A simple and effective machine learning model for predicting the stability of intracranial aneurysms using CT angiography.

Background: It is vital to accurately and promptly distinguish unstable from stable intracranial aneurysms (IAs) to facilitate treatment optimization and avoid unnecessary treatment. The aim of this study is to develop a simple and effective predictive model for the clinical evaluation of the stability of IAs. Methods: In total, 1,053 patients with 1,239 IAs were randomly divided the dataset into training (70%) and internal validation (30%) datasets. One hundred and ninety seven patients with 229 IAs from another hospital were evaluated as an external validation dataset. The prediction models were developed using machine learning based on clinical information, manual parameters, and radiomic features. In addition, a simple model for predicting the stability of IAs was developed, and a nomogram was drawn for clinical use. Results: Fourteen machine learning models exhibited excellent classification performance. Logistic regression Model E (clinical information, manual parameters, and radiomic shape features) had the highest AUC of 0.963 (95% CI 0.943-0.980). Compared to manual parameters, radiomic features did not significantly improve the identification of unstable IAs. In the external validation dataset, the simplified model demonstrated excellent performance (AUC = 0.950) using only five manual parameters. Conclusion: Machine learning models have excellent potential in the classification of unstable IAs. The manual parameters from CTA images are sufficient for developing a simple and effective model for identifying unstable IAs.

Establishment of a nomogram to predict the overall survival of patients with collecting duct renal cell carcinoma.

BACKGROUND: Collecting duct carcinoma (CDC) is a rare histological type of renal cell carcinoma that lacks a prognostic prediction model. In this study, we developed a nomogram to predict the prognosis of CDC patients. METHODS: Data for patients (n = 247) diagnosed with CDC from 2004 to 2015 were obtained from the Surveillance, Epidemiology, and End Results (SEER) database, and the patients were randomized into training (n = 165) and validation (n = 82) cohorts. Survival outcomes were evaluated by the Kaplan-Meier method. Significant variables determined by univariate and multivariate Cox regression analyses were used to construct the nomogram. C-indexes and calibration plots were applied to evaluate the performance of the nomogram. RESULTS: CDC patients had a median overall survival (OS) of 18.0 months (95% confidence interval: 13.7-22.3); 1-year, 3-year, and 5-year OS rates were 58.7%, 34.2%, and 29.4%, respectively. Independent prognostic factors, including age at diagnosis, tumor size, tumor grade, T stage, N stage, M stage, and surgery information, were identified by multivariate analysis. The nomogram was constructed based on significant factors in the training cohort. The C-indexes were 0.769 (training cohort) and 0.767 (validation cohort). The calibration curves for survival rates showed that the predicted and observed values were consistent. CONCLUSIONS: This study constructed a nomogram to predict prognosis in patients with CDC. The nomogram performed well in predicting the 1-year, 3-year, and 5-year OS, which can help doctors actively monitor and follow up patients.

Aflatoxin B1 as a complicit in intestinal damage caused by Eimeria ovinoidalis in lambs: Novel insights to reveal parasite-gut battle.

Mycotoxins, unavoidable contaminants in feed and feed ingredients, have the potential to influence the incidence and severity of various diseases upon ingestion. Sheep coccidiosis is an enteric disease caused by protozoa of Eimeria spp. However, the extent to which the presence of aflatoxin b1 (AFB1) synergistically exacerbates damage to intestinal health in lambs with Eimeria remains unclear. 50-day-old female lambs were randomly assigned to a 2 × 2 factorial arrangement of treatments for 15 days to assess the impact of AFB1 exposure on lambs with or without Eimeria (E.) ovinoidalis infection. Our findings reveal that AFB1 synergistically intensifies damage to intestinal health in lambs challenged by E. ovinoidalis. This is evidenced by disruptions to the intestinal microbiota and reductions in the production of short-chain fatty acids. AFB1 further aggravates damage to the cecal mechanical barrier. Additionally, AFB1 contributes to the entry of lipopolysaccharide into the bloodstream, activating the inflammatory response. Interestingly, AFB1 exposure history results in an early peak of oocyst excretion and a decreased number of oocyst excretion in E. ovinoidalis infected lambs. This may be closely linked to the destruction of the intestinal epithelial cell structure and its apoptosis, as indicated by a decreased ratio of Bcl-2 to Bax and increased caspase-3 levels. Mechanistically, proteomics analysis identified mitochondrial dysfunction (inhibition of the oxidative phosphorylation pathway) as the primary factor intensifying intestinal epithelial cell destruction caused by coccidia, exacerbated by AFB1 through the inhibiting the conversion of NADH to NAD+ in the cecum of lambs via down-regulation of the PGC-1α/NRF1/TFAM pathway. Overall, these results offer novel insights into the AFB1 complicity in accelerating intestinal damage caused by E. ovinoidalis in lambs. Targeting the mitochondrial oxidative phosphorylation pathway of the intestine may represent a new therapeutic strategy against the detrimental effects of mycotoxin and coccidia.

Polygala tenuifolia willd. Extract alleviates LPS-induced acute lung injury in rats via TLR4/NF-κB pathway and NLRP3 inflammasome suppression.

BACKGROUND: Acute lung injury (ALI) has received considerable attention in the field of critical care as it can lead to high mortality rates. Polygala tenuifolia, a traditional Chinese medicine with strong expectorant properties, can be used to treat pneumonia. Owing to the complexity of its composition, the main active ingredient is not yet known. Thus, there is a need to identify its constituent compounds and mechanism of action in the treatment of ALI using advanced technological means. PURPOSE: We investigated the anti-inflammatory mechanism and constituent compounds with regard to the effect of P. tenuifolia Willd. extract (EPT) in lipopolysaccharide (LPS)-induced ALI in vivo and in vitro. METHODS: The UHPLC-Q-Exactive Orbitrap MS technology was used to investigate the chemical profile of EPT. Network pharmacology was used to predict the targets and pathways of action of EPT in ALI, and molecular docking was used to validate the binding of polygalacic acid to Toll-like receptor (TLR) 4. The main compounds were determined using LC-MS. A rat model of LPS-induced ALI was established, and THP-1 cells were stimulated with LPS and adenosine triphosphate (ATP) to construct an in vitro model. Pathological changes were observed using hematoxylin and eosin staining, Wright-Giemsa staining, and immunohistochemistry. The expression of inflammatory factors (NE, MPO, Ly-6 G, TNF-α, IL-1ß, IL-6, and iNOS) was determined using enzyme-linked immunosorbent assay, real-time fluorescence quantitative polymerase chain reaction, and western blotting. The LPS + ATP-induced inflammation model in THP-1 cells was used to verify the in vivo experimental results. RESULTS: Ninety-nine compounds were identified or tentatively deduced from EPT. Using network pharmacology, we found that TLR4/NF-κB may be a relevant pathway for the prevention and treatment of ALI by EPT. Polygalacic acid in EPT may be a potential active ingredient. EPT could alleviate LPS-induced histopathological lung damage and reduce the wet/dry lung weight ratio in the rat model of ALI. Moreover, EPT decreased the white blood cell and neutrophil counts in the bronchoalveolar lavage fluid and decreased the expression of genes and proteins of relevant inflammatory factors (NE, MPO, Ly-6 G, TNF-α, IL-1ß, IL-6, and iNOS) in lung tissues. It also increased the expression of endothelial-type nitric oxide synthase expression. Western blotting confirmed that EPT may affect TLR4/NF-κB and NLRP3 signaling pathways in vivo. Similar results were obtained in THP-1 cells. CONCLUSION: EPT reduced the release of inflammatory factors by affecting TLR4/NF-κB and NLRP3 signaling pathways, thereby attenuating the inflammatory response of ALI. Polygalacic acid is the likely compounds responsible for these effects.

Effects of Short-Term Tillage on Rhizosphere Soil Nitrogen Mineralization and Microbial Community Composition in the Double-Cropping Rice Field.

Soil extracellular enzyme plays a vital role in changing soil nitrogen (N) mineralization of rice field. However, the effects of soil extracellular enzyme activities (EEA) and microbial community composition response to N mineralization of rice field under short-term tillage treatment needed to be further explored. In this study, we investigated the impact of short-term (8-year) tillage practices on rhizosphere soil N transformation rate, soil enzyme activities, soil microorganism community structure and their N mineralization function genes in double-cropping rice field in southern China. The experiment consisted of four tillage treatments: rotary tillage with crop straw input (RT), conventional tillage with crop straw input (CT), no-tillage with crop straw retention (NT), and rotary tillage with all crop straws removed as a control (RTO). The results indicated that rhizosphere soil N transformation rate in paddy field in NT and RTO treatments were significantly lower than that in RT and CT treatments. Compared with NT and RTO treatments, soil protease, urease, ß-glucosaminidase and arginase activities with CT treatment were significantly improved, as were abundances of soil sub, npr and chiA with CT and RT treatments. Moreover, diversity of overall soil bacterial communities in NT and RTO treatments were significantly lower than that in RT and CT treatments. Soil chitinolytic and bacterial ureolytic communities were also obviously changed combined with tillage and crop straw input practices.

Sarcopenia and survival in colorectal cancer without distant metastasis: a systematic review and meta-analysis.

BACKGROUND AND AIM: Despite prior attempts to evaluate the effects of sarcopenia on survival among patients with colorectal cancer (CRC), the results of these studies have not been consistent. The present study aimed to evaluate the association between sarcopenia and survival among patients having CRC without distant metastasis by aggregating multiple studies. METHODS: We performed a literature search using computerized databases and identified additional studies from among the bibliographies of retrieved articles. The quality of each study was evaluated using the Newcastle-Ottawa Scale, and meta-analyses were performed to evaluate overall survival (OS) and disease-free survival (DFS). RESULTS: Thirteen studies with up to 6600 participants were included in the meta-analyses, with a mean age of 63.6 years (range: 18-93 years). We found that preoperative sarcopenia was associated with worse OS (hazard ratio [HR]: 1.61; 95% confidence interval [CI]: 1.38-1.88) and worse DFS (HR: 1.57; 95% CI: 1.10-2.24). Compared with patients without sarcopenia after tumor resection, those with postoperative sarcopenia had worse OS (HR: 1.76; 95% CI: 1.47-2.10) and DFS (HR: 1.79; 95% CI: 1.46-2.20). CONCLUSION: These meta-analyses suggest that sarcopenia, no matter observed before or after tumor resection, is associated with worse OS and DFS in patients with CRC who have no distant metastasis.

Prevalence of subthreshold depression and its related factors in Chinese college students: A cross-sectional study.

Objective: To investigate the prevalence of subthreshold depression among Chinese college students and to explore the related factors. Methods: The research subjects were Chinese college students participating in the "2022 Psychology and Behavior Investigation of Chinese Residents (PBICR-2022)". Data on respondents' general characteristics, quality of life, perceived pressure, family communication, perceived social support, self-efficacy, and depression status were gathered. To investigate the association between each variable and the risk of subthreshold depression, statistical analyses, including chi-square tests and rank sum tests were conducted. Furthermore, a binary stepwise logistic regression was employed to establish the regression model of the factors related to subthreshold depression among Chinese college students. Results: A prevalence of subthreshold depression of about 39.7 % was found among the 8934 respondents. Logistic regression analysis revealed that respondents who are female, have chronic diseases, are in debt, experience significant impacts from epidemic control policies, have lower self-assessed quality of life, experience challenges in family communication, perceive lower social support, have lower self-efficacy, and feel higher perceived pressure are more likely to develop subthreshold depression compared to the control group. (P < 0.05). Conclusion: The prevalence rate of subthreshold depression among Chinese college students was found to be approximately 40 %. Female college students suffering from chronic diseases, with households in debt, greatly impacted by epidemic control policies, and experiencing high perceived stress, may be at risk for subthreshold depression among Chinese college students. On the other hand, strong family communication, perceived social support, and self-efficacy were identified as potential protective factors. In order to facilitate timely screening, diagnosis, and treatment of subthreshold depression in Chinese college students, it is crucial for the government, local communities, colleges, and families to prioritize the mental health of college students and implement targeted measures accordingly.

Assessment of the influence of levees along Yangtze River on Oncomelania hupensis, the intermediate host of Schistosoma japonicum.

BACKGROUND: Oncomelania hupensis is the exclusive intermediate host of Schistosoma japonicum in China. Snail control is an essential component of schistosomiasis elimination programme. With 70 years of continuous efforts, the range of O. hupensis had reduced significantly, but slowed down in last decades. A large number of levees against flooding were constructed along Yangtze River and its affiliated lakes in the middle and lower reaches, which influenced the hydrology and ecology in the alluvial plains. The purpose of this study was to assess the impact of levees on the distribution of O. hupensis in the middle and lower reaches of the Yangtze River. METHODS: The snail habitats were digitalised by hand-held GPS system. The years for discovery and elimination of snail habitats were extracted from historical records. The accumulated snail-infested range for each habitat was calculated on the basis of annual reports. The current distribution of O. hupensis was determined by systematic and environmental sampling. The geographical distribution of levees was obtained from satellite imagery. To assess the impact of levees, the data pertaining to O. hupensis were divided into two parts: inside and outside the Yangtze River. Joinpoint regression was utilised to divide the study time span and further characterise the regression in each period. The 5-year-period moving averages of eliminated area infested by snails were calculated for the habitats inside and outside Yangtze River. The moving routes of corresponding geographical median centres were simulated in ArcGIS. Hotspot analysis was used to determine the areas with statistical significance clustering of O. hupensis density. RESULTS: Three periods were identified according to Joinpoint regression both inside and outside Yangtze River. The area infested by O. hupensis increased in the first two periods. It decreased rapidly outside Yangtze River year over year after 1970, while that inside the Yangtze River did not change significantly. Furthermore, the latter was significantly higher than the former. It was observed that the present density of O. hupensis inside Yangtze River was lower than outside the Yangtze River. The median centre for eliminated ranges inside Yangtze River wavered between the east (lower reach) and the west (middle reach). In contrast, the median centre for eliminated ranges continuously moved from the east to the west. CONCLUSIONS: Our findings indicated that the levees had a considerable negative impact on the distribution of O. hupensis outside Yangtze River. Some hotspots observed in the irrigation areas need a sluice system at the inlet of branch for snail control. The major distribution of O. hupensis located in Hubei might be caused by severe waterlogging. The intensive surveillance should be implemented there. The biggest two freshwater lakes, the major endemic regions historically, were identified as cold spots. The long-term impact of Three Gorges Dam on the distribution of O. hupensis in the lakes should be monitored and evaluated.

Imbalance of mitochondrial quality control regulated by STING and PINK1 affects cyfluthrin-induced neuroinflammation.

Nervous system diseases are a global health problem, and with the increase in the elderly population around the world, their incidence will also increase. Harmful substances in the environment are closely related to the occurrence of nervous system diseases. China is a large agricultural country, and thus the insecticide cyfluthrin has been widely used. Cyfluthrin is neurotoxic, but the mechanism of this injury is not clear. Inflammation is an important mechanism for the occurrence of nervous system diseases. Mitochondria are the main regulators of the inflammatory response, and various cellular responses, including autophagy, directly affect the regulation of inflammatory processes. Mitochondrial damage is related to mitochondrial quality control (MQC) and PTEN-induced kinase 1 (PINK1). As an anti-inflammatory factor, stimulator of interferon genes (STING) participates in the regulation of inflammation. However, the relationship between STING and mitochondria in the process of cyfluthrin-induced nerve injury is unclear. This study established in vivo and in vitro models of cyfluthrin exposure to explore the role of MQC and to clarify the mechanism of action of STING and PINK1. Our results showed that cyfluthrin can increase the reactive oxygen species (ROS) level, resulting in mitochondrial damage and inflammation. In this process, an imbalance in MQC leads to the aggravation of mitochondrial damage, and high STING expression drives the occurrence of inflammation. We established a differential expression model of STING and PINK1 to further determine the underlying mechanism and found that the interaction between STING and PINK1 regulates MQC to affect the levels of mitochondrial damage and inflammation. When STING and PINK1 expression are downregulated, mitochondrial damage and STING-induced inflammation are significantly alleviated. In summary, a synergistic effect between STING and PINK1 on cyfluthrin-induced neuroinflammation may exist, which leads to an imbalance in MQC by inhibiting mitochondrial biogenesis and division/fusion, and PINK1 can reduce STING-driven inflammation.

Liver-specific delivery of spherical DNA frameworks for alleviation of hepatic ischemic reperfusion injury.

DNA nanostructures have long been developed for biomedical purposes, but their controlled delivery in vivo proposes a major challenge for disease theranostics. We previously reported that DNA nanostructures on the scales of tens and hundreds nanometers showed preferential renal excretion or kidney retention, allowing for sensitive evaluation and effective protection of kidney function, in response to events such as unilateral ureter obstruction or acute kidney injury. Encouraged by the positive results, we redirected our focus to the liver, specifically targeting organs noticeably lacking DNA materials, to explore the interaction between DNA nanostructures and the liver. Through PET imaging, we identified SDF and M13 as DNA nanostructures exhibiting significant accumulation in the liver among numerous candidates. Initially, we investigated and assessed their biodistribution, toxicity, and immunogenicity in healthy mice, establishing the structure-function relationship of DNA nanostructures in the normal murine. Subsequently, we employed a mouse model of liver ischemia-reperfusion injury (IRI) to validate the nano-bio interactions of SDF and M13 under more challenging pathological conditions. M13 not only exacerbated hepatic oxidative injury but also elevated local apoptosis levels. In contrast, SDF demonstrated remarkable ability to scavenge oxidative responses in the liver, thereby mitigating hepatocyte injury. These compelling results underscore the potential of SDF as a promising therapeutic agent for liver-related conditions. This aimed to elucidate their roles and mechanisms in liver injury, providing a new perspective for the biomedical applications of DNA nanostructures.

Organic solvents-free and ambient-pressure drying melamine formaldehyde resin aerogels with homogeneous structures, outstanding mechanical strength and flame retardancy.

Atmospheric drying method for fabricating aerogels is considered the most promising way for casting aerogels on a large scale. However, the organic solvent exchange, remaining environmental pollution risk, is a crucial step in mitigating the impact of surface tension during the atmospheric drying process, especially for wet gel formed through the alkoxy-derived sol-gel process, such as melamine-formaldehyde resin (MF) aerogel. Herein, a tough polymer-assisted in situ polymerization was proposed to fabricate MF resin aerogel with a combination of mechanical toughness and strength, enabling it to withstand the capillary force during water evaporation. The monolithic MF resin aerogel through the sol-gel method can be directly prepared without additional network strengthening or organic solvent exchange. The resulting MF resin aerogel exhibits a homogeneous as well as hierarchical structure with macropores and mesopores (~6 µm and ~5 nm), high compressive modulus of 31.8 MPa, self-extinguishing property, and high-temperature thermal insulation with 97 % heat decrease for butane flame combustion. This work presents a straightforward and environmentally friendly method for fabricating MF resin aerogels with nanostructures and excellent performance in open conditions, exhibiting various applications.

Efficacy and mechanism of action of Yanxiao Di'naer formula for non-alcoholic steatohepatitis treatment based on metabolomics and RNA sequencing.

ETHNOPHARMACOLOGICAL RELEVANCE: Nonalcoholic fatty liver disease (NAFLD) is the most prevalent chronic liver disease worldwide. Nonalcoholic steatohepatitis (NASH) is a crucial component of this disease spectrum. The Yanxiao Di'naer formula (YXDNE) is an Uyghur medical extract that has been used in folk medicine to treat hepatitis for a long time. However, the role and mechanism of action of YXDNE in NASH treatment remains unclear. OBJECTIVE: The objective of this study was to assess the effectiveness of YXDNE in treating NASH induced by injections of carbon tetrachloride combined with a high-fat high-cholesterol diet (HFHCD), and to clarify the underlying mechanisms. METHODS: The compounds in the YXDNE extract were analysed for classification and proportions using ultra-performance liquid chromatography-mass spectrometry. The efficacy of YXDNE in treating abnormal lipid metabolism was evaluated in L02 cells in vitro. In addition, a C57BL/6 mouse model of NASH was established to evaluate the therapeutic efficacy of YXDNE in vivo. Metabolomics and RNA sequencing were used to analyse the therapeutic effects of YXDNE on the liver. The corresponding signalling pathways were found to target AMPKα1, PPARα, and NF-κB. The efficacy of YXDNE was validated using inhibitors or silencing RNA (siRNA) against AMPKα1 and PPARα. RESULTS: This study confirmed that YXDNE treatment ameliorated NASH in a murine model of this disease. Metabolomics analysis suggested that YXDNE efficacy was associated with fatty acid catabolism and AMPK signalling pathways. RNA sequencing results showed that YXDNE efficacy in treating NASH was highly correlated with the AMPK, PPARα and NF-κB pathways. Both in vitro and in vivo experimental data demonstrated that YXDNE affected the expression of p-AMPKα1, PPARα, p-NF-κB, IκB, and p-IκB. The efficacy of YXDNE in treating NASH in vitro was cancelled when AMPK was inhibited with Compound C or PPARα was modulated via siRNA. CONCLUSIONS: YXDNE may have a therapeutic effect on abnormal lipid metabolism in L02 cells and in a murine model of NASH by affecting the AMPKα1/PPARα/NF-κB signalling pathway. Therefore, YXDNE has the potential for clinical application in the prevention and treatment of NASH.

Clinical efficacy of intradermal type I collagen injections in treating skin photoaging in patients from high-altitude areas.

BACKGROUND: Photoaging, a result of chronic sun exposure, leads to skin damage and pigmentation changes. Traditional treatments may have limitations in high-altitude areas like Yunnan Province. Intradermal Col Ι injections stimulate collagen production, potentially improving skin quality. This study aims to assess the efficacy and safety of this treatment for photoaging. AIM: To evaluate the efficacy and safety of intradermal type Ι collagen (Col Ι) injection for treating photoaging. METHODS: This prospective, self-controlled study investigated the impact of intradermal injections of Col Ι on skin photodamage in 20 patients from the Yunnan Province. Total six treatment sessions were conducted every 4 wk ± 3 d. Before and after each treatment, facial skin characteristics were quantified using a VISIA skin detector. Skin thickness data were assessed using the ultrasound probes of the Dermalab skin detector. The Face-Q scale was used for subjective evaluation of the treatment effect by the patients. RESULTS: The skin thickness of the right cheek consistently increased after each treatment session compared with baseline. The skin thickness of the left cheek significantly increased after the third through sixth treatment sessions compared with baseline. The skin thickness of the right zygomatic region increased after the second to sixth treatment sessions, whereas that of the left zygomatic region showed a significant increase after the fourth through sixth treatment sessions. The skin thickness of both temporal regions significantly increased after the fifth and sixth treatment sessions compared with baseline (P < 0.05). These findings were also supported by skin ultrasound images. The feature count for the red areas and wrinkle feature count decreased following the treatment (P < 0.05). VISIA assessments also revealed a decrease in the red areas after treatment. The Face-Q-Satisfaction with Facial Appearance Overall and Face-Q-Satisfaction with Skin scores significantly increased after each treatment session. The overall appearance of the patients improved after treatment. CONCLUSION: Intradermal Col Ι injection improves photoaging, with higher patient satisfaction and fewer adverse reactions, and could be an effective treatment method for populations residing in high-altitude areas.

Untargeted metabonomics and TLR4/ NF-κB signaling pathway analysis reveals potential mechanism of action of Dendrobium huoshanense polysaccharide in nonalcoholic fatty liver disease.

Nonalcoholic fatty liver disease (NAFLD) is marked by hepatic steatosis accompanied by an inflammatory response. At present, there are no approved therapeutic agents for NAFLD. Dendrobium Huoshanense polysaccharide (DHP), an active ingredient extracted from the stems of Dendrobium Huoshanense, and exerts a protective effect against liver injury. However, the therapeutic effects and mechanisms of action DHP against NAFLD remain unclear. DHP was extracted, characterized, and administered to mice in which NAFLD had been induced with a high-fat and high-fructose drinking (HFHF) diet. Our results showed that DHP used in this research exhibits the characteristic polysaccharide peak with a molecular weight of 179.935 kDa and is composed primarily of Man and Glc in a molar ratio of 68.97:31.03. DHP treatment greatly ameliorated NAFLD by significantly reducing lipid accumulation and the levels of liver function markers in HFHF-induced NAFLD mice, as evidenced by decreased serum levels of aspartate aminotransferase (AST), alanine aminotransferase (ALT), total cholesterol (TC) and total triglyceride (TG). Furthermore, DHP administration reduced hepatic steatosis, as shown by H&E and Oil red O staining. DHP also inhibited the Toll-like receptor 4 (TLR4)/nuclear factor-kappa B (NF-κB) signaling pathway expression, thereby reducing levels of hepatic proinflammatory cytokines. Besides, untargeted metabolomics further indicated that 49 metabolites were affected by DHP. These metabolites are strongly associated the metabolism of glycine, serine, threonine, nicotinate and nicotinamide, and arachidonic acid. In conclusion, DHP has a therapeutic effect against NAFLD, whose underlying mechanism may involve the modulation of TLR4/NF-κB, reduction of inflammation, and regulation of the metabolism of glycine, serine, threonine, nicotinate and nicotinamide metabolism, and arachidonic acid metabolism.

Long noncoding RNA UCA1 promotes the chondrogenic differentiation of human bone marrow mesenchymal stem cells via regulating PARP1 ubiquitination.

Bone marrow mesenchymal stem cells (BMSCs) possess the potential to differentiate into cartilage cells. Long noncoding RNA (lncRNAs) UCA1 has been confirmed to improve the chondrogenic differentiation of marrow mesenchymal stem cells (MSCs). Herein, we further investigated the effects and underlying mechanisms in these processes. the expression of UCA1 was positively associated with chondrogenic differentiation and the knockdown of UCA1 has been shown to attenuate the expression of chondrogenic markers. RNA pull down assay and RNA immunoprecipitation showed that UCA1 could directly bind to PARP1 protein. UCA1 could improve PARP1 protein via facilitating USP9X-mediated PARP1 deubiquitination. Then these processes stimulated the NF-κB signaling pathway. In addition, PARP1 was declined in UCA1 knockdown cells, and silencing of PARP1 could diminishes the increasing effects of UCA1 on the chondrogenic differentiation from MSCs and signaling pathway activation. Collectively, these outcomes suggest that UCA1 could act as a mediator of PARP1 protein ubiquitination and develop the chondrogenic differentiation of MSCs.

Gut microbiota from B-cell-specific TLR9-deficient NOD mice promote IL-10+ Breg cells and protect against T1D.

Introduction: Type 1 diabetes (T1D) is an autoimmune disease characterized by the destruction of insulin-producing ß cells. Toll-like receptor 9 (TLR9) plays a role in autoimmune diseases, and B cell-specific TLR9 deficiency delays T1D development. Gut microbiota are implicated in T1D, although the relationship is complex. However, the impact of B cell-specific deficiency of TLR9 on intestinal microbiota and the impact of altered intestinal microbiota on the development of T1D are unclear. Objectives: This study investigated how gut microbiota and the intestinal barrier contribute to T1D development in B cell-specific TLR9-deficient NOD mice. Additionally, this study explored the role of microbiota in immune regulation and T1D onset. Methods: The study assessed gut permeability, gene expression related to gut barrier integrity, and gut microbiota composition. Antibiotics depleted gut microbiota, and fecal samples were transferred to germ-free mice. The study also examined IL-10 production, Breg cell differentiation, and their impact on T1D development. Results: B cell-specific TLR9-deficient NOD mice exhibited increased gut permeability and downregulated gut barrier-related gene expression. Antibiotics restored gut permeability, suggesting microbiota influence. Altered microbiota were enriched in Lachnospiraceae, known for mucin degradation. Transferring this microbiota to germ-free mice increased gut permeability and promoted IL-10-expressing Breg cells. Rag-/- mice transplanted with fecal samples from Tlr9 fl/fl Cd19-Cre+ mice showed delayed diabetes onset, indicating microbiota's impact. Conclusion: B cell-specific TLR9 deficiency alters gut microbiota, increasing gut permeability and promoting IL-10-expressing Breg cells, which delay T1D. This study uncovers a link between TLR9, gut microbiota, and immune regulation in T1D, with implications for microbiota-targeted T1D therapies.

Laboratory exploration of the use of ripasudil in descemetorhexis with a human ex vivo model.

The aim of the study was to investigate the effect of ripasudil on corneal endothelial cell survival and migration after two types of descemetorhexis on a human ex vivo model. Eleven human corneoscleral buttons were incubated in either 50 ml organ culture medium containing 10 µM ripasudil or 50 µl dimethyl sulfoxide (DMSO), the vehicle in ripasudil for 2 days prior to wound creation then for 14 days after. The wound was created with either full trephination scoring or by shallow trephination plus manual peeling. At day 14, immunohistochemistry with vimentin and Na+/K+/ATPase markers was conducted. Tissues were assessed at day 3, 7 and 14 for morphology, cell migration, cell viability and cell density. Full trephination scoring created more damage on tissues compared to shallow trephination with full Descemet membrane peeling. In the full trephination scoring group, no differences in cell viability were noted when ripasudil and DMSO were compared. With the peeling method, Ripasudil could protect the endothelial cell death and maintain the morphology compared to the control. At day 14, no differences in the peripheral cell viability and density were found between ripasudil and DMSO, although the ripasudil group presented significantly increased central cell count and cell viability. Increased cell migration was noted with ripasudil and the initial cell morphology of those migrated cells was similar to that of fibroblasts. In conclusion, ex vivo modelling suggested that peeling resulted in less cell damage than scoring and ripasudil maintained better morphology and promoted migration. These effects might be via transformation of endothelial cells into a more motile spindle-like phenotype.

Research on the Effects of the Relationship between Agronomic Traits and Dwarfing Genes on Yield in Colored Wheat.

This research focuses on 72 approved varieties of colored wheat from different provinces in China. Utilizing coefficients of variation, structural equation models, and correlation analyses, six agronomic traits of colored wheat were comprehensively evaluated, followed by further research on different dwarfing genes in colored wheat. Using the entropy method revealed that among the 72 colored wheat varieties, 10 were suitable for cultivation. Variety 70 was the top-performing variety, with a comprehensive index of 87.15%. In the final established structural equation model, each agronomic trait exhibited a positive direct effect on yield. Notably, plant height, spike length, and flag leaf width had significant impacts on yield, with path coefficients of 0.55, 0.40, and 0.27. Transcriptome analysis and real-time fluorescence quantitative polymerase chain reaction (RT-qPCR) validation were used to identify three dwarfing genes controlling plant height: Rht1, Rht-D1, and Rht8. Subsequent RT-qPCR validation clustering heatmap results indicated that Rht-D1 gene expression increased with the growth of per-acre yield. Rht8 belongs to the semi-dwarf gene category and has a significant positive effect on grain yield. However, the impact of Rht1, as a dwarfing gene, on agronomic traits varies. These research findings provide crucial references for the breeding of new varieties.

High-Resolution Spatiotemporal Modeling for PM2.5 Major Components in the Pearl River Delta and Its Implications for Epidemiological Studies.

Distinguishing the effects of different fine particulate matter components (PMCs) is crucial for mitigating their effects on human health. However, the sparse distribution of locations where PM is collected for component analysis makes it challenging to investigate the relevant health effects. This study aimed to investigate the agreement between data-fusion-enhanced exposure assessment and site monitoring data in estimating the effects of PMCs on gestational diabetes mellitus (GDM). We first improved the spatial resolution and accuracy of exposure assessment for five major PMCs (EC, OM, NO3-, NH4+, and SO42-) in the Pearl River Delta region by a data fusion model that combined inputs from multiple sources using a random forest model (10-fold cross-validation R2: 0.52 to 0.61; root mean square error: 0.55 to 2.26 µg/m3). Next, we compared the associations between exposures to PMCs during pregnancy and GDM in a hospital-based cohort of 1148 pregnant women in Heshan, China, using both site monitoring data and data-fusion model estimates. The comparative analysis showed that the data-fusion-based exposure generated stronger estimates of identifying statistical disparities. This study suggests that data-fusion-enhanced estimates can improve exposure assessment and potentially mitigate the misclassification of population exposure arising from the utilization of site monitoring data.

Bile acid-gut microbiota imbalance in cholestasis and its long-term effect in mice.

Cholestasis is a common morbid state that may occur in different phases; however, a comprehensive evaluation of the long-term effect post-recovery is still lacking. In the hepatic cholestasis mouse model, which was induced by a temporary complete blockage of the bile duct, the stasis of bile acids and liver damage typically recovered within a short period. However, we found that the temporary hepatic cholestasis had a long-term effect on gut microbiota dysbiosis, including overgrowth of small intestinal bacteria, decreased diversity of the gut microbiota, and an overall imbalance in its composition accompanied by an elevated inflammation level. Additionally, we observed an increase in Escherichia-Shigella (represented by ASV136078), rich in virulence factors, in both small and large intestines following cholestasis. To confirm the causal role of dysregulated gut microbiota in promoting hepatic inflammation and injury, we conducted gut microbiota transplantation into germ-free mice. We found that recipient mice transplanted with feces from cholestasis mice exhibited liver inflammation, damage, and accumulation of hepatic bile acids. In conclusion, our study demonstrates that cholestasis disrupts the overall load and structural composition of the gut microbiota in mice, and these adverse effects persist after recovery from cholestatic liver injury. This finding suggests the importance of monitoring the structural composition of the gut microbiota in patients with cholestasis and during their recovery. IMPORTANCE: Our pre-clinical study using a mouse model of cholestasis underscores that cholestasis not only disrupts the equilibrium and structural configuration of the gut microbiota but also emphasizes the persistence of these adverse effects even after bile stasis restoration. This suggests the need of monitoring and initiating interventions for gut microbiota structural restoration in patients with cholestasis during and after recovery. We believe that our study contributes to novel and better understanding of the intricate interplay among bile acid homeostasis, gut microbiota, and cholestasis-associated complications. Our pre-clinical findings may provide implications for the clinical management of patients with cholestasis.