Comparative secretome analysis reveals cross-talk between type III secretion system and flagella assembly in Pseudomonas plecoglossicida.

The Gram-negative bacterium Pseudomonas plecoglossicida has caused visceral granulomas disease in several farmed fish species, including large yellow croaker (Larimichthys crocea), which results in severe economic losses. Type III secretion systems (T3SS) are protein secretion and translocation nanomachines widely employed by many Gram-negative bacterial pathogens for infection and pathogenicity. However, the exact role of T3SS in the pathogenesis of P. plecoglossicida infection is still unclear. In this study, a T3SS translocators deletion strain (△popBD) of P. plecoglossicida was constructed to investigate the function of T3SS. Then comparative secretome analysis of the P. plecoglossicida wild-type (WT) and △popBD mutant strains was conducted by label-free quantitation (LFQ) mass spectrometry. The results show that knockout of T3SS translocators popB and popD has an adverse effect on the effector protein ExoU secretion, flagella assembly, and biofilm formation. Further experimental validations also confirmed that popB-popD deletion could affect the P. plecoglossicida flagella morphology/formation, adherence, mobility, and biofilm formation. These data indicate that a cross-talk exists between the P. plecoglossicida T3SS and the flagella system. Our results, therefore, will facilitate the further under-standing of the pathogenic mechanisms leading to visceral granulomas disease caused by P. plecoglossicida.

Histologic image-based ensemble model to identify myenteric plexitis and predict endoscopic postoperative recurrence in Crohn's disease: a multicentre, retrospective study.

BACKGROUND AND AIM: Myenteric plexitis is correlated with postoperative recurrence of Crohn's disease when relying on traditional statistical methods. However, comprehensive assessment of the myenteric plexus remains challenging. This study aimed to develop and validate a deep learning system to predict postoperative recurrence through automatic screening and identification of features of the muscular layer and myenteric plexus. METHODS: In this study, we retrospectively reviewed 205 patients who underwent bowel resection surgery from 2 hospitals. Patients were divided into a training cohort (n=108), an internal validation cohort (n=47) and an external validation cohort (n=50). A total of 190960 patches from 278 whole-slide images of surgical specimens were analysed using ResNet50, and 6144 features were extracted after transfer learning. We used five robust algorithms to construct classification models. The performances of the models were evaluated by the area under the receiver operating characteristic curve in three cohorts. RESULTS: The stacking model achieved satisfactory accuracy in predicting postoperative recurrence of CD in the training cohort (AUC: 0.980; 95% CI 0.960-0.999), internal validation cohort (AUC: 0.908; 95% CI 0.823-0.992), and external validation cohort (AUC: 0.868; 95% CI 0.761-0.975). The accuracy for identifying the severity of myenteric plexitis was 0.833, 0.745, and 0.694 in the training cohort, internal validation cohort and external validation cohort, respectively. CONCLUSIONS: Our work initially established an interpretable stacking model based on muscular layer and myenteric plexus features extracted from histologic images to identify the severity of myenteric plexitis and predict postoperative recurrence of CD.

Roquin-1 resolves sepsis-associated acute liver injury by regulating inflammatory profiles via miRNA cargo in extracellular vesicles.

Sepsis-associated acute liver injury (SALI) is an independent risk for sepsis-induced death orchestrated by innate and adaptive immune responses. Here, we found that Roquin-1 was decreased during SALI and expressed mainly in monocyte-derived macrophages. Meanwhile, Roquin-1 was correlated with the inflammatory profiles in humans and mice. Mechanically, Roquin-1 in macrophages promoted Ago2-K258-ubiquitination and inhibited Ago2-S387/S828-phosphorylation. Ago2-S387-phosphorylation inhibited Ago2-miRNA's complex location in multivesicular bodies and sorting in macrophages-derived extracellular vesicles (MDEVs), while Ago2-S828-phosphorylation modulated the binding between Ago2 and miRNAs by special miRNAs-motifs. Then, the anti-inflammatory miRNAs in MDEVs decreased TSC22D2 expression directly, upregulated Tregs-differentiation via TSC22D2-STAT3 signaling, and inhibited M1-macrophage-polarization by TSC22D2-AMPKα-mTOR pathway. Furthermore, WT MDEVs in mice alleviated SALI by increasing Tregs ratio and decreasing M1-macrophage frequency synchronously. Our study showed that Roquin-1 in macrophages increased Tregs-differentiation and decreased M1-macrophage-polarization simultaneously via miRNA in MDEVs, suggesting Roquin-1 can be used as a potential tool for SALI treatment and MDEVs engineering.

The Role of Extracellular Vesicles in Colorectal Cancer.

Extracellular vesicles (EVs) are a class of spherical vesicles that are produced by active secretion of cells and encapsulated by phospholipid bilayers. In recent years, numerous studies have shown that EVs play pivotal roles in the regulation of intercellular communication between colorectal cancer (CRC) cells and target cells, and can regulate the proliferation, metastasis, and infiltration of tumor cells by regulating the microenvironment of tumor cells. EVs carry specific molecular substances in source CRC cells and are expected to serve as new molecular markers for the detection of cancers. This review highlights the current state of research and progress of potentially incorporating EVs in the diagnosis and treatment of CRC.

Altered fecal microbiome and metabolome profiles in rat models of short bowel syndrome.

Introduction: Short bowel syndrome (SBS) is featured by impaired nutrients and fluids absorption due to massive small intestine resection. Gut dysbiosis has been implicated in SBS, this study aimed to characterize the metagenomic and metabolomic profiles of SBS and identify potential therapeutic targets. Methods: Fecal samples from SBS and Sham rats (n = 8 per group) were collected for high-throughput metagenomic sequencing. Fecal metabolomics was measured by untargeted liquid chromatography-mass spectrometry. Results: We found that the species-level α-diversity significantly decreased in SBS rats, accompanied by altered microbiome compositions. The beneficial anaerobes from Firmicutes and Bacteroidetes were depleted while microorganisms from Lactobacillus, Escherichia, Enterococcus, and Streptococcus were enriched in faces from SBS rats. LEfSe analysis identified 17 microbial species and 38 KEGG modules that were remarkably distinct between SBS and Sham rats. In total, 1,577 metabolites with known chemical identity were detected from all samples, among them, 276 metabolites were down-regulated and 224 metabolites were up-regulated in SBS group. The typical signatures of SBS fecal metabolome comprised reduced short-chain fatty acids and products of amino acid metabolism (indole derivatives and p-cresol), as well as altered bile acid spectrum. We revealed 215 robust associations between representative differentially abundant microbial species and metabolites, the species with the same changing trend tended to have a similar correlation with some certain metabolites. Conclusion: The fecal microbiome and metabolome significantly altered in SBS. Our findings may lay the foundation for developing new strategies to facilitate intestinal adaptation in SBS patients.

Non-linear association of atherogenic index of plasma with insulin resistance and type 2 diabetes: a cross-sectional study.

BACKGROUND: Although there is numerous evidence on the epidemiological risk factors for insulin resistance (IR)-related metabolic diseases, there is still insufficient evidence to explore the non-linear association of Atherogenic Index of Plasma (AIP) with IR. Therefore, we aimed to elucidate the non-linear relationship between AIP and IR and type 2 diabetes (T2D). METHODS: This cross-sectional study was conducted in the National Health and Nutrition Survey (NHANES) from 2009 to 2018. A total of 9,245 participants were included in the study. The AIP was calculated as log10 (triglycerides/high-density lipoprotein cholesterol). The outcome variables included IR and T2D defined by the 2013 American Diabetes Association guidelines. The weighted multivariate linear regression, weighted multivariate logistic regression, subgroup analysis, generalized additive model, smooth fitting curve and two-part logistic regression were adopted to reveal the relationship of AIP with IR and T2D. RESULTS: After adjustment for age, gender, race, education level, smoking status, alcohol consumption, vigorous/moderate physical activity, body mass index, waist circumference and hypertension, we found that AIP was positively associated with fasting blood glucose (ß = 0.08, 95% CI: 0.06, 0.10), glycosylated hemoglobin (ß = 0.04, 95% CI: 0.39, 0.58), fasting serum insulin (ß = 4.26, 95% CI: 3.73, 4.79), and homeostasis model assessment of insulin resistance (ß = 0.22, 95% CI: 0.18, 0.25). Further studies found that AIP was associated with increased risk of IR (OR = 1.29, 95% CI: 1.26-1.32) and T2D (OR = 1.18, 95% CI: 1.15-1.22). However, the positive association between AIP and IR or T2D was more significant in female than in male (IR: P for interaction = 0.0135; T2D: P for interaction = 0.0024). A non-linear and inverse L-shaped association was found between AIP and IR, while a J-shaped association was found between AIP and T2D. In patients with - 0.47 < AIP < 0.45, increased AIP was significantly associated with increased risk of IR and T2D. CONCLUSIONS: AIP showed an inverse L-shaped association with IR and a J-shaped association with T2D, indicating that AIP should be reduced to a certain level to prevent IR and T2D.

Passivation Effect of the Chlorinated Paraffin Added in the Cutting Fluid on the Surface Corrosion Resistance of the Stainless Steel.

Cutting fluids are the most effective method to lower the cutting temperature and decrease the cutting tool wear. At the same time, the cutting fluids influence the corrosion resistance property of the machined surface. In this study, chlorinated paraffin (CP), which is a common additive in the cutting fluid, was selected as the research objective to study its corrosion resistance property. The passivation effect of CP with different concentrations on the machined surface of stainless steel was studied. Electrochemical measurements and surface morphology investigation were used to characterize the passivation effect of CP with different concentrations. The test results showed that the corrosion resistance of stainless steel in the cutting fluid was enhanced with the increase in CP additive. This reason is that the charge transfer resistance increases and the corrosion current density decreases with the increase in CP additive. The X-ray photoelectron spectroscopy (XPS) results show that the proportion of metal oxides on the processed surface of the stainless steel sample was increased from 20.4% to 22.0%, 32.9%, 26.6%, and 31.1% after adding 1 mL, 2 mL, 4 mL and 6 mL CP in the cutting fluid with a total volume of 500 mL, respectively. The oxidation reaction between CP and the stainless steel sample resulted in an increase in metal oxides proportion, which prevented the stainless steel sample from corrosion in cutting fluid.

Investigation of trends in gut microbiome associated with colorectal cancer using machine learning.

Background: The rapid growth of publications on the gut microbiome and colorectal cancer (CRC) makes it feasible for text mining and bibliometric analysis. Methods: Publications were retrieved from the Web of Science. Bioinformatics analysis was performed, and a machine learning-based Latent Dirichlet Allocation (LDA) model was used to identify the subfield research topics. Results: A total of 5,696 publications related to the gut microbiome and CRC were retrieved from the Web of Science Core Collection from 2000 to 2022. China and the USA were the most productive countries. The top 25 references, institutions, and authors with the strongest citation bursts were identified. Abstracts from all 5,696 publications were extracted for a text mining analysis that identified the top 50 topics in this field with increasing interest. The colitis animal model, expression of cytokines, microbiome sequencing and 16s, microbiome composition and dysbiosis, and cell growth inhibition were increasingly noticed during the last two years. The 50 most intensively investigated topics were identified and further categorized into four clusters, including "microbiome sequencing and tumor," "microbiome compositions, interactions, and treatment," "microbiome molecular features and mechanisms," and "microbiome and metabolism." Conclusion: This bibliometric analysis explores the historical research tendencies in the gut microbiome and CRC and identifies specific topics of increasing interest. The developmental trajectory, along with the noticeable research topics characterized by this analysis, will contribute to the future direction of research in CRC and its clinical translation.

A LASSO-based model to predict central lymph node metastasis in preoperative patients with cN0 papillary thyroid cancer.

Introduction: Central lymph node metastasis (CLNM) is common in papillary thyroid carcinoma (PTC). Prophylactic central lymph node dissection (PCLND) in clinically negative central compartment lymph node (cN0) PTC patients is still controversial. How to predict CLNM before the operation is very important for surgical decision making. Methods: In this article, we retrospectively enrolled 243 cN0 PTC patients and gathered data including clinical characteristics, ultrasound (US) characteristics, pathological results of fine-needle aspiration (FNA), thyroid function, eight gene mutations, and immunoenzymatic results. Least absolute shrinkage and selection operator (LASSO) analysis was used for data dimensionality reduction and feature analysis. Results: According to the results, the important predictors of CLNM were identified. Multivariable logistic regression analysis was used to establish a new nomogram prediction model. The receiver operating characteristic (ROC) curve, calibration curve, and decision curve analysis (DCA) curve were used to evaluate the performance of the new prediction model. Discussion: The new nomogram prediction model was a reasonable and reliable model for predicting CLNM in cN0 PTC patients, but further validation is warranted.

Earlier anti-TNF therapy reduces the risk of malnutrition associated with alterations in body composition in patients with Crohn's disease.

Background: Anti-TNF therapy has been found to exert an influence on long-term nutritional status and even reverse malnutrition in patients with Crohn's disease. Aims: to observe the effect of anti-TNF therapy on nutritional status in patients with Crohn's disease, investigate the correlation between the timing of anti-TNF therapy and the human body composition and examine independent body composition factors for predicting malnutrition in these patients. Methods: This was a retrospective study of 115 patients with Crohn's disease. Body composition parameters were assessed by bioelectrical impedance analysis. The nutritional status of the patients was determined by NRS2002 and MNA. Results: The BMI, BFMI, FFMI, BCMI, SMI, BMC, intracellular water, protein and BMR were significantly lower in patients without any biologic agents (p < 0.05). Negative correlations were found between BMC, intracellular water, extracellular water, protein and BMR and the interval between the first symptom and first dose by Spearman's correlation analysis (r < 0, p < 0.05). Low BMI (OR 0.602, 95% CI 0.434-0.836, p = 0.002), low FFMI (OR 0.678, 95% CI 0.507-0.906, p = 0.009), and low BCMI (OR 0.564, 95% CI 0.367-0.868, p = 0.009) were independent risk factors for malnutrition in Crohn's disease patients. Anti-TNF therapy tended to reduce the malnutrition probability as assessed by Cox regression analysis (OR: 0.217, 95% CI 0.057-0.821, p = 0.024). Conclusion: Body composition analysis is predictive of malnutrition in patients with Crohn's disease. Early application of anti-TNF therapy significantly affected skeletal muscle mass, fat mass and bone mineral content, supporting their long-term nutritional status and reducing their probability of malnutrition.

Pathological Nodal Staging Score for Gastric Signet Ring Cell Carcinoma: A Clinical Tool of Adequate Nodal Staging.

Background: Gastric signet ring cell carcinoma (GSRCC) is a subset of gastric cancer with distinct histological and inconsistent prognosis outcome. Currently, the association between the adequate regional lymph node and proper nodal staging in GSRCC is rarely noticed. Materials and methods: Clinical data of GSRCC were retrieved from the Surveillance, Epidemiology, and End Results database. Beta-binomial distribution model was employed for the estimation of the probability of missing nodal disease, followed by the development of a nodal staging score (NSS). Results: A total of 561 GSRCC patients were included in this study, with 193 in lymph node-negative and 368 in lymph node-positive diagnoses. As the number of examined lymph nodes increased, the probability of missing nodal disease decreased rapidly, with T stage-specific curves. The probability of missing nodal disease in T4 was lower than that in T1. NSS calculation indicated that T1 stage patients commonly had NSS > 0.8. However, with the NSS of T2−T4 to reach 0.8, the number of examined lymph node was required to be larger than 12 in T2, 17 in T3 and 27 in T4. NSS ≥ 0.75 (quantile 75%) subgroup in T2−T4 subgroups tended to have better outcome; however, without significant prognostic value. Conclusions: NSS is served as a reliable and feasible tool in adequate nodal staging of GSRCC with statistical basis and provides further evidence for clinical decision making.

Landscape of Artificial Intelligence in Breast Cancer (2000-2021): A Bibliometric Analysis.

BACKGROUND: Breast cancer remains one of the leading malignancies in women with distinct clinical heterogeneity and intense multidisciplinary cooperation. Remarkable progresses have been made in artificial intelligence (AI). A bibliometric analysis was taken to characterize the current picture of development of AI in breast cancer. MATERIALS AND METHODS: Search process was performed in the Web of Science Core Collection database with analysis and visualization performed by R software, VOSviewer, CiteSpace and Gephi. Latent Dirichlet Allocation (LDA), a machine learning based algorithm, was used for analysis of topic terms. RESULTS: A total of 511 publications in the field of AI in breast cancer were retrieved between 2000 to 2021. A total of 103 publications were from USA with 2482 citations, making USA the leading country in the field of AI in breast cancer, followed by China. Mem Sloan Kettering Canc Ctr, Radboud Univ Nijmegen, Peking Univ, Sichuan Univ, ScreenPoint Med BV, Lund Univ, Duke Univ, Univ Chicago, Harvard Med Sch and Univ Texas MD Anderson Canc Ctr were the leading institutions in the field of AI in breast cancer. AI, breast cancer and classification, mammography were the leading keywords. LDA topic modeling identified top fifty topics relating the AI in breast cancer. A total of five primary clusters were found within the network of fifty topics, including radiology feature, lymph node diagnosis and model, pathological tissue and image, dataset classification and machine learning, gene expression and survival. CONCLUSIONS: This research depicted AI studies in breast cancer and presented insightful topic terms with future perspective.

Elastocaloric determination of the phase diagram of Sr2RuO4.

One of the main developments in unconventional superconductivity in the past two decades has been the discovery that most unconventional superconductors form phase diagrams that also contain other strongly correlated states. Many systems of interest are therefore close to more than one instability, and tuning between the resultant ordered phases is the subject of intense research1. In recent years, uniaxial pressure applied using piezoelectric-based devices has been shown to be a particularly versatile new method of tuning2,3, leading to experiments that have advanced our understanding of the fascinating unconventional superconductor Sr2RuO4 (refs. 4-9). Here we map out its phase diagram using high-precision measurements of the elastocaloric effect in what we believe to be the first such study including both the normal and the superconducting states. We observe a strong entropy quench on entering the superconducting state, in excellent agreement with a model calculation for pairing at the Van Hove point, and obtain a quantitative estimate of the entropy change associated with entry to a magnetic state that is observed in proximity to the superconductivity. The phase diagram is intriguing both for its similarity to those seen in other families of unconventional superconductors and for extra features unique, so far, to Sr2RuO4.

Preoperative Anti-TNF Therapy is Associated with a Shorter Length of Resected Bowel in Patients Undergoing Ileocolic Resection for Crohn's Disease.

BACKGROUND: Massive or repeated intestinal resections for Crohn's disease (CD) could lead to disabling consequences. The present study aimed to assess the effect of preoperative anti-TNF therapy on the length of resected bowel and identify risk factors for postoperative morbidity following ileocolic resection for CD. METHODS: Patients undergoing elective ileocolic resection for CD were included prospectively. Medical variables including demographics, Montréal classification, preoperative treatment, surgical details and 30-day postoperative morbidity were collected. Potential impact of preoperative anti-TNF treatment on length of ileocolic specimen and risk factors for postoperative morbidity were investigated. RESULTS: One hundred and eight-four patients were included in this study, and 66 (35.9%) of them received anti-TNF agents within 8 weeks prior to surgery. Primary anastomosis was performed in 145 patients (78.8%). The mean length of resected intestine was 10 cm shorter in subjects receiving preoperative anti-TNF treatment than those without preoperative anti-TNF therapy (P < 0.001). The rates of postoperative overall, infectious and intra-abdominal septic morbidity were 29.9%, 19.0% and 7.6%, respectively. In multivariate analysis, anti-TNF therapy < 8 weeks before surgery was independently associated with a shorter length of resected bowel but didn't increase overall and septic complications, while systemic steroids use within 8 weeks prior to surgery independently increased overall complications and intra-abdominal sepsis. CONCLUSIONS: Preoperative anti-TNF therapy was associated with a shorter length of resected bowel but not the overall and septic postoperative complications in ileocolic resection for CD. Weaning off systemic steroids before surgery may improve postoperative outcomes in patients with CD.

Review article: insights into the bile acid-gut microbiota axis in intestinal failure-associated liver disease-redefining the treatment approach.

BACKGROUND: Intestinal failure-associated liver disease (IFALD) increases mortality of patients with intestinal failure (IF), but lacks effective prevention or treatment approaches. Bile acids, gut microbiota and the host have close and complex interactions, which play a central role in modulating host immune and metabolic homeostasis. Increasing evidence suggests that derangement of the bile acid-gut microbiota (BA-GM) axis contributes to the development of IFALD. AIMS: To review the BA-GM axis in the pathogenesis and clinical applications of IFALD, and to explore future directions for effective disease management. METHODS: We conducted a literature search on bile acid and gut microbiota in IF and liver diseases. RESULTS: The BA-GM axis demonstrates a unique IF signature manifesting as an increase in primary-to-secondary bile acids ratio, disturbed enterohepatic circulation, blunted bile acid signalling pathways, gut microbial dysbiosis, and altered microbial metabolic outputs. Bile acids and gut microbiota shape the compositional and functional alterations of each other in IF; collaboratively, they promote immune dysfunction and metabolic aberration in the liver. Diagnostic markers and treatments targeting the BA-GM axis showed promising potential in the management of IFALD. CONCLUSIONS: Bile acids and gut microbiota play a central role in the development of IFALD and make attractive biomarkers as well as therapeutic targets. A multitarget, individualised therapy aiming at different parts of the BA-GM axis may provide optimal clinical benefits and requires future investigation.

Bloodstream Infection in Patients With Intestinal Fistula: A Retrospective Study.

BACKGROUND: To delineate the clinical characteristics of intestinal fistula patients with Bloodstream infection (BSI). METHODS: Retrospective case series in Surgical Intensive Care Unit (SICU), Shanghai Ninth People's Hospital, Shanghai JiaoTong University School of Medicine, Shanghai, China. Among a cohort of 204 patients with a diagnosis of intestinal fistula, 46 who were complicated with BSI were analysed retrospectively. Data was collected from January 1, 2018 to February 1, 2020. RESULTS: Among the 204 patients with intestinal fistula, 46 patients showed positive blood cultures, which clearly had BSIs. Parenteral nutrition (PN) time (OR 1.08, 95% CI 1.04∼1.12, P < 0.01), transferred from external ICU (OR 3.68, 95% CI 1.48∼9.17, P = 0.01), septic shock (OR 4.61, 95% CI 1.77∼11.97, P < 0.01), APACHE II (OR 1.11, 95% CI 1.01∼1.22, P = 0.04) were significantly associated with BSI in patients with intestinal fistula. When APACHE II score exceeds 12.0 points or PN time exceeds 18.0 D, the chance of BSI in patients with intestinal fistula increases significantly. In addition, compared with the non-BSI group, BSI group had a higher mortality and expenses in ICU, longer stay in ICU and total hospital stay, and worse quality of life (all P < 0.05). A total of 105 isolates from samples (including sputum, pus and blood) of 46 patients in the BSI group, among which were mainly gram negative rods and fungi, as well as blood isolates. Importantly, in patients with intestinal fistula, BSIs caused by fungi accounted for 23.4%. CONCLUSION: Long-term PN, transfer from external ICU, septic shock, and higher APACHE II scores are often associated with an increased probability of BSIs in patients with intestinal fistula and a higher mortality. Gram-negative bacteria are the main pathogenic bacteria in intestinal fistula patients with BSI, and patients with intestinal fistula are more likely to develop fungal BSIs.

MiR-125-5p/IL-6R axis regulates macrophage inflammatory response and intestinal epithelial cell apoptosis in ulcerative colitis through JAK1/STAT3 and NF-κB pathway.

This study explored the effects of miR-125-5p and interleukin-6 receptor (IL-6 R) on ulcerative colitis (UC) cell models and mouse models. The sera derived from UC patients and healthy subjects were collected for expression analysis. UC in vitro models and in vivo model were constructed and used. Expressions of miR-125-5p, IL-6 R, AK1/STAT3 and NF-κB pathways, and inflammatory factors, histopathology and apoptosis were determined by conducting a series of molecular experiments. The relationship between miR-125-5p and IL-6 R was analyzed by TargetScan7.2 and verified by dual-luciferase assay. The disease activity index (DAI) score, weight change, and colon length of the mice were recorded and analyzed. Decreased expression of miR-125-5p in the sera of UC patients was related to the increased expression of its target gene IL-6 R. In vitro, up-regulation of miR-125-5p decreased IL-6 R expression, contents of inflammatory factors in THP-1 cells and cell apoptosis of NCM460, and inhibited the activation of JAK1/STAT3 and NF-κB pathway. However, down-regulation of miR-125-5p produced the opposite effects to its up-regulation. IL-6 R overexpression partially reversed the effects of miR-125-5p up-regulation on UC cell models. In vivo, miR-125-5p overexpression significantly improved the severity of colitis, including DAI score, colon length, tissue damage, apoptosis, and inflammatory response, in the mice in the UC group. In addition, miR-125-5p up-regulation significantly reduced the expression of IL-6 R in the UC mice, and reduced the expression levels of JAK1, STAT3 and p65 phosphorylation. MiR-125-5p targeting IL-6 R regulates macrophage inflammatory response and intestinal epithelial cell apoptosis in ulcerative colitis through JAK1/STAT3 and NF-κB pathway.

High-sensitivity heat-capacity measurements on Sr2RuO4 under uniaxial pressure.

A key question regarding the unconventional superconductivity of [Formula: see text] remains whether the order parameter is single- or two-component. Under a hypothesis of two-component superconductivity, uniaxial pressure is expected to lift their degeneracy, resulting in a split transition. The most direct and fundamental probe of a split transition is heat capacity. Here, we report measurement of heat capacity of samples subject to large and highly homogeneous uniaxial pressure. We place an upper limit on the heat-capacity signature of any second transition of a few percent of that of the primary superconducting transition. The normalized jump in heat capacity, [Formula: see text], grows smoothly as a function of uniaxial pressure, favoring order parameters which are allowed to maximize in the same part of the Brillouin zone as the well-studied van Hove singularity. Thanks to the high precision of our measurements, these findings place stringent constraints on theories of the superconductivity of [Formula: see text].

Sphingosine kinase 1 regulates HMGB1 translocation by directly interacting with calcium/calmodulin protein kinase II-δ in sepsis-associated liver injury.

Previously, we confirmed that sphingosine kinase 1 (SphK1) inhibition improves sepsis-associated liver injury. High-mobility group box 1 (HMGB1) translocation participates in the development of acute liver failure. However, little information is available on the association between SphK1 and HMGB1 translocation during sepsis-associated liver injury. In the present study, we aimed to explore the effect of SphK1 inhibition on HMGB1 translocation and the underlying mechanism during sepsis-associated liver injury. Primary Kupffer cells and hepatocytes were isolated from SD rats. The rat model of sepsis-associated liver damage was induced by intraperitoneal injection with lipopolysaccharide (LPS). We confirmed that Kupffer cells were the cells primarily secreting HMGB1 in the liver after LPS stimulation. LPS-mediated HMGB1 expression, intracellular translocation, and acetylation were dramatically decreased by SphK1 inhibition. Nuclear histone deacetyltransferase 4 (HDAC4) translocation and E1A-associated protein p300 (p300) expression regulating the acetylation of HMGB1 were also suppressed by SphK1 inhibition. HDAC4 intracellular translocation has been reported to be controlled by the phosphorylation of HDAC4. The phosphorylation of HDAC4 is modulated by CaMKII-δ. However, these changes were completely blocked by SphK1 inhibition. Additionally, by performing coimmunoprecipitation and pull-down assays, we revealed that SphK1 can directly interact with CaMKII-δ. The colocalization of SphK1 and CaMKII-δ was verified in human liver tissues with sepsis-associated liver injury. In conclusion, SphK1 inhibition diminishes HMGB1 intracellular translocation in sepsis-associated liver injury. The mechanism is associated with the direct interaction of SphK1 and CaMKII-δ.

Previous Intestinal Resection Is Associated with Postoperative Complications in Crohn's Disease: A Cohort Study.

BACKGROUND: To assess the influence of a previous intestinal resection on postoperative complications for Crohn's disease (CD). METHODS: Data on patients with CD undergoing surgery in our department from January 2016 through December 2019 were retrospectively reviewed. Information collected included demographic details, surgical data, and postoperative outcome. A cross-sectional study design was employed. Associations between postoperative complications and preoperative clinical indicators were further analyzed. RESULTS: Of the 129 patients with CD studied, 62 patients (48.06%) underwent previous resection. These patients were more likely to be older (P = 0.031), have longer disease duration (P = 0.025), use less 5-aminosalicylic acid/sulfasalazine preoperatively (P = 0.013), have lower body mass index (P = 0.003), and have a higher American Society of Anesthesiologists (ASA) Physical Status Classification System score (P = 0.043). Patients who had previous surgery had a longer duration of operation (P = 0.003), greater estimated blood loss (P = 0.001), and longer hospital stay (P < 0.001) and were more inclined to develop postoperative complications (P = 0.047), particularly anastomotic leak (P = 0.021) and severe (Clavien-Dindo grade III/IV) complications (P = 0.038). After multivariate analysis, previous intestinal resection (P = 0.019), preoperative use of steroids (P = 0.026), and ASA score of more than II (P < 0.001) were determined to be the independent prognostic risk factors for postoperative complications. During the 30-day follow-up period, there was no postoperative mortality or readmission. CONCLUSIONS: Previous intestinal resection in patients with CD is an independent predictor of overall postoperative complications.