Vascular smooth muscle cells (VSMCs) play a key role in atherogenesis and plaque vulnerability. The present study sought to investigate the mechanism of atherosclerosis progression through tar-induced VSMC necroptosis, a recently described form of necrosis. Methods The effect of tar on atherosclerosis progression and VSMC necroptosis was examined in ApoE−/− mice and cultured VSMCs. The role of necroptosis in tar-induced plaque development was evaluated in RIPK3-deletion mice (ApoE−/−RIPK3−/−). The key proteins of necroptosis in carotid plaques of smokers and non-smokers were also examined. Quantitative proteomics of mice aortas was conducted to further investigate the underlying mechanism. Pharmacological approaches were then applied to modulate the expression of targets to verify the regulatory process of tar-induced necroptosis. Results Tar administration led to increased atherosclerotic plaque area and reduced collagen and VSMCs in ApoE−/− mice. The expression of RIPK1、RIPK3、and MLKL in VSMCs of plaques were all increased in tar-exposed mice and smokers. RIPK3 deletion protected against VSMC loss and plaque progression stimulated by tar. In mechanistic studies, quantitative proteomics analysis of ApoE−/− mice aortas suggested that tar triggered endoplasmic reticulum (ER) stress. PERK-eIF2α-CHOP axis was activated in tar-treated VSMCs and atherosclerotic plaque. Inhibition of ER stress using 4PBA significantly reduced plaque progression and VSMC necroptosis. Further study revealed that ER stress resulted in calcium (Ca2+) release into mitochondria and cytoplasm. Elevated Ca2+ levels lead to mitochondrial dysfunction and excessive reactive oxygen species (ROS) production, which consequently promote RIPK3-dependent necroptosis. In addition, Ca2+/calmodulin-dependent protein kinase II (CaMKII) activated by cytosolic Ca2+ overload binds to RIPK3, accounting for necroptosis. Conclusion The findings revealed that cigarette tar promoted atherosclerosis progression by inducing RIPK3-dependent VSMC necroptosis and identified novel avenues of ER stress and Ca2+ overload.

Abstract Background Emerging proofs have shown that differentially expressed circular RNAs (circRNAs) are closely associated with the pathophysiological process of spinal cord injury (SCI). Mesenchymal stem cell (MSC)-exosomes have been demonstrated to possess favorable therapeutic effects in diseases. Herein, this work aimed to investigate the action of circ_0006640 transferred by MSC-exosomes functional recovery after SCI. Methods SCI animal models were established by spinal cord contusion surgery in mice and lipopolysaccharide (LPS)-stimulated mouse microglial cell line BV2. Levels of genes and proteins were detected by qRT-PCR and Western blot. Properties of BV2 cells were characterized using CCK-8 assay, flow cytometry and ELISA analysis. The oxidative stress was evaluated. Dual-luciferase reporter assay was used for verifying the binding between miR-382-5p and circ_0006640 or IGF-1 (Insulin-like Growth Factor 1). Exosome separation was conducted by using the commercial kit. Results Circ_0006640 expression was lower in SCI mice and LPS-induced microglial cells. Circ_0006640 overexpression protected microglial cells from LPS-induced apoptotic, inflammatory and oxidative injury. Mechanistically, circ_0006640 directly sponged miR-382-5p, which targeted IGF-1. MiR-382-5p was increased, while IGF-1 was decreased in SCI mice and LPS-induced microglial cells. Knockdown of miR-382-5p suppressed apoptosis, inflammation and oxidative stress in LPS-induced microglial cells, which were reversed by IGF-1 deficiency. Moreover, miR-382-5p up-regulation abolished the protective functions of circ_0006640 in LPS-induced microglial cells. Additionally, circ_0006640 was packaged into MSC-exosomes and could be transferred by exosomes. Exosomal circ_0006640 also had protective effects on microglial cells via miR-382-5p/IGF-1 axis. Conclusion Circ_0006640 transferred by BMSC-exosomes suppressed LPS-induced apoptotic, inflammatory and oxidative injury via miR-382-5p/IGF-1 axis, indicating a new insight into the clinical application of exosomal circRNA-based therapeutic in the function recovery after SCI.

In order to solve the problems of casualties and property losses caused by the delay transprotation of emergency materials after the earthquake disaster, a hybrid algorithm considering time division was proposed. Firstly, according to the location of the epicenter, the disaster point and its material needs were determined; Secondly, according to the constraints of road damage in the disaster area, the distribution mode of the demand in the disaster area were determined; Thirdly, according to the road damage and recovery, the "golden 72 hours" after the earthquake was divided into multiple times and multiple distribution methods; Finally, the "Luding 9·5 earthquake in Sichuan Province" was selected as the background for simulation. The results show that compared with the traditional genetic algorithm, the total distribution cost of hybrid algorithm is reduced by 9.53%, and the total distribution time is reduced by 7.03%. In the multi-time scene, the total delivery time of the overall scheme is reduced by 6.33% and the total delivery cost is reduced by 18 .9% compared with that without considering the time scene. The method of joint distribution by dividing time periods after the earthquake can effectively solve the problem of emergency demand in the disaster area and improve the efficiency of emergency materials distribution.

Abstract Background The Chinese government has invested significant resources to build many rural healthcare stations. However, in the face of convenient medical paths and accessible medical resources, the utilization rate of health services for older adults in rural areas is surprisingly low. This study explored why health-seeking behavior among older adults in rural China was not active. Methods Data were collected through participatory rural appraisal (PRA) with 108 participants in 12 villages in southern China. Daily schedule and social and resource mapping were employed to outline the range of activities and the routine of the older adults, as well as in-depth interviews to understand the logic of their healthcare choices. Data collected were analyzed by content analysis. Results Three themes were generated: (1) perceptions of health status (being healthy or sick): the rural older adults used the ability to handle routine chores as a measure of health status; (2) prioritization of solving symptoms over curing diseases: the older adults preferred the informal self-medication to cope with diseases, as long as there were no symptoms and no pain; (3) ‘unpredictable’ troubles: they tended to favor the ‘optimal’ solution of keeping their lives in order rather than the best medical treatment options. Conclusion This study showed that the medical practices of the rural elderly were profoundly influenced by their perceptions of health and their life experiences. In the face of diseases, they tended to keep their lives in order, preferring self-treatment practices that address symptoms or selectively following medical advice rather than medical and science-based clinical solutions. In the future, the construction of rural health care should focus on changing the ‘inaccessibility’ of healthcare resources at the subjective level of the rural elderly and develop culturally adaptable health education.

Abstract Objective The exact mechanism and target molecules of liver fibrosis have remained largely elusive. Here, we investigated the role of long noncoding RNA Gm9866(lncRNA-Gm9866) on liver fibrosis. Methods The transcription of lncRNA-Gm9866 in activated cells and mouse fibrotic livers was determined by quantitative polymerase chain reaction (qRT-PCR). The effects of lentivirus-mediated knockdown or overexpression of lncRNA-Gm9866 in liver fibrosis were examined in vitro and in vivo. Furthermore, bioinformatics analysis, cell samples validation, fluorescence in situ hybridization (FISH) co-localization, RNA binding protein immunoprecipitation (RIP), actinomycin D test and Western blot (WB) were carried out to explore the potential mechanism of lncRNA-Gm9866. Results The expression of α-smooth muscle actin (α-SMA), Collagen I (COL-1) and lncRNA-Gm9866 were significantly increased in tissues and cells. Overexpressing lncRNA-Gm9866 promoted the activation of hepatic stellate cells (HSCs). Silencing lncRNA-Gm9866 inhibited the activation of HSCs and transforming growth factor-β1 (TGFβ1) induced fibrosis. Overexpressing lncRNA-Gm9866 promoted hepatocytes (HCs) apoptosis and the expression of pro-fibrogenic genes, inhibited the proliferation and migration of HCs. Knockdown of lncRNA-Gm9866 inhibited the apoptosis of HCs, the expression of pro-fibrogenic genes, TGFβ1 induced fibrosis and the occurrence of carbon tetrachloride (CCl4)-induced liver fibrosis, and promoted the proliferation and migration of HCs. Mechanistically, lncRNA-Gm9866 may directly bine with Fam98b. Silencing Fam98b in stably overexpressing lncRNA-Gm9866 cell lines reversed the increase of pro-fibrogenic genes and pro-apoptotic genes, fibrosis related pathway protein TGFβ1, Smad2/3, p-Smad2/3 and Notch3 induced by overexpressing lncRNA-Gm9866. Conclusions LncRNA-Gm9866 may regulate TGFβ/Smad and Notch pathways by targeting Fam98b to regulate liver fibrosis. LncRNA-Gm9866 may be a new target for diagnosis and treatment of liver fibrosis.

Highlights Classification and catalytic mechanism of nanozymes with different mimicking activities are dissertated. Activity prediction and rational design methods of nanozymes are highlighted, including density functional theory, machine learning, biomimetic and chemical design. The roles of nanozymes in different synergistic theranostic strategies for tumor are summarized and explained by representative examples in the past five years.

Early flowering promotes early maturity, production, and the capacity to counteract biotic and abiotic stresses, making it an important agronomic trait in zucchini. The present study demonstrated that the zucchini inbred line ‘19’ consistently flowered early, taking significantly fewer days to bloom the first female flower (DFF) than the inbred line ‘113’. Genetic analysis revealed that DFF, an inheritable quantitative trait, is controlled by multiple genes. Based on the strategy of quantitative trait locus (QTL) sequencing (QTL-seq) combined with linkage analysis, three QTLs for DFF were identified on chromosomes 4, 11, and 20. This study used additional F2 populations grown under different environmental conditions for QTL mapping analysis of DFF with insertion/deletion (InDel) markers to validate these results. Using the composite interval mapping (CIM) method of R/qtl software, we only identified one major locus under all environmental conditions, located in a 117-kb candidate region on chromosome 20. Based on gene annotation, gene sequence alignment, and qRT-PCR analysis, we found that the Cp4.1LG20g08050 gene encoding a RING finger protein may be a candidate gene for the opposite regulation of early flowering in zucchini. In summary, these results lay a foundation for a better understanding of early flowering and improving early flowering-based breeding strategies in zucchini.

Tumor vasculature is pivotal in regulating tumor perfusion, immune cell infiltration, metastasis, and invasion. The vascular status of the tumor is intricately linked to its immune landscape and response to immunotherapy. Vessel co-option means that tumor tissue adeptly exploits pre-existing blood vessels in the para-carcinoma region to foster its growth rather than inducing angiogenesis. It emerges as a significant mechanism contributing to anti-angiogenic therapy resistance. Different from angiogenic tumors, vessel co-option presents a distinctive vascular-immune niche characterized by varying states and distribution of immune cells, including T-cells, tumor-associated macrophages, neutrophils, and hepatic stellate cells. This unique composition contributes to an immunosuppressive tumor microenvironment that is crucial in modulating the response to cancer immunotherapy. In this review, we systematically reviewed the evidence and molecular mechanisms of vessel co-option in liver cancer, while also exploring its implications for anti-angiogenic drug resistance and the immune microenvironment, to provide new ideas and clues for screening patients with liver cancer who are effective in immunotherapy.

Background: Cinnamaldehyde (CMD) is a major functional component of Cinnamomum verum and has shown treatment effects against diverse bone diseases. This study aimed to assess the anti-diabetic osteoporosis (DOP) potential of diabetes mellitus (DM) and to explore the underlying mechanism driving the activity of CMD.Methods: A DOP model was induced via an intraperitoneal injection of streptozocin (STZ) into Sprague–Dawley rats, and then two different doses of CMD were administered to the rats. The effects of CMD on the strength, remodeling activity, and histological structure of the bones were assessed. Changes in the netrin-1 related pathways also were detected to elucidate the mechanism of the anti-DOP activity by CMD.Results: CMD had no significant effect on the body weight or blood glucose level of the model rats. However, the data showed that CMD improved the bone strength and bone remodeling activity as well as attenuating the bone structure destruction in the DOP rats in a dose-dependent manner. The expression of netrin-1, DCC, UNC5B, RANKL, and OPG was suppressed, while the expression of TGF-β1, cathepsin K, TRAP, and RANK was induced by the STZ injection. CMD administration restored the expression of all of these indicators at both the mRNA and protein levels, indicating that the osteoclast activity was inhibited by CMD.Conclusion: The current study demonstrated that CMD effectively attenuated bone impairments associated with DM in a STZ-induced DOP rat model, and the anti-DOP effects of CMD were associated with the modulation of netrin-1/DCC/UNC5B signal transduction.

Research indicated that Paclitaxel (PTX) can induce immunogenic cell death (ICD) through immunogenic modulation. However, the combination of PTX and ICD has not been extensively studied in breast cancer (BRCA). The TCGA-BRCA and GSE20685 datasets were enrolled in this study. Samples from the TCGA-BRCA dataset were consistently clustered based on selected immunogenic cell death-related genes (ICD-RGs). Next, candidate genes were obtained by overlapping differentially expressed genes (DEGs) between BRCA and normal groups, intersecting genes common to DEGs between cluster1 and cluster2 and hub module genes, and target genes of PTX from five databases. The univariate Cox algorithm and the least absolute shrinkage and selection operator (LASSO) were performed to obtain biomarkers and build a risk model. Following observing the immune microenvironment in differential risk subgroups, single-gene gene set enrichment analysis (GSEA) was carried out in all biomarkers. Finally, the expression of biomarkers was analyzed. Enrichment analysis showed that 626 intersecting genes were linked with inflammatory response. Further five biomarkers (CHI3L1, IL18, PAPLN, SH2D2A, and UBE2L6) were identified and a risk model was built. The model's performance was validated using GSE20685 dataset. Furthermore, the biomarkers were enriched with adaptive immune response. Lastly, the experimental results indicated that the alterations in IL18, SH2D2A, and CHI3L1 expression after treatment matched those in the public database. In this study, Five PTX-ICD-related biomarkers (CHI3L1, IL18, PAPLN, SH2D2A, and UBE2L6) were identified to aid in predicting BRCA treatment outcomes.

Herein, a Bi3O4Cl/MnxZn1-xFe2O4 composite photocatalyst based on MnxZn1-xFe2O4 is fabricated by hydrothermal and roasting methods. The performances of the obtained photocatalysts were detected via XRD, SEM, EDS, TEM, UV–vis, PL and nitrogen absorption-desorption equipment, which indicated the successful combination of nanosheet Bi3O4Cl and granular MnxZn1-xFe2O4. The activity of the photocatalyst was investigated under solar light with rhodamine B (RhB) as a simulated pollutant, which achieved high catalytic and magnetic properties. In addition, 99.5 % degradation of RhB was displayed by MB-10(10 %MnxZn1-xFe2O4/Bi3O4Cl). The Bi3O4Cl/MnxZn1-xFe2O4 photocatalyst was regarded as having excellent kinetic properties for recycling and magnetism due to its low hysteresis loss illustrated in the hysteresis loop images. In addition, the average recovery of the samples was 91.3 %, which successfully verified the excellent stability of the composites in RhB degradation. This paper demonstrates that the doping of magnetic material onto Bi3O4Cl is a feasible approach to remove RhB. The recovery of the photocatalyst, which provides low cost and highly efficient photocatalysis, is guiding a brand-new strategy for the elimination of organic contaminants.

IntroductionSchizophrenia is a complex psychiatric disorder, of which molecular pathogenesis remains largely unknown. Accumulating evidence suggest that gut microbiota may affect brain function via the complex gut-brain axis, which may be a potential contributor to schizophrenia. However, the alteration of gut microbiota showed high heterogeneity across different studies. Therefore, this study aims to identify the consistently altered gut microbial taxa associated with schizophrenia.MethodsWe conducted a systematic search and synthesis of the up-to-date human gut microbiome studies on schizophrenia, and performed vote counting analyses to identify consistently changed microbiota. Further, we investigated the effects of potential confounders on the alteration of gut microbiota.ResultsWe obtained 30 available clinical studies, and found that there was no strong evidence to support significant differences in α-diversity and β-diversity between schizophrenic patients and healthy controls. Among 428 differential gut microbial taxa collected from original studies, we found that 8 gut microbial taxa were consistently up-regulated in schizophrenic patients, including Proteobacteria, Gammaproteobacteria, Lactobacillaceae, Enterobacteriaceae, Lactobacillus, Succinivibrio, Prevotella and Acidaminococcus. While 5 taxa were consistently down-regulated in schizophrenia, including Fusicatenibacter, Faecalibacterium, Roseburia, Coprococcus and Anaerostipes.DiscussionThese findings suggested that gut microbial changes in patients with schizophrenia were characterized by the depletion of anti-inflammatory butyrate-producing genera, and the enrichment of certain opportunistic bacteria genera and probiotics. This study contributes to further understanding the role of gut microbiota in schizophrenia, and developing microbiota-based diagnosis and therapy for schizophrenia.

Curcumin (Cur) as a natural pigment and biological component, can be widely used in food and beverages. However, the water insolubility of Cur significantly limits its applications. In this study, we prepared a series of nanocrystals via ultrasound-assisted method to improve the solubility and availability of Cur. The results showed artemisia sphaerocephala krasch polysaccharide (ASKP), gum arabic (GA) and wheat protein (WP) were outstanding stabilizers for nanocryatals except traditional agent, poloxamer 188 (F68). The obtained curcumin nanocrystals (Cur-NC) displayed a rod-shaped, crystal- and nanosized structure, and extremely high loading capacity (more over 80 %, w/w). Compared with raw powder, Cur-NC greatly improved the water solubility and dispersibility, and the slow and complete release of Cur of Cur-NC also endowed them excellent antioxidant capacities even at 10 μg/mL. Importantly, as functional factor additive in beverages (e.g. water and emulsion), Cur-NC could increase the content of Cur to at least 600 μg/mL and retain a good stability. Overall, we provided an effective improvement method for the liposoluble active molecules (e.g. Cur) based on the nanocrystals, which not only tremendously enhanced its water solubility, but also strengthened its bioactivity. Notably, our findings broadened the application of water-insoluble compounds.

Insecticides are an indispensable and important tool for agricultural production. However, the inappropriate application of insecticides can cause damage to the food chain and ecosystem. Orius similis is an important predatory and natural enemy of Frankliniella occidentalis. Imidacloprid is widely used to control pests, but will inevitably exert adverse effects on O. similis. In order to determine the effect of different imidacloprid treatments on the ability of O. similis to prey on the 2nd-instar nymphs of F. occidentalis, we determined the toxicity and predation of imidacloprid on different stages of O. similis under contact and ingestion treatments. In addition, we used the Holling disc equation to evaluate the ability of O. similis to search and exhibit predatory activity following contact and ingestion treatments. Analysis showed that the highest LC10 and LC20 values for imidacloprid contact and ingestion toxicity treatment were 17.06 mg/L and 23.74 mg/L, respectively. Both imidacloprid treatments led toa reduction in the predatory of O. similis on prey. The functional responses of the 3rd to 5th instar nymphs, along with female and male O. similis adults to the 2nd-instar nymphs of F. occidentalis were consistent with the Holling type II response following contact and ingestion with imidacloprid. However, following imidacloprid treatment, the handing time (Th) of O. similis with single F. occidentalis was prolonged and the instantaneous attack rate (a) was reduced after imidacloprid treatment. The predatory capacity (a/Th) of female O. similis adults when treated with the LC10 concentration of imidacloprid by ingestion was 52.85; this was lower than that of the LC10 concentration of imidacloprid in the contact treatment (57.67). The extent of predation of O. similis on the 2nd-instar nymphs of F. occidentalis was positively correlated with prey density, although the search effect was negatively correlated with prey density. The most extensive search effect was exhibited by adult O. similis females. Simulations with the Hessell-Varley interference model showed that an increase in the number of O. similis would reduce search efficiency regardless of whether they were treated with imidacloprid or not. Thus, O. similis, especially female adults, exhibited strong potential for controlling the 2nd-instar nymphs of F. occidentalis. The toxicity of ingestion following treatment with the same concentration of imidacloprid in O. similis was greater than that of contact treatment. When using O. similis to control F. occidentalis in the field, we should increase the number of female adults released, and prolong the interval between imidacloprid treatment and O. similis exposure. This strategy will improve the control ability of O. similis, coordinate both chemical and biological control, reduce the impact of pesticides on the environment, and improve the efficiency of agricultural production.

Abstract Background Subjective cognitive decline (SCD) is a preclinical, asymptomatic stage of Alzheimer's disease (AD). Early identification and assessment of progressive SCD is crucial for preventing the onset of AD. Methods The study recruited 60 individuals diagnosed with SCD from the Alzheimer's Disease Neuroimaging Initiative (ADNI) database. Participants were divided into two groups: progressive SCD (pSCD, 23 individuals) and stable SCD (sSCD, 37 individuals) based on their progression to mild cognitive impairment (MCI) within 5 years. Cortical thickness, volumes of the hippocampus subfield, and subcortical regions were analyzed using T1‐weighted images and the FreeSurfer software. Network‐based statistics (NBS) were performed to compare structural covariance networks (SCNs) between the two groups. Results Results showed that the pSCD group showed significant atrophy of the hippocampal‐fimbria (p = .018) and cortical thinning in the left transverse temporal (cluster size 71.84 mm2, cluster‐wise corrected p value = .0004) and left middle temporal gyrus (cluster size 45.05 mm2, cluster‐wise corrected p value = .00639). The combination of these MRI features demonstrated high accuracy (AUC of 0.86, sensitivity of 78.3%, and specificity of 89.3%). NBS analysis revealed that pSCD individuals showed an increase in structural networks within the default mode network (DMN) and a decrease in structural connections between the somatomotor network (Motor) and DMN networks. Conclusion Our findings demonstrate that atrophy of the hippocampus and thinning of the cortex may serve as effective biomarkers for early identification of individuals at high risk of cognitive decline. Changes in connectivity within and outside of the DMN may play a crucial role in the pathophysiology of pSCD.

Rapid advances in nanomedicine have enabled potential applications in cancer therapy. The enhanced permeability and retention (EPR) effect is the primary rationale for the passive targeting of nanoparticles in oncology. However, growing evidence indicates that the accumulation of nanomaterials via the EPR effect could be more efficient. Inspired by our clinical observation of the Gap Junction connecpion between folliculostellate cells and pituitary adenoma cells, we designed a novel drug delivery system that targets tumours by coating folliculostellate cell (FS) membranes onto PLGA nanoparticles (NPs). The resulting FSNPs, inheriting membrane proteins from the folliculostellate cell membrane, significantly enhanced the EPR effect compared to nanoparticles without cancer cell membranes. We further demonstrated that mitotane encapsulation improved the therapeutic efficacy of mitotane in both heterotopic and orthotopic pituitary adenoma models. Owing to its significant efficacy, our FS cell membrane-coated nanoplatforms has the potential to be translated into clinical applications for the treatment of invasive pituitary adenoma.

Background: Micheliolide (MCL), which is the active metabolite of parthenolide, has demonstrated promising clinical application potential. However, the effects and underlying mechanisms of MCL on atherosclerosis are still unclear. Method: ApoE−/− mice were fed with high fat diet, with or without MCL oral administration, then the plaque area, lipid deposition and collagen content were determined. In vitro, MCL was used to pretreat macrophages combined by ox-LDL, the levels of ferroptosis related proteins, NRF2 activation, mitochondrial function and oxidative stress were detected. Results: MCL administration significantly attenuated atherosclerotic plaque progress, which characteristics with decreased plaque area, less lipid deposition and increased collagen. Compared with HD group, the level of GPX4 and xCT in atherosclerotic root macrophages were increased in MCL group obviously. In vitro experiment demonstrated that MCL increased GPX4 and xCT level, improved mitochondrial function, attenuated oxidative stress and inhibited lipid peroxidation to suppress macrophage ferroptosis induced with ox-LDL. Moreover, MCL inhibited KEAP1/NRF2 complex formation and enhanced NRF2 nucleus translocation, while the protective effect of MCL on macrophage ferroptosis was abolished by NRF2 inhibition. Additionally, molecular docking suggests that MCL may bind to the Arg483 site of KEAP1, which also contributes to KEAP1/NRF2 binding. Furthermore, Transfection Arg483 (KEAP1-R483S) mutant plasmid can abrogate the anti-ferroptosis and anti-oxidative effects of MC in macrophages. KEAP1-R483S mutation also limited the protective effect of MCL on atherosclerosis progress and macrophage ferroptosis in ApoE−/− mice. Conclusion: MCL suppressed atherosclerosis by inhibiting macrophage ferroptosis via activating NRF2 pathway, the related mechanism is through binding to the Arg483 site of KEAP1 competitively.

Highlights The loss mechanisms of irreversible Li in electrolytes with various salts (e.g., lithium hexafluorophosphate (LiPF6), lithium difluoro(oxalato)borate (LiDFOB), and lithium bis(fluorosulfonyl)amide (LiFSI)) are systemically revealed. A universal procedure for the electrolyte design of Li metal batteries is proposed: (i) decouple and find the main reason for the irreversible Li loss; (ii) add the corresponding electrolyte additive.

In this study, Laoxianghuang polysaccharide was used as the experimental material to examine the protective effects on stomach mucosa. The polysaccharide was first extracted by hot water and then purified by Sevag methods deproteinization, DEAE-52 cellulose anion-exchange chromatography column, and CL-6B agarose gel column. The ethanol-damaged human gastric mucosal epithelial cells (GES-1) model and the GES-1 scratch injury model were used to evaluate gastric mucosal protective activity of the polysaccharide in vitro. Results showed that six fractions of Laoxianghuang polysaccharide were obtained, including PFCP, PFCP-1, PFCP-2, PFCP-3, PFCP-2-1, and PFCP-2-2. After ethanol damaged to GES-1, each fraction of Laoxianghuang polysaccharide improved cellular activity, increased the activity of superoxide dismutase (SOD), catalase (CAT), and inhibited malondialdehyde (MDA) content, exhibiting good antioxidant capacity to reduce mucosal damage. Among them, PFCP-2-1 (50 μg/mL) had the best effect on improving SOD enzyme activity and reducing MDA content, and PFCP-2-1 (5 μg/mL) had the best effect on improving CAT enzyme activity, which was significant compared with the model group (P0.05). In conclusion, Laoxianghuang polysaccharide PFCP-2-1 may exert gastric mucosal protective activity by enhancing cellular antioxidant capacity as well as promoting the proliferation and migration of GES-1.

ABSTRACTUsing listed companies from 2010 to 2019 in China, we investigate whether firms engage in opinion shopping activities when firms dismiss the auditors following a goodwill impairment. We find that firms tend to dismiss the incumbent auditors after receiving a goodwill impairment opinion and engage in opinion shopping with their successor auditors. Furthermore, the successor’s auditor quality is similar to the predecessor’s audit quality following a dismissal. Moreover, firms with low-quality internal control system and low analyst coverage level are more motivated to engage in opinion shopping subsequently after receiving a goodwill impairment opinion. Our findings would be of interest to corporate governance activists, auditors, investors and regulators.

Abstract Background Conducting an extensive study on the spatial heterogeneity of the overall carbon budget and its influencing factors and the decoupling status of carbon emissions from economic development, by undertaking simulation projections under different carbon emission scenarios is crucial for China to achieve its targets to peak carbon emissions by 2030 and to achieve carbon neutrality by 2060. There are large disparities in carbon emissions from energy consumption, the extent of land used for carbon absorption, and the status of decoupling of emissions from economic development, among various regions of China. Results Based on night light data and land use data, we investigated carbon budget through model estimation, decoupling analysis, and scenario simulation. The results show that the carbon deficit had a continuous upward trend from 2000 to 2018, and there was a significant positive spatial correlation. The overall status of decoupling first improved and then deteriorated. Altogether, energy consumption intensity, population density of built-up land, and built-up land area influenced the decoupling of carbon emissions from economic development. There are significant scenarios of carbon emissions from energy consumption for the study area during the forecast period, only in the low-carbon scenario will the study area reach the expected carbon emissions peak ahead of schedule in 2027; the peak carbon emissions will be 6479.27 million tons. Conclusions China’s provincial-scale carbon emissions show a positive correlation with economic development within the study period. It is necessary to optimize the economic structure, transforming the economic development mode, and formulating policies to control the expansion of built-up land. Efforts must be made to improve technology and promote industrial restructuring, to effectively reduce energy consumption intensity.

Abstract Background Periodontitis is a common chronic oral disease which seriously affects people's quality of life. Although human herpes simplex virus (HSV) is also found in periodontal lesions, the association between HSV infection and periodontitis is unclear. Methods The National Health and Nutrition Examination Survey (NHANES) data for 2009–2010, 2011–2012 and 2013–2014 was combined, and the association between HSV infection and periodontitis in the general population and particular subgroups was investigated through weighted multi-logistic analyses. Results There were 4,733 participants aged 30–50 years old with clinically assessed periodontitis concurrent with HSV infection. In general analysis, after adjusted for covariates, both HSV-1 (OR = 1.09, P

Abstract Reprogramming of vascular smooth muscle cell (VSMC) differentiation plays an essential role in abdominal aortic aneurysm (AAA). However, the underlying mechanisms are still unclear. We explore the expression of FAM3A, a newly identified metabolic cytokine, and whether and how FAM3A regulates VSMC differentiation in AAA. We discover that FAM3A is decreased in the aortas and plasma in AAA patients and murine models. Overexpression or supplementation of FAM3A significantly attenuate the AAA formation, manifested by maintenance of the well-differentiated VSMC status and inhibition of VSMC transformation toward macrophage-, chondrocyte-, osteogenic-, mesenchymal-, and fibroblast-like cell subpopulations. Importantly, FAM3A induces KLF4 ubiquitination and reduces its phosphorylation and nuclear localization. Here, we report FAM3A as a VSMC fate-shaping regulator in AAA and reveal the underlying mechanism associated with KLF4 ubiquitination and stability, which may lead to the development of strategies based on FAM3A to restore VSMC homeostasis in AAA.

Purpose: To evaluate the safety and efficacy of different power modes(constant power and variable power) percutaneous microwave ablation (MWA) for treating hepatocellular carcinoma (HCC) and to predict the risk factors of recurrence after MWA. Materials and methods: In this retrospective study, a total of 112 patients with solitary HCC were included from January 2015 to January 2021. All patients received MWA through a percutaneous approach that was guided by ultrasound, 45 patients received variable power MWA, and the remaining 67 were treated with constant power MWA. The complete ablation rates, local recurrence rates, complications, and short-term survival were analyzed. Possible risk factors for tumor recurrence were analyzed. Results: The complete ablation rates were 95.9% for the first ablation and 100% for the second ablation for ≤3 cm lesions. The complete ablation rates were 84.2%(95.9% versus 84.2%, p = 0.039) for the first ablation and 94.7% (100% versus 94.7%, p = 0.113) for the second ablation for 3–5 cm lesions. Local and distant recurrence rates were 18.7%(21/112) and 14.3%(16/112). The 1-, 2-year survival rates were 86.3 and 66.3%, respectively. Subgroup analysis showed that 1-, 2-year survival rates were 91.1% and 78.5% in ≤3 cm group, and were 74.4% and 40.9% in 3–5 cm group, respectively. Univariate analysis revealed that a positive correlation existed between the HBV DNA replication(p = 0.007), AFP level of pre-MWA(p = 0.001) and post-MWA(p

SET and MYND domain protein 2 (SMYD2) can methylate histone H3 at lysine36 (H3K36) and some non-histone substrates to play a role in tumorigenesis. However, It is unclear how SMYD2 contributes to chronic kidney disease (CKD). Here, AZ505 or LLY507, which could inhibit SMYD2, were used in cisplatin-induced CKD to investigate the effects and possible mechanisms by which they might act. We found that high expression of SMYD2 in cisplatin-induced CKD. However, AZ505 or LLY507 can significantly inhibit its expression, improve renal function injury and fibrosis induced by cisplatin, inhibit the transition of epithelial cells to a fibrogenic phenotype and fibrosis-related proteins, inhibit the expression of Inflammatory Cytokines (such as IL-6 and TNF-α), And inhibit the phosphorylation of pro-fibrosis molecule Smad3 and signal transduction and transcription activator-3 (STAT3) and up-regulated the expression of renal protective factor Smad7. In cultured tubular epithelial cells, AZ505 also can inhibit the expression of EMT, fibrosis-related proteins, and inflammatory cytokines in cisplatin-induced tubular epithelial cells. Based on these findings, SMYD2 may be a critical regulator of cisplatin-induced CKD and targeted pharmacological inhibition of SMYD2 may prevent cisplatin-induced CKD through Smad3 or STAT3-related signaling pathways.

Abstract Histologically, melanoma tissues had fewer positive cells percentage of pyroptosis-related genes (PRGs), GZMA, GSDMB, NLRP1, IL18, and CHMP4A in epidermal than in normal skin. Pyroptosis, a new frontier in cancer, affects the tumor microenvironment and tumor immunotherapy. Nevertheless, the role of pyroptosis remains controversial, which reason is partly due to the heterogeneity of the cellular composition in melanoma. In this study, we present a comprehensive analysis of the single-cell transcriptome landscape of pyroptosis in melanoma specimens. Our findings reveal dysregulation in the expression of PRGs, particularly in immune cells, such as CD8+ cells (representing CD8+ T cells) and CD57+ cells (representing NK cells). Additionally, the immunohistochemical and multiplex immunofluorescence staining experiments results further confirmed GZMA+ cells and GSDMB+ cells were predominantly expressed in immune cells, especially in CD8 + T cells and NK cells. Melanoma specimens secreted a minimal presence of GZMA+ merged CD8+ T cells (0.11%) and GSDMB+ merged CD57+ cells (0.08%), compared to the control groups exhibiting proportions of 4.02% and 0.62%, respectively. The aforementioned findings indicate that a reduced presence of immune cells within tumors may play a role in diminishing the ability of pyroptosis, consequently posing a potential risk to the anti-melanoma properties. To quantify clinical relevance, we constructed a prognostic risk model and an individualized nomogram (C-index=0.58, P = 0.002), suggesting a potential role of PRGs in malignant melanoma prevention. In conclusion, our integrated single-cell and bulk RNA-seq analysis identified immune cell clusters and immune gene modules with experiment validation, contributing to our better understanding of pyroptosis in melanoma.

Abstract Background “Rhubarb-Peach Kernel” herb pair (RP) one of the most frequently used drug pairs, has been used in traditional medicine in China to treat inflammation and diseases associated with pain. Although it is widely used clinically and has a remarkable curative effect, the mechanism of RP treatment for endometriosis (EMs) remains unclear due to its complicated components. The aim of this study was to investigate the anti-endometriosis effect of RP, with emphasis on apoptosis via network pharmacology prediction, molecular docking and experimental verification. Methods The related ingredients and targets of RP in treating EMs were screened out using Traditional Chinese Medicine Systems Pharmacology (TCMSP), Tool for Molecular mechanism of Traditional Chinese Medicine (BATMAN-TCM), and GeneCards database. The data of the protein–protein interaction (PPI) network was obtained by the Search Tool for the Retrieval of Interaction Gene/Proteins (STRING) Database. The Metascape database was adopt for Kyoto encyclopedia of genes and genomes (KEGG) enrichment analysis. After that, the molecular docking of the main active ingredients and apoptosis targets was performed. Finally, the pro-apoptotic effect of RP was verified in hEM15a cells. Results A total of 32 RP compounds were collected. Forty-two matching targets were picked out as the correlative targets of RP in treating EMs. Among these, 18 hub targets including P53, CASP3 were recognized by the PPI network. KEGG enrichment analysis discovered that the regulation of apoptosis was one of the potential mechanisms of RP against EMs. Anthraquinone compounds, flavonoids, and triterpenes in RP were identified as crucial active ingredients, involved in the pro-apoptotic effect, which were confirmed subsequently by molecular docking. Additionally, it was verified that RP treatment promoted apoptosis and inhibited the proliferation of EMs cells (assessed by MTT and Flow cytometry). Moreover, the induction of apoptosis in treated EMs cells may be due to the regulation of apoptosis-related protein expression, including P53, BAX, and CASP3. Conclusions The results of our study demonstrated that RP may exert its therapeutic effects on EMs through the potential mechanism of promoting apoptosis. Anthraquinones, flavonoids and triterpenoids are the possible pro-apoptotic components in RP.

Abstract Epigenetic modifications play important roles during the pathogenesis of multiple myeloma (MM). Herein, we found that protein arginine methyltransferase 1 (PRMT1) was highly expressed in MM patients, which was positively correlated with MM stages. High PRMT1 expression was correlated with adverse prognosis in MM patients. We further showed that silencing PRMT1 inhibited MM proliferation and tumorigenesis in vitro and in vivo. Mechanistically, we revealed that the knockdown of PRMT1 reduced the oxidative phosphorylation (OXPHOS) of MM cells through NDUFS6 downregulation. Meanwhile, we identified that WTAP, a key component of the m6A methyltransferase complex, was methylated by PRMT1, and NDUFS6 was identified as a bona fide m6A target of WTAP. Finally, we found that the combination of PRMT1 inhibitor and bortezomib synergistically inhibited MM progression. Collectively, our results demonstrate that PRMT1 plays a crucial role during MM tumorigenesis and suggeste that PRMT1 could be a potential therapeutic target in MM.

Abstract Background This study aimed to screen the impact factors for clinical symptoms of prenatally diagnosed choledochal cysts (CDCs), to warn about the occurrence of clinical symptoms and the timing of surgery. Methods Medical records of patients with prenatally diagnosed CDCs admitted to our hospital from April 2013 to April 2018 were retrospectively reviewed. Fetal hilar or abdominal cysts were found by prenatal ultrasonogram. All patients underwent laparoscopic cyst excision and hepaticojejunostomy in our center. Univariate analysis and multivariate logistic regression analysis were performed to screen the factors related to clinical symptoms intimately. Results Two hundred eighteen cases were included. One hundred thirty-four patients (134/218, 61.5%) presented clinical symptoms before surgery. The results of univariate analysis showed that patients with clinical symptoms had earlier time of prenatal diagnosis (P = 0.002), higher values of GGT, TBIL, DBIL (P

The transformation and upgrading of resource-exhausted cities are crucial for regional sustainable development, but how to help them overcome innovation challenges remains to be explored. Based on data from 2003 to 2016, this study used a difference-in-differences (DID) method to examine the impact of China’s support policy for resource-exhausted cities on urban innovation and tests for long-term mechanisms. The results indicate that the support policy significantly enhanced regional innovation levels. The mechanism tests showed that these policies promoted urban innovation through long-term mechanisms of increasing marketization and upgrading industrial structures. Further analysis revealed that the innovation-promoting effects of the policies were more significant in resource-exhausted cities located in the eastern region, those not dependent on coal, those with a low reliance on extractive industries, and those with a favorable talent environment. The findings suggest that the government should provide policy support to achieve the transformation, upgrading, and sustainable development of resource-exhausted cities through urban innovation.

Improvements in phase stability and dielectric characteristics can broaden the applications of zirconia in ceramics. Herein, a series of Y2O3-stabilized zirconia (YSZ) ceramics are synthesized using solid-state sintering, followed by an investigation into their phase evolution, grain size, dielectric constant, and breaking field. As the Y2O3 content increases from 0 wt% to 4 wt%, the as-grown YSZ ceramics undergo a distinct phase transformation, transitioning from monoclinic to monoclinic + tetragonal and further to monoclinic + tetragonal + cubic, before finally returning to monoclinic + cubic. Significant changes occur in the internal microstructure and grain size of the ceramics as the phase composition alters, resulting in a reduction in grain size from 3.17 μm to 0.27 μm. Moreover, their dielectric constants exhibit an increasing trend as the Y2O3 content increases, rising from 3.92 to 13.2. Importantly, the dielectric breakdown field of these YSZ ceramics shows a similar variation to the phase evolution, ranging from 0.11 to 0.15 MV/cm. This study sheds light on the phase evolution and dielectric properties of YSZ ceramics, offering an efficient strategy for enhancing their dielectric performances.

The gait rehabilitation knee exoskeleton is an advanced rehabilitative assistive device designed to help patients with knee joint dysfunction regain normal gait through training and activity support. This paper introduces a design framework based on the process knowledge representation method to optimize the design and control efficiency of the knee exoskeleton. This framework integrates knowledge of design objects and processes, specifically including requirements, functions, principle work areas, and the representation and multi-dimensional dynamic mapping of the Behavior–Structure (RFPBS) matrix, achieving multi-dimensional dynamic mapping of the knee exoskeleton. This method incorporates biomechanical and physiological knowledge from the rehabilitation process to more effectively simulate and support gait movements during rehabilitation. Research results indicate that the knee rehabilitation exoskeleton design, based on the RFPBS process knowledge representation model, accomplishes multi-dimensional dynamic mapping, providing a scientific basis and effective support for the rehabilitation of patients with knee joint dysfunction.

Pinus is an important economic tree species, but pine wilt disease (PWD) seriously threatens the survival of pine trees. PWD caused by Bursaphelenchus xylophilus is a major quarantine disease worldwide that causes significant economic losses. However, more information about its molecular pathogenesis is needed, resulting in a lack of effective prevention and treatment measures. In recent years, effectors have become a hot topic in exploring the molecular pathogenic mechanism of pathogens. Here, we identified a specific effector, BxNMP1, from B. xylophilus. In situ hybridization experiments revealed that BxNMP1 was specifically expressed in dorsal gland cells and intestinal cells, and RT–qPCR experiments revealed that BxNMP1 was upregulated in the early stage of infection. The sequence of BxNMP1 was different in the avirulent strain, and when BxNMP1-silenced B. xylophilus was inoculated into P. thunbergii seedlings, the disease severity significantly decreased. We demonstrated that BxNMP1 interacted with the thaumatin-like protein PtTLP-L2 in P. thunbergii. Additionally, we found that the β-1,3-glucanase PtGLU interacted with PtTLP-L2. Therefore, we hypothesized that BxNMP1 might indirectly interact with PtGLU through PtTLP-L2 as an intermediate mediator. Both targets can respond to infection, and PtTLP-L2 can enhance the resistance of pine trees. Moreover, we detected increased salicylic acid contents in P. thunbergii seedlings inoculated with B. xylophilus when BxNMP1 was silenced or when the PtTLP-L2 recombinant protein was added. In summary, we identified a key virulence effector of PWNs, BxNMP1. It positively regulates the pathogenicity of B. xylophilus and interacts directly with PtTLP-L2 and indirectly with PtGLU. It also inhibits the expression of two targets and the host salicylic acid pathway. This study provides theoretical guidance and a practical basis for controlling PWD and breeding for disease resistance.

Finger technique is a crucial aspect of piano learning, and hand exoskeleton mechanisms effectively assist novice piano players in maintaining correct finger technique consistently. Addressing current issues with exoskeleton robots, such as the inability to provide continuous correction of finger technique and their considerable weight, a novel hand exoskeleton robot has been developed to enhance finger technique through continuous correction and reduced weight. Initial data are gathered using finger joint angle sensors to analyze movements during piano playing, focusing on the trajectory and angular velocity of key strikes. This analysis informs the design of a 6-bar double-closed-loop mechanism with an end equivalent sliding pair, using analytical methods to establish the relationship between motor extension and input rod rotation. Simulation studies assess the exoskeleton’s motion space and dynamics, confirming its capability to meet structural and functional demands for accurate key striking. Prototype testing validates the exoskeleton’s ability to maintain correct finger positioning and mimic natural strike speeds, thus improving playing technique while ensuring comfort and safety.

Pipelines are an important transportation form in industry. However, pipeline corrosion, particularly that occurring internally, poses a significant threat to safe operations. To detect the internal corrosion of a pipeline, a method utilizing piezoelectric sensors alongside singular spectrum analysis is proposed. Two piezoelectric patches are affixed to the exterior surface of the pipeline, serving the roles of an actuator and a sensor, respectively. During the detection, the signals excited by the actuator are transmitted through the pipeline’s wall and are received by PZT2 through different paths, and the corresponding piezoelectric sensor captures the signals. Then, the response signals are denoised by singular spectrum analysis, and the first several wave packets in the response signals are selected to establish a feature for pipeline corrosion detection. At last, the envelope area of the selected packets is calculated as a feature to detect corrosion. To validate the proposed method, corrosion monitoring experiments are performed. The experimental results indicate that the envelope area of the first several wave packets from the response signals, following singular spectrum analysis, can serve as a feature to assess the degree of pipeline corrosion, and the index has a monotonic relationship with the corrosion depth of the pipeline. This method provides an effective way for pipeline corrosion monitoring.

Pharmaceutical excipient PEG400 is a common component of traditional Chinese medicine compound preparations. Studies have demonstrated that pharmaceutical excipients can directly or indirectly influence the disposition process of active drugs in vivo, thereby affecting the bioavailability of drugs. In order to reveal the pharmacokinetic effect of PEG400 on baicalin in hepatocytes and its mechanism, the present study first started with the effect of PEG400 on the metabolic disposition of baicalin at the hepatocyte level, and then the effect of PEG400 on the protein expression of baicalin-related transporters (BCRP, MRP2, and MRP3) was investigated by using western blot; the effect of MDCKII-BCRP, MDCKII-BCRP, MRP2, and MRP3 was investigated by using MDCKII-BCRP, MDCKII-MRP2, and MDCKII-MRP3 cell monolayer models, and membrane vesicles overexpressing specific transporter proteins (BCRP, MRP2, and MRP3), combined with the exocytosis of transporter-specific inhibitors, were used to study the effects of PEG400 on the transporters in order to explore the possible mechanisms of its action. The results demonstrated that PEG400 significantly influenced the concentration of baicalin in hepatocytes, and the AUC0–t of baicalin increased from 75.96 ± 2.57 μg·h/mL to 106.94 ± 2.22 μg·h/mL, 111.97 ± 3.98 μg·h/mL, and 130.42 ± 5.26 μg·h/mL (p ˂ 0.05). Furthermore, the efflux rate of baicalin was significantly reduced in the vesicular transport assay and the MDCKII cell model transport assay, which indicated that PEG400 had a significant inhibitory effect on the corresponding transporters. In conclusion, PEG400 can improve the bioavailability of baicalin to some extent by affecting the efflux transporters and thus the metabolic disposition of baicalin in the liver.

This study aims to establish a rapid and convenient microwave-assisted digestion method for sample pretreatment to determine amino acid profiles in natural products. This method was applied to analyze the amino acid profiles of Quisqualis Fructus (QF) from different planted origins. The microwave-assisted digestion conditions were optimized by a response surface methodology (RSM), and 17 amino acids in different planted origins of QF were determined by an automatic amino acid analyzer according to the optimized digestion conditions. The contents of 17 amino acids in QF from different planted origins were further analyzed by fingerprint and chemometric analysis. The temperature of microwave digestion at 167 °C, time of microwave digestion at 24 min, and a solid–liquid ratio of 46.5 g/mL was selected as the optimal digestion conditions. The total content of 17 amino acids in QF from different planted origins ranged from 71.88 to 91.03 mg/g. Amino acid composition and nutritional evaluation indicated that the content of medicinal amino acids was higher than aromatic amino acids. The results of fingerprint analysis reflected that the similarity between the 16 batches of QF ranged from 0.889 to 0.999, while chemometrics analysis indicated amino acid content in QF varied from different planted origins, and six important differential amino acids were screened. Compared with the traditional extraction method, microwave-assisted digestion with response surface optimized has the advantages of rapidity, convenience, and reliability, which could be used to study the amino acid profiles in natural products. The amino acid profile of QF indicated that it has a rich medicinal nutritional value. Different planted origins of QF have a high degree of similarity and could be effectively distinguished by chemometric analysis.

The effect of the ZrO2 doping amounts on the corrosion properties and mechanical properties of the molybdenum alloys in molten zinc was investigated. Among them, the Mo-1.5 wt% ZrO2 alloy has good corrosion resistance (at 460 °C) and excellent mechanical properties. Compared with that of pure molybdenum, the tensile strength of the Mo-1.5 wt%ZrO2 increased by 16.69% in the rotary forged state and 58.26% in the 1200 °C annealed states, and the compressive strength increased by 16.53% and 84.46%, respectively. At a corrosion temperature of 460 °C, a MoZn7 corrosion layer was formed, which isolates the molybdenum matrix from direct contact with the molten zinc. The distribution of ZrO2 particles in the corrosion layer, which changes the diffusion path of zinc and molybdenum atoms, thus slowing down the corrosion process. The thickness of the corrosion layer gradually decreases with increasing doping amount, where the corrosion layer thickness of the Mo-2.0 wt% ZrO2 is 45.21% lower than that of the pure molybdenum. At a corrosion temperature of 560 °C, the molybdenum matrix is exposed to molten zinc and the grains peel off. As the bond between Mo grains is better than the bond between Mo grains and zirconia, the grain spalling of the zirconia-doped molybdenum alloys is severer than that of pure molybdenum.

Abstract Two extreme cases of static stability are voltage stability and power angle stability. The general stability analysis only focuses on one of the voltage stability or power angle stability. The stability limit and state change are studied for a certain kind of stability characteristics. In this paper, the stability limits of static voltage and power angle are derived, respectively. Therefore, different stability characteristics and their interrelationships can be further studied. The index to judge the dominant stability characteristic is defined. The proposed index only needs the system wide‐area measurement information to quickly and accurately judge the dominant static stability characteristics. The dominant instability (DI) characteristic index proposed in this paper is equal to 1 or −1, which can help to quickly identify whether the power angle stability or voltage stability is dominant. The effectiveness of the method is proved by a simple system.

In view of the rapid development and application of blockchain technology, this paper considers a secondary supply chain system consisting of a single upstream supplier and a downstream e-tailer that implements blockchain technology and a traditional e-tailer that does not implement blockchain technology. We establish the demand function of two channels based on consumers' sensitivity to the blockchain and use the Stackelberg game model to compare and analyse the e-tailers' profits from the two channels. For the basic properties, interestingly, we find that there exists a critical threshold on the cost sensitivity to effort that helps each e-tailer decide whether to implement effort. If the cost sensitivity to effort is high, the two-sided e-tailers will reduce their effort as much as possible to obtain greater profits. Conversely, if the cost sensitivity to effort is low, they will increase their effort to obtain more benefits. We also discuss the role of blockchain technology in competition between e-tailers and analyse the impact of the product brand effect brought by the traceability characteristic of blockchain on the competition between e-tailers. To check the robustness of the core results and to investigate different forms of supply chain configurations, this paper further develops the analysis of the supplier entering agency agreements with two-sided e-tailers. Under this scenario, the supplier sells their products directly to consumers through two-sided e-platforms and shares revenue with e-tailers as platform agency fees. These core ideas remain valid in the extended model.

In the context of extensive disciplinary integration, researchers worldwide have increasingly focused on musical ability. However, despite the wide range of available music ability tests, there remains a dearth of validated tests applicable to China. The Music Ear Test (MET) is a validated scale that has been reported to be potentially suitable for cross-cultural distribution in a Chinese sample. However, no formal translation and cross-cultural reliability/validity tests have been conducted for the Chinese population in any of the studies using the Music Ear Test. This study aims to assess the factor structure, convergence, predictiveness, and validity of the Chinese version of the MET, based on a large sample of Chinese participants (n≥1235). Furthermore, we seek to determine whether variables such as music training level, response pattern, and demographic data such as gender and age have intervening effects on the results. In doing so, we aim to provide clear indications of musical aptitude and expertise by validating an existing instrument, the Music Ear Test, and provide a valid method for further understanding the musical abilities of the Chinese sample.

ABSTRACTLimited information on the virome and bacterial community hampers our ability to discern systemic ecological risk factors that cause cattle diarrhea, which has become a pressing issue in the control of disease. A total of 110 viruses, 1,011 bacterial genera, and 322 complete viral genomes were identified from 70 sequencing samples mixed with 1,120 fecal samples from 58 farms in northeast China. For the diarrheic samples, the identified virome and bacterial community varied in terms of composition, abundance, diversity, and geographic distribution in relation to different disease-associated ecological factors; the abundance of identified viruses and bacteria was significantly correlated with the host factors of clinical status, cattle type, and age, and with environmental factors such as aquaculture model and geographical location (P < 0.05); a significant interaction occurred between viruses and viruses, bacteria and bacteria, as well as between bacteria and viruses (P < 0.05). The abundance of SMB53, Butyrivibrio, Facklamia, Trichococcus, and Turicibacter was significantly correlated with the health status of cattle (P < 0.05). The proportion of BRV, BCoV, BKV, BToV, BoNoV, BoNeV, BoAstV, BEV, BoPV, and BVDV in 1,120 fecal samples varied from 1.61% to 12.05%. A series of significant correlations were observed between the prevalence of individual viruses and the disease-associated ecological factors. A genome-based phylogenetic analysis revealed high variability of 10 bovine enteric viruses. The bovine hungarovirus was initially identified in both dairy and beef cattle in China. This study elucidates the fecal virome and bacterial community signatures of cattle affected by diarrhea, and reveals novel disease-associated ecological risk factors, including cattle type, cattle age, aquaculture model, and geographical location.IMPORTANCEThe lack of data on the virome and bacterial community restricts our capability to recognize ecological risk factors for bovine diarrhea disease, thereby hindering our overall comprehension of the disease’s cause. In this study, we found that, for the diarrheal samples, the identified virome and bacterial community varied in terms of composition, abundance, diversity, configuration, and geographic distribution in relation to different disease-associated ecological factors. A series of significant correlations were observed between the prevalence of individual viruses and the disease-associated ecological factors. Our study aims to uncover novel ecological risk factors of bovine diarrheal disease by examining the pathogenic microorganism-host-environment disease ecology, thereby providing a new perspective on the control of bovine diarrheal diseases.

Background: Ubiquitination and deubiquitination modifications play pivotal roles in eukaryotic life processes, regulating protein dynamics via the ubiquitin-proteasome pathway. Dysregulation can impact disease development, including cancer and neurodegenerative disorders. Increasing evidence highlights their role in tumorigenesis, modulating key proteins. OTUD3, a deubiquitinase, stabilizes PTEN, suppressing tumor growth by inhibiting PI3K-AKT signaling. Yet, further OTUD3 substrates remain underexplored.Methods: We employed the In vivo ubiquitination assay to investigate the ubiquitination role of OTUD3 on KPTN within the cellular context. Additionally, CRISPR/Cas9 editing and Immunofluorescence were utilized to study the impact of OTUD3 on the mTOR signaling pathway in cells. Furthermore, Cell proliferation assay and NMR were employed to explore the effects of OTUD3 on cellular growth and proliferation.Results: OTUD3 serves as a deubiquitinase for KPTN. OTUD3 interacts with KPTN, facilitated by the OTU domain within OTUD3. Further investigations confirmed KPTN’s ubiquitination modification, primarily at lysine residue 49. Ubiquitination experiments demonstrated OTUD3’s ability to mediate KPTN’s deubiquitination without affecting its protein levels. This suggests KPTN’s ubiquitination is a function-regulated, non-degradable modification. Under various amino acid starvation or stimulation conditions, overexpressing OTUD3 reduces mTORC1 signaling activation, while knocking out OTUD3 further enhances it. Notably, OTUD3’s regulation of mTORC1 signaling relies on its deubiquitinase activity, and this effect is observed even in PTEN KO cells, confirming its independence from PTEN, a reported substrate. OTUD3 also promotes GATOR1’s lysosomal localization, a process requiring KPTN’s involvement. Ultimately, OTUD3 affects cellular metabolic pool products by downregulating the mTORC1 pathway, significantly inhibiting tumor cell growth and proliferation.Discussion: Our experiments shed light on an alternative perspective regarding the intrinsic functions of OTUD3 in inhibiting tumor development. We propose a novel mechanism involving KPTN-mediated regulation of the mTORC1 signaling pathway, offering fresh insights into the occurrence and progression of tumor diseases driven by related genes. This may inspire new approaches for drug screening and cancer treatment, potentially guiding future therapies for relevant tumors.

BackgroundNumerous observational studies have investigated the risk of prostate cancer (PCa) in patients diagnosed with Parkinson’s Disease (PD). However, the existence of a definitive association remains uncertain.MethodsSystematic searches were performed on PubMed, Web of Science, Scopus, and Google Scholar for studies published up to October 1, 2023. For Mendelian randomized (MR) causal inference, we employed pooled data from the IPDGC and PRACTICAL Consortium. The inverse variance weighted (IVW) method served as the principal technique for estimating odds ratios (ORs) and 95% confidence intervals (CIs) for the associations under investigation.ResultsCumulative analysis of nine studies revealed no significant association between patients diagnosed with PD and the subsequent incidence of PCa ([relative ratio] RR = 0.89, 95%CI = 0.73 to 1.08, P = 0.237). However, subgroup analyses indicated a reduced occurrence of PCa in Caucasian patients with PD (RR = 0.81, 95%CI = 0.69 to 0.95, P = 0.011). MR analyses failed to establish a significant link between increased genetic susceptibility to PD and the risk of PCa (IVW OR = 1.025, 95%CI = 0.997 to 1.054, P = 0.082). Sensitivity analyses further corroborated the robustness of these results.ConclusionBoth observational meta-analysis and MR analysis based on genetic variation do not support an association between PD patients and the subsequent risk of PCa. Further research is warranted to unravel the potential underlying mechanisms linking these two diseases.Systematic review registrationhttps://www.crd.york.ac.uk/PROSPERO/, identifier CRD42023473527.

Water pollution is becoming an increasingly serious issue, which threatens human survival. However, existing technology for addressing this issue has not developed adequately, and the recovery of polluted water remains difficult. Therefore, it is critical to develop innovative wastewater treatment technology, which is highly effective, uses little energy, and produces no secondary pollution. In this study, a Z-type heterojunction BiOCl/MnxZn1-xFe2O4 magnetic composite photocatalyst was created by the hydrothermal method. Using RhB as the target dye, the photocatalytic performances of the composite samples were assessed. The structure of composite samples was studied by SEM, X-ray diffraction, and UV–vis diffuse reflectance spectroscopy.The findings demonstrate that the heterojunction created by the addition of MnxZn1-xFe2O4 and BiOCl lowers the rate at which photogenerated electrons and holes recombine. Meanwhile, the prepared BiOCl/MnxZn1-xFe2O4 magnetic composite photocatalyst exhibited a notable catalytic degradation effect on RhB. Among them, the degradation rate of BiMn-5 was as high as 94.6%, showing better photocatalytic performance than other composite samples with different mass ratios. In addition, the product can be recycled. After five repeated tests, the average degradation rate remained as high as 88.7%. Therefore, the BiOCl/MnxZn1-xFe2O4 magnetic composite photocatalyst developed herein can be a new technology for efficient and environmentally friendly sewage treatment in line with contemporary needs.

African swine fever virus (ASFV) infection is a major public and socioeconomic concern that has a serious impact on the global swine industry. Unfortunately, there are currently no commercially available vaccines or antiviral agents that are both safe and effective against ASFV. In the study, we use primary porcine alveolar macrophages to screen a kinase inhibitor library for anti-ASFV compounds. Six candidate compounds that inhibited ASFV infection with inhibition of > 90% were identified, among which brincidofovir exhibited optimal inhibitory effects on ASFV. Brincidofovir reduces ASFV replication in a dose-dependent manner (IC50 = 2.76 nM) without cytotoxicity (CC50 = 58 μM). It possesses the ability to reduce viral titres and inhibit viral structural protein expression. Time-of-addition assays suggest that the compound interferes with the post-invasion stage of the viral infection cycle. In pig challenge experiments, brincidofovir was indicated to protect pigs against ASFV-induced lethality by decreasing the viral load in organs and peripheral blood, while it alleviated the histopathological changes associated with ASFV infection. Furthermore, brincidofovir also decreased viral shedding in pigs with ASFV infection. Our data together demonstrate that brincidofovir may serve as a potentially effective agent for the prevention and control of ASFV infection, whereas further investigations are still required.