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To screen eminent litchi varieties suitable for the development of natural antioxidant products, the total phenol, total proanthocyanidin, total flavonoid contents and A-type oligomeric procyanidin fractions in the pericarps of seven diverse litchi cultivars were analyzed. The in vitro antioxidant activities including DPPH, ABTS+ free radical scavenging and FRAP were determined. The results demonstrated that the total phenols, total proanthocyanidins, total flavonoids as well as total A-type oligomeric procyanidins contained in the pericarp extract of 'Hemaoli' were the highest. In addition, the primary and secondary mass spectra of the contained substances were analyzed and identified by electrospray liquid-mass spectrometry with quadrupole time-of-flight mass spectrometry (HPLC-Q-TOF-MS/MS). The mass spectrometry results demonstrated that the oligomeric procyanidin fractions contained in litchi pericarps were mainly epicatechin, procyanidin A2, procyanidin A4, A-type trimer and tetramer. Moreover, the content of A-type oligomeric procyanidins in litchi pericarp varied significantly (P

Abstract Background Multiple psychosocial factors have been associated with dementia, while the individual or joint effects of various psychosocial states on dementia remain unrevealed due to the complex interplay between those factors. Here, the authors examined the associations of psychosocial factors and patterns with subsequent risk of dementia, and if the associations could be modified by genetic susceptibility to dementia. Methods UK Biobank dementia-free participants were followed from one year after recruitment (median date: 24 January, 2010) until 31 October, 2022. Psychosocial states were measured by 22 items related to five dimensions, including psychiatric history, recent stressful life events, current psychiatric symptoms, social contact, and individual socioeconomic state. We identified clusters of individuals with distinct psychosocial patterns using latent class analysis. Cox proportional hazards models were used to evaluate the association between psychosocial items, as well as psychosocial patterns, and risk of dementia. We further performed stratification analyses by apolipoprotein E (APOE) genotype, polygenic risk score (PRS) of dementia, and family history of dementia. Results Of 497,787 included participants, 54.54% were female. During a median follow-up of 12.70 years, we identified 9,858 (1.98%) patients with newly diagnosed dementia. We identified seven clusters with distinct psychosocial patterns. Compared to individuals with a pattern of ‘good state’, individuals with other unfavorable patterns, featured by varying degrees of poor psychological state (‘fair state’ and ‘mildly, moderately, and extremely poor psychological state’), low social contact or socioeconomic state (‘living alone’ and ‘short education years’), were all at an increased risk of dementia (hazard ratios [HR] between 1.29 and 2.63). The observed associations showed no significant differences across individuals with varying APOE genotypes, levels of PRS, and family histories of dementia. Conclusion Unfavorable psychosocial patterns are associated with an increased risk of dementia, independent of genetic susceptibility. The findings highlight the importance of surveillance and prevention of cognitive decline among individuals with suboptimal psychosocial state.

Abstract With the advancements in Industry 4.0 and the global demand for sustainable energy, power electronics devices are emerging as pivotal components for modern industrial, transportation, and energy delivery. Ensuring the security of these devices is of paramount importance for safeguarding the reliable operation of critical systems against any threats. In recent years, the issue of intentional electromagnetic interference (IEMI) attack and their related countermeasures have gained widespread attention in both military and civilian power electronics sectors. Here, a review of IEMI in power electronics is provided. Starting from the electromagnetic compatibility standards, the test setups for evaluating the device immunity are introduced. Due to different attack modes and propagation paths, IEMI illuminations are typically categorized into conduction and radiation, where their susceptibility studies, applications, and defence strategies are discussed, respectively. Finally, the existing challenges, ongoing trends, and future topics in this field are discussed.

Abstract Background Psychological and trauma-related factors are associated with many diseases and mortality. However, a comprehensive assessment of the association between psycho-trauma exposures and aging acceleration is currently lacking. Methods Using data from 332,359 UK Biobank participants, we calculated biological aging acceleration, indexed by the presence of leukocyte telomere length (LTL) deviation (i.e., the difference between genetically determined and observed LTL > 0). The acceleration of facial aging (i.e., looking older than the chronological age) was assessed using a self-report question. Then, we estimated the associations of each psycho-trauma factor with biological and facial aging acceleration, using logistic regression models adjusted for multiple important covariates. Furthermore, restricted to 99,180 participants with complete psychological and trauma-related data, we identified clusters of individuals with distinct psycho-trauma patterns using the latent class analysis method and assessed their associations with aging acceleration using similar models. Results We observed most of the studied psycho-trauma factors were associated with biological and facial aging acceleration. Compared to the “Absence of trauma and psychopathology” cluster, the “adverse childhood experiences (ACEs) with psychopathology” cluster showed strong associations with those aging measurements (odds ratio [OR] = 1.13 [1.05 − 1.23] for biological and 1.52 [1.18 − 1.95] for facial aging acceleration), while no such association was observed for the “ACEs without psychopathology” cluster (1.04 [0.99 − 1.09] and 1.02 [0.84 − 1.24]. Conclusions Our study demonstrated significant associations of psycho-trauma factors with both biological and facial aging acceleration. The differential aging consequences observed among ACEs exposed individuals with and without psychopathology prompt interventions aimed to improve individuals’ psychological resilience to prevent aging acceleration.

BackgroundThe Epithelial–Mesenchymal Transition (EMT) is a very important process involved in cancer invasion and metastasis. Additionally, the Cathepsin K (CTSK) gene is closely related to the degradation of the extracellular matrix, which is a critical component of the EMT. The purpose of this study was to determine the relationships between EMT-related genes and immune cell infiltration and their prognostic value in Thyroid carcinoma (THCA). The effect of the CTSK gene on the aggressive biological features of THCA was assessed.MethodsWithin the framework of the present study, the THCA cohort was analyzed in detail based on data obtained from The TCGA database in the context of the EMT. The TCGA-THCA cohort was then divided into two groups, namely, high- and low-risk groups, based on the calculated EMT scores. Finally, based on the findings from the Weighted Gene Co-Expression Network Analysis (WGCNA) algorithm, LASSO regression analysis, and Kaplan−Meier plotter, we selected five genes (CTSK, C3ORF80, FBLN2, PRELP and SRPX2) associated with patient prognosis. Furthermore, this study examined the presence of various immune cells within the THCA samples using three distinct algorithms, namely ssGSEA, xCell, and MCPcounter. Additional studies have been conducted to establish the roles of CTSK in THCA cell proliferation and migration using various assays, such as CCK8, colony formation, EdU proliferation, Transwell migration and wound healing assays. Additionally, the involvement of CTSK in the regulation of various EMT-related markers was confirmed using Western blot analysis.ResultsBased on EMT scores, TCGA-THCA patients were further divided into two groups, and the study revealed that patients in the high-risk group had a worse prognosis than those in the low-risk group. Among the five genes linked to the prognostic value of EMT (CTSK, C3ORF80, FBLN2, PRELP, and SRPX2), CTSK exhibited notably elevated expression in the high-risk cohort. This group also exhibited pronounced immune cell infiltration, with a marked correlation observed between CTSK expression and the levels of macrophages, MDSCs, and various T-cell subtypes. Furthermore, in vitro studies demonstrated that reducing CTSK expression led to significant reductions in THCA cell viability; clonogenic, proliferative, motility and migratory capacities; and the expression of key EMT-related proteins, including N-cadherin, vimentin, slug, and snail.ConclusionOur results suggest that the expression of CTSK, a gene associated with the EMT, may be associated with THCA onset and progression and thus may serve as a promising prognostic biomarker.

IntroductionAtherosclerosis (AS) is considered the underlying cause of many diseases, particularly cardiovascular and cerebrovascular diseases. Inulin, a type of fructan, has shown potential in improving atherosclerosis, although there are conflicting findings. It is hypothesized that the polymerization degree of inulin may largely influence its therapeutic effectiveness. Therefore, this study aimed to investigate the effects and mechanisms of short-chain and long-chain inulin in AS.MethodsApoE−/− mice fed a high fat diet (HFD) were used to establish an atherosclerosis model. These mice received daily oral administration of either short-chain or long-chain inulin for 12 weeks. Plasma lipid metabolism-related indices were measured using biochemical analysis, and plasma immunological indices were analyzed via ELISA. The aorta, aortic root regions, liver tissue, adipose tissue, and colon tissue were examined through various staining techniques, including ORO staining, hematoxylin and eosin staining, Alcian blue staining, and immunofluorescent or immunohistochemical assays. Microbiome analysis was conducted in the cecal content.ResultsThe results indicated that both short-chain and long-chain inulin substantially reduced the formation of atherosclerotic plaques. Inulin also improved plasma lipid concentrations and hepatic lipid metabolism, and partially alleviated both localized (atherosclerotic lesions) and systemic inflammation. Short-chain inulin was more effective than long-chain inulin in reducing atherosclerotic plaques formation, enhancing lipid metabolism and reducing inflammation. Additionally, both types of inulin showed similar effectiveness in enhancing intestinal epithelial barrier integrity, gut microbiota composition and functionality.ConclusionThese findings suggest that inulin has a protective role against atherosclerosis by enhancing lipid metabolism, reducing inflammation, and improving intestinal barrier and gut microbiota. As a dietary intervention, short-chain inulin is more effective than long-chain inulin, offering clinical implications for using inulin as a therapeutic agent for atherosclerosis.

Extraction of coconut paring oil (CPO) from processing by-products adds value to the product and reduces resource wastage. This study aims to assess the impact of 20 kHz, 20/80 kHz and 20/40/80 kHz of multi-frequency ultrasonic-assisted enzymatic extraction (MFUAEE) on the yield, physicochemical properties, fatty acid composition, total phenolic content, antioxidant activity, and emulsion stability of CPO derived from wet coconut parings (WCP). Results revealed that the CPO extraction yield with MFUAEE was 32.58 % − 43.31 % higher compared to AEE. The tri-frequency 20/40/80 kHz mode of multi-frequency ultrasound pretreatment exhibited the highest CPO extraction yield (70.08 %). The oil extracted through MFUAEE displayed similar fatty acid profiles to AEE, but had lower peroxide value, K232 and K270 values. Particularly, MFUAEE oil contained higher total phenolic content and exhibited potent DPPH free radical scavenging capacity. Results observed by SEM indicated that the pretreatment with multi-frequency ultrasound more efficiently disrupts the cellular structure of the WCP. Additionally, MFUAEE enhanced emulsion stability through the cavitation effect of ultrasound. These findings suggest that MFUAEE is a valuable approach for method for obtaining CPO with elevated extraction yield and superior quality, thereby enhancing the utilization of coconut by-products.

Diffuse gliomas in adults are highly infiltrative and largely incurable. Whole exome sequencing (WES) has been demonstrated very useful in genetic analysis. Here WES was performed to characterize genomic landscape of adult-type diffuse gliomas to discover the diagnostic, therapeutic and prognostic biomarkers. Somatic and germline variants of 66 patients with adult-type diffuse gliomas were detected by WES based on the next-generation sequencing. TCGA and CGGA datasets were included to analyze the integrated diagnosis and prognosis. Among 66 patients, the diagnosis of 9 cases was changed, in which 8 cases of astrocytoma were corrected into IDH-wildtype glioblastoma (GBM), and 1 oligodendroglioma without 1p/19q co-deletion into astrocytoma. The distribution of mutations including ATRX/TP53 differed in three cohorts. The genetic mutations in GBM mainly concentrated on the cell cycle, PI3K and RTK pathways. The mutational landscape of astrocytoma was more similar to that of GBM, with the highest frequency in germline variants. Patients with IDH-mutant astrocytoma harboring SNVs of PIK3CA and PIK3R1 showed a significantly worse overall survival (OS) than wild-type patients. AEBP1 amplification was associated with shorter OS in GBM. Our study suggests that clinical sequencing can recapitulate previous findings, which may provide a powerful approach to discover diagnostic, therapeutic and prognostic markers for precision medicine in adult-type diffuse gliomas.

Abstract Hemoglobin A1c (HbA1c) plays a crucial role in diabetes management. We aimed to evaluate the analytical performance of a new enzymatic method kit for HbA1c measurement. The performance of the enzymatic method, including precision, accuracy, and linearity, was evaluated. Moreover, the interference effect from conventional interferents, Hb derivatives, Hb variants, and common drugs were assessed. In addition, the agreement of HbA1c results was compared between enzymatic methods, cation-exchange high-performance liquid chromatography (HPLC), and immunoassays. The intra-assay, between-assay, and total precision of HbA1c were all lower than 2%. HbA1c showed good linearity within the range of 3.96–20.23%. The enzymatic assay yielded results consistent with the external quality control samples, with a bias of less than ± 6% from the target values. The enzymatic method showed no interference from bilirubin, intralipid, vitamin C, Hb derivatives, common Hb variants, as well as antipyretic analgesics and hypoglycemic drugs. The HbA1c results of the enzymatic assay showed good agreement and accuracy compared to those obtained from the HPLC method and the immunoassay. The enzymatic method kit performed on the BS-600M chemistry analyzer is a reliable and robust method for measuring HbA1c. It is suitable for routine practice in clinical chemistry laboratories.

Abstract The aim of this study was to explore the impact of chronic apical periodontitis (CAP) on atherosclerosis in apoE−/− mice fed high-fat diet (HFD). This investigation focused on the gut microbiota, metabolites, and intestinal barrier function to uncover potential links between oral health and cardiovascular disease (CVD). In this study, CAP was shown to exacerbate atherosclerosis in HFD-fed apoE−/− mice, as evidenced by the increase in plaque size and volume in the aortic walls observed via Oil Red O staining. 16S rRNA sequencing revealed significant alterations in the gut microbiota, with harmful bacterial species thriving while beneficial species declining. Metabolomic profiling indicated disruptions in lipid metabolism and primary bile acid synthesis, leading to elevated levels of taurochenodeoxycholic acid (TCDCA), taurocholic acid (TCA), and tauroursodeoxycholic acid (TDCA). These metabolic shifts may contribute to atherosclerosis development. Furthermore, impaired intestinal barrier function, characterized by reduced mucin expression and disrupted tight junction proteins, was observed. The increased intestinal permeability observed was positively correlated with the severity of atherosclerotic lesions, highlighting the importance of the intestinal barrier in cardiovascular health. In conclusion, this research underscores the intricate interplay among oral health, gut microbiota composition, metabolite profiles, and CVD incidence. These findings emphasize the importance of maintaining good oral hygiene as a potential preventive measure against cardiovascular issues, as well as the need for further investigations into the intricate mechanisms linking oral health, gut microbiota, and metabolic pathways in CVD development.

To address the issue of severe network congestion in the scenario of massive machine-type communications (mMTC), where machine-type communication devices (MTCD) employing traditional random access schemes often encountered challenges leading to a large number of MTCD failing to access the network successfully, a novel approach called preamble retransmission-based dynamic access class barring (PRT-ACB) was proposed.By utilizing the number of MTCD preamble retransmissions, the MTCD attempting to initiate access in each random access opportunity (RAO) were categorized into different sets of high and low priority.In conjunction with an estimation model for the number of payloads in each RAO, high and low-priority limiting factors and available preamble pools were dynamically adjusted based on the access load in each RAO.This allowed more MTCD to successfully access the network before reaching the maximum number of preamble transfers.Simulation results have demonstrated that the proposed scheme effectively enhances the MTCD successful access rate and reduces the time delay required for MTCD to access the network.The proposed scheme can serve as a solution to alleviate the congestion caused by a massive influx of communication devices attempting simultaneous network access.

Abstract Straw returning is an important strategy for effectively using straw resources to improve soil fertility and quality, but the effects of this process on reactive intermediates (RIs) formation in paddy water are not fully explored. In this study, we conducted a field experiment to explore the effects of straw returning on RIs formation including triplet chromophoric dissolved organic matter (3CDOM*), hydroxyl radicals (•OH), and singlet oxygen (1O2) in paddy water. It was found that straw returning considerably increased the steady-state concentration of RIs, and the application of rice straw with 25% and 75% organic replacement ratio increased RIs concentration by 2.52 and 2.25 times, respectively. The optical spectroscopy, Fourier transform ion cyclotron resonance mass spectrometry (FT-ICR-MS) analysis and structural equation model showed that straw returning produces abundant humified and aromatic DOM containing fulvic acid, lignin and protein-like substances, which could induce more RIs under irradiation. In addition, straw returning significantly accelerated imidacloprid (IMD) degradation, yielding degradation products that were highly toxic to aquatic animals (i.e., fish and daphnia) but less toxic to aquatic plants (i.e., green algae). This study would offer an innovative viewpoint on the effects of straw returning on the photochemistry of paddy water and the naturally occurring abiotic degradation pathway of organic contaminants.

Abstract Microbial interactions can lead to different colonization outcomes of exogenous species, be they pathogenic or beneficial in nature. Predicting the colonization of exogenous species in complex communities remains a fundamental challenge in microbial ecology, mainly due to our limited knowledge of the diverse mechanisms governing microbial dynamics. Here, we propose a data-driven approach independent of any dynamics model to predict colonization outcomes of exogenous species from the baseline compositions of microbial communities. We systematically validate this approach using synthetic data, finding that machine learning models can predict not only the binary colonization outcome but also the post-invasion steady-state abundance of the invading species. Then we conduct colonization experiments for commensal gut bacteria species Enterococcus faecium and Akkermansia muciniphila in hundreds of human stool-derived in vitro microbial communities, confirming that the data-driven approaches can predict the colonization outcomes in experiments. Furthermore, we find that while most resident species are predicted to have a weak negative impact on the colonization of exogenous species, strongly interacting species could significantly alter the colonization outcomes, e.g., Enterococcus faecalis inhibits the invasion of E. faecium invasion. The presented results suggest that the data-driven approaches are powerful tools to inform the ecology and management of microbial communities.

Abstract Cryptococcus is a family of strongly infectious pathogens that results in a wide variety of symptoms, particularly threatening the patients undergoing the immune‐deficiency or medical treatment. Rapidly identifying Cryptococcus subtypes and accurately quantifying their contents remain urgent needs for infection control and timely therapy. However, traditional detection techniques heavily rely on expensive, specialized instruments, significantly compromising their applicability for large‐scale population screening. In this work, we report a portable microwell array chip platform integrated with a deep learning‐based image recognition program, which enables rapid, precise quantification of the specific subtypes of Cryptococcus. The platform features four zones of microwell arrays preloaded with the subtype‐targeted CRISPR–Cas12a system that avoid dependence on slow, instrumental‐mediated target amplification, achieving rapid (10 min), high specificity for identifying the sequence of Cryptococcus. The deep learning‐based image recognition program utilizing segment anything model (SAM) significantly enhances automation and accuracy in identifying target concentrations, which eventually achieves ultra‐low limit of detection (0.5 pM) by personal smartphones. This platform can be further customized to adapt to various scenarios in clinical settings.

BackgroundVaginal microbiota is involved in human papillomavirus (HPV) infection and cervical cancer (CC) progression, and the specific changes in vaginal microbial composition during this process remains uncertain.ObjectiveThis study aimed to observe the changes in the specific composition of vaginal microorganisms in different cervical lesions and identify biomarkers at different stages of lesions.MethodsIn this study we used the illumina high-throughput gene sequencing technology to determine the V4 region of 16SrRNA and observed the vaginal microbial composition in different cervical lesions.ResultsThe vaginal microbiota of patients with high-risk HPV infection and cervical lesions is significantly different from that of the normal population, but there is no significant difference in the richness of vaginal microbes. The diversity of vaginal species in CC patients is higher than that in high-risk HPV infection or CIN patients. The main manifestation is an increase in the diversity of vaginal microbes, a decrease in the relative abundance of cyanobacteria and Lactobacillus, and an increase in the relative abundance of dialister, peptonephila and other miscellaneous bacteria. There are characteristic vaginal biomarker in normal women, high risk HPV patients and CC patients. In detail, the biomarker in the normal group was varibaculum, the biomarker in the high-risk HPV group was saccharopolyspora, the biomarker of the CC group was the Proteobacteria, Corynebacterium, Coprococcus, Peptococcus and Ruminococcus.ConclusionsThe study indicated that the compositions of vaginal microbes in different cervical lesions is different. The vaginal microbial composition has a certain diagnostic effect on healthy women, patients with high-risk HPV infection and cervical lesions. These microbes may serve as potential biomarkers for CC. It also provided an effective way for the treatment of HPV infections and cervical lesions.

Background The associations between cardiovascular disease (CVD) and multiple psychiatric disorders and suicide attempt, and whether different genetic susceptibilities affect such links, have not been investigated clearly. Methods and Results Based on the UK Biobank, we conducted a matched cohort study involving 63 923 patients who were first hospitalized with a CVD diagnosis between 1997 and 2020, and their 127 845 matched unexposed individuals. Cox models were used to examine the subsequent risk of psychiatric disorders and suicide attempt (ie, anxiety, depression, stress‐related disorder, substance misuse, psychotic disorder, and suicide behaviors) following CVD. We further performed stratified analyses by polygenic risk score for each studied psychiatric condition to detect the possible effects of genetic susceptibility on the observed associations. We found an increased risk of any psychiatric disorders and suicide attempt among CVD patients, compared with matched unexposed individuals, particularly within 1 year following the CVD (fully adjusted hazard ratio [HR] within 1 year, 1.83 [95% CI, 1.58–2.12]; HR after 1 year, 1.24 [95% CI, 1.16–1.32]). By subtype, the risk elevations existed for any psychiatric disorders and suicide attempt following most categories of CVDs. Analyses stratified by polygenic risk score revealed little impact of genetic predisposition to studied psychiatric conditions on these observed links. Conclusions Patients hospitalized for CVD were at increased subsequent risk of multiple types of psychiatric disorders and suicide attempt, especially in the first year after hospitalization, irrespective of their genetic susceptibilities to studied psychiatric conditions, and these findings underscore the necessity of developing timely psychological interventions for this vulnerable population.

BackgroundBladder cancer (BLCA) was recognized as a significant public health challenge due to its high incidence and mortality rates. The influence of molecular subtypes on treatment outcomes was well-acknowledged, necessitating further exploration of their characterization and application. This study was aimed at enhancing the understanding of BLCA by mapping its molecular heterogeneity and developing a robust prognostic model using single-cell and bulk RNA sequencing data. Additionally, immunological characteristics and personalized treatment strategies were investigated through the risk score.MethodsSingle-cell RNA sequencing (scRNA-seq) data from GSE135337 and bulk RNA-seq data from several sources, including GSE13507, GSE31684, GSE32894, GSE69795, and TCGA-BLCA, were utilized. Molecular subtypes, particularly the basal-squamous (Ba/Sq) subtype associated with poor prognosis, were identified. A prognostic model was constructed using LASSO and Cox regression analyses focused on genes linked with the Ba/Sq subtype. this model was validated across internal and external datasets to ensure predictive accuracy. High- and low-risk groups based on the risk score derived from TCGA-BLCA data were analyzed to examine their immune-related molecular profiles and treatment responses.ResultsSix molecular subtypes were identified, with the Ba/Sq subtype being consistently associated with poor prognosis. The prognostic model, based on basal-squamous subtype-related genes (BSSRGs), was shown to have strong predictive performance across diverse clinical settings with AUC values at 1, 3, and 5 years indicating robust predictability in training, testing, and entire datasets. Analysis of the different risk groups revealed distinct immune infiltration and microenvironments. Generally higher tumor mutation burden (TMB) scores and lower tumor immune dysfunction and exclusion (TIDE) scores were exhibited by the low-risk group, suggesting varied potentials for systemic drug response between the groups. Finally, significant differences in potential systemic drug response rates were also observed between risk groups.ConclusionsThe study introduced and validated a new prognostic model for BLCA based on BSSRGs, which was proven effective in prognosis prediction. The potential for personalized therapy, optimized by patient stratification and immune profiling, was highlighted by our risk score, aiming to improve treatment efficacy. This approach was promised to offer significant advancements in managing BLCA, tailoring treatments based on detailed molecular and immunological insights.

Summary: Pyrrolidine (PyD) has an important impact on the environment and human health. However, there is currently no method for trace detection of PyD. Here, we successfully designed diaminomethylene-4H-pyran (1) as the first specific fluorescent probe for PyD. Only by adding PyD to probe 1, there is blue fluorescence at 455 nm, and the color of the solution changes from colorless to yellow. The detection limit is 1.12 × 10−6 M, and the response time is less than 5 min. Meanwhile, probe 1 can also sense the gaseous PyD and detect PyD in actual water samples. Moreover, due to the low biological toxicity, probe 1 can detect the exogenous PyD in zebrafish. The preliminary mechanism shows that probe 1 and PyD undergo a combination-type chemical reaction to generate a new substance 1-PyD. Therefore, the 100% atom utilization reaction enables probe 1 to exhibit specific adsorption and removal of PyD.

IntroductionThe ratio of lysine (Lys) to methionine (Met) with 3.0: 1 is confirmed as the “ideal” profile for milk protein synthesis, but whether this ratio is suitable for milk protein synthesis under HS needs to be further studied.MethodsTo evaluate the molecular mechanism by which HS and Lys to Met ratios affect mammary cell functional capacity, an immortalized bovine mammary epithelial cell line (MAC-T) is incubated with 5 doses of Met while maintaining a constant concentration of Lys. The MAC-T cells was treated for 6 h as follow: Lys: Met 3.0: 1 (control 37°C and IPAA 42°C) or treatments under HS (42°C) with different ratios of Lys: Met at 2.0: 1 (LM20), 2.5: 1 (LM25), 3.5: 1 (LM35) and 4.0: 1 (LM40). RNA sequencing was used to assess transcriptome-wide alterations in mRNA abundance.ResultsThe significant difference between control and other groups was observed base on PCA analysis. A total of 2048 differentially expressed genes (DEGs) were identified in the IPAA group relative to the control group. Similarly, 226, 306, 148, 157 DEGs were detected in the LM20, LM25, LM35 and LM40 groups, respectively, relative to the IPAA group. The relative mRNA abundance of HSPA1A was upregulated and anti-apoptotic genes (BCL2L1 and BCL2) was down-regulated in the IPAA group, compared to the control group (p < 0.05). Compared with the IPAA group, the relative mRNA abundance of anti-apoptotic genes and casein genes (CSN1S2 and CSN2) was up-regulated in the LM25 group (p < 0.05). The DEGs between LM25 and IPAA groups were associated with the negative regulation of transcription RNA polymerase II promoter in response to stress (GO: 0051085, DEGs of BAG3, DNAJB1, HSPA1A) as well as the mTOR signaling pathway (ko04150, DEGs of ATP6V1C2, WNT11, WNT3A, and WNT9A). Several DEGs involved in amino acids metabolism (AFMID, HYKK, NOS3, RIMKLB) and glycolysis/gluconeogenesis (AFMID and MGAT5B) were up-regulated while DEGs involved in lipolysis and beta-oxidation catabolic processes (ALOX12 and ALOX12B) were down-regulated.ConclusionThese results suggested that increasing Met supply (Lys: Met at 2.5: 1) may help mammary gland cells resist HS-induced cell damage, while possibly maintaining lactation capacity through regulation of gene expression.

Abstract The online physician interactive community (OPIC) is a platform designed for medical workers to discuss medical issues. Physician users can create content in OPIC by posting and replying to posts to discuss the solutions of medical problems with other users. The OPIC plays an important role in bringing together physicians from different medical specialties and disseminating medical experience. However, most OPIC users are not very active in replying to posts, which makes it difficult to fulfill users’ needs for medical information exchange and the development of OPIC is difficult. Current research has given little attention to the communication of physician users in the OPIC. It is necessary to examine how reposting links are established between users in OPIC. This study builds a user interaction network based on the perspective of social network analysis using user repost data from a well-known OPIC in China. Then, an exponential random graph model (ERGM) was applied to quantitatively analyze this user interaction network. Some reposting patterns among OPIC users were discovered. There is significant reciprocity in OPIC of reposting interactions between users. Users with homogeneous characteristics in terms of professional status, community honor status, and geographic location were more likely to interact with each other. In addition, users who added a profile, had a higher level of social effort, and generated more neutral content were more likely to receive responses from others. This study reveals the interaction patterns between physician users in OPIC, which enriches the related research within the OPIC domain and helps to improve communication between users in OPIC.

Abstract Anxiety/stress-related disorders have been associated with multiple diseases, whereas a comprehensive assessment of the structure and interplay of subsequent associated diseases and their genetic underpinnings is lacking. Here, we first identify 136, out of 454 tested, medical conditions associated with incident anxiety/stress-related disorders attended in specialized care using a population-based cohort from the nationwide Swedish Patient Register, comprising 70,026 patients with anxiety/stress-related disorders and 1:10 birth year- and sex-matched unaffected individuals. By combining findings from the comorbidity network and disease trajectory analyses, we identify five robust disease clusters to be associated with a prior diagnosis of anxiety/stress-related disorders, featured by predominance of psychiatric disorders, eye diseases, ear diseases, cardiovascular diseases, and skin and genitourinary diseases. These five clusters and their featured diseases are largely validated in the UK Biobank. GWAS analyses based on the UK Biobank identify 3, 33, 40, 4, and 16 significantly independent single nucleotide polymorphisms for the link to the five disease clusters, respectively, which are mapped to several distinct risk genes and biological pathways. These findings motivate further mechanistic explorations and aid early risk assessment for cluster-based disease prevention among patients with newly diagnosed anxiety/stress-related disorders in specialized care.

Spectral clustering (SC) is a hot research topic in graph theory today, which is centered on constructing similarity matrix. Many previous works have studied how to construct a higher-quality similarity matrix. However, most of these works ignore the connection between constructing similarity matrix and the overall distribution of the datasets. This problem will lead to low quality and lack of robustness in the similarity matrix when the data volume and dimensionality are expanded, which leads to poor clustering performance. Therefore, to solve the above problems, an Adaptive Fuzzy Spectral Clustering (AFSC) model is proposed in this paper. The model considers the local neighbor and global fuzzy affiliation information of the samples to construct the objective function, which can obtain the similarity matrix that satisfies the overall distribution of the datasets. Meanwhile, we propose a weight definition method to balance the above two kinds of information, which can prevent the adverse effect of information loss on the quality of the similarity matrix. The similarity matrix obtained by the AFSC model will have high quality and strong robustness, which leads to excellent clustering performance. In experiments, we verified that the AFSC model can obtain excellent clustering performance and outperform some state-of-the-art clustering models as it is applied to several datasets of different sizes and dimensions.

Background: We sought to establish a prospective hospital-based cohort, featuring detailed multidimensional data of trauma patients with active follow-ups, which can be a reliable data source for all studies focusing on the effects or underlying mechanistic pathways of environmental and biological factors on multiple interested trauma-related outcomes, particularly the incidence and trajectory of trauma-related psychopathology, in a Chinese population. Methods: The China Severe Trauma Cohort (CSTC) enrolled all traumatized individuals aged 12 to 80 years admitted to the Trauma Center of West China Hospital between March 1st, 2020 and July 8th, 2022. The bio-sample and detailed questionnaire data were collected at recruitment, and phone/internet follow-ups were scheduled at 1, 3, 6, and 12 months after the baseline. Long-term health outcomes are planned to be obtained from administrative databases through data linkage. Results: A total of 2,500 trauma patients were enrolled (response rate = 87.1%) with an average age of 46.01 years, and most of the participants were males (62.6%). The proportions of participants with blood and fecal sample collected at baseline were 93.8% and 66.3%, respectively. As of August 31st, 2022, the follow-up rate was 90.0%, 77.0%, 76.5%, and 89.0% for 1-, 3-, 6-, and 12-month follow-ups, respectively. Fall/wrench (47.6%) and traffic accident (26.2%) were the top causes of current trauma. The most common psychopathology at recruitment was sleep disturbance (39.4%), followed by depression (22.6%), anxiety (18.2%), and acute stress reaction (7.8%), all of which showed recovering trajectories during the follow-up period, particularly the first 3 months after baseline. Conclusion: CSTC provides a platform with multidimensional data to study both short-term and long-term trauma-related health consequences, prompting early identification and intervention for individuals with high risk of health decline after trauma exposures.

Abstract Background Irritable bowel syndrome (IBS) is a common functional gastrointestinal disorder characterized by abdominal pain, discomfort, and changes in bowel habits. The mechanism underlying IBS remains unclear, and little evidence exists for clarifying the causal relationship between blood metabolites and IBS. Methods We conducted a Mendelian randomization (MR) study using two samples. Exposure data for 7824 Europeans were extracted from a genome-wide association study (GWAS) on metabolite levels. The IBS GWAS data from the GWAS database were used for the initial analysis. The primary analysis of causal relationships was conducted using inverse-variance weighting (IVW) with MR-Egger and weighted medians as supplementary analyses. Sensitivity analyses were performed using a combination of the Cochran’s Q test, MR-Egger intercept test, Mendelian randomization pleiotropy residual sum and outlier, and leave-one-out analysis. For significant associations, replication and meta-analyses were performed using additional independent IBS case GWAS data released by the FinnGen Consortium R9. To identify the metabolites, score regression, confounding analysis, and reverse MR were performed to further assess the causal relationships between the metabolites. Results After rigorous screening, we identified four known metabolites to be associated with IBS (stearate, odds ratio [OR]: 0.74, 95% confidence interval [CI]: 0.59–0.92; arginine, OR: 1.36, 95% CI: 1.07–1.74; 1-palmitoylglycerol, OR:1.49, 95% CI: 1.07–2.07; 1-palmitoylglycerophosphoinositol, OR: 0.84, 95% CI: 0.71–0.99). Conclusions MR analysis revealed a causal relationship between the four metabolites and IBS, providing preliminary evidence for the pathogenesis of IBS. Our results provide novel insights into the potential biomarkers of IBS.

While price schedules can help improve the economic efficiency of renewable energy-powered microgrids, time-of-use (TOU) pricing has been identified as an effective way for microgrid development, which is presently limited by its high costs. In this study, we propose an evolutionary game theoretic model to explore optimal TOU pricing for development of renewable energy-powered microgrids by applying a multi-agent system, that comprises a government agent, local utility company agent, and different types of consumer agents. In the proposed model, we design objective functions for the company and the consumers and obtain a Nash equilibrium using backward induction. Two pricing strategies, namely, the TOU seasonal pricing and TOU monthly pricing, are evaluated and compared with traditional fixed pricing. The numerical results demonstrate that TOU schedules have significant potential for development of renewable energy-powered microgrids and are recommended for an electric company to replace traditional fixed pricing. Additionally, TOU monthly pricing is more suitable than TOU seasonal pricing for microgrid development.

Abstract Parkinson’s disease (PD), one of the most devastating neurodegenerative brain disorders, is characterized by the progressive loss of dopaminergic neurons in the substantia nigra (SN) and deposits of α-synuclein aggregates. Currently, pharmacological interventions for PD remain inadequate. The cell necroptosis executor protein MLKL (Mixed-lineage kinase domain-like) is involved in various diseases, including inflammatory bowel disease and neurodegenerative diseases; however, its precise role in PD remains unclear. Here, we investigated the neuroprotective role of MLKL inhibition or ablation against primary neuronal cells and human iPSC-derived midbrain organoids induced by toxic α-Synuclein preformed fibrils (PFFs). Using a mouse model (Tg-Mlkl −/− ) generated by crossbreeding the SNCA A53T synuclein transgenic mice with MLKL knockout (KO)mice, we assessed the impact of MLKL deficiency on the progression of Parkinsonian traits. Our findings demonstrate that Tg-Mlkl −/− mice exhibited a significant improvement in motor symptoms and reduced phosphorylated α-synuclein expression compared to the classic A53T transgenic mice. Furthermore, MLKL deficiency alleviated tyrosine hydroxylase (TH)-positive neuron loss and attenuated neuroinflammation by inhibiting the activation of microglia and astrocytes. Single-cell RNA-seq (scRNA-seq) analysis of the SN of Tg-Mlkl −/− mice revealed a unique cell type-specific transcriptome profile, including downregulated prostaglandin D synthase (PTGDS) expression, indicating reduced microglial cells and dampened neuron death. Thus, MLKL represents a critical therapeutic target for reducing neuroinflammation and preventing motor deficits in PD.

This study explores the development of an innovative Fabry-Perot Interferometer (FPI) designed for temperature sensing and environmental monitoring. The device is constructed by embedding optical fibers within a 3D-printed resin scaffold, forming a structure with an open Fabry-Perot cavity. Intended as an integral component of Cyber-Physical-Social Systems (CPSS), this FPI structure aims to enhance the system’s capacity to sense changes in external environmental conditions. Within the CPSS context, the FPI offers several advantages, including simple manufacturing processes, low production costs, and high sensitivity. These benefits contribute to providing precise environmental feedback to the system, which is essential in implementing effective security and privacy protection strategies. Experimental evaluations have shown that the FPI exhibits a high linear sensitivity of 14.330 nm/°C within a temperature range of 34.9°C–38.5°C, confirming its potential for application in CPSS for temperature monitoring and environmental sensing.

Abstract Background Wound healing has long been a subject of great interest for pathologists. Previous research has established the effectiveness of topical application of chitooligosaccharides (COSs) on wound healing. However, studies on their potential usefulness as food additives to improve wound healing are lacking. Objective Here, we investigated whether dietary supplementation with COSs could promote wound healing using Beagle dogs as an animal model. Methods Nine dogs were evenly assigned randomly into control, 0.5% COSs and 1% COSs groups. Control dogs were fed with a non‐supplemented dietary formula (vehicle). Dogs in 0.5% COSs and 1% COSs groups were fed with a dietary formula supplemented with 0.5% and 1% COSs. After 8 weeks of feeding, dogs in each group underwent surgery with three matching full‐thickness 2 × 2‐cm skin defects were created with a scalpel on the left side of the dorsal midline, 2 cm apart from each other. Wounds were photographed and the healing percentage was determined on day 0, 2, 4, 7, 9, 11, 14, 16, 18 and 21. The healing process was assessed by daily gross examination, histologic examination and Masson's trichrome staining on days 7, 14 and 21. Considering the important role of the transforming growth factor‐β (TGF‐β1) signalling pathway in wound healing, immunostaining was used to evaluate TGF‐β1 expression. Results The results showed that wound healing was accelerated; collagen synthesis and TGF‐β1 expression were enhanced in response to dietary supplementation with COSs. Conclusions This study makes an original contribution to the understanding of wound healing in dogs and other animals and supports the use of COSs as a supplement to be added to animal diets.

Abstract Background Working in a standing posture is considered to improve musculoskeletal comfort and can help enhance office workers’ performance in the long term. However, there is a lack of a quantitative, real-time measure that reflects on whether office workers can immediately become more concentrated and work more efficiently when they switch to a standing posture. Methods To tackle this problem, this study proposed that the number of effective computer interactions could be used as a real-time indicator to measure the productivity of office workers whose work is primarily computer-based. Using this metric, we conducted an exploratory study to investigate the correlation between posture and productivity changes at a 10-minute resolution for eight participants. Results The study found that when allowed to use sit-stand desks to adjust postures, participants chose to switch to standing posture for about 47 min on average once a day; standing work was most frequent between 2:30 − 4:00 pm, followed by 10:30 − 11:30 am, during which time the number of computer interactions also became higher, showing a significant positive correlation. In addition, participants were approximately 6.5% more productive than when they could only work in a sitting posture. Conclusion This study revealed that posture changes could have an immediate improvement in productivity.

Fragrance is a valuable trait in rice varieties, with its aroma significantly influencing consumer preference. In this study, we conducted comprehensive metabolome and transcriptome analyses to elucidate the genetic and biochemical basis of fragrance in the Shangsixiangnuo (SSXN) variety, a fragrant indica rice cultivated in Guangxi, China. Through sensory evaluation and genetic analysis, we confirmed SSXN as strongly fragrant, with an 806 bp deletion in the BADH2 gene associated with fragrance production. In the metabolome analysis, a total of 238, 233, 105 and 60 metabolic compounds exhibited significant changes at the seedling (S), reproductive (R), filling (F), and maturation (M) stages, respectively. We identified four compounds that exhibited significant changes in SSXN across all four development stages. Our analyses revealed a significant upregulation of 2-acetyl-1-pyrroline (2AP), the well-studied aromatic compound, in SSXN compared to the non-fragrant variety. Additionally, correlation analysis identified several metabolites strongly associated with 2AP, including ethanone, 1-(1H-pyrrol-2-yl)-, 1H-pyrrole, and pyrrole. Furthermore, Weighted Gene Co-expression Network Analysis (WGCNA) analysis highlighted the magenta and yellow modules as particularly enriched in aroma-related metabolites, providing insights into the complex aromatic compounds underlying the fragrance of rice. In the transcriptome analysis, a total of 5582, 5506, 4965, and 4599 differential expressed genes (DEGs) were identified across the four developmental stages, with a notable enrichment of the common pathway amino sugar and nucleotide sugar metabolism in all stages. In our correlation analysis between metabolome and transcriptome data, the top three connected metabolites, phenol-, 3-amino-, and 2AP, along with ethanone, 1-(1H-pyrrol-2-yl)-, exhibited strong associations with transcripts, highlighting their potential roles in fragrance biosynthesis. Additionally, the downregulated expression of the P4H4 gene, encoding a procollagen-proline dioxygenase that specifically targets proline, in SSXN suggests its involvement in proline metabolism and potentially in aroma formation pathways. Overall, our study provides comprehensive insights into the genetic and biochemical mechanisms underlying fragrance production in rice, laying the foundation for further research aimed at enhancing fragrance quality in rice breeding programs.

Currently, microscopic research on the tensile fracture properties of recycled brick coarse aggregate concrete has mainly adopted microscopy techniques, which can clearly observe the actual damage situations of each phase material but are unable to individually analyze the effect of a specific material factor on the tensile properties of recycled concrete. This brings much uncertainty to the practical application of recycled concrete. Therefore, this study proposes a cohesive zone model (CZM) for simulating the tensile fracture of recycled brick coarse aggregate (RBCA) concrete. To this end, the study explores the effects of various critical factors on the fracture mode and bearing capacity of recycled brick aggregate concrete, including the replacement rate of recycled brick coarse aggregate, pore structure, interfacial transition zone (ITZ) strength, mortar strength, and volume fraction of brick aggregate. The results indicate that, when the minor to major axis ratio of elliptical pores is 0.5 ≤ K < 1, the following order of influence can be observed: random convex polygonal pores, circular pores, and elliptical pores. Moreover, excessively strengthening the ITZ and mortar does not significantly enhance the tensile performance of RBCA concrete. The distribution location of aggregate has a significant impact on the crack shape of recycled concrete, as does the pore structure, due to their randomness. Therefore, this article also discusses these. These findings contribute to a comprehensive understanding of the tensile properties of recycled brick coarse aggregate and provide insights into optimizing its behavior.

As an important class of nitrogen-containing fused heterocyclic compounds, imidazo[1,2-a]pyridines often exhibit significant biological activities, such as analgesic, anticancer, antiosteoporosis, anxiolytic, etc. Using Y(OTf)3 as a Lewis acid catalyst, a simple and efficient method has been developed for the synthesis of C3-alkylated imidazo[1,2-a]pyridines through the three-component aza-Friedel–Crafts reaction of imidazo[1,2-a]pyridines, aldehydes, and amines in the normal air atmosphere without the protection of inert gas and special requirements for anhydrous and anaerobic conditions. A series of imidazo[1,2-a]pyridine derivatives were obtained with moderate to good yields, and their structures were confirmed by 1H NMR, 13C NMR, and HRMS. Furthermore, this conversion has the advantages of simple operation, excellent functional group tolerance, high atomic economy, broad substrate scope, and can achieve gram-level reactions. Notably, this methodology may be conveniently applied to the further design and rapid synthesis of potential biologically active imidazo[1,2-a]pyridines with multifunctional groups.

In the global context of carbon neutrality, higher education parks are an important strategic position for achieving China’s goal of carbon peaking and carbon neutralization. Strategies from the perspective of life cycle to guide early low-carbon planning and design are an effective way to achieve carbon emission reduction goals. As the scale of university construction gradually expands, the “urban” attributes of them are becoming prominent. However, there is no quantitative study on analyzing the life cycle carbon emission strategies at both the building and urban scale based on sustainability rating systems. This study first extracts the design strategies according to BREEAM, LEED, DGNB and relative assessment standards for campuses and cities in China at the building and urban scale based on the 7-dimensional low-carbon strategy framework, then sorts out and compares the proportions of carbon-emission-related strategies across various dimensions and life cycle stages. It then summarizes the applications and concerns of low-carbon design strategies at different design scales. Finally, the weighting and calculation methods of life cycle carbon emissions in different sustainability rating systems are compared, the scope and methods of carbon emission benchmarks under different standards are compiled, and the evaluation method for locally applicable carbon emission benchmarks in China is proposed in light of China’s national conditions, which provides guidance for the design process and standard formulation.

Abstract Mitochondria are dynamic organelles with multiple functions. They participate in necrotic cell death and programmed apoptotic, and are crucial for cell metabolism and survival. Mitophagy serves as a cytoprotective mechanism to remove superfluous or dysfunctional mitochondria and maintain mitochondrial fine-tuning numbers to balance intracellular homeostasis. Growing evidences show that mitophagy, as an acute tissue stress response, plays an important role in maintaining the health of the mitochondrial network. Since the timely removal of abnormal mitochondria is essential for cell survival, cells have evolved a variety of mitophagy pathways to ensure that mitophagy can be activated in time under various environments. A better understanding of the mechanism of mitophagy in various diseases is crucial for the treatment of diseases and therapeutic target design. In this review, we summarize the molecular mechanisms of mitophagy-mediated mitochondrial elimination, how mitophagy maintains mitochondrial homeostasis at the system levels and organ, and what alterations in mitophagy are related to the development of diseases, including neurological, cardiovascular, pulmonary, hepatic, renal disease, etc., in recent advances. Finally, we summarize the potential clinical applications and outline the conditions for mitophagy regulators to enter clinical trials. Research advances in signaling transduction of mitophagy will have an important role in developing new therapeutic strategies for precision medicine.

Ticks are one of the most important vectors that can transmit pathogens to animals and human beings. This study investigated the dominant tick-borne bacteria carried by ticks and tick-borne infections in forestry populations in Arxan, Inner Mongolia, China. Ticks were collected by flagging from May 2020 to May 2021, and blood samples were collected from individuals at high risk of acquiring tick-borne diseases from March 2022 to August 2023. The pooled DNA samples of ticks were analyzed to reveal the presence of tick-borne bacteria using high-throughput sequencing of the 16S rDNA V3–V4 region, and species-specific polymerase chain reaction (PCR) related to sequencing was performed to confirm the presence of pathogenic bacteria in individual ticks and human blood samples. All sera samples were examined for anti-SFGR using ELISA and anti-B. burgdorferi using IFA and WB. A total of 295 ticks (282 Ixodes persulcatus and 13 Dermacentor silvarum) and 245 human blood samples were collected. Rickettsia, Anaplasma, Borrelia miyamotoi, and Coxiella endosymbiont were identified in I. persulcatus by high-throughput sequencing, while Candidatus R. tarasevichiae (89.00%, 89/100), B. garinii (17.00%, 17/100), B. afzelii (7.00%, 7/100), and B. miyamotoi (7.00%, 7/100) were detected in I. persulcatus, as well the dual co-infection with Candidatus R. tarasevichiae and B. garinii were detected in 13.00% (13/100) of I. persulcatus. Of the 245 individuals, B. garinii (4.90%, 12/245), R. slovaca (0.82%, 2/245), and C. burnetii (0.41%, 1/245) were detected by PCR, and the sequences of the target genes of B. garinii detected in humans were identical to those detected in I. persulcatus. The seroprevalence of anti-SFGR and anti-B. burgdorferi was 5.71% and 13.47%, respectively. This study demonstrated that Candidatus R. tarasevichiae and B. garinii were the dominant tick-borne bacteria in I. persulcatus from Arxan, and that dual co-infection with Candidatus R. tarasevichiae and B. garinii was frequent. This is the first time that B. miyamotoi has been identified in ticks from Arxan and R. solvaca has been detected in humans from Inner Mongolia. More importantly, this study demonstrated the transmission of B. garinii from ticks to humans in Arxan, suggesting that long-term monitoring of tick-borne pathogens in ticks and humans is important for the prevention and control of tick-borne diseases.

Background: Tumor treating fields (TTF) was first approved for treatment of glioblastoma. Recently, the LUNAR study demonstrated that TTF + standard therapy (ST) extended survival in patients with advanced non-small cell lung cancer (NSCLC). This primary objective of this study is to analyze the cost-effectiveness of this treatment from the United States healthcare payers’ perspective.Methods: A 3-health-state Markov model was established to compare the cost-effectiveness of TTF + ST and that of ST alone. Clinical data were extracted from the LUNAR study, supplemented by additional cost and utility data obtained from publications or online sources. One-way sensitivity analysis, probabilistic sensitivity analysis, and scenario analysis were conducted. The willingness-to-pay (WTP) threshold per quality-adjusted life-years (QALYs) gained was set to $150,000. The main results include total costs, QALYs, incremental cost-effectiveness ratio (ICER) and incremental net monetary benefit (INMB). Subgroup analyses were conducted for two types of ST, including immune checkpoint inhibitor, and docetaxel.Results: During a 10-year time horizon, the costs of TTF + ST and ST alone were $431,207.0 and $128,125.9, and the QALYs were 1.809 and 1.124, respectively. The ICER of TTF + ST compared to ST was $442,732.7 per QALY, and the INMB was -$200,395.7 at the WTP threshold. The cost of TTF per month was the most influential factor in cost-effectiveness, and TTF + ST had a 0% probability of being cost-effective at the WTP threshold compared with ST alone.Conclusion: TTF + ST is not a cost-effective treatment for advanced NSCLC patients who progressed after platinum-based therapy from the perspective of the United States healthcare payers.

Background: Many researchers have investigated the use of Chinese herbs to delay the progression of chronic kidney disease (CKD) through their effects on colonic microflora and microbiota-derived metabolites. However, whether FuZhengHuaYuJiangZhuTongLuo (FZHY) has effects that are similar to those of AST-120 on CKD needs to be elucidated. Methods: In this study, we compared the effects of FZHY and AST-120 on the colonic microbiota and plasma metabolites in the CKD rat model. We developed a unilateral ureteral obstruction (UUO)-induced CKD rat model and then administered FZHY and AST-120 to these model rats. Non-targeted metabolomic LC-MS analysis, 16S rRNA sequencing, and histopathological staining were performed on plasma, stool, and kidney tissues, respectively, and the joint correlation between biomarkers and metabolites of candidate bacteria was analyzed. Results: Our results showed that administering FZHY and AST-120 effectively ameliorated UUO-induced abnormal renal function and renal fibrosis and regulated the composition of microbiota and metabolites. Compared to the UUO model group, the p_Firmicutes and o_Peptostreptococcales_Tissierellales were increased, while 14 negative ion metabolites were upregulated and 21 were downregulated after FZHY treatment. Additionally, 40 positive ion metabolites were upregulated and 63 were downregulated. On the other hand, AST-120 treatment resulted in an increase in the levels of g_Prevotellaceae_NK3B31_group and f_Prevotellaceae, as well as 12 upregulated and 23 downregulated negative ion metabolites and 56 upregulated and 63 downregulated positive ion metabolites. Besides, FZHY increased the levels of candidate bacterial biomarkers that were found to be negatively correlated with some poisonous metabolites, such as 4-hydroxyretinoic acid, and positively correlated with beneficial metabolites, such as l-arginine. AST-120 increased the levels of candidate bacterial biomarkers that were negatively correlated with some toxic metabolites, such as glycoursodeoxycholic acid, 4-ethylphenol, and indole-3-acetic acid. Conclusion: FZHY and AST-120 effectively reduced kidney damage, in which, the recovery of some dysregulated bacteria and metabolites are probably involved. As their mechanisms of regulation were different, FZHY might play a complementary role to AST-120 in treating CKD.

Chitooligosaccharides (COS) have attracted significant attention due to their unique biological activities, water solubility, and absorbable properties. The objective of the present study was to investigate the impact of COS-supplemented diets on the immune response, antioxidative capacity, hematology, serum biochemistry, and modulation of intestinal microbiota in growing beagles. Twelve weaning male beagles (6 weeks old; weighing 3.6 ± 0.6 kg) were fed either a control diet (food without COS, n = 6) or a COS-supplemented diet (n = 6) twice daily for 7 weeks. Blood samples collected at weeks 4 and 7 indicated that hematology and serum biochemistry remained unaffected by COS supplementation. Compared with the control group, the test group showed higher levels of serum antibodies against the canine distemper virus and parvovirus, higher levels of immunoglobulin A, G, and M, and increased activities of superoxide dismutase, glutathione peroxidase, and catalase. In addition, COS was observed to modulate the intestinal flora by enhancing the presence of probiotics, such as Muribaculaceae, Prevotellaceae_Ga6A1_group, Lactobacillus, Collinsella, Blautia, and Lachnospiraceae_NK4A136_group. In summary, a COS-supplemented diet could effectively improve dog health by regulating immune function and antioxidant responses and modulating intestinal microbiota. This study highlights the potentiality of using COS as a valuable nutraceutical for growing dogs.

The disheveled-associated antagonist of β-catenin homolog 3 (DACT3) has been recognized as a tumor suppressor in various cancers. However, the function of DACT3 on glioma malignant progression along with potential molecular mechanisms is poorly clarified. This research aimed to investigate how DACT3 contributes to suppressing the progression of glioma. In our investigation, a pronounced decrease in DACT3 expression was observed in glioma tissues. Through the overexpression of DACT3, we noted a significant suppression in the proliferation, invasion, and migration of glioma cells, while concurrently observing an increase in cell adhesion. Our exploration into the molecular mechanisms revealed that DACT3 executes its tumor-suppressive role by impeding the expression of notch 1 intracellular domain (NICD) and translocating into the nucleus by downregulating the expression of β-catenin. Consequently, this process leads to the suppression of Notch1 signaling. To summarize, our findings reveal the function of DACT3 to inhibit glioma progression via the Notch1 signaling pathway in β-catenin dependent manner. This study stands as the pioneer in examining the role of DACT3 in glioma progression and comprehensively elucidating its molecular mechanisms in glioma development. Therefore, our results suggest that DACT3 holds promise as both a prognostic factor and a potential biomarker for guiding treatment strategies in glioma patients (Graphical Abstract).

Hepatocellular carcinoma is one of the leading cancers worldwide and is a potential consequence of fibrosis. Therefore, the identification of key cellular and molecular mechanisms involved in liver fibrosis is an important goal for the development of new strategies to control liver-related diseases. Here, single-cell RNA sequencing data (GSE136103 and GES181483) of clinical liver non-parenchymal cells were analyzed to identify cellular and molecular mechanisms of liver fibrosis. The proportion of endothelial subpopulations in cirrhotic livers was significantly higher than that in healthy livers. Gene ontology and gene set enrichment analysis of differentially expressed genes in the endothelial subgroups revealed that extracellular matrix (ECM)-related pathways were significantly enriched. Since anthrax toxin receptor 2 (ANTXR2) interacts with the ECM, the expression of ANTXR2 in the liver endothelium was analyzed. ANTXR2 expression in the liver endothelium of wild-type (WT) mice significantly decreased after a 4-time sequential injection of carbon tetrachloride (CCl4) to induce liver fibrosis. Next, conditional knockout mice selectively lacking Antxr2 in endothelial cells were generated. After endothelial-specific Antxr2 knockout mice were subjected to the CCl4 model, the degree of liver fibrosis in the knockout group was significantly more severe than that in the control group. In addition, ANTXR2 in human umbilical vein endothelial cells promoted matrix metalloproteinase 2 (MMP2) activation to degrade the ECM in vitro. Finally, endothelial-specific overexpression of Antxr2 alleviated the development of liver fibrosis following adeno-associated virus treatment. Collectively, these results suggested that endothelial ANTXR2 plays a protective role in liver fibrosis. This function of ANTXR2 may be achieved by promoting MMP2 activation to degrade the ECM.

The exploration and comprehensive assessment of fractured-vuggy reservoir information have perennially constituted focal points and challenges within the domain of oil and gas reservoir evaluation. The verification of geological phenomena, identification of various fracture and hole types, and the quantitative characterization thereof currently present pressing challenges. This study meticulously examines the deep carbonate reservoirs within the Dengying Formation in the Penglai gas region of the Sichuan Basin. The Core Rolling Scan images reveal five discernible features: unfilled holes, filled holes, filled fractures, open fractures, and algae. The analysis pinpoints three primary challenges in semantic segmentation recognition: the amalgamation of feature scales, class imbalance, and the scarcity of datasets with substantial sample sizes. To address these challenges, this paper introduces a Multi-Scale Feature Aggregation Pyramid Network model (MFAPNet), achieving a pixel accuracy of 68.04% in recognizing the aforementioned five types. Lastly, the model is employed in calculating core porosity, exposing a scaling relationship between wellbore image porosity and core porosity ranging from 1.5 to 3 times. To a certain extent, it reveals the correlation between the wellbore image logging data and the actual formation of the Dengying Formation in the Penglai Gas Field of the Sichuan Basin, and also provides a basis for the subsequent logging evaluation of the formation. The partial code and CHA355 dataset are publicly available at https://github.com/zyng886/MFAPNet.

Background Treatment of large segmental bone defects is still a major clinical challenge, and bone grafting is the main method. The development of novel bone graft substitutes will help solve this problem. Methods Porous bioceramics hydroxyapatite (HA) scaffolds coated with different ratios of HA/β-tricalcium phosphate (β-TCP) were prepared by 3D printing. The scaffolds were sampled and tested in large segmental bone defect rabbit models. X-ray, micro-computed tomography (CT), hematoxylin and eosin (HE) staining, Van-Gieson staining, and type I collagen staining were performed to find the best scaffolds for large segmental bone defect treatment. Results The average length, diameter, compressive strength, and porosity of the bioceramics scaffolds were 15.05 ± 0.10 mm, 4.98 ± 0.06 mm, 11.11 ± 0.77 MPa, and 54.26 ± 5.38%, respectively. Postoperative lateral radiographs suggested the scaffold group got better bone healing and stability than the blank group. Micro-CT showed new bones grew into the scaffold from the two ends of the fracture along the scaffold and finally achieved bony union. The new bone volume around the scaffolds suggested the 3:7 HA/β-TCP-coated bioceramic scaffolds were more favorable for the healing of large segmental bone defects. The results of HE, Van-Gieson, and type I collagen staining also suggested more new bone formation in 3:7 HA/β-TCP-coated bioceramic scaffolds. Conclusion 3:7 HA/β-TCP-coated porous bioceramics scaffolds are more conducive to the repair of large bone defects in rabbits. The results of this study can provide some reference and theoretical support in this area.

Objective To screen the risk factors of severe postpartum hemorrhage that can be found at 32 weeks of pregnancy through univariate and multivariate analysis and establish the risk prediction diagram. Methods A retrospective analysis was performed on pregnant women who gave birth and received blood transfusion in Women's Hospital of Nanjing Medical University from 2019 to 2021. According to the blood transfusion volume during and after operation, the patients were divided into low/moderate transfusion group (transfusion volume

Abstract. Luteolin is a natural flavonoid that has a variety of pharmacological activities, such as anti-inflammatory, anti-allergic, anti-bacterial, anti-viral, apoptosis inhibition, cell autophagy regulation, and anti-tumor activity. It is one of the main ingredients of an expert-recommended herbal formula for the prevention and treatment of coronavirus disease 2019 (COVID-19). This suggests that luteolin has strong pharmacological effects on the prevention and treatment of COVID-19. The aims of this study were to identify the molecular targets of luteolin and to infer the possible mechanisms by which it exerts its pharmacological effects. The GSE159787 data set was obtained from the Gene Expression Omnibus online database, and differentially expressed genes were analyzed. There were 22 upregulated differentially expressed genes enriched in the COVID-19 signaling pathway, suggesting that the upregulation of these genes may be closely related to the occurrence of COVID-19. Molecular docking results showed that luteolin had strong binding efficiency to 20 of these 22 key genes. Six of these genes (CFB, EIF2AK2, OAS1, MAPK11, OAS3, and STAT1) showed strong binding activity. Luteolin can regulate the COVID-19 signaling pathway by combining with these targets, which may have a therapeutic effect on COVID-19.

Abstract Background Anastomosis for gastrointestinal reconstruction has been contentious after low anterior resection of rectal cancer for the past 30 years. Despite the abundance of randomized controlled trials (RCTs) on colon J-pouch (CJP), straight colorectal anastomosis (SCA), transverse coloplast (TCP), and side-to-end anastomosis (SEA), most studies are small and lack reliable clinical evidence. We conducted a systematic review and network meta-analysis to evaluate the effects of the four anastomoses on postoperative complications, bowel function, and quality of life in rectal cancer. Methods We assessed the safety and efficacy of CJP, SCA, TCP, and SEA in adult patients with rectal cancer after surgery by searching the Cochrane Library, Embase, and PubMed databases to collect RCTs from the date of establishment to May 20, 2022. Anastomotic leakage and defecation frequency were the main outcome indicators. We pooled data through a random effects model in a Bayesian framework and assessed model inconsistency using the deviance information criterion (DIC) and node-splitting method and inter-study heterogeneity using the I-squared statistics (I 2 ). The interventions were ranked according to the surface under the cumulative ranking curve (SUCRA) to compare each outcome indicator. Results Of the 474 studies initially evaluated, 29 were eligible RCTs comprising 2631 patients. Among the four anastomoses, the SEA group had the lowest incidence of anastomotic leakage, ranking first (SUCRASEA = 0.982), followed by the CJP group (SUCRACJP = 0.628). The defecation frequency in the SEA group was comparable to those in the CJP and TCP groups at 3, 6, 12, and 24 months postoperatively. In comparison, the defecation frequency in the SCA group 12 months after surgery all ranked fourth. No statistically significant differences were found among the four anastomoses in terms of anastomotic stricture, reoperation, postoperative mortality within 30 days, fecal urgency, incomplete defecation, use of antidiarrheal medication, or quality of life. Conclusions This study demonstrated that SEA had the lowest risk of complications, comparable bowel function, and quality of life compared to the CJP and TCP, but further research is required to determine its long-term consequences. Furthermore, we should be aware that SCA is associated with a high defecation frequency.

A highly sensitive and selective electrogenerated chemiluminescence (ECL) biosensor was developed for the determination of matrix metalloproteinase 3 (MMP-3) in serum via the target-induced cleavage of an oligopeptide. One ECL probe (named as Ir-peptide) was synthesized by covalently linking a new cyclometalated iridium(III) complex ([(3-pba)2Ir(bpy-COOH)](PF6)) (3-pba = 3-(2-pyridyl) benzaldehyde, bpy-COOH = 4′-methyl-2,2′-bipyridine-4-carboxylic acid) with an oligopeptide (CGVPLSLTMGKGGK). An ECL biosensor was fabricated by firstly casting Nafion and gold nanoparticles (AuNPs) on a glassy carbon electrode and then self-assembling both of the ECL probes, 6-mercapto-1-hexanol and zwitterionic peptide, on the electrode surface, from which the AuNPs could be used to amplify the ECL signal and Ir-peptide could serve as an ECL probe to detect the MMP-3. Thanks to the MMP-3-induced cleavage of the oligopeptide contributing to the decrease in ECL intensity and the amplification of the ECL signal using AuNPs, the ECL biosensor could selectively and sensitively quantify MMP-3 in the concentration range of 10–150 ng·mL−1 and with both a limit of quantification (26.7 ng·mL−1) and a limit of detection (8.0 ng·mL−1) via one-step recognition. In addition, the developed ECL biosensor showed good performance in the quantization of MMP-3 in serum samples, with a recovery of 92.6% ± 2.8%–105.6% ± 5.0%. An increased level of MMP-3 was found in the serum of rheumatoid arthritis patients compared with that of healthy people. This work provides a sensitive and selective biosensing method for the detection of MMP-3 in human serum, which is promising in the identification of patients with rheumatoid arthritis.

Straw burning is a significant source of atmospheric pollutants, releasing particulate matter and trace gases. Capturing the characteristics of straw burning and understanding its influencing factors are important prerequisites for regulating straw burning. Based on the fire points detected by the Moderate-resolution Imaging Spectroradiometer (MODIS) in Hunan province, China, from 2010 to 2020, this study analyzed the spatiotemporal variations of straw burning and employed Geographically Weighted Regression (GWR) models to investigate the underlying forces driving straw burning. The results show that the spatiotemporal characteristics of straw burning in Hunan Province can be categorized into two distinct periods: 2010 to 2014 and 2015 to 2020. The period from 2010 to 2014 witnessed a rapid increase, while the period from 2015 to 2020 experienced fluctuating decreases. The shift is closely linked to the implementation of the straw burning ban policy in 2015. Spatially, the areas with a high number of fire points are primarily located in the southern regions, especially in the border regions between Chenzhou, Yongzhou, Hengyang, and Shaoyang cities. A significant change was found in the impact of economic development and human activity factors on straw burning before and after 2015. These factors include crop yield, Gross Domestic Product (GDP), and road network development. From the implementation of the straw burning ban policy, increases in GDP and settlement density will have a dampening effect on straw burning in a region. Straw burning locations may shift towards regions with relatively slow economic development. The results could serve as a foundation for decision-making to address the issue of straw burning.

Abstract Mesenchymal glioblastoma (GBM) is highly resistant to radio‐and chemotherapy and correlates with worse survival outcomes in GBM patients; however, the underlying mechanism determining the mesenchymal phenotype remains largely unclear. Herein, it is revealed that FBXO7, a substrate‐recognition component of the SCF complex implicated in the pathogenesis of Parkinson's disease, confers mesenchymal properties and chemoresistance in GBM by controlling Rbfox2‐mediated alternative splicing. Specifically, FBXO7 ubiquitinates Rbfox2 Lys249 through K63‐linked ubiquitin chains upon arginine dimethylation at Arg341 and Arg441 by PRMT5, leading to Rbfox2 stabilization. FBXO7 controls Rbfox2‐mediated splicing of mesenchymal genes, including FoxM1, Mta1, and Postn. FBXO7‐induced exon Va inclusion of FoxM1 promotes FoxM1 phosphorylation by MEK1 and nuclear translocation, thereby upregulates CD44, CD9, and ID1 levels, resulting in GBM stem cell self‐renewal and mesenchymal transformation. Moreover, FBXO7 is stabilized by temozolomide, and FBXO7 depletion sensitizes tumor xenografts in mice to chemotherapy. The findings demonstrate that the FBXO7‐Rbfox2 axis‐mediated splicing contributes to mesenchymal transformation and tumorigenesis, and targeting FBXO7 represents a potential strategy for GBM treatment.

Tumor metastasis is the leading cause of mortality among advanced cancer patients. Understanding its mechanisms and treatment strategies is vital for clinical application. Arginine methylation, a post-translational modification catalyzed by protein arginine methyltransferases (PRMTs), is implicated in diverse physiological processes and disease progressions. Previous research has demonstrated PRMTs' involvement in tumor occurrence, progression, and metastasis. This review offers a comprehensive summary of the relationship between PRMTs, prognosis, and metastasis in various cancers. Our focus centers on elucidating the molecular mechanisms through which PRMTs regulate tumor metastasis. We also discuss relevant clinical trials and effective PRMT inhibitors, including chemical compounds, long non-coding RNA (lncRNA), micro-RNA (miRNA), and nanomaterials, for treating tumor metastasis. While a few studies present conflicting results, the overall trajectory suggests that inhibiting arginine methylation exhibits promise in curtailing tumor metastasis across various cancers. Nonetheless, the underlying mechanisms and molecular interactions are diverse. The development of inhibitors targeting arginine methylation, along with the progression of clinical trials, holds substantial potential in the field of tumor metastasis, meriting sustained attention.