Identification of S100A8/A9 involved in thromboangiitis obliterans development using tandem mass tags-labeled quantitative proteomics analysis.

Thromboangiitis obliterans (TAO) is characterized by inflammation and obstruction of small-and medium-sized distal arteries, with limited pharmacotherapies and surgical interventions. The precise pathogenesis of TAO remains elusive. By utilizing the technology of tandem mass tags (TMT) for quantitative proteomics and leveraging bioinformatics tools, a comparative analysis of protein profiles was conducted between normal and TAO rats to identify key proteins driving TAO development. The results unveiled 1385 differentially expressed proteins (DEPs) in the TAO compared with the normal group-comprising 365 proteins with upregulated expression and 1020 proteins with downregulated expression. Function annotation through gene ontology indicated these DEPs mainly involved in cell adhesion, positive regulation of cell migration, and cytosol. The principal signaling pathways involved regulation of the actin cytoskeleton, vascular smooth contraction, and focal adhesion. The roles of these DEPs and associated signaling pathways serve as a fundamental framework for comprehending the mechanisms underpinning the onset and progression of TAO. Furthermore, we conducted a comprehensive evaluation of the effects of S100A8/A9 and its inhibitor, paquinimod, on smooth muscle cells (SMCs) and in TAO rats. We observed that paquinimod reduces SMCs proliferation and migration, promotes phenotype switching and alleviates vascular stenosis in TAO rats. In conclusion, our study revealed that the early activation of S100A8/A9 in the femoral artery is implicated in TAO development, targeting S100A8/A9 signaling may provide a novel approach for TAO prevention and treatment.

Sensory neuronal control of skin barrier immunity.

Peripheral sensory neurons recognize diverse noxious stimuli, including microbial products and allergens traditionally thought to be targets of the mammalian immune system. Activation of sensory neurons by these stimuli leads to pain and itch responses as well as the release of neuropeptides that interact with their cognate receptors expressed on immune cells, such as dendritic cells (DCs). Neuronal control of immune cell function through neuropeptide release not only affects local inflammatory responses but can impact adaptive immune responses through downstream effects on T cell priming. Numerous neuropeptide receptors are expressed by DCs but only a few have been characterized, presenting opportunities for further investigation of the pathways by which cutaneous neuroimmune interactions modulate host immunity.

Pre-exposure prophylaxis (PrEP) knowledge, use, and discontinuation among Lake Victoria fisherfolk in Uganda: a cross-sectional population-based study.

Background: There are limited population-level data on the pre-exposure prophylaxis (PrEP) care continuum in eastern Africa. Here, we assessed the PrEP care continuum following PrEP rollout in a Ugandan community with ~40% HIV seroprevalence. Methods: We used cross-sectional population-based data collected between September 3 and December 19, 2018 from a Lake Victoria fishing community in southern Uganda to measure levels of self-reported PrEP knowledge, ever use, and discontinuation following 2017 PrEP rollout via a U.S. President's Emergency Plan for AIDS Relief (PEPFAR)-supported phased implementation program. Our analysis included HIV-seronegative persons reporting having ever received an HIV test result. We examined associations between demographic, behavioral, and health utilization factors with each outcome using age-adjusted modified Poisson regression. Results: There were 1,401 HIV-seronegative participants, of whom 1,363 (97.3%) reported ever receiving an HIV test result. Median age was 29 years (IQR: 23-36), and 42.3% (n=577) were women. Most (85.5%; n=1,166) participants reported PrEP knowledge, but few (14.5%; n=197) reported ever using PrEP. Among 375 (47.7%) men and 169 (29.3%) women PrEP-eligible at time of survey, 18.9% (n=71) and 27.8% (n=47) reported ever using PrEP, respectively. Over half (52.3%, n=103) of those who had ever used PrEP, self-reported current use. Conclusion: In this Lake Victoria fishing community, there were low levels of PrEP use despite high levels of PrEP awareness and eligibility, particularly among men. Efforts that enhance awareness of HIV risk and increase PrEP accessibility may help increase PrEP use among HIV-seronegative persons in African settings with high HIV burden.

Yinchen gongying decoction mitigates CCl4-induced chronic liver injury and fibrosis in mice implicated in inhibition of the FoxO1/TGF-ß1/ Smad2/3 and YAP signaling pathways.

ETHNOPHARMACOLOGICAL RELEVANCE: Liver fibrosis (LF) is a common reversible consequence of chronic liver damage with limited therapeutic options. Yinchen Gongying decoction (YGD) composed of two homologous plants: (Artemisia capillaris Thunb, Taraxacum monochlamydeum Hand.-Mazz.), has a traditionally application as a medicinal diet for acute icteric hepatitis. However, its impact on LF and underlying mechanisms remain unclear. AIM OF THE STUDY: This study aims to assess the impact of YGD on a carbon tetrachloride (CCl4) induced liver fibrosis and elucidate its possible mechanisms. The study seeks to establish an experimental foundation for YGD as a candidate drug for hepatic fibrosis. MATERIALS AND METHODS: LC-MS/MS identified 11 blood-entry components in YGD, and network pharmacology predicted their involvement in the FoxO signaling pathway, insulin resistance, and PI3K-AKT signaling pathway. Using a CCl4-induced LF mouse model, YGD's protective effects were evaluated in comparison to a positive control and a normal group. The underlying mechanisms were explored through the assessments of hepatic stellate cells (HSCs) activation, fibrotic signaling, and inflammation. RESULTS: YGD treatment significantly improved liver function, enhanced liver morphology, and reduced liver collagen deposition in CCl4-induced LF mice. Mechanistically, YGD inhibited HSC activation, elevated MMPs/TIMP1 ratios, suppressed the FoxO1/TGF-ß1/Smad2/3 and YAP pathways, and exhibited anti-inflammatory and antioxidant effects. Notably, YGD improved the insulin signaling pathway. CONCLUSION: YGD mitigates LF in mice by modulating fibrotic and inflammatory pathways, enhancing antioxidant responses, and specifically inhibiting FoxO1/TGF-ß1/Smad2/3 and YAP signal pathways.

Efficient removal of phosphorus and nitrogen from aquatic environment using sepiolite-MgO nanocomposites: preparation, characterization, removal performance, and mechanism.

Excessive phosphorus will lead to eutrophication in aquatic environment; the efficient removal of phosphorus is crucial for wastewater engineering and surface water management. This study aimed to fabricate a nanorod-like sepiolite-supported MgO (S-MgO) nanocomposite with high specific surface area for efficient phosphate removal using a facile microwave-assisted method and calcining processes. The impact of solution pH, adsorbent dosage, contact time, initial phosphate concentrations, Ca2+ addition, and N/P ratio on the phosphate removal was extensively examined by the batch experiments. The findings demonstrated that the S-MgO nanocomposite exhibited effective removal performance for low-level phosphate (0 ~ 2.0 mM) within the pH range of 3.0 ~ 10.0. Additionally, the nanocomposite can synchronously remove phosphate and ammonium in high-level nutrient conditions (> 2.0 mM), with the maximum removal capacities of 188.49 mg P/g and 89.78 mg N/g. Quantitative and qualitative analyses confirmed the successful harvesting of struvite in effluent with high-phosphate concentrations, with the mechanisms involved attributed to a synergistic combination of sorption and struvite crystallization. Due to its proficient phosphate removal efficiency, cost-effectiveness, and substantial removal capacity, the developed S-MgO nanocomposite exhibits promising potential for application in phosphorus removal from aquatic environments.

Reducing SULT2B1 promotes the interaction of LncRNAgga3-204 with SMAD4 to inhibit the macrophage inflammatory response and delay atherosclerosis progression.

Inflammation is a crucial pathophysiological mechanism in atherosclerosis (AS). This study aims to investigate the impact of sulfotransferase family 2b member 1 (SULT2B1) on the inflammatory response of macrophages and the progression of AS. Here, we reported that SULT2B1 expression increased with the progression of AS. In AS model mice, knockdown of Sult2b1 led to remission of AS and reduced inflammation levels. Further exploration of the downstream molecular mechanisms of SULT2B1 revealed that suppressing Sult2b1 in macrophages resulted in decreased levels of 25HC3S in the nucleus, elevated expression of Lxr, and increased the transcription of Lncgga3-204. In vivo, knockdown of Lncgga3-204 aggravated the inflammatory response and AS progression, while the simultaneous knockdown of both Sult2b1 and Lncgga3-204 exacerbated AS and the inflammatory response compared with knockdown of Sult2b1 alone. Increased binding of Lncgga3-204 to SMAD4 in response to oxidized-low density lipoprotein (ox-LDL) stimulation facilitated SMAD4 entry into the nucleus and regulated Smad7 transcription, which elevated SMAD7 expression, suppressed NF-κB entry into the nucleus, and ultimately attenuated the macrophage inflammatory response. Finally, we identified the presence of a single nucleotide polymorphism (SNP), rs2665580, in the SULT2B1 promoter region in monocytes from coronary artery disease (CAD) patients. The predominant GG/AG/AA genotypes were observed in the Asian population. Elevated SULT2B1 expression in monocytes with GG corresponded to elevated inflammatory factor levels and more unstable coronary plaques. To summarize, our study demonstrated that the critical role of SULT2B1/Lncgga3-204/SMAD4/NF-κB in AS progression. SULT2B1 serves as a novel biomarker indicating inflammatory status, thereby offering insights into potential therapeutic strategies for AS.

Association of oral microbiome with oral human papillomavirus infection: a population study of the National Health and Nutrition Examination Survey, 2009-2012.

BACKGROUND: Oral human papillomavirus(HPV) infection and the oral microbiome are associated with oropharyngeal cancer. However, population-based data on the association of oral microbiome with oral HPV infection are limited. METHOD: We performed a cross-sectional analysis of 5,496 participants aged 20-59 in National Health and Nutrition Examination Surveys(NHANES):2009-2012. The association between either oral microbiome alpha diversity or beta diversity and oral HPV infection was assessed using multivariable logistic regression or principal coordinate analyses(PCoA) and multivariate analysis of variance(PERMANOVA). RESULTS: For alpha diversity, we found a lower number of observed Amplicon sequence variants(ASVs) (adjusted odds ratio[aOR] = 0.996; 95%CI = 0.992-0.999) and reduced Faith's Phylogenetic Diversity(aOR = 0.95; 95%CI = 0.90-0.99) associated with high-risk oral HPV infection in the overall population. This trend was observed in males for both high-risk and any oral HPV infection. Beta diversity showed differentiation of oral microbiome community by high-risk oral HPV infection as measured by Bray-Curtis dissimilarity (R2 = 0.054%; P = .029) and unweighted UniFrac distance (R2 = 0.046%; P = .045) among the overall population, and associations were driven by males. CONCLUSIONS: Both oral microbiome alpha diversity(within-sample richness and phylogenetic diversity) and beta diversity(heterogeneous dispersion of oral microbiome community) are associated with HPV infection. Longitudinal studies are needed to characterize the role of the microbiome in the natural history of oral HPV infection.

Euvolemic automated transfusion to treat severe anemia in sickle cell disease patients at risk of circulatory overload.

BACKGROUND: Red blood cell (RBC) transfusion remains a major treatment for sickle cell disease (SCD). Patients with SCD have a high prevalence of renal impairment and cardiorespiratory disease, conferring risk of transfusion-associated circulatory overload (TACO). STUDY DESIGN AND METHODS: We describe an approach, titled euvolemic automated transfusion (EAT), to transfuse SCD patients with severe anemia who are at risk of TACO. In EAT, plasmapheresis is performed using donor RBCs, rather than albumin or plasma, as replacement fluid. Euvolemia is maintained. A retrospective analysis was conducted of patients with SCD who underwent EAT at our institution over a 10-year period, to evaluate the efficacy and safety of EAT. RESULTS: Eleven SCD patients underwent 109 EAT procedures (1-59 procedures per patient). The median age was 42 years (IQR = [30-49]) and 82% (n = 9) were female. Most (82%; n = 9) patients had severe chronic kidney disease and 55% (n = 6) had heart failure. One (9%) patient had a history of life-threatening TACO. Mean pre- and post-procedure Hct values were 19.8% (SD ± 1.6%) and 29.1% (SD ± 1.4%), respectively. The average Hct increment was 3.2% per RBC unit. Only two EAT-related complications were recorded during the 109 procedures: central line-associated infection and citrate toxicity (muscle cramping). EAT used an average of two RBC units less than that projected for standard automated RBC exchange. CONCLUSION: Our findings suggest that EAT is safe and effective to treat patients with SCD and severe anemia, who are at risk for TACO. EAT requires fewer RBC units compared to automated RBC exchange.

Sorting Technology for Mesenchymal Stem Cells from a Single Tissue Source.

Mesenchymal stem cells (MSCs) are adult stem cells that can be obtained, enriched and proliferated in vitro. They owned enormous potential in fields like regenerative medicine, tissue engineering and immunomodulation. However, though isolated from the same origin, MSCs are still essentially heterogeneous cell populations with different phenotypes and functions. This heterogeneity of MSCs significantly affects their therapeutic efficacy and brings obstacles to scientific research. Thus, reliable sorting technology which can isolate or purify MSC subpopulations with various potential and differentiation pathways is urgently needed. This review summarized principles, application status and clinical implications for these sorting methods, aiming at improving the understanding of MSC heterogeneity as well as providing fresh perspectives for subsequent clinical applications.

Association between late gadolinium enhancement and outcome in dilated cardiomyopathy: A meta-analysis.

BACKGROUND: The prognostic value of late gadolinium enhancement (LGE) derived from cardiovascular magnetic resonance (CMR) is well studied, and several new metrics of LGE have emerged. However, some controversies remain; therefore, further discussion is needed, and more precise risk stratification should be explored. AIM: To investigate the associations between the positivity, extent, location, and pattern of LGE and multiple outcomes in dilated cardiomyopathy (DCM). METHODS: PubMed, Ovid MEDLINE, and Cochrane Library were searched for studies that investigated the prognostic value of LGE in patients with DCM. Pooled hazard ratios (HRs) and 95% confidence intervals were calculated to assess the role of LGE in the risk stratification of DCM. RESULTS: Nineteen studies involving 7330 patients with DCM were included in this meta-analysis and covered a wide spectrum of DCM, with a mean left ventricular ejection fraction between 21% and 50%. The meta-analysis revealed that the presence of LGE was associated with an increased risk of multiple adverse outcomes (all-cause mortality, HR: 2.14; arrhythmic events, HR: 5.12; and composite endpoints, HR: 2.38; all P < 0.001). Furthermore, every 1% increment in the extent of LGE was associated with an increased risk of all-cause mortality. Analysis of a subgroup revealed that the prognostic value varied based on different location and pattern of LGE. Additionally, we found that LGE was a stronger predictor of arrhythmic events in patients with greater left ventricular ejection fraction. CONCLUSION: LGE by CMR in patients with DCM exhibited a substantial value in predicting adverse outcomes, and the extent, location, and pattern of LGE could provide additional information for risk stratification.

Genome-wide Mendelian randomization identifies putatively causal gut microbiota for multiple peptic ulcer diseases.

Objective: The pathogenesis of peptic ulcer diseases (PUDs) involves multiple factors, and the contribution of gut microbiota to this process remains unclear. While previous studies have associated gut microbiota with peptic ulcers, the precise nature of the relationship, whether causal or influenced by biases, requires further elucidation. Design: The largest meta-analysis of genome-wide association studies was conducted by the MiBioGen consortium, which provided the summary statistics of gut microbiota for implementation in the Mendelian randomization (MR) analysis. Summary statistics for five types of PUDs were compiled using the FinnGen Consortium R8 release data. Various statistical techniques, including inverse variance weighting (IVW), MR-Egger, weighted median (WM), weighted mode, and simple mode, were employed to assess the causal relationships between gut microbiota and these five PUDs. Result: In the intestinal microbiome of 119 known genera, we found a total of 14 causal associations with various locations of PUDs and reported the potential pathogenic bacteria of Bilophila et al. Among them, four had causal relationships with esophageal ulcer, one with gastric ulcer, three with gastroduodenal ulcer, four with duodenal ulcer, and two with gastrojejunal ulcer. Conclusion: In this study, the pathogenic bacterial genera in the gut microbiota that promote the occurrence of PUDs were found to be causally related. There are multiple correlations between intestinal flora and PUDs, overlapping PUDs have overlapping associated genera. The variance in ulcer-related bacterial genera across different locations underscores the potential influence of anatomical locations and physiological functions.

New insight into circRNAs: characterization, strategies, and biomedical applications.

Circular RNAs (circRNAs) are a class of covalently closed, endogenous ncRNAs. Most circRNAs are derived from exonic or intronic sequences by precursor RNA back-splicing. Advanced high-throughput RNA sequencing and experimental technologies have enabled the extensive identification and characterization of circRNAs, such as novel types of biogenesis, tissue-specific and cell-specific expression patterns, epigenetic regulation, translation potential, localization and metabolism. Increasing evidence has revealed that circRNAs participate in diverse cellular processes, and their dysregulation is involved in the pathogenesis of various diseases, particularly cancer. In this review, we systematically discuss the characterization of circRNAs, databases, challenges for circRNA discovery, new insight into strategies used in circRNA studies and biomedical applications. Although recent studies have advanced the understanding of circRNAs, advanced knowledge and approaches for circRNA annotation, functional characterization and biomedical applications are continuously needed to provide new insights into circRNAs. The emergence of circRNA-based protein translation strategy will be a promising direction in the field of biomedicine.

Association of radiotherapy with thoracic vertebral fractures in esophageal squamous cell carcinoma: A retrospective cohort study.

To investigate the association between radiotherapy (RT) and thoracic vertebral fractures in esophageal squamous cell carcinoma (ESCC) and explore the risk factors of thoracic vertebral fracture in ESCC who underwent RT. This retrospective cohort study including 602 consecutive ESCC patients examined the association between RT and thoracic vertebral fractures using multivariable Cox proportional hazard models and relevant risk factors of thoracic vertebral fractures based on clinical and RT parameters in patients with ESCC. Followed for a median follow-up of 24 months, 54 patients had thoracic vertebral fractures. The multivariable analysis revealed RT as an independent risk factor after adjusting for clinical risk factors. Univariable analyses associated a 5-Gy increase in vertebral dose to single vertebrae and a 1-time increase in RT fraction with higher risk of vertebral fracture. Adding RT factors (vertebral dose and fraction) and mean vertebral hounsfield unit to the Cox models containing conventional clinical risk factors significantly improved the χ2 value for predicting vertebral fractures (all P < .001). This study revealed RT, as well as increased vertebral dose and RT fractions, as a significant, consistent, and strong vertebral fracture predictor in ESCC. Combined vertebral dose, RT fractions, and vertebral hounsfield unit provided optimal risk stratification for ESCC patients.

PTBP1 plays an important role in the development of gastric cancer.

BACKGROUND: Polypyrimidine tract binding protein 1 (PTBP1) has been found to play an important role in the occurrence and development of various tumors. At present, the role of PTBP1 in gastric cancer (GC) is still unknown and worthy of further investigation. METHODS: We used bioinformatics to analyze the expression of PTBP1 in patients with GC. Cell proliferation related experiments were used to detect cell proliferation after PTBP1 knockdown. Skeleton staining, scanning electron microscopy and transmission electron microscopy were used to observe the changes of actin skeleton. Proliferation and actin skeleton remodeling signaling pathways were detected by Western Blots. The relationship between PTBP1 and proliferation of gastric cancer cells was further detected by subcutaneous tumor transplantation. Finally, tissue microarray data from clinical samples were used to further explore the expression of PTBP1 in patients with gastric cancer and its correlation with prognosis. RESULTS: Through bioinformatics studies, we found that PTBP1 was highly expressed in GC patients and correlated with poor prognosis. Cell proliferation and cycle analysis showed that PTBP1 down-regulation could significantly inhibit cell proliferation. The results of cell proliferation detection related experiments showed that PTBP1 down-regulation could inhibit the division and proliferation of GC cells. Furthermore, changes in the morphology of the actin skeleton of cells showed that PTBP1 down-regulation inhibited actin skeletal remodeling in GC cells. Western Blots showed that PTBP1 could regulate proliferation and actin skeleton remodeling signaling pathways. In addition, we constructed PTBP1 Cas9-KO mouse model and performed xenograft assays to further confirm that down-regulation of PTBP1 could inhibit the proliferation of GC cells. Finally, tissue microarray was used to further verify the close correlation between PTBP1 and poor prognosis in patients with GC. CONCLUSIONS: Our study demonstrates for the first time that PTBP1 may affect the proliferation of GC cells by regulating actin skeleton remodeling. In addition, PTBP1 is closely related to actin skeleton remodeling and proliferation signaling pathways. We suppose that PTBP1 might be a potential target for the treatment of GC.

Population prevalence of antiretroviral therapy sharing and its association with HIV viremia in rural Uganda: a cross-sectional population-based study.

INTRODUCTION: Antiretroviral treatment (ART) sharing has been reported among fishermen and sex workers in Uganda and South Africa. However, no population-based studies have documented ART diversion prevalence (including sharing [giving/receiving], buying and selling) or its relationship with viremia among men and women living with HIV in Africa. METHODS: In 2018-2020, we surveyed people living with HIV aged 15-49 years in 41 communities in the Rakai Community Cohort Study, a population-based cohort in south-central Uganda. We assessed the prevalence and correlates of self-reported lifetime and past-year ART diversion, stratifying by age and gender and documenting sources of diverted drugs. We used log-binomial regression to quantify the relationship between diversion patterns and viremia (viral load >40 copies/ml), reported as unadjusted and adjusted prevalence ratios (aPR) with 95% confidence intervals (CI). RESULTS: Of 2852 people living with HIV and self-reporting current ART use, 266 (9.3%) reported lifetime ART diversion. Giving/receiving drugs were most common; few participants reported buying, and none reported selling. Men (12.9%) were more likely to report lifetime diversion than women (7.4%), with men aged 25-34 reporting high levels of sharing (18.9%). Friends were the most common sources of shared drugs, followed by spouses/sexual partners. Patterns of lifetime and past-year diversion were similar. Among participants with viral load results, 8.6% were viraemic. In adjusted analyses, people who reported only giving ART were nearly twice as likely to be viraemic than those who reported no diversion (aPR: 1.94, 95% CI: 1.10-3.44), and those reporting only receiving ART were less likely to exhibit viremia (aPR: 0.46, 95% CI: 0.12-1.79), although the latter was not statistically significant. Reporting both giving and receiving ART was not associated with viremia (aPR: 0.79, 95% CI: 0.43-1.46). Reporting buying ART, though rare, was also correlated with higher rates of viremia, but this relationship was not statistically significant (aPR: 1.98, 95% CI: 0.72-5.45). CONCLUSIONS: ART sharing is common among persons reporting ART use in rural Uganda, particularly among men. Sharing ART was associated with viremia, and receiving ART may facilitate viral suppression. HIV programmes may benefit from considering ART sharing in counselling messages.

Image acquisition as novel colonoscopic quality indicator: a single-center retrospective study.

Purpose: In order to reduce the incidence and mortality of colorectal cancer, improving the quality of colonoscopy is the top priority. At present, the adenoma detection rate is the most used index to evaluate the quality of colonoscopy. So, we further verified the relevant factors influencing the quality of colonoscopy and found out the novel quality indicators by studying the relationship between the influencing factors and the adenoma detection rate. Materials/methods: The study included 3824 cases of colonoscopy from January to December 2020. We retrospectively recorded the age and sex of the subjects; the number, size, and histological features of lesions; withdrawal time and the number of images acquired during colonoscopy. We analyzed the associated factors affecting adenoma and polyp detection, and verified their effectiveness with both univariate and multivariate logistic regression analyses. Results: Logistic regression analyses showed that gender, age, withdrawal time and the number of images acquired during colonoscopy could serve as independent predictors of adenoma/polyp detection rate. In addition, adenoma detection rate (25.36% vs. 14.29%) and polyp detection rate (53.99% vs. 34.42%) showed a marked increase when the number of images taken during colonoscopy was ≥29 (P<0.001). Conclusions: Gender, age, withdrawal time and the number of images acquired during colonoscopy are influencing factors for the detection of colorectal adenomas and polyps. And we can gain higher adenoma/polyp detection rate when endoscopists capture more colonoscopic images.

Atomic-scale insights into the interfacial charge transfer in a NiO/CeO2 heterostructure for electrocatalytic hydrogen evolution.

To understand the underlying mechanism of the interfacial charge transfer and local chemical state variation in the nonprecious-based hydrogen evolution reaction (HER) electrocatalysts, a model system of the NiO/CeO2 heterostructure was chosen for investigation using a combination of the advanced electron microscopic characterization and first-principles calculations. The results directly proved that interfacial charge transfer occurs from Ni to Ce, leading to reduction in the valence state of Ce and increased formation of VO. This would optimize ΔGH* and facilitate the hydrogen evolution process, resulting in outstanding HER performance in 1 M KOH with a low overpotential of 99 mV at the current density of 10 mA•cm-2 and a modest Tafel slope of 78.4 mV•dec-1 for the NiO/CeO2 heterostructure sample. Therefore, the improved HER performance could be attributed to the synergistic coupling interactions and electron redistribution at the interface of NiO and CeO2. These results concretely demonstrate the direct determination of the interfacial structure of the heterostructure and provide atomistic insights to unravel the underlying mechanism of interfacial charge transfer induced HER performance improvement.

The anti-tumor effects of Celastrus orbiculatus Thunb. and its monomer composition: A review.

ETHNOPHARMACOLOGICAL RELEVANCE: Celastrus orbiculatus Thunb. has been included in "The Plant List" (http://www. theplantlist.org) and is the most widely researched species in its genus. It is called Nanshe Teng in China. Celastrus orbiculatus Thunb. is a plant of Euonymus and it's medicinal part is the vine and stem. It is also called Alias Dragon grass, Yellow Yine, etc. It has good anti-tumor, anti-inflammatory and other effects. More and more studies have shown that Celastrus orbiculatus Thunb. has a significant therapeutic effect on a variety of malignant tumors. The research on Celastrus orbiculatus Thunb. has a good application prospect for the development of anti-tumor drugs. However, no systematic reports on Celastrus orbiculatus Thunb. have been published before. AIM OF THE REVIEW: This paper summarizes the metabolic products for anti-tumor and the mechanism for anti-tumor of Celastrus orbiculatus Thunb. to provide reference for further development and research. MATERIALS AND METHODS: The relevant information on Celastrus orbiculatus Thunb. was collected from the scientific databases including PubMed, CNKI, ScienceDirect, Wiley, Springer, Web of Science, Google Scholar, Baidu Scholar, Pharmacopoeia of the People's Republic of China and Flora Republicae Popularis Sinicae, etc. RESULTS: At present, more than 200 compounds have been identified from Celastrus orbiculatus Thunb., including terpenoids, flavonoids, phenylpropanoids, polyketides and benzene derivatives, etc. Pharmacological studies have shown that Celastrus orbiculatus Thunb. has a variety effects of inhibiting tumor cell proliferation, inducing tumor cell apoptosis, inhibiting tumor cells invasion, metastasis and angiogenesis, reversing multi-drug resistance, and also collaborativing Micro RNA to inhibit tumor growth, etc. It has a significant effect on gastric cancer, liver cancer, lung cancer, etc. The extracts of Celastrus orbiculatus Thunb. have been widely used in experiments, and the toxic and side effects are small. CONCLUSIONS: Celastrus orbiculatus Thunb. is rich in chemical constituents, diverse in pharmacological activities and abundant in resources, which is widely used in clinics from traditional to modern. However, there is no systematic report on the chemical compounds and anti-tumor effects of Celastrus orbiculatus Thunb. We organize and summarize it to provide reference for further development and research.

Antibiotic Resistance of Helicobacter pylori and Related Risk Factors in Yangzhou, China: A Cross-Sectional Study.

BACKGROUND: The antibiotic resistance of Helicobacter pylori (H. pylori) is a common cause of treatment failure. Previous studies showed that H. pylori resistance may be related to some characteristics of patients. This study intended to investigate the resistance of H. pylori to five commonly used antibiotics and risk factors in Yangzhou, China. METHODS: We recruited the subjects who joined the endoscopic screening program organized by the Affiliated Hospital of Yangzhou University between April 2018 and September 2019 and endoscopists would take biopsy samples from the antrum and the corpus of the stomach. The antrum biopsy specimens were used to culture H. pylori. Next, we extracted DNA from H. pylori strains and performed the specific DNA amplification. Finally, we use gene chip technology to test the susceptibility to clarithromycin, levofloxacin, metronidazole, amoxicillin and tetracycline. Multivariate logistic analyses were also performed to determine the risk factors for antibiotic resistance of H. pylori. RESULTS: A total of 461 H. pylori strains were finally collected. The resistance rate of H. pylori to clarithromycin, levofloxacin, metronidazole, amoxicillin and tetracycline was 41.0%, 44.9%, 38.8%, 6.3% and 1.1%, respectively. In addition, 16 multi-resistance patterns were detected, and strains resistant to all five antibiotics were not found. Multivariate analysis showed that past medical history and clinical outcomes were significantly associated with the resistance to clarithromycin. Drinking, gastrointestinal symptoms and a family history of gastric cancer were significantly associated with the resistance of H. pylori to levofloxacin. Especially gastrointestinal symptoms were significantly associated with the resistance of H. pylori to any antibiotic. CONCLUSION: The resistance rates of H. pylori to clarithromycin, levofloxacin and metronidazole were very high in Yangzhou, China, various factors were related to bacterial resistance, and grasping these influencing factors can guide treatment.

Celastrus orbiculatus Thunb. extract inhibits EMT and metastasis of gastric cancer by regulating actin cytoskeleton remodeling.

ETHNOPHARMACOLOGICAL RELEVANCE: The traditional Chinese medicine herb Celastrus orbiculatus Thunb. is an important folk medicinal plant in China that has been used as an anti-inflammatory, antitumor, and analgesic in various diseases. Recent years, many studies have reported the significant effects of Celastrus orbiculatus Thunb. extract (COE) on gastric cancer. However, the specific mechanism by which COE regulates gastric cancer cytoskeleton remodeling and thus inhibits EMT has not yet been reported. AIM OF STUDY: To study the effect and mechanism of COE in inhibiting the epithelial-mesenchymal transition (EMT) and metastasis of gastric cancer cells, laying an experimental foundation for the clinical application and further development of COE. METHODS: The high-content cell dynamic tracking system was used to continuously track the trajectory of cell movement in real time. Through the high-content data, the average movement distance and movement speed of the cells are calculated. Additionally, the dynamic images of the cell movement in the high-content imaging system are derived to analyze the impact of COE on the movement of gastric cancer cells. Cytoskeleton staining experiment was performed to detect the effect of COE on the assembly of gastric cancer cell cytoskeleton proteins. Western blot was employed to detect the changes of EMT and metastasis-related proteins in the gastric cancer cells treated by COE. The effect of COE on the key regulatory protein Cofilin-1 (CFL1) of cell movement was examined by Western blot and protein degradation experiment. The effect of COE on EMT and metastasis of the gastric cancer cells lacking CFL1 was assessed by a transwell assay. The in vivo inhibitory effect of COE on EMT and metastasis of gastric cancer was determined by the animal living image system. IHC assays were used to detect the levels of EMT-related proteins in COE reversal in vivo. RESULT: The results showed that the movement distance and average movement speed of gastric cancer cells after COE treatment were significantly lower than those of the control group. Cytoskeleton staining experiments revealed that COE can significantly change the distribution of skeletal proteins in gastric cancer cells. Additionally, COE treatment significantly reduced the expression of Matrix metalloproteinases (MMP-2, MMP-9) and other proteins. Furthermore, COE can significantly accelerate the degradation of CFL1 protein, and both COE treatment and CFL1 deletion can significantly inhibit EMT and metastasis of gastric cancer cells. Lastly, the number of peritoneal metastases of gastric cancer cells was significantly reduced in animals after COE treatment. COE can reverse the levels of EMT-related proteins while reducing the expression levels of CFL1 protein in vivo. CONCLUSION: COE can significantly inhibit EMT and metastasis of gastric cancer cells in vivo and in vitro. This effect may be achieved by reducing the stability of CFL1 and inhibiting the assembly of actin in gastric cancer cells.