Prediction of neoplastic gallbladder polyps in patients with different age level based on preoperative ultrasound: a multi-center retrospective real-world study.

BACKGROUND: The prevalence of neoplastic polyps in gallbladder polyps (GPs) increases sharply with age and is associated with gallbladder carcinoma (GBC). This study aims to predict neoplastic polyps and provide appropriate treatment strategies based on preoperative ultrasound features in patients with different age level. METHODS: According to the age classification of WHO, 1523 patients with GPs who underwent cholecystectomy from January 2015 to December 2019 at 11 tertiary hospitals in China were divided into young adults group (n=622), middle-aged group (n=665) and elderly group (n=236). Linear scoring models were established based on independent risk variables screened by the Logistic regression model in different age groups. The area under ROC (AUC) to evaluate the predictive ability of linear scoring models, long- and short- diameter of GPs. RESULTS: Independent risk factors for neoplastic polyps included the number of polyps, polyp size (long diameter), and fundus in the young adults and elderly groups, while the number of polyps, polyp size (long diameter), and polyp size (short diameter) in the middle-aged groups. In different age groups, the AUCs of its linear scoring model were higher than the AUCs of the long- and short- diameter of GPs for differentiating neoplastic and non-neoplastic polyps (all P<0.05), and Hosmer-Lemeshow goodness of fit test showed that the prediction accuracy of the linear scoring models was higher than the long- and short- diameter of GPs (all P>0.05). CONCLUSION: The linear scoring models of the young adults, middle-aged and elderly groups can effectively distinguish neoplastic polyps from non-neoplastic polyps based on preoperative ultrasound features.

Development and validation of a prognostic model for predicting post-discharge mortality risk in patients with ST-segment elevation myocardial infarction (STEMI) undergoing primary percutaneous coronary intervention (PPCI).

BACKGROUND: Accurately predicting post-discharge mortality risk in patients with ST-segment elevation myocardial infarction (STEMI) undergoing primary percutaneous coronary intervention (PPCI) remains a complex and critical challenge. The primary objective of this study was to develop and validate a robust risk prediction model to assess the 12-month and 24-month mortality risk in STEMI patients after hospital discharge. METHODS: A retrospective study was conducted on 664 STEMI patients who underwent PPCI at Xiangtan Central Hospital Chest Pain Center between 2020 and 2022. The dataset was randomly divided into a training cohort (n = 464) and a validation cohort (n = 200) using a 7:3 ratio. The primary outcome was all-cause mortality following hospital discharge. The least absolute shrinkage and selection operator (LASSO) regression model was employed to identify the optimal predictive variables. Based on these variables, a regression model was constructed to determine the significant predictors of mortality. The performance of the model was evaluated using receiver operating characteristic (ROC) curve analysis and decision curve analysis (DCA). RESULTS: The prognostic model was developed based on the LASSO regression results and further validated using the independent validation cohort. LASSO regression identified five important predictors: age, Killip classification, B-type natriuretic peptide precursor (NTpro-BNP), left ventricular ejection fraction (LVEF), and the usage of angiotensin-converting enzyme inhibitors/angiotensin receptor blockers/angiotensin receptor-neprilysin inhibitors (ACEI/ARB/ARNI). The Harrell's concordance index (C-index) for the training and validation cohorts were 0.863 (95% CI: 0.792-0.934) and 0.888 (95% CI: 0.821-0.955), respectively. The area under the curve (AUC) for the training cohort at 12 months and 24 months was 0.785 (95% CI: 0.771-0.948) and 0.812 (95% CI: 0.772-0.940), respectively, while the corresponding values for the validation cohort were 0.864 (95% CI: 0.604-0.965) and 0.845 (95% CI: 0.705-0.951). These results confirm the stability and predictive accuracy of our model, demonstrating its reliable discriminative ability for post-discharge all-cause mortality risk. DCA analysis exhibited favorable net benefit of the nomogram. CONCLUSION: The developed nomogram shows potential as a tool for predicting post-discharge mortality in STEMI patients undergoing PPCI. However, its full utility awaits confirmation through broader external and temporal validation.

An Experimental Investigation of the Precipitation Utilization of Plants in Arid Regions.

What represents a water source for the ecological restoration of a plant in an arid region is still up to debate. To address this issue, we conducted an in situ experiment in the Ulan Buh Desert of China, to study desert plants absorbing atmospheric water vapor. We selected Tamarisk, a common drought-salt-tolerant species in the desert, for ecological restoration as our research subject, used a newly designed lysimeter to monitor precipitation infiltration, and a sap flow system to track reverse sap flow that occurred in the shoot, branch, and stem during the precipitation event, and observed the precipitation redistribution process of the Tamarisk plot. The results showed that Tamarisk indeed directly absorbs precipitation water: when precipitation occurs, the main stem, lateral branch, and shoot all show the signs of reversed sap flow, and the reversed sap flow accounted for 21.5% of the annual sap flow in the shoot and branch, and 13.6% in the stem. The precipitation event in the desert was dominated by light precipitation events, which accounted for 81% of the annual precipitation events. It was found that light precipitation can be directly absorbed by the Tamarisk leaves, especially during nighttime or cloudy days. Even when the precipitation is absent, it was found that desert plants can still absorb water from the unsaturated atmospheric vapor; even the absorbed atmospheric water vapor was transported from the leaves to the stem, forming a reversed sap flow, as a reversed sap flow was observed when the atmospheric relative humidity reached 75%. This study indicated that the effect of light precipitation on desert plants was significant and should not be overlooked in terms of managing the ecological and hydrological systems in arid regions.

Mechanically strong micro-nano fibrillated cellulose paper with improved barrier and water-resistant properties for replacing plastic.

Replacing nonbiodegradable plastics with environmentally friendly cellulose materials has emerged as a key trend in environmental protection. This study highlights the development of a strong and hydrophobic micro-nano fibrillated cellulose paper (MNP) through the incorporation of micro-nano fibrillated cellulose fiber (MNF) and chitin nanocrystal (Ch), followed by the impregnation of polymethylsiloxane (PMHS). A low-acid, heat-assisted colloidal grinding strategy was employed to prepare MNF with a high aspect ratio effectively. Ch was incorporated as a reinforcing matrix into the cellulose fiber scaffold through straightforward mechanical mixing and mechanical hot-pressing treatments. Compared to pure MNP, the 5Ch-MNP exhibited a 25 % improvement in tensile strength, reaching 170 MPa, and showed enhanced barrier properties against oxygen and water vapor. The impregnation of PMHS rapidly confers environmentally resistant hydrophobic properties to 1 % PMHS-5Ch-MNP, leading to a water contact angle exceeding 112°, and a 290 % increase in tensile strength under wet conditions. Additionally, the paper demonstrated excellent antibacterial adhesion properties, with the adhesion rates for E. coli and S. aureus exceeding 98 %. This study successfully produced functional cellulose paper with remarkable mechanical properties and barrier properties, as well as hydrophobicity, using a simple, efficient, and environmentally friendly method, making it a promising substitute for petroleum-based plastics.

Dual inhibition of CYP17A1 and HDAC6 by abiraterone-installed hydroxamic acid overcomes temozolomide resistance in glioblastoma through inducing DNA damage and oxidative stress.

Glioblastoma (GBM) is a highly aggressive and treatment-resistant brain tumor, necessitating novel therapeutic strategies. In this study, we present a mechanistic breakthrough by designing and evaluating a series of abiraterone-installed hydroxamic acids as potential dual inhibitors of CYP17A1 and HDAC6 for GBM treatment. We established the correlation of CYP17A1/HDAC6 overexpression with tumor recurrence and temozolomide resistance in GBM patients. Compound 12, a dual inhibitor, demonstrated significant anti-GBM activity in vitro, particularly against TMZ-resistant cell lines. Mechanistically, compound 12 induced apoptosis, suppressed recurrence-associated genes, induced oxidative stress and initiated DNA damage response. Furthermore, molecular modeling studies confirmed its potent inhibitory activity against CYP17A1 and HDAC6. In vivo studies revealed that compound 12 effectively suppressed tumor growth in xenograft and orthotopic mouse models without inducing significant adverse effects. These findings highlight the potential of dual CYP17A1 and HDAC6 inhibition as a promising strategy for overcoming treatment resistance in GBM and offer new hope for improved therapeutic outcomes.

The role of Map1b in regulating osteoblast polarity, proliferation, differentiation and migration.

Osteoblast polarity, proliferation, differentiation, and migration are essential for maintaining normal bone structure and function. While the microtubule-associated protein Map1b has been extensively studied in nerve cells, its role in bone cells is less known. We investigated the functional significance of Map1b in mouse bone marrow stromal cells (ST2) and elucidated its relationship and influence on cytoskeletal polarity and Golgi organization. Our results suggest that Map1b, as a microtubule regulatory protein, can also regulate the expression of cyclin PCNA, p-H3(S10) and migration-related protein integrin ß1, thereby affecting the proliferation and migration of osteoblasts. The downstream target gene Rgc32 was screened by RNA sequencing. Furthermore, Map1b, as a downstream mediator, regulates the Wnt5a signaling pathway. This study expands our understanding of the involvement of Map1b in bone biology and highlights its crucial role in governing osteoblast polarity, proliferation, and migration, thereby providing a basis for developing novel therapeutic strategies targeting Map1b in orthopedic medicine and promoting precision treatment modalities. Further investigations on the precise mechanisms underlying Map1b's influence on bone cell function and disease progression are needed.

First-in-Class Dual EZH2-HSP90 Inhibitor Eliciting Striking Antiglioblastoma Activity In Vitro and In Vivo.

Structural analysis of tazemetostat, an FDA-approved EZH2 inhibitor, led us to pinpoint a suitable site for appendage with a pharmacophoric fragment of second-generation HSP90 inhibitors. Resultantly, a magnificent dual EZH2/HSP90 inhibitor was pinpointed that exerted striking cell growth inhibitory efficacy against TMZ-resistant Glioblastoma (GBM) cell lines. Exhaustive explorations of chemical probe 7 led to several revelations such as (i) compound 7 increased apoptosis/necrosis-related gene expression, whereas decreased M phase/kinetochore/spindle-related gene expression as well as CENPs protein expression in Pt3R cells; (ii) dual inhibitor 7 induced cell cycle arrest at the M phase; (iii) compound 7 suppressed reactive oxygen species (ROS) catabolism pathway, causing the death of TMZ-resistant GBM cells; and (iv) compound 7 elicited substantial in vivo anti-GBM efficacy in experimental mice xenografted with TMZ-resistant Pt3R cells. Collectively, the study results confirm the potential of dual EZH2-HSP90 inhibitor 7 as a tractable anti-GBM agent.

Micro- and nano-hybrid cellulose fibers prepared by straightforward and high-efficiency hot water soaking-assisted colloid grinding for high-performance cellulose paper.

Micro- and nano-hybrid cellulose fiber (MNCF) stands out as a versatile cellulosic nanomaterial with promising applications in various fields owing to its excellent intrinsic nature and outstanding characteristics. However, the inefficiency in preparing MNCF, attributed to a complex multi-step processing, hinders its widespread adoption. In this study, a straightforward and highly efficient method for MNCF preparation was developed via a hot water soaking-assisted colloid grinding strategy. Active water molecules in hot water facilitating stronger transverse shrinkage and longitudinal expansion in fiber crystallized region, and thus improving the fibrillation degree of cellulose fibers. As a result, MNCFs with a mean diameter of 37.5 ± 22.2 nm and high concentration (2 wt%) were successfully achieved though pure mechanical method. The micro and nano-hybrid structure leads to the corresponding resulting cellulose paper with micro- and nano-hybrid structure possesses a compact stacking and fewer defects, leading to extraordinary mechanical properties including tensile strength of 204.5 MPa, Young's modulus of 6.3 GPa and elongation of 10.1 %. This work achieves significant progress towards straightforward and highly efficient production of MNCFs, offering an appreciable prospect for the development of multifunctional MNCF-based materials.

Sex-specific impact of mild obesity on the prognosis of ST-segment elevation myocardial infarction.

This study aimed to clarify the existence of the mild obesity paradox in patients with ST-segment elevation myocardial infarction (STEMI) and assess the impact of mild obesity on the prognosis of STEMI. A retrospective cohort study was conducted on STEMI patients who underwent percutaneous coronary intervention at Xiangtan Central Hospital from January 1, 2020 to July 31, 2022. After excluding individuals with a body mass index (BMI) of no less than 35 kg/m2, subjects were divided into the mildly obese group (BMI, 30-35 kg/m2) and non-obese group (BMI < 30 kg/m2). The cardiovascular events and death were deemed the composite endpoints and were employed as the outcome event. The study recruited 664 patients with STEMI, including 515 males and 149 females. The mildly obese group of male patients exhibited a lower incidence of composite endpoints than the non-obese group (22.4% vs. 41.3%, P < 0.001). For female patients, no significant difference was observed in the incidence of composite endpoints between the two groups (43.6% vs. 43.8%, P = 0.987). After adjusting for confounding factors, the multivariable Cox regression analysis revealed mild obesity as an independent protective factor for male patients [hazard ratio (HR) 0.47; 95% confidence interval (CI) 0.32-0.69; P < 0.001]. Nevertheless, mild obesity was not associated with the prognosis of female patients (HR 0.96; 95% CI 0.47-1.94; P = 0.9). In male STEMI patients, mild obesity presented a paradoxical effect in improving the prognosis and functioned as an independent protective factor for the prognosis of STEMI. However, no association between mild obesity and prognosis was found in female patients, possibly due to distinct physiological and metabolic characteristics between male and female patients, which deserved further investigation and validation.

Changes in vegetation in China's drylands are closely related to afforestation compared with climate change.

The response of vegetation to climate change and human activities has attracted considerable attention. However, quantitative studies on the effects of climate change and human activities on dryland vegetation in different seasons remain unclear. This study investigated the impacts of precipitation, temperature, soil water storage (SWS) (top [0-7 cm], shallow [7-28 cm], and middle [28-100 cm] layers), vapor pressure deficit (VPD), and afforestation on vegetation as well as their relative contribution rates during the rainy season ([RS], June to September), dry season ([DS], November to April), transition season ([TS], May and October), and all year period (AY) in China's drylands from 2001 to 2020 using the first-difference method. Areas with precipitation and SWS showing significant positive correlation with dryland vegetation (p < 0.05) were found to be larger in RS than in DS and TS, and the positive effect of SWS increased with soil depth in the 0-28 cm interval. Increasing VPD induced a significant negative effect on vgetation during RS but it was not predominant in DS and TS. Afforestation showed an extremely significant positive correlated with dryland vegetation across >60 % of China's dryland areas (p < 0.01), but this improvement was found to be limited to regions with the highest afforestation area. Moreover, dryland vegetation dynamics were driven by afforestation in all seasons, with contribution rates of 64.23 %-71.46 %. The effects of SWS and VPD on vegetation driven by precipitation and temperature exceeded the direct effects of precipitation and temperature. Among climatic factors, VPD showed a major regulating effect on dryland vegetation at the top and shallow soil layers in almost all seasons, whereas the relative contribution rate of SWS increased with soil layer. The findings can provide a scientific reference for the sustainable development and protection of drylands under global warming.

Genome-wide identification of the Pinus tabuliformis CONSTANS-like gene family and their potential roles in reproductive cone development.

The CONSTANS-like (COL) genes, as a core transcription factor in the photoperiod regulation pathway, play a key role in plant reproduction development. However, their molecular characterization has rarely been studied in Pinus tabuliformis. Here, 10 PtCOL genes were identified in the P. tabuliformis genome and multiple sequence alignments have indicated that the PtCOL proteins contained highly conserved B-BOX1 and CCT domains. Sequence similarity analysis showed that PtCOL1 and PtCOL3 had the higher similarity with Norway spruce COLs (PaCOL2 and PaCOL1) and Arabidopsis COLs (AtCOL3, 4 and 5), respectively. Phylogeny and gene structure analyses revealed that PtCOLs were divided into three subgroups, each with identical or similar distributions of exons, introns, and motifs. Moreover, 10 PtCOLs were distributed on 6 chromosomes and PtCOL9 has syntenic gene pairs in both Ginkgo biloba and Sequoiadendron giganteum. Interestingly, in transcriptome profiles, most PtCOLs exhibited a diurnal oscillation pattern under both long (LD) and short (SD) day conditions. Additionally, PtCOLs were highly expressed in needles and female cones, and showed different spatial expression patterns. Among the ten PtCOLs, PtCOL1/3 heterologous overexpression Arabidopsis displayed a delayed-flowering phenotype under SD, indicating that they are likely to play a crucial role in the reproductive development. Additionally, PtCOL1 and PtCOL3 were not only capable of interacting with each other, but they were each capable of interacting with themselves. Furthermore, PtCOL1 and PtCOL3 were also involved in the MADS-box protein-protein interaction (PPI) network in P. tabuliformis cone development. Direct interactions of PtDAL11 with PtCOL1/3 impeded PtCOL1/3 translocation into the nucleus. In summary, this study provided comprehensive understanding for the functions of the PtCOL gene family and revealed their biological roles in the photoperiod-dependent P. tabuliformis cone development.

Perceptions of medical error among general practitioners in rural China: a qualitative interview study.

BACKGROUND: Medical error (ME) is a serious public health problem and a leading cause of death. The reported adverse incidents in China were much less than western countries, and the research on patient safety in rural China's primary care institutions was scarce. This study aims to identify the factors contributing to the under-reporting of ME among general practitioners in township health centres (THCs). METHODS: A qualitative semi-structured interview study was conducted with 31 general practitioners working in 30 THCs across 6 provinces. Thematic analysis was conducted using a grounded theory approach. RESULTS: The understanding of ME was not unified, from only mild consequence to only almost equivalent to medical malpractice. Common coping strategies for THCs after ME occurs included concealing and punishment. None of the participants reported adverse events through the National Clinical Improvement System website since they worked in THCs. Discussions about ME always focused on physicians rather than the system. CONCLUSIONS: The low reported incidence of ME could be explained by unclear concept, unawareness and blame culture. It is imperative to provide supportive environment, patient safety training and good examples of error-based improvements to rural primary care institutions so that ME could be fully discussed, and systemic factors of ME could be recognised and improved there in the future.

The effect of root orientation on inferior alveolar nerve injury after extraction of impacted mandibular third molars based on propensity score-matched analysis: a retrospective cohort study.

BACKGROUND: The injury of the inferior alveolar nerve (IAN) is one of the most serious complications of impacted mandibular third molars (IMTMs) extraction. The influence of the root orientation of IMTMs on IAN injury is still controversial. A deeper understanding of the risk factors of IAN injury conduces to better prevention of IAN injury. This study aims to explore whether root orientation is an independent risk factor of IAN injury during IMTMs extraction using the statistical strategy of propensity score matching (PSM). METHODS: This retrospective cohort study included 379 patients with 539 cases of high-risk IMTMs screened by panoramic radiography and cone beam computed tomography. The IAN injury incidence after extraction of different groups of IMTMs was analyzed using the chi-square test or Fisher's exact test. The correlation between third molar root orientation and impaction depth/contact degree with IAN was evaluated by the Lambda coefficient. Based on PSM for balancing confounding factors including age, sex, impaction depth, and contact degree, the effect of root orientation on the incidence of IAN injury was further analyzed using Fisher's exact test. RESULTS: There were significant group differences in IAN injury incidence in impaction depth, root orientation, and contact degree of root-IAC before PSM. Root orientation was correlated with impaction depth and contact degree of root-IAC. After PSM, there were 9 cases with IAN injury and 257 cases without IAN injury. There were significant group differences between the buccal and non-buccal groups after PSM, and the risk of IAN injury was higher when the root was located on the buccal side of IAC (OR = 8.448, RR = 8). CONCLUSIONS: Root orientation is an independent risk factor of IAN injury, and the risk is higher when the root is located on the buccal side of IAC. These findings could help better evaluate the risk of inferior alveolar nerve injury before the extraction of IMTMs.

Excretory/Secretory Products from Schistosoma japonicum Eggs Alleviate Ovalbumin-Induced Allergic Airway Inflammation.

INTRODUCTION: Excretory/secretory products (ESPs) derived from helminths have been reported to effectively control allergic inflammation, which have better therapeutic prospects than live parasite infections. However, it remains unknown whether ESPs from schistosome eggs can protect against allergies, despite reports alleging that schistosome infection could alleviate disordered allergic inflammation. METHOD: In the present study, we investigated the protective effects of ESPs from Schistosoma japonicum eggs (ESP-SJE) on asthmatic inflammation. Firstly, we successfully established an allergic airway inflammation model in mice by alum-adjuvanted ovalbumin (OVA) sensitization and challenge. ESP-SJE were administered intraperitoneally on days -1 and 13 (before sensitization), on day 20 (before challenge), and on days 21-24 (challenge phase). RESULTS: The results showed that ESP-SJE treatment significantly reduced the infiltration of inflammatory cells, especially eosinophils into the lung tissue, inhibited the production of the total and OVA-specific IgE during OVA-sensitized and -challenged phases, respectively, and suppressed the secretion of Th2-type inflammatory cytokines (IL-4). Additionally, ESP-SJE treatment significantly upregulated the regulatory T cells (Tregs) in the lung tissue during OVA challenge. Furthermore, using liquid chromatography-mass spectrometry analysis and Treg induction experiments in vitro, we might identify nine potential therapeutic proteins against allergic inflammation in ESP-SJE. The targets of these candidate proteins included glutathione S-transferase, egg protein CP422 precursor, tubulin alpha-2/alpha-4 chain, actin-2, T-complex protein 1 subunit beta, histone H4, whey acidic protein core region, and molecular chaperone HtpG. CONCLUSION: Taken together, the results discussed herein demonstrated that ESP-SJE could significantly alleviate OVA-induced asthmatic inflammation in a murine model, which might be mediated by the upregulation of Treg in lung tissues that may be induced by the potential modulatory proteins. Therefore, potential proteins in ESP-SJE might be the best candidates to be tested for therapeutic application of asthma, thus pointing out to a possible new therapy for allergic airway inflammation.

Dysregulated lipid metabolism in TMZ-resistant glioblastoma: pathways, proteins, metabolites and therapeutic opportunities.

Glioblastoma (GBM) is a highly aggressive and lethal brain tumor with limited treatment options, such as the chemotherapeutic agent, temozolomide (TMZ). However, many GBM tumors develop resistance to TMZ, which is a major obstacle to effective therapy. Recently, dysregulated lipid metabolism has emerged as an important factor contributing to TMZ resistance in GBM. The dysregulation of lipid metabolism is a hallmark of cancer and alterations in lipid metabolism have been linked to multiple aspects of tumor biology, including proliferation, migration, and resistance to therapy. In this review, we aimed to summarize current knowledge on lipid metabolism in TMZ-resistant GBM, including key metabolites and proteins involved in lipid synthesis, uptake, and utilization, and recent advances in the application of metabolomics to study lipid metabolism in GBM. We also discussed the potential of lipid metabolism as a target for novel therapeutic interventions. Finally, we highlighted the challenges and opportunities associated with developing these interventions for clinical use, and the need for further research to fully understand the role of lipid metabolism in TMZ resistance in GBM. Our review suggests that targeting dysregulated lipid metabolism may be a promising approach to overcome TMZ resistance and improve outcomes in patients with GBM.

Facile Fabrication of Anthocyanin-Nanocellulose Hydrogel Indicator Label for Intelligent Evaluation of Minced Pork Freshness.

In order to develop a reliable and rapid method for meat freshness detection, nanocellulose (TOCNF) prepared via the TEMPO (2,2,6,6-tetramethylpiperidine oxidation) oxidation method was used as raw material to prepare hydrogels using Zn2+ coordination and binding. Physicochemical properties such as water absorption and porosity were analyzed. It was further used to select suitable hydrogels for the preparation of indication labels after anthocyanin adsorption, and it was applied in the freshness detection of fresh minced pork. Five percent TOCNF (w/w) aqueous solution was homogenized by high shear for 4 min, and 20% (w/w) zinc chloride solution was added to it, so that the concentration of zinc ions could reach 0.25 mol/L. After standing for 24 h, the hydrogel was obtained with good water absorption and a porous three-dimensional network structure. The activation energies of volatile base nitrogen (TVBN) and anthocyanin indicating label color changes were 59.231 kJ/mol and 69.453 kJ/mol, respectively. The difference between the two is within 25 kJ/mol, so the prepared indicator label can accurately visualize the shelf life of fresh pork.

Arecoline aggravates acute ulcerative colitis in mice by affecting intestinal microbiota and serum metabolites.

Arecoline is an alkaloid extracted from betel nut, which has various pharmacological effects. In the present study, we showed that arecoline aggravated experimental acute ulcerative colitis (UC) induced by dextran sodium sulfate (DSS) in mice. We measured body weight and colon length, evaluated disease activity index, colon pathology sections, and levels of colonic inflammatory factors. Arecoline exacerbated the clinical signs of UC and the colonic inflammatory response in mice. The results of 16S rRNA sequencing of fecal samples showed a significant decrease in the percentage of probiotic bacteria Ligilactobacillus, Limosilactobacillus and Lactobacillus and a significant increase in the percentage of conditionally pathogenic bacteria Odoribacter and Bacteroides after arecoline treatment. Serum untargeted metabolomics showed that arecoline intervention reduced the levels of ergothioneine, pentostatin, diadenosine tetraphosphate and other metabolites and modulated nicotinate and nicotinamide metabolism, metabolic pathways, glyoxylate and dicarboxylate metabolism, and other metabolic pathways of intestinal microorganisms. According to the combined microbial and metabolite analysis, arecoline influences metabolite levels by modulating the intestinal microbiota. In summary, it was found that arecoline treatment exacerbated colonic injury and intestinal inflammatory responses in UC mice, disrupted the host's intestinal flora, and affected changes in flora metabolites, thereby exacerbating the development of colonic inflammation. Therefore, the consumption of betel nut can be associated with the risk of aggravating UC.

MicroRNA-1 targets ribosomal protein genes to regulate the growth, development and reproduction of Schistosoma japonicum.

Eggs laid by mature female schistosomes are primarily responsible for the pathogenesis of schistosomiasis and critical for transmission. Consequently, elucidating the mechanism of sexual maturation as well as egg production may lead to new strategies for the control of schistosomiasis. MicroRNAs (miRNAs) are involved in multiple biological processes including reproduction in many organisms, yet their roles have not been well characterized in schistosomes. Here, we investigated microRNA-1 (miR-1), which was downregulated gradually in both male and female Schistosoma japonicum after they reached sexually maturity. The expression of miR-1, as shown with quantitative reverse transcription PCR (qRT-PCR), was lower in the reproductive organs of adult females compared with the somatic tissues. Overexpression of miR-1 in adult worms destroyed the morphological architecture of reproductive organs and reduced the subsequent oviposition, which may be due to the activation of apoptosis pathways. Through in silico analysis, 34 potential target genes of miR-1 were identified, including five ribosomal protein genes, called rp-s13, rp-l7ae, rp-l14, rp-l11 and rp-s24e. In vitro dual-luciferase reporter gene assays and miRNA overexpression experiments further validated that these ribosomal protein genes were directly regulated by miR-1. In contrast to the gene expression of miR-1, qRT-PCR and in situ hybridization experiments demonstrated these ribosomal protein genes were enriched in the sexual organs of adult females. Using RNA interference to silence the ribosomal protein genes in different developmental stages in a mouse model system, we demonstrated that these miR-1 target genes not only participated in the reproductive development of S. japonicum, but also were required for the growth and survival of the parasite in the early developmental stages. Taken together, our data suggested that miR-1 may affect the growth, reproduction and oviposition of S. japonicum by targeting the ribosomal protein genes, which provides insights for exploration of new anti-schistosome strategies.

A Bayesian network model to predict neoplastic risk for patients with gallbladder polyps larger than 10 mm based on preoperative ultrasound features.

BACKGROUND: Polyp size of 10 mm is insufficient to discriminate neoplastic and non-neoplastic risk in patients with gallbladder polyps (GPs). The aim of the study is to develop a Bayesian network (BN) prediction model to identify neoplastic polyps and create more precise criteria for surgical indications in patients with GPs lager than 10 mm based on preoperative ultrasound features. METHODS: A BN prediction model was established and validated based on the independent risk variables using data from 759 patients with GPs who underwent cholecystectomy from January 2015 to August 2022 at 11 tertiary hospitals in China. The area under receiver operating characteristic curves (AUCs) were used to evaluate the predictive ability of the BN model and current guidelines, and Delong test was used to compare the AUCs. RESULTS: The mean values of polyp cross-sectional area (CSA), long, and short diameter of neoplastic polyps were higher than those of non-neoplastic polyps (P < 0.0001). Independent neoplastic risk factors for GPs included single polyp, polyp CSA ≥ 85 mm 2, fundus with broad base, and medium echogenicity. The accuracy of the BN model established based on the above independent variables was 81.88% and 82.35% in the training and testing sets, respectively. Delong test also showed that the AUCs of the BN model was better than that of JSHBPS, ESGAR, US-reported, and CCBS in training and testing sets, respectively (P < 0.05). CONCLUSION: A Bayesian network model was accurate and practical for predicting neoplastic risk in patients with gallbladder polyps larger than 10 mm based on preoperative ultrasound features.

Inhibition of signal peptidase complex expression affects the development and survival of Schistosoma japonicum.

Background: Schistosomiasis, the second most neglected tropical disease defined by the WHO, is a significant zoonotic parasitic disease infecting approximately 250 million people globally. This debilitating disease has seriously threatened public health, while only one drug, praziquantel, is used to control it. Because of this, it highlights the significance of identifying more satisfactory target genes for drug development. Protein translocation into the endoplasmic reticulum (ER) is vital to the subsequent localization of secretory and transmembrane proteins. The signal peptidase complex (SPC) is an essential component of the translocation machinery and functions to cleave the signal peptide sequence (SP) of secretory and membrane proteins entering the ER. Inhibiting the expression of SPC can lead to the abolishment or weaker cleavage of the signal peptide, and the accumulation of uncleaved protein in the ER would affect the survival of organisms. Despite the evident importance of SPC, in vivo studies exploring its function have yet to be reported in S. japonicum. Methods: The S. japonicum SPC consists of four proteins: SPC12, SPC18, SPC22 and SPC25. RNA interference was used to investigate the impact of SPC components on schistosome growth and development in vivo. qPCR and in situ hybridization were applied to localize the SPC25 expression. Mayer's carmalum and Fast Blue B staining were used to observe morphological changes in the reproductive organs of dsRNA-treated worms. The effect of inhibitor treatment on the worm's viability and pairing was also examined in vitro. Results: Our results showed that RNAi-SPC delayed the worm's normal development and was even lethal for schistosomula in vivo. Among them, the expression of SPC25 was significantly higher in the developmental stages of the reproductive organs in schistosomes. Moreover, SPC25 possessed high expression in the worm tegument, testes of male worms and the ovaries and vitellarium of female worms. The SPC25 knockdown led to the degeneration of reproductive organs, such as the ovaries and vitellarium of female worms. The SPC25 exhaustion also reduced egg production while reducing the pathological damage of the eggs to the host. Additionally, the SPC-related inhibitor AEBSF or suppressing the expression of SPC25 also impacted cultured worms' pairing and viability in vitro. Conclusions: These data demonstrate that SPC is necessary to maintain the development and reproduction of S. japonicum. This research provides a promising anti-schistosomiasis drug target and discovers a new perspective on preventing worm fecundity and maturation.