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Abstract Background Since 2015, an infliximab biosimilar, CT-P13, has been approved for commercial use in many countries, easing the economic burden borne by society and patients. Many clinical trials investigating CT-P13 for the treatment of IBD have been conducted and reported that it may be a substitute for infliximab. However, the differences between the efficacy of CT-P13 and infliximab-originator require further elucidation. Methods Data on the rates of clinical response, clinical remission, and mucosal healing of IBD were pooled for random-effects model meta-analysis using Stata MP 17. A total of 30 studies were included. Results The pooled risk of clinical remission rate of patients with Crohn’s disease and ulcerative colitis who were naïve to biologics at 08–14 weeks were 0.66 (95% CI, 0.58–0.75) and 0.48 (95% CI, 0.43–0.54), respectively, and at 100–104 weeks were 0.66 (95% CI, 0.49 to 0.84) and 0.71 (95% CI, 0.62 to 0.79) respectively. The pooled risk of clinical remission rate of patients with Crohn’s disease and ulcerative colitis who were transitioned from the original agent at 24–32 weeks were 0.84 (95% CI, 0.77–0.92) and 0.78 (95% CI, 0.63–0.93), respectively, and at 48–54 weeks were 0.72 (95% CI, 0.62 to 0.82) and 0.78 (95% CI, 0.71 to 0.86) respectively. The pooled rates for mucosal healing in ulcerative colitis were 0.56 (95% CI: 0.46 to 0.67) at 08–14 weeks, and 0.64 (95% CI: 0.42 to 0.85) at 48–54 weeks. RCT studies showed no significant change in efficacy after switching, whether Crohn’s disease or ulcerative colitis. Conclusions CT-P13 is effective in short and long-term periods. The application of CT-P13 for the management of IBD was promising.

Abstract Acute lung injury (ALI) is a common critical respiratory disease in clinical practice, especially in the ICU, with a high mortality rate. The pathogenesis of ALI is relatively complex, mainly involving inflammatory response imbalance, oxidative stress, cell apoptosis, and other aspects. However, currently, the treatment measures taken based on the above mechanisms have not had significant effects. Recent research shows that mitochondrial dysfunction and pyroptosis play an important role in ALI, but there is not much analysis on the relationship between mitochondrial dysfunction and pyroptosis at present. This article reviews the situation of mitochondrial dysfunction in ALI, pyroptosis in ALI, whether mitochondrial dysfunction is related to pyroptosis in ALI, and how to do so, and further analyzes the relationship between them in ALI. This review describes how to alleviate mitochondrial dysfunction, and then suppress the associated immunological pyroptosis, providing new ideas for the clinical treatment of ALI.

Abstract Epigenetic reprogramming plays a critical role in cancer progression of cancer, and N6-methyladenosine (m6A) is the most common RNA modification in eukaryotes. The purpose of this study was to explore the related modification mode of m6A regulator construction and evaluate the invasion and migration of thyroid cancer. Our results showed that m6A levels were significantly increased in papillary thyroid cancer (PTC) and anaplastic thyroid cancer (ATC) samples, which may have been induced by the down-regulation of demethylase fat mass and obesity-associated gene (FTO). Moreover, FTO inhibited PTC and ATC invasion and metastasis through the epithelial-to-mesenchymal transition (EMT) pathway in vivo and in vitro. Mechanistically, an m6A-mRNA epitranscriptomic microarray showed that Cadherin 12 (CDH12) is the key target gene mediated by FTO in an m6A-dependent manner. CDH12 promotes invasion and metastasis through the EMT pathway in thyroid cancer, both in vivo and in vitro. Furthermore, we found that insulin-like growth factor 2 mRNA-binding protein 2 (IGF2BP2) is an important m6A reading protein, that regulates the stability of CDH12 mRNA and mediates EMT progression, thereby promoting the invasion and metastasis of PTC and ATC. Thus, FTO, IGF2BP2 and CDH12 may be effective therapeutic targets for PTC and ATC with significant invasion or distant metastasis. Schematic summary of FTO-IGF2BP2 axis in modulation of CDH12 mRNA m6A and upregulation of CDH12 expression in the invasion and metastasis of thyroid carcinoma.

Abstract. Background:. China is one of the countries with the largest burden of gastrointestinal and liver diseases (GILD) in the world. The GILD constitutes various causes of mortality and disability. The study aimed to investigate the trend of GILD in China using the Global Burden of Diseases Study 2019 (GBD 2019) data resources from 1990 to 2019. Methods:. The data on the age-standardized mortality rates (ASMR) and disability-adjusted life years (DALYs) for GILD in China from 1990 to 2019 were collected from the GBD 2019 data resources. Furthermore, the ranking of the main causes of deaths and DALYs, as well as the trends of ASMR, DALYs, years of life lost (YLLs), and years of life lost due to disability (YLDs) per 1,000,000 in GILD were reported. Results:. The ASMR and DALYs for stomach cancer, liver cancer, and esophageal cancer, which ranked top three among the GILDs from 1990 to 2019, were gradually decreasing. Significant decreases in the ASMR and DALYs were found in diarrheal diseases and acute hepatitis (A, E, and C). However, noteworthy increases were found in those of colon and rectum cancer (CRC) and pancreatic cancer. Trend of DALYs, mortality, and YLLs rates for most of GILD were decreasing from 1990 to 2019, except the burden of CRC and pancreatic cancer with an increasing trend. The DALYs, mortality and YLLs of most GILD diseases showed decreasing trends from 1990 to 2019, except the burden of CRC and pancreatic cancer with an increasing trends. Conclusions:. The result of the GBD 2019 showed that the rates of most GILDs decreased in China; however, gastrointestinal and liver cancer, such as stomach cancer still held the top ranking. Furthermore, the shift from infectious diseases to non-communicable causes among GILD burden is occurring.

Cancer is a leading cause of global morbidity and mortality. Tumor cells grow in a complex microenvironment, comprising immune cells, stromal cells, and vascular cells, collaborating to support tumor growth and facilitate metastasis. Transforming growth factor-beta (TGF-β) is a multipotent factor that can not only affect fibrosis promotion but also assume distinct roles in the early and late stages of the tumor. Matrix metalloproteinases (MMPs) primarily function to degrade the extracellular matrix, a pivotal cellular player in tumor progression. Moreover, endothelial-to-mesenchymal transition (EndMT), similar to epithelial-to-mesenchymal transition, is associated with cancer progression by promoting angiogenesis, disrupting the endothelial barrier, and leading to cancer-associated fibroblasts. Recent studies have underscored the pivotal roles of TGF-β and MMPs in EndMT. This review delves into the contributions of TGF-β and MMPs, as well as their regulatory mechanisms, within the tumor microenvironment. This collective understanding offers fresh insights into the potential for combined targeted therapies in the fight against cancer.

Background: Ovarian cancer, a fatal gynecological malignancy, is primarily managed through surgery and chemotherapy. However, a significant challenge arises as patients frequently experience relapse due to chemotherapy resistance. This study delves into the complex functions and underlying mechanisms of macrophages in chemotherapy resistance in ovarian cancer. Method: The single-cell transcriptome sequencing data of ovarian cancer with or without chemotherapy were analyzed. Then, corresponding cell types were identified, and macrophages were extracted from all cells. Following the standardized single-cell analysis using the Seurat package, 15 distinct macrophage clusters were found and differentially expressed genes among them were analyzed. Moreover, their association with chemotherapy resistance was explored through cell proportions and gene expression. Result: In the single-cell transcriptomic analysis of ovarian cancer tissues before and after chemotherapy, the cellular proportion of CXCL5+ macrophages, THBS1+ macrophages, and MMP9+ macrophages were significantly increased following chemotherapy. Further investigation revealed that these macrophage subpopulations upregulated the expression of multiple pro-tumorigenic angiogenic or invasive factors, in addition to CXCL5, THBS1, and MMP9, including CTSL, CXCL1, and CCL18. Finally, pathway enrichment analysis revealed the significant activation of signaling pathways, such as NOD-like receptor, MAPK, and TNF in these macrophage subpopulations, which provides direction for studying the mechanism of these subpopulations. Conclusion: CXCL5+, THBS1+, and MMP9+ macrophage subpopulations exhibit an increased cellular prevalence post-chemotherapy and pro-tumorigenic molecular expression profiles, suggesting a close association with chemoresistance in ovarian cancer. These findings contribute to our understanding of the roles and mechanisms of macrophages in ovarian cancer chemoresistance, providing a theoretical basis and direction for the development of therapies targeting macrophages in overcoming ovarian cancer chemoresistance.

Abstract Background Helicobacter pylori (H. pylori) infection is prevalent and associated with the development of various gastric diseases. On the other hand, inflammatory bowel disease (IBD) is an immune‐related intestinal disorder influenced by factors like gut microbiota imbalance, genetic predisposition, and environmental influences. Despite extensive research on the H. pylori–IBD relationship, a comprehensive bibliometric analysis in this area is lacking. Therefore, this study aims to use bibliometric methods to explore research trends, hotspots, and frontiers in H. pylori and IBD‐related research, offering valuable insights for future research and clinical practice. Methods We retrieved relevant literature on H. pylori and IBD from the Web of Science Core Collection (WoSCC) and Scopus databases covering 2007 to 2024. We perform a comprehensive analysis within the WoSCC literature. We compare these findings with relevant results from Scopus. Results Research on H. pylori and IBD has remained prominent in recent years. The United States leads in output, with strong contributions from authors, institutions, and journals. China, despite being a developing country, shows rapid article growth, signaling growing research potential. Key topics include Crohn's disease, gut microbiota, H. pylori infection, and ulcerative colitis. Newer interests include health, cancer prevention, and chronic gastritis. Conclusion Over the past, research on H. pylori and IBD has primarily centered around epidemiology and clinical studies. The question of whether H. pylori definitively offers protective effects against IBD remains unresolved. Therefore, further investigation could explore the underlying mechanisms of their relationship or initiate long‐term prospective cohort studies to gather more compelling evidence.

Abstract Background Acyl-CoA-binding domain-containing 3 (ACBD3) is a multifunctional protein, that plays essential roles in cellular signaling and membrane domain organization. Although the precise roles of ACBD3 in various cancers remain unclear. Thus, we aimed to determine the diverse roles of ACBD3 in pan-cancers. Methods Relevant clinical and RNA-sequencing data for normal tissues and 33 tumors from The Cancer Genome Atlas (TCGA) database, the Human Protein Atlas, and other databases were applied to investigate ACBD3 expression in various cancers. ACBD3-binding and ACBD3-related target genes were obtained from the STRING and GEPIA2 databases. The possible functions of ACBD3-binding genes were explored using Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) enrichment analyses. We also applied the diagnostic value and survival prognosis analysis of ACBD3 in pan-cancers using R language. The mutational features of ACBD3 in various TCGA cancers were obtained from the cBioPortal database. Results When compared with normal tissues, ACBD3 expression was statistically upregulated in eleven cancers and downregulated in three cancers. ACBD3 expression was remarkably different among various pathological stages of tumors, immune and molecular subtypes of cancers, cancer phosphorylation levels, and immune cell infiltration. The survival of four tumors was correlated with the expression level of ACBD3, including pancreatic adenocarcinoma, adrenocortical carcinoma, sarcoma, and glioma. The high accuracy in diagnosing multiple tumors and its correlation with prognosis indicated that ACBD3 may be a potential biomarker of pan-cancers. Conclusion According to our pan-cancer analysis, ACBD3 may serve as a remarkable prognostic and diagnostic biomarker of pan-cancers as well as contribute to tumor development. ACBD3 may also provide new directions for cancer treatment targets in the future.

Abstract Background Ferroptosis is related to the immunosuppression of tumors and plays a critical role in cancer progression. Fanconi anemia complementation group D2 (FANCD2) is a vital gene that regulates ferroptosis. However, the mechanism of action of FANCD2 in Hepatitis B-related hepatocellular carcinoma (HCC) remains unknown. In this study, we investigated the prognostic significance and mechanism of action of FANCD2 in Hepatitis B-related HCC. Methods The expression of FANCD2 in Hepatitis B-related HCC was explored using The Cancer Genome Atlas (TCGA) and validated using the Gene Expression Omnibus (GEO) database. Univariate and multivariate Cox regression analyses and Kaplan–Meier survival curves were used to analyze the relationship between FANCD2 expression and the overall survival of patients with Hepatitis B-related HCC. Protein–protein interaction networks for FANCD2 were built using the STRING website. In addition, correlations between FANCD2 expression and the dryness index, tumor mutational burden, microsatellite instability (MSI), immune pathways, genes involved in iron metabolism, and sorafenib chemotherapeutic response were analyzed. Results Our results indicated that FANCD2 was significantly overexpressed in Hepatitis B-related HCC and demonstrated a strong predictive ability for diagnosis (Area Under Curve, 0.903) and prognosis of the disease. High FANCD2 expression was associated with poor prognosis, high-grade tumors, high expression of PDL-1, high MSI scores, and low sorafenib IC50 in Hepatitis B-related HCC. BRCA1, BRCA2, FAN1, and FANCC were vital proteins interacting with FANCD2. The expression level of FANCD2 significantly correlated with the infiltration levels of Treg cells, B cells, CD8 + T cells, CD4 + T cells, neutrophils, macrophages, myeloid dendritic cells, and NK cells in Hepatitis B-related HCC. FANCD2 was positively correlated with the tumor proliferation signature pathway, DNA repair, and cellular response to hypoxia. Conclusion Our study indicated that FANCD2 was a potential novel biomarker and immunotherapeutic target against Hepatitis B-related HCC, which might be related to the chemotherapeutic response to sorafenib.

Objectives This study aimed to assess the internal law and time trend of hospitalisation for oesophagogastric variceal bleeding (EGVB) in cirrhosis and develop an effective model to predict the trend of hospitalisation time.Design We used a time series covering 72 months to analyse the hospitalisation for EGVB in cirrhosis. The number of inpatients in the first 60 months was used as the training set to establish the autoregressive integrated moving average (ARIMA) model, and the number over the next 12 months was used as the test set to predict and observe their fitting effect.Setting and data Case data of patients with EGVB between January 2014 and December 2019 were collected from the Affiliated Hospital of Southwest Medical University.Outcome measures The number of monthly hospitalised patients with EGVB in our hospital.Results A total of 877 patients were included in the analysis. The proportion of EGVB in patients with cirrhosis was 73% among men and 27% among women. The peak age at hospitalisation was 40–60 years. The incidence of EGVB varied seasonally with two peaks from January to February and October to November, while the lowest number was observed between April and August. Time-series analysis showed that the number of inpatients with EGVB in our hospital increased annually. The sequence after the first-order difference was a stationary series (augmented Dickey-Fuller test p=0.02). ARIMA (0,1,0) (0,1,1)12 with a minimum Akaike Information Criterion value of 260.18 could fit the time trend of EGVB inpatients and had a good short-term prediction effect. The root mean square error and mean absolute error were 2.4347 and 1.9017, respectively.Conclusions The number of hospitalised patients with EGVB at our hospital is increasing annually, with seasonal changes. The ARIMA model has a good prediction effect on the number of hospitalised patients with EGVB in cirrhosis.

BackgroundGender disparity is pervasive in academic medicine. This study aimed to assess the disparity between men and women with regard to first and senior author positions in primary studies on liver cancer over the last two decades.MethodsWe conducted a review of articles published in high-impact factor journals of the field of Gastroenterology and Hepatology in 2005, 2010, 2015 and 2020. First and senior authors of all ages were considered as the study population. The authors' genders were determined using the online artificial intelligence tool genderize.io (https://genderize.io/). The disparity between men and women authors was assessed using the linear-by-linear association test.Results665 original articles from 10 journals were reviewed. The point prevalence of first women authors was 25.0% compared with 75.0% for men. The point prevalence of senior women authors was 16.3% compared with 83.7% for men. From 2000 to 2020, the proportion of first women authors increased 14.4% to 26.8% compared with 85.6%-73.2% for men (P = 0.009), and the proportion of senior women authors increased from 7.4% to 19.5%, compared with 92.6%-80.5% for men (P = 0.035). The factor independently associated with a reduced representation of women among first authors was the region of author. The factor independently associated with a reduced representation of women among senior authors was the impact factor of journals.ConclusionThe findings indicated a remarkable increase in the proportion of women, both first and senior authors, over the past two decades in the field of liver cancers. However, the representation of women authors in this area is far less than that of men.

Chronic pain can induce not only nociceptive but also depressive emotions. A previous study demonstrated that betaine, a commonly used nutrient supplement, has an anti-nociceptive effect, but whether betaine can alleviate chronic pain-induced depressive emotion is elusive. Our current study found that betaine administration significantly eliminated complete Freund’s adjuvant (CFA)-induced pain-related depressive-like behaviour. Mechanistically, betaine treatment inhibited microglia and astrocyte activation. Furthermore, betaine significantly promoted the transition of microglia from the M1 to the M2 phenotype, as well as the transition of astrocytes from the A1 to the A2 phenotype. Additionally, the release of pro-inflammatory factors such as IL-18, IL-1β and IL-6 and anti-inflammatory factors such as IL-10 in the hippocampus induced by CFA were also reversed by betaine administration. Overall, betaine has therapeutic effects on pain-related depressive-like phenotypes caused by CFA, possibly through altering the polarization of microglia and astrocytes to reduce neuroinflammation.

In the early stage, N4-acetylcytidine (ac4C) was regarded as a conservative nucleoside present on tRNA and rRNA. Recently, studies have shown that ac4C also exists in human and yeast mRNA. N-Acetyltransferase-like protein 10 (NAT10) is the first enzyme to be found to catalyze ac4C production in eukaryotic RNA and has acetyltransferase activity and RNA-binding activity. Here, we first describe the structure and cellular localization of NAT10. Then, we conclude the active roles of NAT10 as the ac4C “writer” in mRNA stability and translation efficiency, oocyte maturation, bone remodeling, and fatty acid metabolism. With respect to disease, we focused on the promoting functions of NAT10 in proliferation, metastasis, and apoptosis in multiple tumors. The immune regulatory role of NAT10 in systemic lupus erythematosus and the maintenance role of NAT10 in virus RNA stability and replication in influenza A virus are also introduced. This review identifies NAT10 as a potential target for diagnosis, therapy, and prognosis in clinical application.

Abstract Malignant melanoma is one of the most common tumours and has the highest mortality rate of all types of skin cancers worldwide. Traditional and novel therapeutic approaches, including surgery, targeted therapy and immunotherapy, have shown good efficacy in the treatment of melanoma. At present, the mainstay of treatment for melanoma is immunotherapy combined with other treatment strategies. However, immune checkpoint inhibitors, such as PD-1 inhibitors, are not particularly effective in the clinical treatment of patients with melanoma. Changes in mitochondrial function may affect the development of melanoma and the efficacy of PD-1 inhibitors. To elucidate the role of mitochondria in the resistance of melanoma to PD-1 inhibitors, this review comprehensively summarises the role of mitochondria in the occurrence and development of melanoma, targets related to the function of mitochondria in melanoma cells and changes in mitochondrial function in different cells in melanoma resistant to PD-1 inhibitors. This review may help to develop therapeutic strategies for improving the clinical response rate of PD-1 inhibitors and prolonging the survival of patients by activating mitochondrial function in tumour and T cells.

Background: Fibroblast growth factor 1 (FGF1) is extensively amplified in many tumors and accelerates tumor invasion and metastasis. However, the role and precise molecular mechanism by which FGF1 participates in thyroid cancer (TC) are still unclear. Methods: Quantitative real-time polymerase chain reaction- and western blotting were used to detect the mRNA and protein levels of FGF1, high mobility group A (HMGA1), epithelial-to-mesenchymal transition (EMT)-related factors, and FGF receptors in both TC tissues and cell lines. Immunohistochemistry was conducted to examine the expression of FGF1 and HMGA1. Immunofluorescence staining was used to detect the coexpression of FGF1 and HMGA1. Transwell and wound healing assays were conducted to evaluate the effects of FGF1 on the capacity of invasion and migration in cells. Results: FGF1 was upregulated in papillary thyroid carcinoma (PTC) tissues and cell lines and was relatively higher in PTC tissues with cervical lymph node metastasis. Furthermore, FGF1 promotes invasion and metastasis through the EMT pathway. Mechanistically, FGF1 promotes EMT through intracellular function independent of FGF receptors. Interestingly, we demonstrated that FGF1 could upregulate HMGA1 in TC cells, and the correlation of FGF1 and HMGA1 was positive in PTC tissues. FGF1 and HMGA1 had obvious colocalization in the nucleus. We further revealed that FGF1 promotes the invasion and migration of TC cells through the upregulation of HMGA1. Conclusion: Intracellular FGF1 could promote invasion and migration in TC by mediating the expression of HMGA1 independent of FGF receptors, and FGF1 may be an effective therapeutic target in TC.

YTHDF1 is the most versatile and powerful reader protein of N6-methyladenosine (m6A)-modified RNA, and it can recognize both G(m6A)C and A(m6A)C RNAs as ligands without sequence selectivity. YTHDF1 regulates target gene expression by different mechanisms, such as promoting translation or regulating the stability of mRNA. Numerous studies have shown that YTHDF1 plays an important role in tumor biology and nontumor lesions by mediating the protein translation of important genes or by affecting the expression of key factors involved in many important cell signaling pathways. Therefore, in this review we focus on some of the roles of YTHDF1 in tumor biology and diseases.

Background & Aims: Nonalcoholic steatohepatitis (NASH) is a chronic liver disease that is manifested clinically by an increase in hepatic triglycerides, inflammation, and fibrosis. The pathogenesis of NASH remains incompletely understood. Sirtuin 6 (Sirt6), a nicotinamide adenine dinucleotide–dependent deacetylase, has been implicated in fatty liver disease; however, the underlying molecular mechanisms in the NASH pathogenesis are elusive. The aims of this study were to elucidate the role of hepatic Sirt6 in NASH. Methods: Wild-type, liver-specific Sirt6 knockout (KO), hepatic stellate cell (HSC)-specific Sirt6 knockout (HSC-KO), and Sirt6 transgenic mice were subjected to a Western diet for 4 weeks. Hepatic phenotypes were characterized and underlying mechanisms were investigated. Results: Remarkably, both the liver-KO and HSC-KO mice developed much worse NASH than the wild-type mice, whereas the transgenic mice were protected from the diet-induced NASH. Our cell signaling analysis showed that Sirt6 negatively regulates the transforming growth factor β–Smad family member 3 (Smad3) pathway. Biochemical analysis showed a physical interaction between Sirt6 and Smad3 in hepatic stellate cells. Moreover, our molecular data further showed that Sirt6 deacetylated Smad3 at key lysine residues K333 and K378, and attenuated its transcriptional activity induced by transforming growth factor β in hepatic stellate cells. Conclusions: Our data suggest that SIRT6 plays a critical role in the protection against NASH development and it may serve as a potential therapeutic target for NASH.

Objective: Because of the modest immunotherapeutic response among ovarian carcinoma (OC) patients, it is significant to evaluate antitumor immune response and develop more effective precision immunotherapeutic regimens. Here, this study aimed to determine diverse immune subtypes of OC.Methods: This study curated the expression profiles of prognostic immunologically relevant genes and conducted consensus clustering analyses for determining immune subtypes among OC patients in TCGA cohort. With Boruta algorithm, characteristic genes were screened for conducting an immune scoring system through principal component analysis algorithm. The single-sample gene set enrichment analysis and ESTIAMTE methods were adopted for quantifying the immune infiltrates and responses to chemotherapeutic agents were estimated with pRRophetic algorithm. Two immunotherapeutic cohorts were used for investigating the efficacy of immune score in predicting therapeutic benefits.Results: Two immune subtypes were conducted among 377 OC patients. Immune subtype 2 was characterized by worse clinical prognosis, more frequent genetic variations and mutations, enhanced immune infiltrates, and increased expression of MHC molecules and programmed cell death protein 1/programmed death ligand 1 (PD-1/PD-L1). In total, 30 prognosis-relevant characteristic immune subtype–derived genes were identified for constructing the immune score of OC patients. High immune score was linked with more dismal prognosis, decreased immune infiltrations, and expression of MHC molecules. High immune score presented favorable sensitivity to doxorubicin and vinorelbine and reduced sensitivity to cisplatin. In addition, immune score possessed the potential in predicting benefits from anti–PD-1/PD-L1 therapy.Conclusion: Collectively, our findings propose two complex and diverse immune subtypes of OC. Quantitative assessment of immune subtypes in individual patients strengthens the understanding of tumor microenvironment features and promotes more effective immunotherapeutic regimens.

Considering the hazards of high salt intake and the current status of research on low-sodium meat products, this study was to analyze the effect of ultrasound combined with glycerol-mediated low-sodium salt curing on the quality of pork tenderloin by analyzing the salt content, water activity (aw), cooking loss, and texture. The results of scanning electron microscope (SEM) analysis, Raman spectroscopy, ultraviolet fluorescence, and surface hydrophobicity were proposed to reveal the mechanism of the effect of combined ultrasound and glycerol-mediated low sodium salt curing on the quality characteristics of pork tenderloin. The results showed that the co-mediated curing could reduce salt content, aw, and cooking loss (p < 0.05), improve texture and enhance product quality. Compared with the control group, the co-mediated curing increased the solubility of the myofibrillar protein, improved the surface hydrophobicity of the protein, increased the content of reactive sulfhydryl groups (p < 0.05), and changed the protein structure. The SEM results showed that the products treated using a co-mediated curing process had a more detailed and uniform pore distribution. These findings provide new insights into the quality of ultrasonic-treated and glycerol-mediated low-salt cured meat products.

Endotoxemia is a severe inflammation response induced by infection especially bacterial endotoxin translocation, which severely increases mortality in combination with acute colon injury. Bromodomain-containing protein 4 (BRD4) is an important Bromo and Extra-Terminal (BET) protein to participate in inflammatory responses. However, it is still unknown about the specific connection between BRD4 and inflammation-related pyroptosis in endotoxemia colon. Here, through evaluating the mucous morphology and the expression of tight junction proteins such as occludin and ZO1, we found the upregulation of BRD4 in damaged colon with poor tight junction in an endotoxemia mouse model induced by lipopolysaccharides (LPS). Firstly, the BRD4 inhibitor JQ1 was used to effectively protect colon tight junction in endotoxemia. As detected, high levels of pro-inflammation cytokines IL6, IL1β and IL18 in endotoxemia colon were reversed by JQ1 pretreatment. In addition, JQ1 injection reduced endotoxemia-induced elevation of the phosphorylated NF κB and NLRP3/ASC/caspase 1 inflammasome complex in colon injury. Furthermore, activated pyroptosis markers gasdermins in endotoxemia colon were also blocked by JQ1 pretreatment. Together, our data indicate that BRD4 plays a critical role in regulating pyroptosis-related colon injury induced by LPS, and JQ1 as a BRD4 inhibitors can effectively protect colon from endotoxemia-induced inflammation injury.

Objectives. To investigate the effects of cytotoxin-associated gene A- (CagA-) positive Helicobacter pylori on proliferation, invasion, autophagy, and expression of miR-125b-5p in colon cancer cells. Methods. Colon cancer cells were cocultured with H. pylori (CagA+) to analyze the effects of H. pylori on miR-125b-5p and autophagy. Colon cancer cells infected with H. pylori (CagA+) were mimicked by transfection of CagA plasmid. The effects of CagA on the proliferation, invasion, and autophagy of colon cancer cells were analyzed. Cell counting kit-8 (CCK-8), clone formation, and Transwell assays were used to detect cell viability, proliferation, and invasion ability, respectively. Proteins and miRNAs were detected by western blotting and qPCR, respectively. Results. H. pylori (CagA+) inhibited expression of miR-125b-5p and promoted autophagy in colon cancer cells. MiR-125 b-5p was underexpressed in colon cancer cells after CagA overexpression. CagA promoted colon cancer cell proliferation, invasion, and autophagy. Overexpression of miR-125b-5p inhibited the proliferation, invasion, and autophagy of colon cancer cells and reversed the effects of CagA. Conclusion. H. pylori (CagA+) infection may promote the development and invasion of colon cancer by inhibiting miR-125b-5p.

Patients with ovarian cancer are often in a hypercoagulable state and have a high risk of venous thrombosis, including deep vein thrombosis and pulmonary embolism. However, arterial thrombosis is relatively rare in ovarian cancer. We report a case a 46-year-old woman with ovarian clear cell carcinoma who developed arterial and venous thrombosis in the lower extremities as the first manifestation. Her arterial thrombosis-related ischemic symptoms were not responsive to anticoagulant treatment of low-molecular-weight heparin, but improved after neoadjuvant chemotherapy and surgery. Therefore, we hypothesize that the optimal therapy for arterial thrombosis in ovarian cancer is treatment for the underlying disease (i.e., ovarian cancer). A thorough investigation is required to determine the relationships between arterial thrombosis and ovarian cancer and antithrombotic treatments for ovarian cancer related-arterial thrombosis.

ABSTRACT PURPOSE: To investigate the effect of curcumin on visfatin and zinc-α2-glycoprotein (ZAG) expression levels in rats with non-alcoholic fatty liver disease (NAFLD). METHODS: Fifty-six male rats were randomly divided into a control group (n=16) and model group (n=40) and were fed on a normal diet or a high-fat diet, respectively. Equal volumes of sodium carboxymethyl cellulose (CMC) were intragastrically administered to the control group for 4 weeks. At the end of the 12th week, visfatin and ZAG protein expression levels were examined by immunohistochemistry. Visfatin mRNA levels were measured by semi-quantitative reverse transcription polymerase chain reaction. RESULTS: Compared with the control group, the model group showed significantly increased expression of visfatin in liver tissue (P < 0.01) and significantly decreased expression of ZAG (P < 0.01). These effects were ameliorated by curcumin treatment. CONCLUSIONS: Visfatin and zinc-α2-glycoprotein may be involved in the pathogenesis of NAFLD. Treatment of NAFLD in rats by curcumin may be mediated by the decrease of visfatin and the increase of non-alcoholic fatty liver disease.

Conventional hypersonic transition prediction relies upon the highly empirical eN method, which is predicated on theoretical approximations of relative disturbance growth. This does not account for the receptivity mechanism and the high degree of variability present in experimental wind-tunnel conditions, which itself leads to high degrees of variability in transition N factors. The amplitude method, which better approximates the broadband nature of boundary-layer disturbances, was previously proposed to account for the effects of receptivity. In this study, high-fidelity simulated second-mode receptivity data for two blunt cones at Mach 10 to broadband disturbances are applied to an iterative approximation of the amplitude method tuned for second-mode dominated flows. The studied geometries consist of 9.525- and 5.080-mm-nose-radius 7 deg half-angle straight cones based on experimental cases from Arnold Engineering Development Center's wind tunnel 9. Amplitude method predictions show improvement over the accuracy of eN estimates using standard threshold N factors. In particular, the less blunt 5.080 mm cone demonstrates the best agreement due to its stronger second-mode response. The results of this work provide a preliminary framework for applying high-fidelity receptivity simulations to the amplitude method for transition prediction in hypersonic flows. [ABSTRACT FROM AUTHOR]