Visceral adipose tissue area predicts major adverse kidney events in patients with acute necrotizing pancreatitis.

BACKGROUND: Given the previously reported harmful effects of abdominal fat burden on kidney function, we aim to investigate the relationship between major adverse kidney events within 30 days (MAKE30) and abdominal obesity in acute necrotizing pancreatitis (ANP) patients and explore the underlying risk factors. METHODS: A retrospective cohort study of all patients admitted within 72 h after the first episode of ANP to a tertiary center between June 2015 and June 2019 was conducted. Automatic image analysis software was used to calculate the area of subcutaneous adipose tissue (SAT), visceral adipose tissue (VAT) and skeletal muscle from computed tomography scans at the umbilical level. The potential risk factors of MAKE30 were analyzed by logistic regression. RESULTS: A total of 208 eligible ANP patients were enrolled, with an incidence of 23% for MAKE30. VAT area was more closely associated with the development of MAKE30, with an area under the ROC curve of 0.69 (cutoff value 200 cm2, 63.8% sensitivity and 66.7% specificity). Multivariate logistic regression analysis demonstrated that VAT area [OR 1.01 (1.01-1.02); p < 0.001] was an independent risk factor in predicting MAKE30. Patients with a VAT area > 200 cm2 had more requirements of renal replacement therapy (32% vs. 12%, P < 0.001), and a significantly higher incidence of other poor clinical outcomes (all p < 0.05). CONCLUSION: Early assessment of the VAT area may help identify ANP patients at high risk of MAKE30, suggesting that it could be a potential indicator for adverse kidney events.

Therapeutic role of extracellular vesicles from human umbilical cord mesenchymal stem cells and their wide therapeutic implications in inflammatory bowel disease and other inflammatory disorder.

The chronic immune-mediated inflammatory condition known as inflammatory bowel disease (IBD) significantly affects the gastrointestinal system. While the precise etiology of IBD remains elusive, extensive research suggests that a range of pathophysiological pathways and immunopathological mechanisms may significantly contribute as potential factors. Mesenchymal stem cells (MSCs) have shown significant potential in the development of novel therapeutic approaches for various medical conditions. However, some MSCs have been found to exhibit tumorigenic characteristics, which limit their potential for medical treatments. The extracellular vesicles (EVs), paracrine factors play a crucial role in the therapeutic benefits conferred by MSCs. The EVs consist of proteins, microRNAs, and lipids, and are instrumental in facilitating intercellular communication. Due to the ease of maintenance, and decreased immunogenicity, tumorigenicity the EVs have become a new and exciting option for whole cell treatment. This review comprehensively assesses recent preclinical research on human umbilical cord mesenchymal stem cell (hUC-MSC)-derived EVs as a potential IBD therapy. It comprehensively addresses key aspects of various conditions, including diabetes, cancer, dermal injuries, neurological disorders, cardiovascular issues, liver and kidney diseases, and bone-related afflictions.

YTHDF3 Regulates the Degradation and Stability of m6A-Enriched Transcripts to Facilitate the Progression of Castration-Resistant Prostate Cancer.

RNA N6-methyladenosine (m6A) readers mediate cancer progression. However, the functional role and potential mechanisms of the m6A readers in prostate cancer tumorigenicity remain to be elucidated. In this study, we demonstrate that YTHDF3 expression is elevated in castration-resistant prostate cancer (CRPC) and positively correlated to high grade, bone metastasis and poor survival. YTHDF3 expression promoted CRPC cell proliferation, epithelial to mesenchymal transition (EMT) and tumour progression. Mechanistically, YTHDF3 promoted the RNA degradation of SPOP and NXK3.1 but stabilized RNA expressions of TWIST1 and SNAI2 dependent on m6A to facilitate cell proliferation and EMT. Additionally, YTHDF3 expression enhanced AKT activity via degrading SPOP in an m6A-dependent manner. Importantly, we found that melatonin can compete with m6A to occupy the m6A-binding cage of YTHDF3, leading to inhibition of YTHFD3 and its target expressions as well as CRPC tumour growth. Our findings uncover an essential role of YTHDF3 in the progression of CRPC and highlight the role of melatonin in anti-CRPC activity.

YTHDF1 regulates GID8-mediated glutamine metabolism to promote colorectal cancer progression in a m6A-dependent manner.

Dysregulation of epigenetics is a hallmark of cancer development, and YTHDF1 stands out as a crucial epigenetic regulator with the highest DNA copy number variation among all N6-methyladenosine (m6A) regulators in colorectal cancer (CRC) patients. Here, we aimed to investigate the specific contribution of YTHDF1 overexpression to CRC progression and its consequences. Through multiple bioinformatic analysis of human cancer databases and clinical CRC samples, we identified GID8/Twa1 as a crucial downstream target of YTHDF1. YTHDF1 manipulates GID8 translation efficiency in a m6A-dependent manner, and high expression of GID8 is associated with more aggressive tumor progression and poor overall survival. Mechanistically, GID8 is intimately associated with glutamine metabolic demands by maintaining active glutamine uptake and metabolism through the regulation of excitatory amino acid transporter 1 (SLC1A3) and glutaminase (GLS), thereby facilitating the malignant progression of CRC. Inhibition of GID8 attenuated CRC proliferation and metastasis both in vitro and in vivo. In summary, we identified a previously unknown target pertaining to glutamine uptake and metabolism in tumor cells, underscoring the potential of GID8 in the treatment of CRC.

Study on the occurrence and influencing factors of gastrointestinal symptoms in hemodialysis patients with uremia.

BACKGROUND: Gastrointestinal symptoms are common in patients with uremia undergoing hemodialysis, and these symptoms seriously affect patients' prognosis. AIM: To assess the occurrence and factors influencing gastrointestinal symptoms in patients with uremia undergoing hemodialysis. METHODS: We retrospectively selected 98 patients with uremia who underwent regular hemodialysis treatment in the blood purification center of our hospital from December 2022 to December 2023. The gastrointestinal symptoms and scores of each dimension were evaluated using the Gastrointestinal Symptom Grading Scale (GSRS). Patients were divided into gastrointestinal symptoms and no gastrointestinal symptom groups according to whether they had gastrointestinal symptoms. The factors that may affect gastrointestinal symptoms were identified by single-factor analysis. Multiple logistic regression analysis was performed to identify independent risk factors for gastrointestinal symptoms. RESULTS: Gastrointestinal symptoms included indigestion, constipation, reflux, diarrhea, abdominal pain, and eating disorders, and the total average GSRS score was 1.35 ± 0.47. This study showed that age, number of tablets, dialysis time, glucocorticoid, parathyroid hormone (PTH), combined diabetes mellitus and C-reactive protein (CRP) were independent risk factors for gastrointestinal symptoms in patients with uremia undergoing hemodialysis, whereas body mass index (BMI), hemoglobin (Hb), and urea clearance index were independent protective factors (P < 0.05). CONCLUSION: Gastrointestinal symptoms are mostly mild in patients with uremia undergoing hemodialysis, most commonly including dyspepsia, eating disorders, and gastroesophageal reflux. The independent influencing factors mainly include the BMI, age, number of pills taken, dialysis time, urea clearance index, Hb, use of glucocorticoids, and thyroid hormone level. PTH, CRP, and diabetes are clinically related factors influencing the occurrence of gastrointestinal symptoms, and targeted prevention can be performed.

Direct Identification of O─O Bond Formation Through Three-Step Oxidation During Water Splitting by Operando Soft X-ray Absorption Spectroscopy.

Anionic redox allows the direct formation of O─O bonds from lattice oxygens and provides higher catalytic in the oxygen evolution reaction (OER) than does the conventional metal ion mechanism. While previous theories have predicted and experiments have suggested the possible O─O bond, it has not yet been directly observed in the OER process. In this study, operando soft X-ray absorption spectroscopy (sXAS) at the O K-edge and the operando Raman spectra is performed on layered double CoFe hydroxides (LDHs) after intercalation with [Cr(C2O4)3]3-, and revealed a three-step oxidation process, staring from Co2+ to Co3+, further to Co4+ (3d6L), and ultimately leading to the formation of O─O bonds and O2 evolution above a threshold voltage (1.4 V). In contrast, a gradual oxidation of Fe is observed in CoFe LDHs. The OER activity exhibits a significant enhancement, with the overpotential decreasing from 300 to 248 mV at 10 mA cm-2, following the intercalation of [Cr(C2O4)3]3- into CoFe LDHs, underscoring a crucial role of anionic redox in facilitating water splitting.

Quantifying future water resource vulnerability in a high-mountain third pole river basin under climate change.

Understanding the water resource vulnerability (WRV) in global mountain regions under climate change is crucial for water resources management and socio-economic development. However, the WRV in the high-mountain Third Pole region (with quite a few transboundary river basins) remains largely unclear. Here, we have applied a comprehensive assessment framework of WRV to a Third Pole high-mountain river basin (Nujiang-Salween River, NSR) and its dependent downstream. The framework consisted of sensitivity, exposure, adaptability, hazard, and water stress indices, considering climate change, socio-economics, government effectiveness, natural disasters, and water supply capacity of the target river basin. Our results indicate that the downstream area (with intensive human activities) often exhibited significantly higher WRV than the mountain region; while the WRV shows an M-shaped change with increasing elevation, with the highest vulnerability occurring in a relatively low elevation range (e.g., 500-1500 m for the NSR basin). In the near future, we find that the spatial pattern of WRV in the basin is alternately influenced by adaptation, water scarcity, and exposure; whereas climate change serves as the main driver affecting the WRV in the far future. These findings enhance our understanding of the WRV in high-mountain transboundary basins of the Third Pole under global change.

Molecular interaction induced dual fibrils towards organic solar cells with certified efficiency over 20.

The nanoscale fibrillar morphology, featuring long-range structural order, provides abundant interfaces for efficient exciton dissociation and high-quality pathways for effective charge transport, is a promising morphology for high performance organic solar cells. Here, we synthesize a thiophene terminated non-fullerene acceptor, L8-ThCl, to induce the fibrillization of both polymer donor and host acceptor, that surpasses the 20% efficiency milestone of organic solar cells. After adding L8-ThCl, the original weak and less continuous nanofibrils of polymer donors, i.e. PM6 or D18, are well enlarged and refined, whilst the host acceptor L8-BO also assembles into nanofibrils with enhanced structural order. By adapting the layer-by-layer deposition method, the enhanced structural order can be retained to significantly boost the power conversion efficiency, with specific values of 19.4% and 20.1% for the PM6:L8-ThCl/L8-BO:L8-ThCl and D18:L8-ThCl/L8-BO:L8-ThCl devices, with the latter being certified 20.0%, which is the highest certified efficiency reported so far for single-junction organic solar cells.

Intraglandular dissemination: a special pathological feature.

Intraglandular dissemination is an important pathological feature of thyroid cancer, yet the biological characteristics of this phenomenon remain relatively underexplored. This paper aims to provide a comprehensive overview of its biological behaviors, protein expressions, and identification methods. Several retrospective studies have found that thyroid cancers with intraglandular dissemination have higher rates of lymph node metastasis, capsule invasion, and vascular invasion, exhibiting more aggressive biological behavior. Immunohistochemistry results show abnormal expression of proteins such as FKBP5, CENPF, CX26, KIF11, PTK7, which are associated with poor prognosis in thyroid cancers with intraglandular dissemination, offering potential guidance for specific targeted therapy in the future. Moreover, adjunctive techniques including ultrasound, fine-needle aspiration, and genetic testing offer valuable support in accurately identifying these cases, facilitating moreproactive treatment and closer follow-up.

Cascade Electrocatalytic Reduction of Nitrate to Ammonia Using a Heterobimetallic Covalent Organic Framework Composed of Cu-Porphyrin and Co-Bipyridine.

The electrocatalytic reduction of nitrate (NO3-) to ammonia (NH3) not only offers an effective solution to environmental problems caused by the accumulation of NO3- but also provides a sustainable alternative to the Haber-Bosch process. However, the conversion of NO3- to NH3 is a complicated process involving multiple steps, leading to a low Faradaic efficiency (FE) for NH3 production. The structural designability of covalent organic frameworks (COFs) renders feasible and precise modulation at the molecular level, facilitating the incorporation of multiple well-defined catalytic sites with different reactivities into a cohesive entity. This promotes the efficiency of the overall reaction through the coupling of multistep reactions. Herein, heterobimetallic CuP-CoBpy was prepared by postmodification, involving the anchoring of cobalt ions to the CuP-Bpy structure. As a result of the cascade effect of the bimetallic sites, CuP-CoBpy achieved an outstanding NH3 yield of 13.9 mg h-1 mgcat.-1 with a high FE of 96.7% at -0.70 V versus the reversible hydrogen electrode and exhibited excellent stability during catalysis. A series of experimental and theoretical studies revealed that the CuP unit facilitates the conversion of NO3- to NO2-, while the CoBpy moiety significantly prompts the reduction of NO2- to NH3. This study demonstrates that tailoring the structural units for the construction of COFs based on each step in the multistep reaction can enhance both the catalytic activity and product selectivity of the overall process.

Exploring the Molecular Mechanism of Schisandrin C for the Treatment of Atherosclerosis via the PI3K/AKT/mTOR Autophagy Pathway.

Atherosclerosis (AS) is a common cardiovascular disease that poses a major threat to health. Schisandra chinensis is a medicinal and edible plant that is commonly used to treat cardiovascular diseases. In this paper, HPLC was used to detect and analyze 5 different components in Schisandra chinensis. Network pharmacological predictions highlight the PI3K/AKT/mTOR pathway as an important pharmacological pathway. The effective ingredient Schisandrin C was screened by the molecular docking technique. ox-LDL-induced HUVECs were used to construct the atherosclerosis model for further experimental verification. The results showed that Schisandrin C interfered with the PI3K/AKT/mTOR autophagy pathway. This study lays a foundation for the further application of Schisandrin C in the prevention and treatment of atherosclerosis in the future.

A repeated cross-sectional pilot study of the relationship between perceived a community with shared future for doctor-patient and benefit finding: the mediating role of health self-consciousness and moderating role of anxiety.

OBJECTIVE: Since January 8, 2023, China has managed COVID-19 as a Class-B infectious disease, marking the epidemic's transition to a low-level stage. This study analyzes the relationship between the public's perceived a community with shared future for doctor-patient (PCSF), health self-consciousness, benefit finding, and anxiety in this stage. Additionally, it compares changes in these variables across different stages of COVID-19. METHODS: Using a repeated cross-sectional design, three surveys were conducted respectively in three different stages of COVID-19 in China. Specifically, the first survey was conducted in Beijing, Dalian, Zhengzhou, Heihe, and Shangrao from November 13 to 20, 2021 in the outbreak stage of COVID-19, yielding 1,252 valid responses out of 1,534 collected questionnaires. The second survey was conducted in Dalian, Zhengzhou, Heihe, Shangrao, and Lanzhou from December 1 to 19, 2021 in the stable stage of COVID-19, with 872 valid responses obtained from 1,075 collected questionnaires. The third survey was conducted in Beijing, Dalian, Zhengzhou, Heihe, Shangrao, Lanzhou, and Chengdu from January 29 to February 4, 2023 in the low epidemic level stage of COVID-19, achieving 2,113 valid responses from the 2,461 questionnaires collected. RESULTS: Unlike in the outbreak stage but similar to the stable stage, the public's anxiety, health self-consciousness and benefit finding decreased while PCSF was improved in the low epidemic level stage. Consistent with both the outbreak and stable stage, PCSF, health self-consciousness, benefit finding, and anxiety showed positive correlations in the low epidemic level stage, with health self-consciousness partially mediating the positive impact of PCSF on benefit finding. Unlike in the stable stage but similar to the outbreak stage, anxiety did not moderate the relationship between PCSF and health self-consciousness in the low epidemic level stage. CONCLUSIONS: The public's health self-consciousness, benefit finding, and anxiety decreased, while PCSF increased in the low epidemic level stage. Furthermore, PCSF had a greater impact on benefit finding, and anxiety's impact on health self-consciousness was significantly reduced. Across different stages of COVID-19, PCSF directly increased benefit finding and also enhanced benefit finding by improving health self-consciousness. Thus, comprehensive intervention measures are beneficial in the low epidemic level stage.

Nonlinear association between the triglyceride-glucose index and diabetes mellitus in overweight and obese individuals: a cross-sectional retrospective analysis.

BACKGROUND: The triglyceride-glucose (TyG) index is linked to both the development and progression of diabetes, while obesity remains a significant risk factor for this disease. However, the relationship between the TyG index and overweight or obese diabetes remains unclear. METHODS: This study was a cross-sectional analysis of data from 40,633 participants with body mass index (BMI) ≥ 24 kg/m2 who were screened from January 2018 to December 2023 at Henan Provincial People's Hospital. Participants were divided into groups of overweight or obese individuals with diabetes and those without diabetes according to the diabetes diagnostic criteria. The TyG index, the dependent variable, was determined using the equation ln [fasting triglycerides (mg/dL) × fasting glucose (mg/dL)/2]. We explored the association between TyG index and diabetes in overweight or obese individuals through multivariate logistic regression, subgroup analysis, generalized additive models, smoothed curve fitting, and analysis of threshold effects. RESULTS: Patients who were overweight or obese and had diabetes had higher TyG index levels than those without diabetes. After adjusting for confounders, our findings indicated a significant association between the TyG index and the risk of diabetes in overweight or obese individuals [odds ratio (OR) = 7.38, 95% confidence interval (CI): 6.98-7.81]. There was a J-shaped nonlinear association between TyG index and diabetes. When TyG index was > 4.46, the risk of diabetes increased sharply. Notably, a high baseline TyG index (Q4 group) correlated with a notably greater risk of diabetes than did the Q1 group, with an OR of 22.72 (95% CI: 20.52-25.16). Subgroup analysis revealed that the association between TyG and diabetes was stronger in females than in males (OR = 7.57, 95% CI: 6.76-8.48,), more significant in individuals with a BMI of 24-28 kg/m2 than in those with a BMI ≥ 28 kg/m2 (OR = 8.40, 95% CI: 7.83-9.02), and increased with age (OR = 8.15, 95% CI: 7.25-9.17) (all P for interaction < 0.001). CONCLUSION: Among overweight or obese individuals, a higher TyG index is associated with an elevated risk of diabetes, especially when TyG is > 4.46. Furthermore, factors such as sex, age, and BMI significantly influence the risk of diabetes in overweight or obese individuals. Specifically, older women with a BMI of 24-28 kg/m2 are at a greater risk of diabetes under similar TyG index conditions.

Comparative efficacy and safety of anlotinib and topotecan as second-line treatment in small cell lung cancer: a retrospective cohort study.

Background: Small cell lung cancer (SCLC) presents considerable challenges regarding the availability of second-line treatment options, which remain limited. The paucity of effective therapeutic choices at this setting emphasizes the urgent requirement for rigorous research and investigation into novel treatment strategies. To address this clinical gap, the current study aimed to compare the efficacy and safety of anlotinib with the standard second-line treatment, topotecan, in patients with relapsed SCLC. Methods: This retrospective collected data from SCLC patients who received either anlotinib or topotecan as second-line treatment. The primary endpoints were progression-free survival (PFS), while the secondary endpoints included the overall survival (OS), objective response rate (ORR), disease control rate (DCR), and safety assessment. Results: The study included 46 SCLC patients, with 20 receiving anlotinib and 26 receiving topotecan as second-line treatment. The anlotinib group showed a significantly longer median PFS compared to the topotecan group [5.6 vs. 2.2 months; hazard ratio (HR) =0.50; 95% confidence interval (CI): 0.27-0.92; P=0.02]. However, there was no statistically significant difference in OS between the two groups (9.1 vs. 7.7 months; HR =0.88; 95% CI: 0.46-1.70; P=0.71). The ORRs were 20.0% and 7.7% (P=0.48), and the DCRs were 70.0% and 23.1% (P=0.007) for the anlotinib and topotecan groups, respectively. Treatment-related adverse events (TRAEs) occurred in 13 patients (65.0%) in the anlotinib group and 20 (76.9%) in the topotecan group (P=0.49). Conclusions: Anlotinib shows the potential to extend PFS and manageable adverse events (AEs) compared to topotecan in the second-line setting for relapsed SCLC.

Abelmoschi Corolla polysaccharides and related metabolite ameliorates colitis via modulating gut microbiota and regulating the FXR/STAT3 signaling pathway.

Ulcerative Colitis (UC) is a chronic inflammatory disease of the intestinal tract with unknown definitive etiology. Polysaccharides are among the most important active components of Abelmoschi Corolla, exhibitings various pharmacological activities such as antioxidation and immunomodulation. However, no studies have yet reported the application of Abelmoschi Corolla Polysaccharides (ACP) in treating UC. This study aims to highlight the therapeutic efficacy of ACP in UC and reveal the underlying mechanism. The potential therapeutic effect is initially verified using a dextran sodium sulfate (DSS)-induced colitis model. 16S rRNA sequencing is performed using feces samples and untargeted metabolomics using serum samples to further reveal that ACP reprograms the dysbiosis triggered by UC progression, increases the abundance of Bacteroides spp., Blautia spp., and Parabacteroides spp. at the genus level and enriches the serum concentration of 7-ketodeoxycholic acid (7-KDA). Furthermore, using the FXR-/- mouse model, it is revealed that Farnesoid X Receptor (FXR) is a key target for ACP and the metabolite 7-KDA to block STAT3 phosphorylation by repairing the intestinal barrier to attenuate UC. Taken together, this work highlights the therapeutic potential of ACP against UC, mainly exerting its effects via modulating gut microbiota and regulating the FXR/STAT3 signaling pathway.

IRnet: Immunotherapy response prediction using pathway knowledge-informed graph neural network.

INTRODUCTION: Immune checkpoint inhibitors (ICIs) are potent and precise therapies for various cancer types, significantly improving survival rates in patients who respond positively to them. However, only a minority of patients benefit from ICI treatments. OBJECTIVES: Identifying ICI responders before treatment could greatly conserve medical resources, minimize potential drug side effects, and expedite the search for alternative therapies. Our goal is to introduce a novel deep-learning method to predict ICI treatment responses in cancer patients. METHODS: The proposed deep-learning framework leverages graph neural network and biological pathway knowledge. We trained and tested our method using ICI-treated patients' data from several clinical trials covering melanoma, gastric cancer, and bladder cancer. RESULTS: Our results demonstrate that this predictive model outperforms current state-of-the-art methods and tumor microenvironment-based predictors. Additionally, the model quantifies the importance of pathways, pathway interactions, and genes in its predictions. A web server for IRnet has been developed and deployed, providing broad accessibility to users at https://irnet.missouri.edu. CONCLUSION: IRnet is a competitive tool for predicting patient responses to immunotherapy, specifically ICIs. Its interpretability also offers valuable insights into the mechanisms underlying ICI treatments.

A sensitive fluorescence assay of serum dipeptidyl peptidase IV activity to predict the suitability of its inhibitors in patients with type 2 diabetes mellitus.

DPP-IV inhibitors, which are close to the natural hypoglycemic pathway of human physiology and have few side effects, have been extensively employed in the management of type 2 diabetes mellitus (T2DM). However, there are currently no specific blood indicators that can indicate or predict a patient's suitability for DPP-IV inhibitors. In this study, based on the self-developed high-specificity fluorescent substrate glycyl-prolyl-N-butyl-4-amino-1, 8-naphthimide (GP-BAN), a detection method of human serum DPP-IV activity was established and optimized. The method demonstrates a favorable lower limit of detection (LOD) at 0.32 ng/mL and a satisfactory lower limit of quantification (LOQ) of 1.12 ng/mL, and can be used for the detection of DPP-IV activity in trace serum (2 µL). In addition, Vitalliptin and Sitagliptin showed similar IC50 values when human recombinant DPP-IV and human serum were used as enzyme sources, and the intra-day and inter-day precision obtained by the microplate analyzer were less than 15 %. These results indicate that the microplate reader based detection technique has good accuracy, repeatability and reproducibility. A total of 700 volunteers were recruited, and 646 serum samples were tested for DPP-IV activity. The results showed that serum DPP-IV activity was higher in patients with T2DM than in controls (P < 0.01). However, the statistical data of family history of diabetes, gender and age of diabetic patients showed no statistical significance, and there was no contrast difference. The DPP-IV activity of serum in T2DM patients ranged from 2.4 µmol/min/L to 78.6 µmol/min/L, with a huge difference of up to 32-fold. These results suggest that it is necessary to test DPP-IV activity in patients with T2DM when taking DPP-IV inhibitors to determine the applicability of DPP-IV inhibitors in T2DM patients. These results suggest that it is necessary to detect the activity of DPP-IV in blood before taking DPP-IV inhibitors in patients with T2DM to judge the applicability of DPP-IV inhibitors in patients with T2DM.

The impact of alternate-day fasting on the salivary gland stem cell compartments in non-obese diabetic mice with newly established Sjögren's syndrome.

Intermittent fasting exerts a profound beneficial influence on a spectrum of diseases through various mechanisms including regulation of immune responses, elimination of senescent- and pathogenic cells and improvement of stem cell-based tissue regeneration in a disease- and tissue-dependent manner. Our previous study demonstrated that alternate-day fasting (ADF) led to alleviation of xerostomia and sialadenitis in non-obese diabetic (NOD) mice, a well-defined model of Sjögren's syndrome (SS). This present study delved into the previously unexplored impacts of ADF in this disease setting and revealed that ADF increases the proportion of salivary gland stem cells (SGSCs), defined as the EpCAMhi cell population among the lineage marker negative submandibular gland (SMG) cells. Furthermore, ADF downregulated the expression of p16INK4a, a cellular senescence marker, which was concomitant with increased apoptosis and decreased expression and activity of NLRP3 inflammasomes in the SMGs, particularly in the SGSC-residing ductal compartments. RNA-sequencing analysis of purified SGSCs from NOD mice revealed that the significantly downregulated genes by ADF were mainly associated with sugar metabolism, amino acid biosynthetic process and MAPK signaling pathway, whereas the significantly upregulated genes related to fatty acid metabolic processes, among others. Collectively, these findings indicate that ADF increases the SGSC proportion, accompanied by a modulation of the SGSC property and a switch from sugar- to fatty acid-based metabolism. These findings lay the foundation for further investigation into the functionality of SGSCs influenced by ADF and shed light on the cellular and molecular mechanisms by which ADF exerts beneficial actions on salivary gland restoration in SS.

Endovascular treatment of ruptured basilar trunk aneurysms: complications and long-term outcomes.

OBJECT: Treatment of ruptured basilar artery trunk (BAT) aneurysms is challenging, and is associated with high complication and mortality rates. Herein, we analyzed the complications, long-term outcomes, and outcome predictors of endovascular treatment for ruptured BAT aneurysms. METHODS: Between January 2011 and July 2023, 36 patients with 36 ruptured BAT aneurysms underwent endovascular treatment at our institution. The postprocedural complications and clinical and angiographic outcomes were subsequently reviewed, and the risk factors for postprocedural complications were evaluated. RESULTS: All 36 aneurysms in 36 patients were treated successfully. The median clinical follow-up time was 47.0 (IQR: 10.5, 84.5) months. Overall, complications occurred in 10 (27.8%) patients, including 3 (8.3%) deaths. Ischemic events occurred in eight (22.2%) patients, while three (8.3%) patients had shunt-dependent hydrocephalus, of whom one (2.8%) patient had both shunt-dependent hydrocephalus and ischemic events. The cumulative survival rates at 3 and 5 years were 93.9% and 87.6%, respectively. The cumulative 3- and 5-year complication-free survival rates were 75.0% and 70.0%, respectively. Multivariate Cox regression analysis revealed that diabetes mellitus (HR:8.76, 95%CI:2.35-32.69, p=0.001), and Glasgow coma scale score ≤ 12 before the procedure (HR:5.04, 95%CI:1.40-18.12, p=0.013) were associated with overall postprocedural complications. The complete aneurysm occlusion rate was 61.5% at a median angiography follow-up time of 6.0 (IQR: 5.0, 6.0) months. CONCLUSIONS: Endovascular treatment is a safe and feasible option for treating ruptured BAT aneurysms. The rate of favorable outcomes at the final follow-up was satisfactory. However, postprocedural complications, particularly ischemic events, should be carefully considered.

Extracellular vesicle-derived miR-146a as a novel crosstalk mechanism for high-fat induced atherosclerosis by targeting SMAD4.

INTRODUCTION: Exosome-miR-146a is significantly increased in patients with Atherosclerosis (AS), but its mechanism and effect on AS have not been fully elucidated. OBJECTIVES: To explore the change rule and mechanism of exosomes release, and the role and molecular mechanism of exosome-miR-146a in AS. METHODS: We isolated and identified exosomes from THP-1 macrophages after treating them with ox-LDL. Then used co-immunoprecipitation and silver staining to identify the proteins involved in regulating exosome release. PKH67 was used to label exosomes to confirm that cells can absorb them, and then co-culture with HVSMCs for cell proliferation and migration detection. The target genes of miR-146a were screened and identified through bioinformatics and luciferase activity assay, and the expression of miR-146a and related proteins was detected through qRT-PCR and Western blot in HUVECs. An AS model in LDLR-/- mice induced by a high-fat diet was developed to investigate the impact of exosome-miR-146a on AS. RESULTS: The results showed that experimental foam cells from AS showed higher expression of miR-146a. It was observed that NMMHC IIA and HSP70 interacted to regulate the release of exosomes. And HUVECs can absorb exosomes derived from macrophages. In addition, we also found that miR-146a directly targeted the SMAD4 gene to modulate the p38 MAPK signaling pathway, thereby mediating HUVECs damage. Furthermore, exosome-miR-146a induced abnormal proliferation and migration of HVSMCs. The expression of miR-146a was significantly reduced in miR-146a-mimics mice and increased in miR-146a inhibitor mice whereas the inhibition of miR-146a effectively reduced while increasing miR-146a worsened AS in mice. CONCLUSION: Our findings expressed the potential of miR-146a as a favorable therapeutic target for AS, however, further exploration is suggestive for deep understanding of the mechanisms regulating exosome-miR-146a release in vivo and to develop effective therapeutic strategies involving miR-146a.