[The research development of programmed cell death in rheumatoid arthritis].

The etiology of rheumatoid arthritis (RA), a chronic inflammatory systemic disease, remains unclear. It is characterized by symmetrical and invasive joint inflammation, primarily affecting distal small joints such as those in the hands and feet. This inflammation can lead to joint deformity and loss of function, and often accompanied by involvement of extra-articular organs like the lungs and heart. Currently, anti-rheumatic drugs only provide symptom improvement but have toxic side effects that require optimization. Therefore, it is crucial to thoroughly analyze the mechanisms underlying RA development for the identification of new drug targets. Programmed cell death (PCD) has been extensively studied in recent years and proved to be one of the key pathogenic factors in RA. Dysregulation of PCD is particularly evident in synoviocytes, immune cells, and osteocytes. This review summarizes various forms of PCD including apoptosis, NETosis, autophagy, pyroptosis, necroptosis, ferroptosis, cuproptosis, as well as their regulatory roles in fibroblast synoviocytes, immune cells and osteocytes. These findings hold significant theoretical implications for optimizing clinical treatment options for RA and developing new target drugs.

Study of kaempferol in the treatment of rheumatoid arthritis through modulation of the NLRP3/CASP1/GSDMD axis and T-cell activation: Based on network pharmacology, single-cell analysis, and experimental validation.

BACKGROUND: Kaempferol (Kae) is a natural flavonol compound with excellent anti-inflammatory and immunomodulatory effects, which is of great importance in the treatment of inflammatory diseases. The efficacy of Kae in the treatment of rheumatoid arthritis (RA) has been demonstrated. However, its relevant pharmacodynamic mechanism requires further investigation. PURPOSES: This study aimed to further explore the potential mechanism of action of Kae in the treatment of RA using network pharmacology, single-cell analysis, and animal experiments. METHODS: Drug target genes were downloaded and screened from the Comparative Toxicogenomics Database (CTD), SwissTargetPrediction database, BindingDB database, and TargetNet database. Transcriptome data from GEO databases (GSE55235, GSE89408, and GSE200815) were selected for disease transcriptome analysis and single-cell matrix data. Network pharmacology and molecular docking were used to investigate the potential mechanism of action of Kae in treating RA. Single-cell analysis, immune infiltration co-expression analyses, and Mendelian-Randomization (MR) studies were conducted to explore the relationship between Kae's target genes and immune cells. Collagen-induced arthritis (CIA) was induced in DBA/1 mouse models through enhanced immunization. Therapeutic efficacy of Kae was assessed using arthritis score, paw swelling index, body weight monitoring, microCT, hematoxylin and eosin (HE) staining, Safranin O-Fast green staining, and Tartrate-resistant acid phosphatase (TRAP) staining. Tissue immunofluorescence and flow cytometry were used to detect expression levels of key genes and immune cell activation status. RESULTS: In vivo experiments demonstrated the efficacy of Kae in treating CIA mice. Network pharmacology indicated that Kae might exert anti-inflammatory effects through the NLRP3/CASP1/GSDMD axis. Immune infiltration, single-cell, and MR analyses revealed close associations between Kae's target genes and CD4+, CD8+, and regulatory T cells. Kae inhibited cellular pyroptosis in joint tissues and down-regulated NLRP3, CASP1, and GSDMD expression. Flow cytometry results showed decreased CD4/CD8 ratio, reduced proportion of CD4+ effector memory T cells (Tem), and increased naïve and regulatory T cells (Treg). CONCLUSION: Kae might exert anti-inflammatory effects by modulating the NLRP3/CASP1/GSDMD axis to inhibit pyroptosis and suppress overactive immune responses by regulating T-cell proliferation. In summary, Kae demonstrated significant therapeutic efficacy in treating RA.

Dual-functional probe-based multi-signal immunosensor platform for tropane alkaloids: Verification and evaluation.

This study aims to realise rapid detecting of tropane alkaloids (TAs) in food. For this purpose, a broad-spectrum single-chain fragment variable was fused with horseradish peroxidase to create an antibody-enzyme complex (AEC) with antigen recognition and catalytic activity. A multi-signal immunosensor platform based on AEC in the direct competitive reaction mode was constructed using 3,3',5,5'-tetramethylbenzidine and 10-acetyl-3,7-dihydroxyphenoxazine as substrates. The sensitivity of TAs in the immunosensor platform ranged from 0.25 µg/kg to 7912.46 µg/kg. Honey was selected as a representative food sample, and the limit of detection of TAs in honey ranged from 0.02 µg/kg to 409.11 µg/kg, with a recovery rate of 65.7 %-117.1 % and a coefficient of variation less than 21.4 %. Results showed that the immunosensor platform possesses satisfactory accuracy and precision, which highlights its potential for practical applications and its suitability as an ideal tool for rapid screening of TAs in food.

A novel triple-signal biosensor based on ZrFe-MOF@PtNPs for ultrasensitive aflatoxins detection.

The development of more sensitive, stable, and portable biosensors is crucial for meeting the growing demands of diverse and complex detection environments. MOF-based nanozymes have emerged as excellent optical reporters, making them ideal signal donors for constructing multi-signal lateral flow immunoassays (LFIA). In this study, a ZrFe-MOF@PtNPs nanocomposite was synthesized by uniformly depositing platinum nanoparticles (PtNPs) onto the surface of ZrFe-MOFs using an impregnation-reduction method. The ZrFe-MOF@PtNPs exhibited broad absorption spectra, excellent peroxidase-like activity (SA = 21.77 U/mg), high solvent stability, and efficient antibody binding capability. A portable LFIA platform was developed based on ZrFe-MOF@PtNPs and a smartphone for the targeted detection of carcinogenic aflatoxins. This method enabled the readout of colorimetric, fluorescent, and catalytic signals, significantly enhancing detection sensitivity, ensuring result accuracy, and expanding the dynamic detection range. For aflatoxin M1, the calculation of the detection limit of the three signal modes reached as low as 0.0062 ng/mL, which is two orders of magnitude more sensitive than AuNPs-LFIA (0.1839 ng/mL). This study provides effective guidance for multifunctional modification of MOFs and serves as a reference for the application of MOF-based nanozymes in point-of-care biosensors.

Search for Cosmic-Ray Boosted Sub-MeV Dark-Matter-Electron Scattering in PandaX-4T.

We report the first search for the elastic scatterings between cosmic-ray boosted sub-MeV dark matter (DM) and electrons in the PandaX-4T liquid xenon experiment. Sub-MeV DM particles can be accelerated by scattering with electrons in the cosmic rays and produce detectable electron recoil signals in the detector. Using the commissioning data from PandaX-4T of 0.63 tonne·year exposure, we set new constraints on DM-electron scattering cross sections for DM masses ranging from 10 eV/c^{2} to 3 keV/c^{2}.

Brown adipose tissue-derived exosomes improve polycystic ovary syndrome in mice via STAT3/GPX4 signaling pathway.

Polycystic ovary syndrome (PCOS) is associated with impaired adipose tissue physiology. Elevated brown adipose tissue (BAT) mass or activity has shown potential in the treatment of PCOS. In this study, we aimed to investigate whether BAT-derived exosomes (BAT-Exos), as potential biomarkers of BAT activity, exert similar benefits as BAT in the treatment of PCOS. PCOS was induced in female C57BL/6J mice orally administered 1 mg/kg of letrozole for 21 days. Subsequently, the animals underwent transplantation with BAT or administered BAT-Exos (200 µg) isolated from young healthy mice via the tail vein; healthy female mice were used as controls. The results indicate that BAT-Exos treatment significantly reduced body weight and improved insulin resistance in PCOS mice. In addition, BAT-Exos improved ovulation function by reversing the acyclicity of the estrous cycle, decreasing circulating luteinizing hormone and testosterone, recovering ovarian performance, and improving oocyte quality, leading to a higher pregnancy rate and litter size. Furthermore, western blotting revealed reduced expression of signal transducer and activator of transcription 3 (STAT3) and increased expression of glutathione peroxidase 4 (GPX4) in the ovaries of mice in the BAT-Exos group. To further explore the role of the STAT3/GPX4 signaling pathway in PCOS mice, we treated the mice with an intraperitoneal injection of 5 mg/kg stattic, a STAT3 inhibitor. Consistent with BAT-Exos treatment, the administration of stattic rescued letrozole-induced PCOS phenotypes. These findings suggest that BAT-Exos treatment might be a potential therapeutic strategy for PCOS and that the STAT3/GPX4 signaling pathway is a critical therapeutic target for PCOS.

Deep learning based method for predicting DNA N6-methyladenosine sites.

DNA N6 methyladenine (6mA) plays an important role in many biological processes, and accurately identifying its sites helps one to understand its biological effects more comprehensively. Previous traditional experimental methods are very labor-intensive and traditional machine learning methods also seem to be somewhat insufficient as the database of 6mA methylation groups becomes progressively larger, so we propose a deep learning-based method called multi-scale convolutional model based on global response normalization (CG6mA) to solve the prediction problem of 6mA site. This method is tested with other methods on three different kinds of benchmark datasets, and the results show that our model can get more excellent prediction results.

Identification of COL3A1 as a candidate protein involved in the crosstalk between obesity and diarrhea using quantitative proteomics and machine learning.

BACKGROUND: Increasing epidemiologic studies have shown a positive correlation between obesity and chronic diarrhea. Nevertheless, the precise etiology remains uncertain. METHODS: We performed a comprehensive proteomics analysis utilizing the data-independent acquisition (DIA) technique on jejunal tissues from patients with obesity and chronic diarrhea (OD, n = 33), obese patients (OB, n = 10), and healthy controls (n = 8). Differentially expressed proteins (DEPs) in OD vs. control and OD vs. OB comparisons were subjected to pathway enrichment and protein-protein interaction (PPI) network analysis. Machine learning algorithms were adopted on overlapping DEPs in both comparisons. The candidate protein was further validated using Western blot, immunohistochemistry (IHC), and in vitro experiments. RESULTS: We identified 189 and 228 DEPs in OD vs. control and OD vs. OB comparisons, respectively. DEPs in both comparisons were co-enriched in extracellular matrix (ECM) organization. Downregulated DEPs were associated with tight junction and ECM-receptor interaction in OD vs. control and OD vs. OB comparisons, respectively. Machine learning algorithms selected 3 proteins from 14 overlapping DEPs in both comparisons, among which collagen alpha-1(III) chain (COL3A1) was identified as a core protein in PPI networks. Western blot and IHC verified the expression of COL3A1. Moreover, the tight junction-related proteins decreased after the knockdown of COL3A1 in Caco2 intestinal cells upon PA challenge, consistent with the proteomics results. CONCLUSIONS: We generated in-depth profiling of a proteomic dataset from samples of OD patients and provided unique insights into disease pathogenesis. COL3A1 was involved in the crosstalk between obesity and intestinal homeostasis via the ECM-receptor interaction pathway.

Bowel function, quality of life, and mental health of patients with high-grade intraepithelial neoplasia or T1 colorectal cancer after organ-preserving versus organ-resection surgeries: a cross-sectional study at a Chinese tertiary care center.

BACKGROUND: This study aimed to determine the postoperative intestinal functioning, quality of life (QoL), and psychological well-being of patients treated either with organ-preserving surgery (OPS) or organ-resection surgery (ORS) for high-grade intraepithelial neoplasia (HIN) or T1 colorectal cancer (CRC). METHODS: This cross-sectional study was conducted at a single tertiary care center. In total, 175 eligible individuals with T1 CRC or HIN were divided into the OPS (n = 103) or ORS (n = 72) group based on whether the relevant segment of the intestine was preserved or resected. Intestinal function was evaluated using low anterior resection syndrome (LARS) scores. QoL was evaluated using the European Organization for Research and Treatment of Cancer Quality of Life Questionnaire (EORTC-QLQ)-C30 and EORTC-QLQ-CR29. Psychological status was evaluated using the Fear of Progression Questionnaire-Short Form and the Self-rating Anxiety and Depression scales. Propensity score matching (PSM) was used to minimize the influence of potential confounders. RESULTS: Overall, 130 of 175 patients (74.29%) responded to the questionnaires; 56 and 74 were in the ORS and OPS groups, respectively. Thirty-five patient pairs were successfully matched through PSM. The mild and severe LARS rates were significantly higher in the ORS group than in the OPS group (P < 0.001). The EORTC-QLQ-C30 and EORTC-QLQ-CR29 scores revealed significantly better physical, role, and emotional functioning and an overall improved state of health (with multiple reduced symptom scores) in the OPS group than in the ORS group (P < 0.05). Significantly more patients were depressed in the ORS group than in the OPS group (P = 0.034), whereas anxiety or fear of disease progression did not differ significantly between the groups. CONCLUSIONS: OPS for the treatment of HIN or T1 CRC was found to be more advantageous for patients in terms of improved intestinal function, QoL, and psychological status than was ORS.

Mix-VIO: A Visual Inertial Odometry Based on a Hybrid Tracking Strategy.

In this paper, we proposed Mix-VIO, a monocular and binocular visual-inertial odometry, to address the issue where conventional visual front-end tracking often fails under dynamic lighting and image blur conditions. Mix-VIO adopts a hybrid tracking approach, combining traditional handcrafted tracking techniques with Deep Neural Network (DNN)-based feature extraction and matching pipelines. The system employs deep learning methods for rapid feature point detection, while integrating traditional optical flow methods and deep learning-based sparse feature matching methods to enhance front-end tracking performance under rapid camera motion and environmental illumination changes. In the back-end, we utilize sliding window and bundle adjustment (BA) techniques for local map optimization and pose estimation. We conduct extensive experimental validations of the hybrid feature extraction and matching methods, demonstrating the system's capability to maintain optimal tracking results under illumination changes and image blur.

Analysis of Related Factors Influencing Hypertension Classification among Centenarians in Hainan, China.

Background: As a population ages, blood pressure levels gradually increase, leading to a higher incidence of hypertension and increased cardiovascular diseases risk. This study examines factors affecting hypertension grading among centenarians in the Hainan Province. Methods: Data from 2014 to 2016 were accessed from the cross-sectional database "Hypertension Levels and Epidemiological Characteristics of the Elderly and Centenarians in Hainan province of China". This study included 690 centenarians with hypertension. Hypertension grading was the dependent variable, analyzed against independent variables including demographic information (sex, age, ethnicity, education level, marital status, cohabitation, and regional distribution), lifestyle factors (smoking, alcohol consumption, and physical activity), body mass index (BMI), and comorbid conditions (diabetes and hyperlipidemia). Logistic regression models, adjusted for these factors, were used to assess the determinants of hypertension grading among the participants. Results: Multivariate regression analysis, after adjusting for other variables, revealed significant associations between BMI, low-density lipoprotein (LDL) levels, and hypertension grades. Individuals with BMI below 18.5 kg/m 2 had a 0.614-fold lower risk of developing grade III hypertension (odds ratio [OR]: 0.614, 95% confidence interval [CI]: 0.390-0.966, p = 0.0350) and a 0.586-fold lower risk for grade II hypertension (OR: 0.586, 95% CI: 0.402-0.852, p = 0.0052). Furthermore, individuals with elevated LDL levels had a 6.087-fold greater risk of progressing from grade I to grade III hypertension (OR: 6.087, 95% CI: 1.635-22.660, p = 0.0071) and a 4.356-fold greater risk of progressing from grade II to grade III hypertension (OR: 4.356, 95% CI: 1.052-18.033, p = 0.0423). Additionally, individuals of Li ethnicity had 1.823-fold greater risk of progressing from grade I to grade II hypertension compared to those of Han ethnicity (OR: 1.823, 95% CI: 1.033-3.218, p = 0.0383). Conclusions: A BMI below 18.5 kg/m 2 , elevated LDL, and ethnicity emerged the primary factors associated with hypertension grading in centenarians. To reduce the risk of hypertension, it is crucial for centenarians to maintain a healthy weight, normal LDL levels, and adopt dietary habits including a low-cholesterol and low-fat diet.

Factors affecting the diagnostic value of liquid-based cytology by EUS-FNA in the diagnosis of pancreatic cystic neoplasms.

Background and Objectives: This study retrospectively evaluated the value of liquid-based cytology (LBC) alone for diagnosing pancreatic cystic neoplasms (PCNs) in a large sample and initially estimated factors that might affect LBC diagnostic ability. Methods: From April 2015 to October 2022, we prospectively enrolled 331 patients with suspected PCNs in our prospective database. Among them, 112 patients chosen to receive surgical resection were included. Only 96 patients who underwent EUS-guided cystic fluid LBC were finally studied. The diagnostic values of LBC for differentiating benign and malignant PCNs and subtypes of PCNs were evaluated. Results: There were 71 female and 25 male patients with a mean age of 47.6 ± 14.4 years. The median cyst size was 43.4 mm. The diagnostic accuracy, sensitivity, specificity, positive predictive value, and negative predictive value of LBC for the differentiation of benign and malignant PCNs were 96.9%, 57.1%, 100%, 100%, and 96.7%, respectively. The overall diagnostic accuracy of LBC for specific cyst types was 33.3% (32/96). Cysts located in the pancreatic body/tail or with irregular shapes were more likely to obtain a definite LBC diagnosis. At the same time, age, sex, tumor size, cystic fluid viscosity, operation time, needle type, and presence of septation were not significantly different. Conclusion: Liquid-based cytology alone is useful for differentiating benign PCNs from malignant PCNs and can successfully characterize the PCN subtypes in one-third of patients. Pancreatic cystic neoplasms located in the body/tail or exhibiting irregular shapes are more likely to obtain a definite LBC diagnosis.

Study on fluid inclusions and stable isotopics of W-Mo ore deposits in the Ningshan-Zhen'an area, South Qinling, China.

The study of the fluid inclusions of W-Mo deposits in the mineralization area of Ningshan-Zhen'an , Shaanxi Province, China shows that the gas-liquid two-phase inclusions are mainly present in W-Mo deposits, and the ore-forming fluid can be divided into four types: high-temperature type, middle-high-temperature type, middle-temperature type and low-temperature type. The formation depths of the W-Mo mineralization range from 4.2 to 8.4 km. The boiling and mixing of fluid may have been important mechanisms for the formation of W-Mo mineralization. The skarn-type mineralization is dominated by magmatic water, the quartz-vein-type mineralization includes both magmatic water and meteoric water, and the meteoric water is more involved in the quartz-fluorite-vein-type, beryl-quartz-vein-type and pegmatite-type mineralization. Magma is the main source of sulfur; that is, magma is the main source of mineralization. Combined with the metallogenic setting and geological characteristics of typical ore deposits, in the process of structural system transformation in South Qinling, the ore-forming magma fluid in the Late Indosinian-Yanshanian period was uplifted and emplaced along the NW-WNW direction and NE-NNE direction, and eventually, NW-WNW fault-controlled skarn-type W-Mo mineralization and quartz-vein-type W-Mo deposits accompanied by greisenization, albitization and potash feldspathization formed.

Core antibiotic resistance genes mediate gut microbiota to intervene in the treatment of major depressive disorder.

INTRODUCTION: The relationship between depression and gut microbiota remains unclear, but an important role of gut microbiota has been verified. The relationship between gut microbiota and antibiotic resistance genes (ARGs) may be a potential new explanatory pathway. METHODS: We collected samples from 63 depressed patients and 30 healthy controls for metagenomic sequencing. The two groups' microbiota characteristics, functional characteristics, and ARG differences were analyzed. RESULTS: We obtained 30 differential KEGG orthologs (KOs) and their producers in 5 genera and 7 species by HUMAnN3. We found 6 KOs from Weissella_cibaria and Lactobacillus_plantaru are potentially coring functional mechanism of gut microbiota. Different metabolites including sphingolipids, pyrans, prenol lipids, and isoflavonoids also showed significance between MDD and HC. We detected 48 significantly different ARGs: 5 ARGs up-regulated and 43 ARGs down-regulated in MDD compared to HC. Based on Cox model results, Three ARGs significantly affected drug efficacy (ARG29, ARG105, and ARG111). Eggerthella, Weissella, and Lactobacillus were correlated with different core ARGs, which indicated different mechanisms in affecting MDD. LIMITATIONS: The present study needs to be replicated in different ethnic groups. At the same time, a larger Chinese cohort study and detailed experimental verification are also the key to further discussion. CONCLUSION: Our findings suggest that ARGs play a role in the interplay between major depressive disorder and gut microbiota. The role of ARGs should be taken into account when understanding the relationship between depression and gut microbiota.

A new, simplified endoscopic scoring system for predicting clinical outcome in gastric low-grade intraepithelial neoplasia: the "e-cout system".

BACKGROUND AND OBJECTIVES: The clinical outcomes of gastric low-grade intraepithelial neoplasia (LGIN) exhibit significant diversity, and the current reliance on endoscopic biopsy for diagnosis poses limitations in devising appropriate treatment strategies for this disease. This study aims to establish a prognostic prediction scoring system (e-Cout system) for gastric LGIN, offering a theoretical foundation for solving this clinical challenge. METHODS: Retrospectively selecting 1013 cases meeting the inclusion and exclusion criteria from over 300,000 cases of upper gastrointestinal endoscopy performed at the Digestive Endoscopy Center of our hospital between 2000 and 2022, the cohort included 484 cases as development cohort and 529 cases for validation. Employing relevant statistical analysis, we used development cohort data to establish the e-Cout system for gastric LGIN, and further used validation cohort data to for internal validation. RESULTS: In the developmental stage, based on accordant regression coefficients, we assigned point values to six risk factors for poor prognosis: 4 points for microvessel (MV) distortion, 3 points for MV thickening, 2 points for ulcer, and 1 point each for lesion size > 2cm, disease duration > 1 year, and hyperemia and redness on the lesion surface. Patients were then categorized into four risk levels: low risk (0-1 point), medium risk (2-3), high risk (4-6), and very high risk (≥7). During the validation stage, significant differences in the three different outcomes of gastric LGIN were observed across all risk levels. The probability of reversal and progression showed a significant decrease and increase, respectively, with escalating of risk levels, and these differences were statistically significant (P< 0.001). CONCLUSIONS: The proposed e-Cout system holds promise in aiding clinicians to predict the probability and risk levels of different clinical outcomes in patients with gastric LGIN. This system is expected to provide an improved foundation and guidance for the selection of clinical strategies for this disease.

Systematic analysis of levels of evidence supporting Chinese clinical practice guidelines for gastrointestinal disease.

BACKGROUND: Clinical practice guidelines (CPGs) inform healthcare decisions and improve patient care. However, an evaluation of guidelines on gastrointestinal diseases (GIDs) is lacking. This study aimed to systematically analyze the level of evidence (LOE) supporting Chinese CPGs for GIDs. METHODS: CPGs for GIDs were identified by systematically searching major databases. Data on LOEs and classes of recommendations (CORs) were extracted. According to the Grades of Recommendation, Assessment, Development, and Evaluation system, LOEs were categorized as high, moderate, low, or very low, whereas CORs were classified as strong or weak. Statistical analyses were conducted to determine the distribution of LOEs and CORs across different subtopics and assess changes in evidence quality over time. FINDINGS: Only 27.9% of these recommendations were supported by a high LOE, whereas approximately 70% were strong recommendations. There was a significant disparity among different subtopics in the proportion of strong recommendations supported by a high LOE. The number of guidelines has increased in the past 5 years, but there has been a concomitant decline in the proportion of recommendations supported by a high LOE. CONCLUSIONS: There is a general lack of high-quality evidence supporting Chinese CPGs for GIDs, and there are inconsistencies in strong recommendations that have not improved. This study identified areas requiring further research, emphasizing the need to bridge these gaps and promote the conduct of high-quality clinical trials. FUNDING: This study was supported by the National Key R&D Program of China (2022YFC2503604 and 2022YFC2503605) and Special Topics in Military Health Care (22BJZ25).

Transcriptome analysis suggests broad jejunal alterations in Linghu's obesity-diarrhea syndrome: A pilot study.

BACKGROUND: Obesity is associated with a significantly increased risk for chronic diarrhea, which has been proposed as Linghu's obesity-diarrhea syndrome (ODS); however, its molecular mechanisms are largely unknown. AIM: To reveal the transcriptomic changes in the jejunum involved in ODS. METHODS: In a cohort of 6 ODS patients (JOD group), 6 obese people without diarrhea (JO group), and 6 healthy controls (JC group), high-throughput sequencing and bioinformatics analyses were performed to identify jejunal mucosal mRNA expression alterations and dysfunctional biological processes. In another cohort of 16 ODS patients (SOD group), 16 obese people without diarrhea (SO group), and 16 healthy controls (SC group), serum diamine oxidase (DAO) and D-lactate (D-LA) concentrations were detected to assess changes in intestinal barrier function. RESULTS: The gene expression profiles of jejunal mucosa in the JO and JC groups were similar, with only 1 differentially expressed gene (DEG). The gene expression profile of the JOD group was significantly changed, with 411 DEGs compared with the JO group and 211 DEGs compared with the JC group, 129 of which overlapped. The enrichment analysis of these DEGs showed that the biological processes such as digestion, absorption, and transport of nutrients (especially lipids) tended to be up-regulated in the JOD group, while the biological processes such as rRNA processing, mitochondrial translation, antimicrobial humoral response, DNA replication, and DNA repair tended to be down-regulated in the JOD group. Eight DEGs (CDT1, NHP2, EXOSC5, EPN3, NME1, REG3A, PLA2G2A, and PRSS2) may play a key regulatory role in the pathological process of ODS, and their expression levels were significantly decreased in ODS patients (P < 0.001). In the second cohort, compared with healthy controls, the levels of serum intestinal barrier function markers (DAO and D-LA) were significantly increased in all obese individuals (P < 0.01), but were higher in the SOD group than in the SO group (P < 0.001). CONCLUSION: Compared with healthy controls and obese individuals without diarrhea, patients with Linghu's ODS had extensive transcriptomic changes in the jejunal mucosa, likely affecting intestinal barrier function and thus contributing to the obesity and chronic diarrhea phenotypes.

The relationship of peripheral blood cell inflammatory biomarkers and psychological stress in unmedicated major depressive disorder.

BACKGROUND: Recent research has explored the linkage between major depressive disorder (MDD) and inflammation, especially via altered peripheral blood immune markers. However, the relationship between several novel leukocyte-derived ratios (LDR) and psychological stress in MDD remains uncertain. This study aimed to explore the relationship between LDR, clinical characteristics, recent life events, and childhood maltreatment in MDD patients. METHODS: A cross-sectional case-control study was conducted involving 59 healthy controls (HC) and 50 unmedicated MDD patients. Subjects underwent psychological assessments and peripheral blood measurements. LDR assessed in this study included neutrophil-to-lymphocyte ratio (NLR), derived NLR (dNLR), monocyte-to-lymphocyte ratio (MLR), platelet-to-lymphocyte ratio (PLR), white blood cell-to-mean platelet volume ratio (WMR), systemic immune inflammation index (SII), multiplication of neutrophil and monocyte counts (MNM), and systemic inflammation response index (SIRI). RESULTS: MDD patients displayed significant alterations in WMR, PLR, and MNM compared to HC, as well as correlations between several LDR and various clinical features (duration of untreated psychosis and dNLR, the nine-item Patient Health Questionnaire and PLR, the 7-item Generalized Anxiety Disorder Questionnaire and SIRI (NLR and dNLR). There was a significant difference in the comparison of WMR in first-episode patients than in recurrent patients. Analyses further revealed an association between Life Event Scale total scores and NLR (dNLR). No correlation was found between Childhood Trauma Questionnaire total (or subscale) scores and LDR. Additionally, WMR and dNLR presented potential predictive value for distinguishing between MDD and HC. CONCLUSION: The study concludes that MDD and some clinical features are associated with alterations in some peripheral blood LDR. These findings emphasize the potential role of peripheral blood LDR in the pathogenesis and clinical heterogeneity of MDD.

Effect of Inconel 718 Filler on the Microstructure and Mechanical Properties of Inconel 690 Joint by Ultrasonic Frequency Pulse Assisted TIG Welding.

Ultrasonic frequency pulse assisted TIG welding (UFP-TIG) experiments were conducted to join Inconel 690 alloy (IN690) by adding Inconel 718 alloy (IN718) as the filler. The effect of the filler on the microstructure, mechanical properties, and ductility dip cracking (DDC) susceptibility of IN690 joints were investigated. The results show that a variety of precipitates, including MC-type carbide and Laves phases, are formed in the weld zone (WZ), which are uniformly dispersed in the interdendritic region and grain boundaries (GBs). The increase in the thickness of the IN718 filler facilitates the precipitation and growth of Laves phases and MC carbides. However, the formation of Laves phases in the WZ exhibits a lower bonding force with the matrix and deteriorates the tensile strength of IN690 joints. Due to the moderate content of Laves phases in the WZ, the IN690 joint with 1.0 mm filler reaches the maximum tensile strength (627 MPa), which is about 96.5% of that of the base metal (BM). The joint with 1.0 mm filler also achieves the highest elongation (35.4%). In addition, the strain-to-fracture tests indicate that the total length of cracks in the joint with the IN718 filler decreases by 66.49% under a 3.8% strain. As a result, the addition of the IN718 filler significantly improves the mechanical properties and DDC resistance of IN690 joints.