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Abstract Background Adolescent malignant-bone tumor patients' fear of cancer recurrence is a significant psychological issue, and exploring the influencing factors associated with fear of cancer recurrence in this population is important for developing effective interventions. This study is to investigate the current status and factors influencing fear of cancer recurrence (FCR) related to malignant bone-tumors in adolescent patients, providing evidence for future targeted mental health support and interventions. Design A cross-sectional survey. Methods In total, 269 adolescent malignant-bone tumor cases were treated at two hospitals in Zhejiang Province, China from January 2023 to December 2023. Patients completed a General Information Questionnaire, Fear of Progression Questionnaire-Short Form (FoP-Q-SF), Family Hardiness Index (FHI), and a Simple Coping Style Questionnaire (SCSQ). Univariate and multivariable logistic regressions analysis were used to assess fear of cancer recurrence. Results A total of 122 (45.4%) patients experienced FCR (FoP-Q-SF ≥ 34). Logistic regression analysis analyses showed that per capita-monthly family income, tumor stage, communication between the treating physician and the patient, patient's family relationships, family hardiness a positive coping score, and a negative coping score were the main factors influencing FCR in these patients (P

Climate change is significantly and enduringly impacting global agricultural supply chains (ASCs), underscoring the urgent need to enhance their climate resilience. This study aims to identify key strategies for building agricultural supply chain resilience (ASCRes) in the context of climate change and their interrelationships. Through a comprehensive literature review and expert consultations, a framework of 12 strategies was developed. Using survey data from 312 Chinese ASC companies, BP-DEMATEL-ISM and PLS-SEM methods were employed to conduct causal analysis and factor level evaluation. The results indicate that “diversification of agricultural products and supply chain (SC) networks,” “Agriculture 4.0 and digital transformation,” and “taking proactive climate action” are critical strategies to enhance ASCRes in the context of climate change. These findings can provide theoretical basis for farmers, ASC companies, and governments to cope with the impact of climate change, so as to build more robust ASC systems.

Abstract Background In patients with hypertrophic cardiomyopathy (HCM), ischemic myocardial fibrosis assessed by late gadolinium enhancement (I-LGE) using cardiovascular magnetic resonance (CMR) have been reported. However, the clinical significance of I-LGE has not been completely understood. We aim to evaluate the I-LGE differ phenotypically from HCM without LGE or nonischemic myocardial fibrosis assessed by late gadolinium enhancement (NI-LGE) in the left ventricle (LV). Methods The patients with HCM whom was underwent CMR were enrolled, using cine cardiac magnetic resonance to evaluate LV function and LGE to detect the myocardial fibrosis. Three groups were assorted: 1) HCM without LGE; 2) HCM with LGE involved the subendocardial layer was defined as I-LGE; 3) HCM with LGE not involved the subendocardial layer was defined as NI-LGE. Results We enrolled 122 patients with HCM in the present study. LGE was detected in 58 of 122 (48%) patients with HCM, and 22 (18%) of patients reported I-LGE. HCM with I-LGE had increased higher left ventricular mass index (LVMI) (P

The Belt and Road initiative is an important strategy of the Chinese government to promote international cooperation, and China-Cambodia cooperation is one of the important initiatives to implement the Belt and Road initiative. In recent years, Cambodia's four coastal provinces have experienced rapid population growth, accelerated urbanization and increased marine exploitation activities, which have put tremendous pressure on the coastal zone ecosystem and urgently require the establishment of a reasonable and effective coastal zone management system. By combing through the current Cambodia's coastal zone management system and institutions, this paper finds that there are five major problems in the management of Cambodian coastal zone, such as lack of comprehensive laws and regulations, poor management of pollutant discharge, enforcement and supervision policies to be improved, insufficient ability to obtain data, and insufficient public participation. The paper puts forward suggestions on improving the coastal zone management system, strengthening coastal zone management capacity building, and enhancing public awareness of coastal zone protection. On this basis, three directions for China-Cambodian coastal zone management cooperation are proposed to provide references for improving Cambodia′s coastal zone management system and promoting in-depth cooperation in the field of coastal zone management between China and Cambodia.

ObjectiveThis study aimed to investigate the health performance of the Urban and Rural Residents Medical Insurance (URRMI) scheme in China and to make practical recommendations and scientific references for its full implementation in China.MethodsThis is a panel study that uses data from the China Family Panel Studies from 2018 to 2020, which is separated into treated and control groups each year, utilizing the key approach of propensity score matching and difference-in-difference (PSM-DID). Using 1-to-1 k-nearest neighbor matching, we proportionate the baseline data. Using difference-in-difference model, we examine the mean treatment impact of the outcome variables. Using a 500-time random sample regression model, we validate the robustness of the model estimation.ResultsThe result was credible after matching, minimizing discrepancies. Good overall performance of self-rated health with an average Hukou status of, respectively, 0.8 and 0.4 in the treated and control group, primarily in rural and urban regions separately. The participation of URRMI significantly impacted self-rated health of residents, with a 0.456-unit improvement probabilities observed (p

The running mode and existing issues of current resource scheduling system operation model of TT＆amp;C network were discussed firstly.Then the development trends of future resource scheduling and management models were summarized, included integration of data transmission, automation of system operation, intelligence of algorithm allocation, coexistence of random access and pre-allocation.In the end, accorded to the management demands of integration, automation and intelligentization, the operating framework of the future resource scheduling model was put forward.After that, the key technologies which need to be broken through of the framework were researched deeply.And the further construction object of resource scheduling research was proposed in order to provided a reference for subsequent engineering applications.

In the process of laser cladding, there are usually problems such as powder plugging and uneven delivery, which affect the quality of the final cladding layer. Therefore, powder convergence characteristics in laser cladding need to be further improved. Gas–solid two-phase flow technology has been widely used in the study of powder flow characteristics because it can precisely regulate the interaction between carrier air and powder flow. In this paper, we systematically review the current status of gas–solid two-phase flow in the field of laser cladding powder, deeply analyze the latest optimization progress of laser cladding nozzle design, and comprehensively explain the key progress of gas–solid two-phase flow technology in improving the uniformity and efficiency of powder field distribution. At the end of this paper, the research results are summarized and a series of prospective prospects are proposed, aiming to provide a valuable reference framework and directional guidance for the subsequent related research.

Background: Methamphetamine is an illegal drug that poses serious public health concerns worldwide. Previous studies have demonstrated a strong association between methamphetamine abuse and non-lethal haemorrhagic stroke. Ischaemic stroke after methamphetamine intake is less common than haemorrhagic stroke. The present study investigated the clinical features and potential pathogenesis in a young methylamphetamine addict that presented with acute ischaemic stroke and reversible middle cerebral artery (MCA) occlusion. Methods: A retrospective data analysis was performed for the young methylamphetamine addict admitted to a hospital for acute ischaemic stroke followed by a literature review to explore the possible pathogenesis. Results: The patient had been receiving methamphetamine for past 2 years. His recurrent headache occurred half an hour after each consumption and was relieved within a few hours. The patient was admitted for acute ischaemic stroke. Urine toxicology screening was positive for methamphetamine. Magnetic resonance angiography revealed occlusion of the right MCA. After discontinuing medication and routine treatment, digital subtraction angiography revealed normal blood flow in the right MCA, indicating reversible MCA occlusion. Conclusion: For young patients with a stroke, a thorough investigation of the history of illicit drug use and toxicological screening of urine and serum samples should be performed. Young methamphetamine users need to be aware of the elevated risk of stroke as well as early signs and symptoms. Transient headaches in young methamphetamine users may be caused by cerebral vasospasms, suggesting the possibility of future catastrophic stroke events.

Based on a mechanism study, the regulation and control mechanism of the hydraulic energy storage system is elaborated in detail, and the regulation and control strategy is formulated for the hydraulic power generation system under the condition of a stable random wave, and the working mode of the wave power generation system is deeply studied. According to the characteristics of a hydraulic system, a control strategy of a three-position four-way electromagnetic directional valve suitable for adaptive energy storage system is proposed. In order to verify the feasibility of the control strategy, a mathematical model of the hydraulic cylinder displacement control system is designed based on the Matlab/Simulink platform, and a PID control strategy is introduced to build a wave simulation loop. Amesim and Simulink co-simulation is used to verify the performance of the wave simulation circuit and the hydraulic power generation system. The simulation results show that the maximum error rate is only 0.8% after PID control is added to the wave power generation simulation loop, the displacement of the hydraulic cylinder can reach the expected value, and the random wave motion can be simulated effectively. In the hydraulic system of wave energy generation, the proposed adaptive control strategy can accelerate the system stability process, reduce the power overshoot significantly, and convert wave energy into electric energy more effectively.

Abstract Background Increased preoperative red cell distribution width (RDW) is associated with poor prognosis in several cancers, but the relationships between preoperative RDW and changes in RDW (ΔRDW) and colorectal cancer (CRC) prognosis remain unclear. Our study aimed to demonstrate the prognostic significance of increased preoperative RDW and ΔRDW for CRC. Methods In this retrospective analysis, we enrolled 833 patients who underwent CRC surgery between 2015 and 2019 at the Affiliated Hospital of Xuzhou Medical University, China. ΔRDW in our study was defined as RDW at 1 month after discharge minus preoperative RDW. According to receiver operating characteristic (ROC) curve analysis, we used cut‐off values of 13.5% for RDW, 0.9% for ΔRDW. The cumulative survival rate was determined using the Kaplan–Meier method, and significant differences were evaluated by the log‐rank test. Multivariable Cox regression model was applied to clarify the independent risk factors for overall survival (OS), which were used to construct a nomogram prediction model. The competing risk method was also applied, and we analyzed only patients with early‐stage disease (stage 0‐II) for sensitivity analysis. Results Multivariable Cox regression analysis demonstrated that age, RDW, ΔRDW, postoperative adjuvant chemotherapy, CEA, CA19‐9, ASA, TNM stage, and pathological type were independent factors for OS in CRC patients (all p

Abstract Background Trilateral South‒South cooperation is envisioned as an equal and empowering partnership model but still faces certain challenges. This study addresses whether and how trilateral South‒South cooperation can transform traditional development assistance for health (DAH) and explores the opportunities and challenges of trilateral South‒South cooperation for transforming future DAH, in the theme of “the emerging development partner’s DAH transformation facilitated by a multilateral organization”. Methods We evaluate a maternal, newborn, and child health (MNCH) project involving the Democratic Republic of Congo (DRC), the United Nations Children’s Fund (UNICEF), and China (hereinafter referred to as the “DRC–UNICEF–China project”). We analyze data from project documents and seventeen semi-structured interviews using a pragmatic analytical framework based on the DAH program logic model and the OECD’s trilateral cooperation framework. Results Evidence from the DRC–UNICEF–China MNCH project suggests that trilateral South‒South cooperation facilitated by a multilateral organization can provide transformative opportunities for emerging development partners’ DAH to generate and deliver context-based, demand-oriented solutions, harmonize rules and procedures, institutionalize mutual learning and knowledge sharing, and increase the visibility of emerging development partners as sources for South‒South development experience transfer. However, the project revealed some challenges, including the neglect of key stakeholders in the complex governance structure, the high transaction costs needed to ensure transparency, and the harm local absence of the emerging development partner poses to long-term DAH engagement. Conclusions This study echoes some of the findings in trilateral SSC literature that claim power structures and philanthropic, normative justification for health equity are often juxtaposed in trilateral SSC partnerships. The opportunities offered by the DRC–UNICEF–China project align with China’s cognitive learning process for strengthening international engagement and global image building. However, challenges may arise as a result of complex governance structures and the entrustment of facilitating partners, which can threaten the effectiveness of trilateral cooperation. We call for strengthening the beneficiary partner’s ownership at all levels, engaging the emerging development partner to better understand the beneficiary partner’s local context(s) and needs, and ensuring available resources to support programmatic activities and long-term partnerships for the health and well-being of the beneficiaries.

Abstract Aim To determine differences in kinesiophobia levels among COPD patients at different time points 6 months after discharge；To identify potential subgroups of COPD patients who perceived different levels of kinesiophobia over time；and to evaluate differences in identified subgroups based on demographic and disease‐related characteristics Design An observational longitudinal study. Methods OPD patients hospitalized in respiratory department of a grade A hospital in Huzhou city from October 2021 to May 2022 were selected as the research objects. TSK scale was used to evaluate the level of kinesiophobia at discharge (T1), 1 month after discharge (T2), 4 months after discharge (T3) and 6 months after discharge (T4). The kinesiophobia level scores at different time points were compared using latent class growth modelling. ANOVA and Fisher's exact tests were used to test differences in demographic characteristics，and univariate analysis and multinomial logistic regression analysis were used to explore the influencing factors. Results During the first 6 months after discharge, kinesiophobia levels decreased significantly in the entire sample of COPD patients. The best‐fitting group‐based trajectory model described three distinctive trajectories: Low kinesiophobia group (31.4% of sample); Medium kinesiophobia group (43.4% of sample)；and High kinesiophobia group (25.2% of sample). Logistic regression results showed that sex, age, course of disease, pulmonary function, education level, BMI, the level of pain, MCFS and mMRC were influencing factors of kinesiophobia trajectory in COPD patients (p

Abstract Primary seminal vesicle Burkitt lymphoma (PSBL) is rare that is not frequently reported. Burkitt lymphoma is often associated with extranodal organs. The diagnosis of carcinoma in seminal vesical can be difficult. In this report, we present a missed case of PSBL in a male patient who underwent radical prostate and seminal vesicle resection. We retrospectively analyzed the clinical data to explore the diagnosis, pathological features, treatment, and prognosis of this rare disease. The patient visited our hospital for dysuria, and the serum prostate-specific antigen (PSA) was moderately elevated. Pelvic magnetic resonance imaging (MRI) and computed tomography (CT) scans suggested a notable enlargement of the seminal vesicle. The patient then underwent radical surgery and the pathology diagnosis revealed Burkitt lymphoma. The diagnosis of PSBL is difficult, and the prognosis is generally poorer than that of other types of lymphoma. However, earlier diagnosis and treatment may help to improve the survival rate among patients with Burkitt lymphoma.

Abstract Background Distant metastasis is the main cause of mortality in colorectal cancer (CRC) patients. N1‐methyladenosine (m1A) is a type of epitranscriptome modification. While its regulatory effect on mRNA and its role in CRC metastasis remain unclear. Methods The m1A methylation profile of mRNAs in CRC was revealed by m1A methylated RNA immunoprecipitation sequencing. The expression of MFAP2 in tumor tissues was measured by immunohistochemistry and then correlated with the clinical characteristics and prognosis of CRC patients. The role of MFAP2 in the invasiveness of CRC cells was evaluated by transwell assays and peritoneal metastatic model in nude mice. The downstream targets of MFAP2 was screened by mass spectrometry analysis. Then the role of MFAP2‐CLK3 signaling axis was verified by cotransfecting MFAP2 siRNA and CLK3 plasmid in CRC cells. Results Microfibril associated protein 2 (MFAP2) mRNA was overexpressed and m1A‐hypermethylated in CRC. High expression of MFAP2 was closely related to lymph node metastasis and distant metastasis, leading to poor prognosis in patients with CRC. In vivo and in vitro studies showed that silencing of MFAP2 inhibited the migration, invasion and metastasis of CRC cells. CDC Like Kinase 3 (CLK3) was a potential downstream target of MFAP2. Further studies showed that MFAP2 depletion might induce autophagic degradation of CLK3, and the role of MFAP2 in the invasiveness of CRC cells was dependent on CLK3. Conclusions Our results uncover a newly identified MFAP2‐CLK3 signaling axis, which is a potential therapeutic target for CRC metastasis.

Facing the increasingly complex and uncertain external environment, the reasonable control of investment risk is the key to realizing the sound operation and high-quality development of enterprises. Based on the innovation perspective, this paper takes A-share non-financial listed companies from 2007 to 2021 as the research sample to explore the impact of the corporate risk-taking level on the high-quality development of enterprises and examines the transmission mechanism of the relationship between the two from the perspectives of innovation efficiency, innovation input, and innovation output. It is found that enterprise risk-taking significantly inhibits the high-quality development of enterprises, by reducing innovation efficiency; innovation efficiency plays a mediating role in the influence of the relationship between the two, which is mainly due to the fact that enterprise risk-taking increases the innovation inputs of enterprises but reduces the innovation outputs of enterprises, and then reduces the innovation efficiency of enterprises and inhibits the high-quality development of enterprises. This heterogeneity study finds that the inhibitory effect of corporate risk-taking on the high-quality development of firms is more pronounced among manufacturing firms, small-scale firms, and firms with higher capital intensity. The findings of this study provide both guidance to help enterprises to reduce risky investment decision-making behaviors and experience for regulators to effectively promote the formulation of policies related to the high-quality development of the real economy.

Colorectal cancer (CRC) is one of the most common malignancies, and the main cause of death from CRC is tumor metastasis. m1A RNA modification plays critical role in many biological processes. However, the role of m1A modification in CRC remains unclear. Here, we find that the m1A demethylase alkB homolog 1, histone H2A dioxygenase (ALKBH1) is overexpressed in CRC and is associated with metastasis and poor prognosis. Upregulation of ALKBH1 expression promotes CRC metastasis in vitro and in vivo. Mechanistically, knockdown of ALKBH1 results in a decrease in methyltransferase 3, N6‐adenosine‐methyltransferase complex catalytic subunit (METTL3) expression, probably due to m1A modification of METTL3 mRNA, followed by m6A demethylation of SMAD family member 7 (SMAD7) mRNA. In addition, downregulation of SMAD7 establishes an aggressive phenotype. More importantly, the cell migration and invasion defects caused by ALKBH1 depletion or METTL3 depletion are significantly reversed by SMAD7 silencing. Considering these results collectively, we propose that ALKBH1 promotes CRC metastasis by destabilizing SMAD7 through METTL3.

Abstract Background Albuminuria is a hallmark of diabetic kidney disease (DKD) that promotes its progression, leading to renal fibrosis. Renal macrophage function is complex and influenced by macrophage metabolic status. However, the metabolic state of diabetic renal macrophages and the impact of albuminuria on the macrophage metabolic state are poorly understood. Methods Extracellular vesicles (EVs) from tubular epithelial cells (HK-2) were evaluated using transmission electron microscopy, nanoparticle tracking analysis and western blotting. Glycolytic enzyme expression in macrophages co-cultured with HSA-treated HK-2 cell-derived EVs was detected using RT-qPCR and western blotting. The potential role of EV-associated HIF-1α in the mediation of glycolysis was explored in HIF-1α siRNA pre-transfected macrophages co-cultured with HSA-treated HK-2 cell-derived EVs, and the extent of HIF-1α hydroxylation was measured using western blotting. Additionally, we injected db/db mice with EVs via the caudal vein twice a week for 4 weeks. Renal macrophages were isolated using CD11b microbeads, and immunohistofluorescence was applied to confirm the levels of glycolytic enzymes and HIF-1α in these macrophages. Results Glycolysis was activated in diabetic renal macrophages after co-culture with HSA-treated HK-2 cells. Moreover, HSA-treated HK-2 cell-derived EVs promoted macrophage glycolysis both in vivo and in vitro. Inhibition of glycolysis activation in macrophages using the glycolysis inhibitor 2-DG decreased the expression of both inflammatory and fibrotic genes. Mechanistically, EVs from HSA-stimulated HK-2 cells were found to accelerate macrophage glycolysis by stabilizing HIF-1α. We also found that several miRNAs and lncRNAs, which have been reported to stabilize HIF-1α expression, were increased in HSA-treated HK-2 cell-derived EVs. Conclusion Our study suggested that albuminuria induced renal macrophage glycolysis through tubular epithelial cell-derived EVs by stabilizing HIF-1α, indicating that regulation of macrophage glycolysis may offer a new treatment strategy for DKD patients, especially those with macroalbuminuria.

Abstract Background The prognosis of patients with advanced gastric cancer (GC) remains unsatisfactory owing to distant metastasis and resistance to concurrent systemic therapy. Cancer-associated fibroblasts (CAFs), as essential participators in the tumor microenvironment (TME), play a vital role in tumor progression. Thus, CAFs-targeting therapy is appealing for remodeling TME and sensitizing GC to conventional systemic therapy. Methods Amphiphilic SN38 prodrug polymeric micelles (PSN38) and encapsulated the hydrophobic esterase-responsive prodrug of Triptolide (TPL), triptolide-naphthalene sulfonamide (TPL-nsa), were synthesized to form PSN38@TPL-nsa nanoparticles. Then, CAFs were isolated from fresh GC tissues and immortalized. TPL at low dose concentration was used to investigate its effect on CAFs and CAFs-induced GC cells proliferation and migration. The synergistic mechanism and antitumor efficiency of SN38 and TPL co-delivery nanoparticle were investigated both in vitro and in vivo. Results Fibroblast activation protein (FAP), a marker of CAFs, was highly expressed in GC tissues and indicated poorer prognosis. TPL significantly reduced CAFs activity and inhibited CAFs-induced proliferation, migration and chemotherapy resistance of GC cells. In addition, TPL sensitized GC cells to SN38 treatment through attenuated NF-κB activation in both CAFs and GC cells. PSN38@TPL-nsa treatment reduced the expression of collagen, FAP, and α-smooth muscle actin (α-SMA) in tumors. Potent inhibition of primary tumor growth and vigorous anti-metastasis effect were observed after systemic administration of PSN38@TPL-nsa to CAFs-rich peritoneal disseminated tumor and patient-derived xenograft (PDX) model of GC. Conclusion TPL suppressed CAFs activity and CAFs-induced cell proliferation, migration and chemotherapy resistance to SN38 of GC. CAFs-targeted TPL and SN38 co-delivery nanoparticles exhibited potent efficacy of antitumor and reshaping TME, which was a promising strategy to treat advanced GC. Graphical Abstract

BackgroundAdherence to a healthy lifestyle could reduce the risk of hypertension and diabetes in general populations; however, whether the associations exist in subjects with dyslipidemia remains unclear. This study aimed to investigate the integrated effect of lifestyle factors on the risk of hypertension, type 2 diabetes mellitus (T2DM), and their comorbidity among subjects with dyslipidemia.MethodsIn total of 9,339 subjects with dyslipidemia were recruited from the baseline survey of the Guangzhou Heart Study. A questionnaire survey and medical examination were performed. The healthy lifestyle score (HLS) was derived from five factors: smoking, alcohol drinking, diet, body mass index, and leisure-time physical activity. Odds ratios (ORs) with 95% confidence interval (95% CI) were calculated by using the logistic regression model and the multinomial logistic regression after adjusting for confounders.ResultsThe prevalence of hypertension, T2DM, and their comorbidity was 47.65, 16.02, and 10.10%, respectively. Subjects with a higher HLS were associated with a lower risk of hypertension, T2DM, and their comorbidity. In comparison to the subjects with 0–2 HLS, the adjusted ORs for subjects with five HLS was 0.48 (95% CI: 0.40–0.57) and 0.67 (95% CI: 0.54–0.84) for hypertension and T2DM. Compared with subjects with 0-2 HLS and neither hypertension nor T2DM, those with five HLS had a lower risk of suffering from only one disease (OR: 0.48, 95% CI: 0.40–0.57) and their comorbidity (OR: 0.35, 95% CI: 0.26–0.47).ConclusionsThe results suggest that the more kinds of healthy lifestyle, the lower the risk of hypertension, T2DM, and their comorbidity among subjects with dyslipidemia. Preventive strategies incorporating lifestyle factors may provide a more feasible approach for the prevention of main chronic diseases.

Abstract Background The effect of a combination of a goal-directed fluid protocol and preoperative carbohydrate loading on postoperative complications in elderly patients still remains unknown. Therefore, we designed this trial to evaluate the relative impact of preoperative carbohydrate loading and intraoperative goal-directed fluid therapy versus conventional fluid therapy (CFT) on clinical outcomes in elderly patients following gastrointestinal surgery. Methods This prospective randomized controlled trial with 120 patients over 65 years undergoing gastrointestinal surgery were randomized into a CFT group (n = 60) with traditional methods of fasting and water-deprivation, and a GDFT group (n = 60) with carbohydrate (200 ml) loading 2 h before surgery. The CFT group underwent routine monitoring during surgery, however, the GDFT group was conducted by a Vigileo/FloTrac monitor with cardiac index (CI), stroke volume variation (SVV), and mean arterial pressure (MAP). For all patients, demographic data, intraoperative parameters and postoperative outcomes were recorded. Results Patients in the GDFT group received significantly less crystalloids fluid (1111 ± 442.9 ml vs 1411 ± 412.6 ml; p 0.05). Conclusions Focused on elderly patients undergoing open gastrointestinal surgery, we found perioperative fluid optimisation may be associated with improvement of bowel function and a lower incidence of postoperative complications. Trial registration ChiCTR, ChiCTR1800018227 . Registered 6 September 2018 - Retrospectively registered.

Abstract Introduction Angiogenesis is a key factor in promoting tumor growth, invasion and metastasis. In this study we aimed to investigate the prognostic value of angiogenesis-related genes (ARGs) in gastric cancer (GC). Methods mRNA sequencing data with clinical information of GC were downloaded from The Cancer Genome Atlas (TCGA) and the Gene Expression Omnibus (GEO) databases. The differentially expressed ARGs between normal and tumor tissues were analyzed by limma package, and then prognosis‑associated genes were screened using Cox regression analysis. Nine angiogenesis genes were identified as crucially related to the overall survival (OS) of patients through least absolute shrinkage and selection operator (LASSO) regression. The prognostic model and corresponding nomograms were establish based on 9 ARGs and verified in in both TCGA and GEO GC cohorts respectively. Results Eighty-five differentially expressed ARGs and their enriched pathways were confirmed. Significant enrichment analysis revealed that ARGs-related signaling pathway genes were highly related to tumor angiogenesis development. Kaplan–Meier analysis revealed that patients in the high-risk group had worse OS rates compared with the low-risk group in training cohort and validation cohort. In addition, RS had a good prognostic effect on GC patients with different clinical features, especially those with advanced GC. Besides, the calibration curves verified fine concordance between the nomogram prediction model and actual observation. Conclusions We developed a nine gene signature related to the angiogenesis that can predict overall survival for GC. It’s assumed to be a valuable prognosis model with high efficiency, providing new perspectives in targeted therapy.

Abstract Background Distant metastasis (DM) is relatively rare in superficial gastric cancer (SGC), especially in patients without lymph node metastasis. This study aimed to explore the main clinical risk factors for DM in patients with superficial gastric cancer‐no lymph node metastasis (SGC‐NLNM) and the prognostic factors for patients with DM. Methods Records of patients with SGC‐NLNM between 2004 and 2015 were collected from the public Surveillance, Epidemiology, and End Results (SEER) database. Both univariate and multivariate logistic regressions were performed to analyze the clinical risk factors for DM. The Kaplan–Meier method and Cox regression model were used to identify prognostic factors for patients with DM. A nomogram was built based on multivariate logistic regression and evaluated by the C‐index, the calibration, and the area under the receiver operating characteristic curve (AUC). Results We developed and validated a nomogram to predict DM in patients with SGC‐NLNM, showing that race, age, primary site, depth, size, and grade were independent risk factors. The built nomogram had a good discriminatory performance, with a C‐index of 0.836 (95% confidence interval [CI]: 0.813–0.859). Calibration plots showed that the predicted DM probability was identical to the actual observations in both the training and validation sets. AUC was 0.846 (95% CI: 0.820–0.871) and 0.801 (95% CI: 0.751–0.850) in the training and validation sets, respectively. The results of the survival analysis revealed that surgery (hazard ratio [HR] = 0.249; 95% CI, 0.125–0.495), chemotherapy (HR = 0.473; 95% CI, 0.353–0.633), and grade (HR = 1.374; 95% CI, 1.018–1.854) were independent prognostic factors associated with cancer‐specific survival (CSS), but radiotherapy was not (log‐rank test, p = 0.676). Conclusions We constructed a sensitive and discriminative nomogram to identify high‐risk patients with SGC‐NLNM who may harbor dissemination at initial diagnosis. The tumor size and primary site were the largest contributors to DM prediction. Compared with radiotherapy, aggressive surgery, and chemotherapy may be better options for patients with DM.

Abstract Background Human defensin-5 (HD-5) is a key antimicrobial peptide which plays an important role in host immune defense, while the short half-life greatly limits its clinical application. The purpose of this study was to investigate the effects of an engineering probiotic producing HD-5 on intestinal barrier and explore its underlying mechanism Methods We constructed the pN8148-SHD-5 vector, and transfected this plasmid into Lactococcus lactis (L. lactis) to create the recombinant NZ9000SHD-5 strain, which continuously produces mature HD-5. NZ9000SHD-5 was administrated appropriately in a dextran sodium sulfate (DSS)-induced colitis model. Alterations in the wounded intestine were analyzed by hematoxylin–eosin staining. The changes of intestinal permeability were detected by FITC-dextran permeability test, the tight junction (TJ) proteins ZO-1 and occludin and cytokines were analyzed by western blotting or enzyme linked immunosorbent assay. In Caco-2 cell monolayers, the permeability were analyzed by transepithelial electrical resistance, and the TJ proteins were detected by western blotting and immunofluorescence. In addition, NF-κB signaling pathway was investigated to further analyze the molecular mechanism of NZ9000SHD-5 treatment on inducing intestinal protection in vitro. Results We found oral administration with NZ9000SHD-5 significantly reduced colonic glandular structure destruction and inflammatory cell infiltration, downregulated expression of several inflammation-related molecules and preserved epithelial barrier integrity. The same protective effects were observed in in vitro experiments, and pretreatment of macrophages with NZ9000SHD-5 culture supernatants prior to LPS application significantly reduced the expression of phosphorylated nuclear transcription factor-kappa B (NF-κB) p65 and its inhibitor IκBα. Conclusions These results indicate the NZ9000SHD-5 can alleviate DSS-induced mucosal damage by suppressing NF-κB signaling pathway, and NZ9000SHD-5 may be a novel therapeutic means for ulcerative colitis.

Kidney disease: Effect of an anti-aging protein An anti-ageing protein called Klotho helps protect against kidney failure in mice and human cells by silencing a long non-coding RNA molecule. The regulatory RNA involved, known as NEAT1, promotes cellular transformations associated with the disease process. A team led by Yao-Ming Xue from Southern Medical University in Guangdong, China, showed that levels of NEAT1 are elevated in mouse models of diabetic kidney disease and in injured human kidney calls. The identification of NEAT1 in kidney disease thus provides a novel therapeutic target. After demonstrating that Klotho and NEAT1 interact directly with each other in cells, they experimentally boosted Klotho expression and observed suppressed levels of NEAT1. As a consequence, the cells displayed lower levels of the proteins linked to the progressive deposition of fibrosis in the kidneys.

BackgroundMore and more evidence indicated that tumor deposit (TD) was significantly associated with local recurrence, distant metastasis (DM), and poor prognosis for patients with colorectal cancer (CRC). This study aims to explore the main clinical risk factors for the presence of TD in CRC patients with no DM (CRC-NDM) and the prognostic factors for TD-positive patients after surgery.MethodsThe data of patients with CRC-NDM between 2010 and 2017 were extracted from the Surveillance, Epidemiology, and End Results (SEER) database. A logistic regression model was used to identify risk factors for TD presence. Fine and Gray’s competing-risk model was performed to analyze prognostic factors for TD-positive CRC-NDM patients. A predictive nomogram was constructed using the multivariate logistic regression model. The concordance index (C-index), the area under the receiver operating characteristic (ROC) curve (AUC), and the calibration were used to evaluate the predictive nomogram. Also, a prognostic nomogram was built based on multivariate competing-risk regression. C-index, the calibration, and decision-curve analysis (DCA) were performed to validate the prognostic model.ResultsThe predictive nomogram to predict the presence of TD had a C-index of 0.785 and AUC of 0.787 and 0.782 in the training and validation sets, respectively. From the competing-risk analysis, chemotherapy (subdistribution hazard ratio (SHR) = 0.542, p < 0.001) can significantly reduce CRC-specific death (CCSD). The prognostic nomogram for the outcome prediction in postoperative CRC-NDM patients with TD had a C-index of 0.727. The 5-year survival of CCSD was 17.16%, 36.20%, and 63.19% in low-, medium-, and high-risk subgroups, respectively (Gray’s test, p

The relationship between the stress-strain characteristics of ice-containing unsaturated soil and its various physical properties has important implications for the design and construction of transportation and building projects. The study also reveals the varying phases of the substance that can be deposited within the pore space. During winter, the freezing-thawing cycles affect the various media that can be deposited within the soil pore space, such as water and other water. The presence of water and others in the soil’s pores can cause a freeze-thawing phenomenon and a significant change in the material’s elastic modulus. This paper presents a method that uses the representative elementary volume (REV) model to perform a representative state variable analysis on an unsaturated ice-containing soil with porosity. The three stress-strain REV models that were developed for the study were designed to analyze the properties of an unsaturated ice-containing soil under freezing-thawing conditions. Then a comprehensive analysis of the soil’s various components was performed. The effects of frozen soil on the change law of the relationship between different porous medium are studied. The study also explores the effects of the presence of porosity on the variation law of the frozen soil relationship between the stress-strain. The paper presents the study of the variation characteristics of the elastic modulus of permafrost soil. It also explores the various factors (porosity, moisture content, ice percentage, and tortuosity) that influence the stress-strain characteristics of unsaturated soil.

Introduction As a key event leading to tubulointerstitial fibrosis in diabetic kidney disease (DKD), epithelial–mesenchymal transition (EMT) has drawn increasing attention from researchers. The antiaging protein Klotho attenuates renal fibrosis in part by inhibiting ERK1/2 signaling in DKD. Early growth response factor 1 (Egr-1), which is activated mainly by ERK1/2, has been shown to play an important role in EMT. However, whether Klotho prevents EMT by inhibiting ERK1/2-dependent Egr-1 expression in DKD is unclear.The aim of this study was to investigate whether Klotho prevents EMT through Egr-1 downregulation by inhibiting the ERK1/2 signaling pathway in DKD.Research design and methods Male C57BL/6J mice fed an high-fat diet for 4 weeks received 120 mg/kg streptozotocin (STZ), which was injected intraperitoneally. Klotho and Egr-1 expression was detected in the renal cortices of these mice on their sacrifice at 6 and 12 weeks after STZ treatment. In In vitro studies, we incubated HK2 cells under high-glucose (HG) or transforming growth factor-β1 (TGF-β1) conditions to mimic DKD. We then transfected the cells with an Klotho-containing plasmid, Klotho small interfering RNA.Results Klotho expression was significantly decreased in the renal cortices of mice with diabetes mellitus (DM) compared with the renal cortices of control mice at 6 weeks after treatment and even more significantly decreased at 12 weeks. In contrast, Egr-1 expression was significantly increased in mice with DM compared with control mice only at 12 weeks. We also found that Klotho overexpression downregulated Egr-1 expression and the (p-ERK1/2):(ERK1/2) ratio in HG-treated or TGF-β1-treated HK2 cells. Conversely, Klotho silencing upregulated Egr-1 expression and the (p-ERK1/2):(ERK1/2) ratio in HG-treated or TGF-β1-treated HK2 cells. Moreover, the effects of si-Klotho were abolished by the ERK1/2 inhibitor PD98059.Conclusions Klotho prevents EMT during DKD progression, an effect that has been partially attributed to Egr-1 downregulation mediated by ERK1/2 signaling pathway inhibition.

PurposeThe goal of current study was to introduce noninvasive and reproducible MRI methods for in vivo functional assessment of lung adenocarcinoma (LUAD).MethodsForty-four patients with pathologically confirmed LUAD were included in this study. All the lesions were classified as adenocarcinoma in situ (AIS), minimally invasive adenocarcinoma (MIA), or invasive adenocarcinoma (IA). The IA lesions were further divided into five subtype patterns, including acinar, lepidic, papillary, micropapillary and solid. Tumors were grouped depending on predominant subtype: low grade (AIS, MIA or lepidic predominant), intermediate grade (papillary or acinar predominant) and high grade (micropapillary, or solid predominant). Spirometry was performed according to American Thoracic Society guidelines. For each patient, Intravoxel incoherent motion diffusion weighted imaging (IVIM-DWI) analysis and oxygen-enhanced MRI (OE-MRI) analysis were performed. Spearman’s test was used to assess the relationship between a) whole lung mean percent signal enhancement (PSE) and pulmonary function tests (PFTs) parameters; b) IVIM-derived parameters and PFTs parameters; c) tumor mean PSE and IVIM-derived parameters. Kruskal -Wallis tests were applied to test the difference of tumor mean PSE and IVIM-derived parameters between different histological tumor grades. Receiver operating characteristics (ROC) analysis was used to evaluate the diagnostic performance.ResultsWhole lung mean PSE was significantly positively correlated with PFTs parameters (r = 0.40 ~ 0.44, P < 0.05). f value derived from IVIM-DWI was significantly negatively correlated with PFTs parameters (r = -0.38 ~ -0.47, P < 0.05). Both tumor mean PSE (P = 0.030 < 0.05) and f (P = 0.022 < 0.05) could differentiate different histological grades. f was negatively correlated with tumor mean PSE (r = -0.61, P < 0.001). For the diagnostic performance, the combination of tumor mean PSE and f outperformed than using tumor mean PSE or f alone in both sensitivity and area under the ROC curve.ConclusionsThe combined measurement of OE-MRI and IVIM-DWI may serve as a promising method for the noninvasive and non-radiation evaluation of pulmonary function. Quantitative analyses achieved by OE-MRI and IVIM-DWI offer an approach of the classification of LUAD subtypes.

Senescent microenvironments play an important role in tumor progression. Here, we report that doxorubicin (DOX)‐pretreated or replicative senescent stromal cells (WI‐38 and HUVEC) promote colorectal cancer (CRC) cell growth and invasion in vitro and in vivo. These pro‐tumorigenic effects were attenuated by exogenous administration of Klotho, an anti‐aging factor. We subsequently identified several senescence‐associated secretory phenotype (SASP)‐associated genes, including CCL2, which were significantly upregulated in both types of senescent stromal cells during replication and DNA damage‐induced senescence. Importantly, we found that the secretion of CCL2 by senescent stromal cells was significantly higher than that seen in nonsenescent cells or in senescent cells pretreated with Klotho. Notably, CCL2 was found to accelerate CRC cell proliferation and invasion, while this effect could be blocked by administration of a specific CCR2 antagonist. We further show that Klotho can suppress NF‐κB activation during DOX‐induced senescence and thus block CCL2 transcription. Low expression of Klotho, or high expression of CCL2 in patient tumor tissues, correlated with poor overall survival of CRC patients. Collectively, our findings suggest that senescent stromal cells are linked to progression of CRC. Klotho can suppress the senescent stromal cell‐associated triggering of CRC progression by inhibiting the expression of SASP factors including CCL2. The identification of key SASP factors such as CCL2 may provide potential therapeutic targets for improving CRC therapy.

Abstract The movement of water into soil is the primary driving force in nutrient transport for crops, and the laws governing this movement can be affected by crop roots and plough pans. The main objectives of this study were to monitor the movement of water during rain along a soil profile influenced by soybean roots and a plough pan and to assess whether these factors influenced the efficacy of using the Richards equation to simulate the transport of soil water along a profile associated with a single rain. Experiments and model simulations were carried out. Our results suggested that the soybean field soil may have had preferential flow paths. Soybean stems and leaves transferred rainwater that otherwise would have fallen farther from the central stalk. The transmission of rainwater by the branches and leaves had a larger effect than the interception of rainwater by the branches and leaves. The effect of the root system on the soil particles may increase soil capillary action and ultimately increase saturated hydraulic conductivity. Saturated hydraulic conductivity was higher near the surface than at depth, because the transmission of water by the root system and the effect of large gaps were greater in the soil near the surface. Saturated hydraulic conductivity for both bare land and land covered with soybean plants decreased linearly from depths of 0–15 cm along the soil profile, particularly in the presence of a plough pan. We developed a linear equation to represent the variation in saturated hydraulic conductivity in the 0–15-cm layer in the black soil area of northeastern China. Using our linear model for saturated hydraulic conductivity as a parameter, the Richards equation more accurately simulated soil water transport along a profile influenced by soybean roots and a plough pan in rainy conditions.

Abstract Background Currently, WeChat is widely used in disease education for patients with Crohn’s disease (CD) in China. It is beneficial for the patients to actively engage in their disease management. Methods In this study, we examined the source and expectations of disease information for Chinese CD patients, analysing the content of popular WeChat public accounts and their potential association with medication adherence. Results Between November 24th, 2017 and April 10th, 2018, online questionnaires were sent to CD patients from eight different large urban hospitals in China. In all, 436 patients with CD were surveyed, and 342 patients responded. Patients most frequently visited Baidu (65%), WeChat (61%) and medical websites such as Haodaifu (35%) when searching for IBD-related information. Among ten WeChat IBD public accounts, the China Crohn’s and Colitis Foundation (CCCF) (73%), “IBD Academic Officer” (21%) and “IBD in love” (21%) were the most popular. CD patients were most interested in information from the internet about diet and day-to-day health-related living with IBD (83%), an introduction to the disease (80%), and medication advances and side effects (80%). The correlation between the information provided by the top five WeChat public accounts and patients’ expectations was low. Additionally, most patients (64%) had greater confidence in overcoming the disease after learning about CD through their internet searches. Medical adherence was also related to internet access and income (p

Software testing is an important means to ensure software quality. Testers need to ensure that every component of the software is tested correctly to achieve high coverage, such as path coverage, decision coverage, and branch coverage. An infeasible path is a path that cannot be traversed by any test cases. The existence of infeasible paths can waste test resources; therefore, detection of infeasible paths are necessary before path testing. This paper presents a static method for the detecting infeasible paths that is based on a satisfiability modulo theory (SMT) solver. First, the proposed method generates a sub-path set and converts the feasibility issues into inequalities. Second, a constraint solver is used to solve the inequalities and, then, the sub-paths are divided into two categories: infeasible sub-paths and undetermined sub-paths. The paths that were expanded from the latter will be tested again to determine their feasibility. Finally, the feasibility of all paths is detected. Most of the detection works are done on the sub-path set; therefore, our method provides an effective solution to the path-explosion problem. The experimental results showed that the proposed method can detect infeasible paths more accurately and effectively than most existing methods.

In this paper, a wideband circularly polarized (CP) crossed-dipole antenna is presented by using parasitic modified patches. Four polygonal metal patches are sequentially rotated around the crossed dipoles. By tuning the electromagnetic coupling characteristic between the patches and the crossed dipoles, the axial-ratio bandwidth (ARBW) of the lower frequency band can be enhanced significantly. Furthermore, four slots are etched on the parasitic patches in a sequential rotation way, modifying the current distribution. Therefore, an extra CP mode produces at the higher band. A wide 3-dB ARBW is realized by combing three CP modes, including the basic CP mode of the cross dipole at the middle frequency band. A prototype of the proposed broadband CP antenna was manufactured and measured to verify the design principle. The measurement results illustrate that the antenna has a wide 10-dB return loss bandwidth of 99.2% (1.24-3.68 GHz) and a broad 3-dB ARBW of 72.7% (1.41-3.02 GHz) for right-hand circular polarization (RHCP). Besides, stable gain and unidirectional radiation patterns are also obtained over the entire band of operation.

The RhoA-ROCK signaling pathway is associated with the protective effects of hydrogen sulfide (H2S) against cerebral ischemia. H2S protects rat hippocampal neurons (RHNs) against hypoxia-reoxygenation (H/R) injury by promoting phosphorylation of RhoA at Ser188. However, effect of H2S on the phosphorylation of ROCK2-related sites is unclear. The present study was designed to investigate whether H2S can play a role in the phosphorylation of ROCK2 at Tyr722, and explore whether this role mediates the protective effect of H/R injury in RHNs. Prokaryotic recombinant plasmids ROCK2wild-pGEX-6P-1 and ROCK2Y722F-pGEX-6P-1 were constructed and transfected into E. coli in vitro, and the expressed protein, GST-ROCK2wild and GST-ROCK2Y722F were used for phosphorylation assay in vitro. Eukaryotic recombinant plasmids ROCK2Y722-pEGFP-N1 and ROCK2Y722F-pEGFP-N1 as well as empty plasmid were transfected into the RHNs. Western blot assay and whole-cell patch-clamp technique were used to detect phosphorylation of ROCK2 at Tyr722 and BKCa channel current in the RHNs, respectively. Cell viability, leakages of intracellular enzymes lactate dehydrogenase (LDH), and nerve-specific enolase (NSE) were measured. The H/R injury was indicated by decrease of cell viability and leakages of intracellular LDH and NSE. The results of Western blot have shown that NaHS, a H2S donor, significantly promoted phosphorylation of GST-ROCK2wild at Tyr722, while no phosphorylation of GST-ROCK2Y722F was detected. The phosphorylation of ROCK2wild promoted by NaHS was also observed in RHNs. NaHS induced more potent effects on protection against H/R injury, phosphorylation of ROCK2 at Tyr722, inhibition of ROCK2 activity, as well as increase of the BKCa current in the ROCK2Y722-pEGFP-N1-transfected RHNs. Our results revealed that H2S protects the RHNs from H/R injury through promoting phosphorylation of ROCK2 at Tyr722 to inhibit ROCK2 activity and potentially by opening channel currents.

Based on glucose (G) transporters (GLUTs), structuring nanoparticles with G as a target are an effective strategy to enhance oral bioavailability and anti-tumor effects of drugs. A novel drug delivery system using G-modified zein (GZ) nanoparticles loaded with docetaxel (DTX) (DTX-GNPs) was prepared and characterized in vitro and in vivo via assessment of cellular uptake, absorption site, pharmacokinetics, ex vivo distribution, and anti-tumor effects. The DTX-GNPs were approximately 120 nm in size. Compared with DTX-NPs, G modification significantly enhanced cellular uptake of DTX-GNPs by 1.22 times in CaCo-2 cells, which was related to GLUT mediation and the enhancement of endocytosis pathways via clathrin, micropinocytosis, and caveolin. Compared to DTX-NPs, G modification significantly enhanced DTX-NP absorption in the jejunum and ileum, delayed plasma concentration peak time, prolonged the average residence time in vivo, and increased oral bioavailability (from 43.82% to 96.04%). Cellular uptake and oral bioavailability of DTX were significantly affected by the G modification ratio. Compared with DTX-NPs, G modification significantly reduced drug distribution in the liver, lungs, and kidneys and increased tumor distribution and tumor growth inhibition rate without obvious systemic toxicity. This study demonstrated the potential of GZ-NPs as nanocarriers for DTX to enhance oral bioavailability and anti-tumor effects.

Asphalt concrete is widely used in road and airport pavements and more recently also in the construction of impervious facings and central cores in dams and dykes. Asphalt concrete may be subjected to strongly acidic water when used in connection with storage of mine tailings (tailings dams). Acidic water reacts with bitumen and mineral materials and may cause deterioration of the behavior of asphalt concrete with time. The present study investigated effects of acidic water with time on aggregate-bitumen adhesion, bitumen penetration value, softening point and ductility, mass change of asphalt materials, and change in tensile strength for porous and impervious asphalt concrete. The test results show that impervious, hydraulic asphalt concrete is very resistant to acidic water and show insignificant deterioration of properties during the 3-year testing period used in the experiments.

Objective. Neuropathic pain with complex mechanisms has become a major public health problem that greatly impacts patients’ quality of life. Therefore, novel and more effective strategies against neuropathic pain need further investigation. Electroacupuncture (EA) has an ameliorating effect on neuropathic pain following spared nerve injury (SNI), but the underlying mechanism remains to be fully clarified. Interferon regulatory factor 8 (IRF8), a critical transcription factor, was reported to be involved in the modulation of neuropathic pain. Here, we focused on exploring whether 2 Hz EA stimulation exerts an inhibitory action on spinal IRF8 in SNI rats. Methods. In this study, SNI rats were treated with 2 Hz EA once every other day for 21 days. Paw withdrawal threshold (PWT) was applied to determine the analgesic effect of 2 Hz EA on SNI rats. The spinal IRF8 and CX3CRl expressions were detected with qRT-PCR and western blot, and immunofluorescence staining was used to evaluate colocation of IRF8 or CX3CRl with microglial activation marker CD11b in the spinal cord. Results. It was found that SNI induced significant elevation of spinal IRF8 and CX3CRl mRNA and protein expression. Additionally, immunofluorescence results showed that SNI elicited the coexpression of IRF8 with CD11b, as well as CX3CRl with CD11b in the spinal cord. Meanwhile, 2 Hz EA treatment of SNI rats not only reduced IRF8 and CX3CRl mRNA and protein expression, but also reversed the coexpression of IRF8 or CX3CRl with CD11b in the spinal cord, along with an attenuation of SNI-evoked mechanical hypersensitivity. Conclusion. This experiment highlighted that 2 Hz EA can inhibit IRF8 expression and microglial activation in the spinal cord of SNI rats. Hence, targeting IRF8 may be a promising therapeutic strategy for 2 Hz EA treatment of neuropathic pain.

Methyl-CpG binding protein 2 (MeCP2) has recently been characterized as an oncogene frequently amplified in several types of cancer. However, its precise role in gastric cancer (GC) and the molecular mechanism of MeCP2 regulation are still largely unknown. Here we report that MeCP2 is highly expressed in primary GC tissues and the expression level is correlated with the clinicopathologic features of GC. In our experiments, knockdown of MeCP2 inhibited tumor growth. Molecular mechanism of MeCP2 regulation was investigated using an integrated approach with combination of microarray analysis and chromatin immunoprecipitation sequencing (ChIP-Seq). The results suggest that MeCP2 binds to the methylated CpG islands of FOXF1 and MYOD1 promoters and inhibits their expression at the transcription level. Furthermore, we show that MeCP2 promotes GC cell proliferation via FOXF1-mediated Wnt5a/β-Catenin signaling pathway and suppresses apoptosis through MYOD1-mediated Caspase-3 signaling pathway. Due to its high expression level in GC and its critical function in driving GC progression, MeCP2 represents a promising therapeutic target for GC treatment.

Disordered intestinal flora and discordant immune response are associated with the development of ulcerative colitis (UC). Recent work has described the ability of macrophages to undergo repolarization toward a proinflammatory M1 or anti-inflammatory M2 phenotype in response to particular bacterium-derived signals. Fusobacterium nucleatum (F. nucleatum, Fn) is a species of intestinal commensal bacteria with potential pathogenicity, but its association with UC and how it may contribute to progression of UC is largely unknown. In this study, we provide new evidence that F. nucleatum accumulated heavily in the intestine of UC patients and was accompanied by the secretion of IFN-γ and the skewing of M1 macrophages. Mechanistically, our data showed that F. nucleatum aggravated dextran sodium sulfate (DSS)-induced colitis in the production of Th1-related cytokines IFN-γ through the AKT2 signaling pathway in vitro and in vivo. To further confirm the disease-relevance of these shifts in macrophage repolarization in response to F. nucleatum, stimulated bone marrow-derived macrophages (BMDMs) were transferred into recipient mice with DSS colitis. This transfer resulted in increased disease activity and inflammatory cytokine production. Taken together, we show clearly that F. nucleatum can promote the progression of UC via proinflammatory M1 macrophage skewing, and targeting F. nucleatum or AKT2 signaling may be a viable means of blocking development of UC.