Search

Aims. Epidemiological data on diabetic retinopathy (DR) in Chinese population is still rather scarce, and risk factors for diabetic retinopathy are inconsistent because of study designs, grading standards, and population samples. Materials and Methods. This hospital-based retrospective study included 1052 type 2 diabetes patients. Diabetic retinopathy was diagnosed by nonmydriatic fundus photography and/or fundus examination apparatus. Logistic regression analysis was performed to evaluate the risk of diabetic retinopathy. Results. A total of 352 (33.5% prevalence) subjects were diagnosed with diabetic retinopathy based on our population. The patients in the DR group not only had significantly higher hemoglobin A1c (HbA1c), fasting plasma glucose (FPG), urinary microalbumin-creatinine ratio (ACR), and systolic blood pressure but also had higher follicle-stimulating hormone (FSH), luteinizing hormone (LH), and sex hormone-binding globulin (SHBG) levels compared to those in the non-DR group. Moreover, we confirmed that diabetes duration and HbA1c are strongly associated with DR risk. We also found that serum LH was an independent risk factor in male diabetic retinopathy patients (OR = 1.086 , 95% CI 1.024–1.152), and the levels of LH were significantly associated with diabetic retinopathy prevalence (P = 0.018). Conclusions. Our study strengthens the argument that diabetes duration and HbA1c are risk factors for patients with DR. Additionally; we firstly confirmed that serum LH was an independent risk factor in male diabetic retinopathy patients. [ABSTRACT FROM AUTHOR]

Aims/Introduction: Type 2 diabetes mellitus is frequently accompanied by fatty liver disease. Lipid accumulation within the liver is considered as one of the risk factors for insulin resistance. Hepatocyte growth factor (HGF) is used to treat liver dysfunction; however, the effect and mechanism of HGF on hepatic lipid metabolism are still not fully understood. Materials and Methods: Male C57BL/6 mice were induced with a high‐fat diet for 12 weeks, followed by a 4‐week treatment of HGF or vehicle saline. The levels of fasting blood glucose, fasting insulin and homeostatic model assessment of insulin resistance were calculated for insulin sensitivity. Biochemical plasma parameters were also measured to assess the effect of HGF on lipid accumulation. Additionally, genes in the lipid metabolism pathway were evaluated in palmitic acid‐treated HepG2 cells and high‐fat diet mice. Results: HGF treatment significantly decreased the levels of fasting blood glucose, hepatic triglyceride and cholesterol contents. Additionally, HGF‐regulated expression levels of sterol regulatory element‐binding protein‐1c/fatty acid synthase, peroxidase proliferator‐activated receptor‐α, and upstream nuclear receptors, such as farnesoid X receptor and small heterodimer partner. Furthermore, c‐Met inhibitor could partially reverse the effects of HGF. Conclusions: HGF treatment can ameliorate hepatic insulin resistance and steatosis through regulation of lipid metabolism. These effects might occur through farnesoid X receptor–small heterodimer partner axis‐dependent transcriptional activity. HGF reduced the levels of fasting blood glucose, blood lipid level, and improved the HFD‐fed mice. HGF significantly regulated lipogenesis‐related genes SREBP‐1c/FAS as well as PPARα, and nuclear receptors such as FXR, SHP. HGF ameliorates hyperglycemia and by improving hepatic insulin resistance and steatosis in HFD‐fed C57BL/6 mice. [ABSTRACT FROM AUTHOR]

Abstract: Objective: Vasculogenic mimicry (VM) indicates that aggressive cancer cells can form de novo vascular networks and provide a perfusion pathway for rapidly growing tumors. MiR-200a has been reported significantly deregulated in ovarian cancer. However, miR-200a regulation of VM and its clinical significance in ovarian cancer remain not elucidated. Methods: In this study, we identified the VM structure by CD34-PAS staining in ovarian cancer tissue. MiR-200a and protein expression was tested by quantitative RT-PCR and western blot. Bioinformatics prediction, luciferase assay and intervention experiments were employed to identify the target of miR-200a. Results: We certified the VM structure in ovarian cancer, and found that the VM positive rate was significantly associated with tumor grade, stage and metastasis. Further study showed that miR-200a expression levels were significantly lower in VM positive ovarian cancer. In addition, our results suggested that miR-200a inhibited VM by negatively regulated EphA2 expression. Consistently, the inverse correlation of miR-200a and EphA2 has also been found in ovarian cancer patients. Moreover, the expression of miR-200a/EphA2 was significantly associated with patient's clinicopathological parameter, such as tumor stage and metastases. Kaplan–Meier curves confirmed that the patients with low miR-200a expression and/or VM positive had a significantly shorter overall survival. Conclusions: Our research demonstrates that VM, miR-200a and EphA2 play key roles in the progression and prognosis of ovarian cancer, and for the first time suggests that miR-200a inhibits VM by directly regulating EphA2. Therefore, we might have identified a genetic mechanism underlying the involvement of miR-200a in ovarian cancer VM. [Copyright &y& Elsevier]

Epidemiologic findings are inconsistent concerning the association of endometrial cancer risk with alcohol consumption. Therefore, we conduct a meta-analysis of studies that assessed the association of alcohol consumption and the risk of endometrial cancer. A systematic literature search up to April 2010 was performed in MEDLINE and EMBASE, and study-specific risk estimates were pooled using a random-effects model. In the present study, six prospective and 14 case-control studies were included. Alcohol intake was not significantly associated with the risk of endometrial cancer among prospective studies (relative risk (RR): 1.04; 95% confidence interval (CI): 0.91-1.18) or among case-control studies (odds ratio (OR): 0.89; 95% CI: 0.76-1.05). However evidence from the results of our stratified analyses revealed that increased risk of endometrial cancer was associated with liquor consumption (RR: 1.22; 95% CI: 1.03-1.45) but null association with wine and beer consumption. In conclusion, alcohol consumption is not associated with the risk of endometrial cancer. Future studies should also examine whether the relation varies according to different type of alcoholic beverages. [ABSTRACT FROM AUTHOR]

Abstract: A novel lyotropic liquid crystalline material poly(aryl ether ketone) copolymer containing phthalazinone moiety and biphenyl mesogen named P-8515 was developed by a mild solution polycondensation method. The molecular weight (M n) was 53,000 and the value of molecular weight distribution index (MDI) was 2.49 detected by GPC. The critical concentration (C ∗) of P-8515 was 36wt% and P-8515 exhibited characteristic nematic lyotropic liquid crystalline phases in NMP solution at different concentrations and the phase morphology changed to a typical threaded texture when shear forces were induced from PLM observations. The T g value was 238°C and the value for 5% weight loss temperature was 515°C in nitrogen from DSC and TGA determinations, respectively. [Copyright &y& Elsevier]

Schematic diagram of Dehy suppressing GC cells. Created with BioRender.com. [Display omitted] • Dehy prominently suppresses GC progression in vitro and in vivo. • Dehy reduces de novo fatty acid synthesis and lipid pool by inhibiting ACLY. • Dehy targets IKKβ directly to promote the ubiquitination and degradation of ACLY. • GC cells trigger autophagy following lipid depletion, while this protective mechanism is blocked by Dehy. • Dehy enhances 5-FU efficacy in PDX models, indicating its potential in GC therapies. Dehydrocostus lactone (Dehy), a natural sesquiterpene lactone from Saussurea lappa Clarke, displays remarkable efficacy in treating cancer and gastrointestinal disorders. However, its anti-gastric cancer (GC) effect remains poorly understood. Our study aimed to elucidate the anti-GC effect of Dehy and its putative mechanism. The anti-GC effect was assessed with MTT, colony formation, wound healing and transwell invasion assays. Cell apoptosis rate was detected by Annexin V-FITC/PI binding assay. Network pharmacology analysis and XF substrate oxidation stress test explored the underlying mechanism and altered metabolic phenotype. Lipogenic enzyme expressions and neutral lipid pool were measured to evaluate cellular lipid synthesis and storage. Biolayer interferometry and molecular docking investigated the direct target of Dehy. Autophagosomes were observed by transmission electron microscopy and MDC staining, while the autophagic flux was detected by mRFP-GFP-LC3 transfection. The clinical significance of ACLY was confirmed by tissue microarrays. Patient-derived xenograft (PDX) models were adopted to detect the clinical therapeutic potential of Dehy. Dehy prominently suppressed GC progression both in vitro and in vivo. Mechanistically, Dehy down-regulated the lipogenic enzyme ACLY, thereby reducing fatty acid synthesis and lipid reservation. Moreover, IKKβ was identified as the direct target of Dehy. Dehy inhibited the phosphorylation of IKKβ, promoting the ubiquitination and degradation of ACLY, thereby resulting in lipid depletion. Subsequently, GC cells initiated autophagy to replenish the missing lipids, whereas Dehy impeded this cytoprotective mechanism by down-regulating LAMP1 and LAMP2 expressions, which disrupted lysosomal membrane functions, ultimately leading to apoptosis. Additionally, Dehy exhibited potential in GC clinical therapy as it enhanced the efficacy of 5-Fluorouracil in PDX models. Our work identified Dehy as a desirable agent for blunting abnormal lipid metabolism and highlighted its inhibitory effect on protective autophagy, suggesting the future development of Dehy as a novel therapeutic drug for GC. [ABSTRACT FROM AUTHOR]

Background: Myeloid-derived suppressor cells (MDSCs) are the major factor in gastric cancer (GC) immune evasion. Nevertheless, the molecular process underlying the expansion of MDSCs induced by tumor-derived exosomes (TDEs) remains elusive. Methods: The levels of exosomal and soluble PD-L1 in ninety GC patients were examined via enzyme-linked immunosorbent assay (ELISA) to determine their prognostic value. To investigate the correlation between exosomal PD-L1 and MDSCs, the percentage of MDSCs in the peripheral blood of 57 GC patients was assessed via flow cytometry. Through ultracentrifugation, the exosomes were separated from the GC cell supernatant and detected via Western blotting, nanoparticle tracking analysis (NTA), and transmission electron microscopy (TEM). The function of exosomal PD-L1 in MDSCs was evaluated via immunofluorescence, Western blotting and flow cytometry in a GC cell-derived xenograft (CDX) model. Results: The overall survival (OS) of GC patients in the high exosomal PD-L1 group was significantly lower than that of patients in the low exosomal PD-L1 group (P = 0.0042); however, there was no significant correlation between soluble PD-L1 and OS in GC patients (P = 0.0501). Furthermore, we found that the expression of exosomal PD-L1 was positively correlated with the proportions of polymorphonuclear MDSCs (PMN-MDSCs, r = 0.4944, P < 0.001) and monocytic MDSCs (M-MDSCs, r = 0.3663, P = 0.005) in GC patients, indicating that exosomal PD-L1 might induce immune suppression by promoting the aggregation of MDSCs. In addition, we found that exosomal PD-L1 might stimulate MDSC proliferation by triggering the IL-6/STAT3 signaling pathway in vitro. The CDX model confirmed that exosomal PD-L1 could stimulate tumor development and MDSC amplification. Conclusions: Exosomal PD-L1 has the potential to become a prognostic and diagnostic biomarker for GC patients. Mechanistically, MDSCs can be activated by exosomal PD-L1 through IL-6/STAT3 signaling and provide a new strategy against GC through the use of exosomal PD-L1 as a treatment target. [ABSTRACT FROM AUTHOR]

Background: Bioactive lipids involved in the progression of various diseases. Nevertheless, there is still a lack of biomarkers and relative regulatory targets. The lipidomic analysis of the samples from platinum-resistant in gastric cancer patients is expected to help us further improve our understanding of it. Methods: We employed LC–MS based untargeted lipidomic analysis to search for potential candidate biomarkers for platinum resistance in GC patients. Partial least squares discriminant analysis (PLS-DA) and variable importance in projection (VIP) analysis were used to identify differential lipids. The possible molecular mechanisms and targets were obtained by metabolite set enrichment analysis and potential gene network screened. Finally, verified them by immunohistochemical of a tissue microarray. Results: There were 71 differential lipid metabolites identified in GC samples between the chemotherapy-sensitivity group and the chemotherapy resistance group. According to Foldchange (FC) value, VIP value, P values (FC > 2, VIP > 1.5, p < 0.05), a total of 15 potential biomarkers were obtained, including MGDG(43:11)-H, Cer(d18:1/24:0) + HCOO, PI(18:0/18:1)-H, PE(16:1/18:1)-H, PE(36:2) + H, PE(34:2p)-H, Cer(d18:1 + hO/24:0) + HCOO, Cer(d18:1/23:0) + HCOO, PC(34:2e) + H, SM(d34:0) + H, LPC(18:2) + HCOO, PI(18:1/22:5)-H, PG(18:1/18:1)-H, Cer(d18:1/24:0) + H and PC(35:2) + H. Furthermore, we obtained five potential key targets (PLA2G4A, PLA2G3, DGKA, ACHE, and CHKA), and a metabolite-reaction-enzyme-gene interaction network was built to reveal the biological process of how they could disorder the endogenous lipid profile of platinum resistance in GC patients through the glycerophospholipid metabolism pathway. Finally, we further identified PLA2G4A and ACHE as core targets of the process by correlation analysis and tissue microarray immunohistochemical verification. Conclusion: PLA2G4A and ACHE regulated endogenous lipid profile in the platinum resistance in GC patients through the glycerophospholipid metabolism pathway. The screening of lipid biomarkers will facilitate earlier precision medicine interventions for chemotherapy-resistant gastric cancer. The development of therapies targeting PLA2G4A and ACHE could enhance platinum chemotherapy effectiveness. [ABSTRACT FROM AUTHOR]

Gastric cancer (GC) is the fifth most common malignancy and the third leading cause of cancer-related deaths worldwide. Similar to other types of tumors, GC cells undergo metabolic reprogramming and switch to a "predominantly glycolytic" metabolic pattern to promote its survival and metastasis, also known as "the Warburg effect", which is characterized by enhanced glucose uptake and lactate production. A large number of studies have shown that targeting cancer cells to enhanced glycolysis is a promising strategy, that can make cancer cells more susceptible to other conventional treatment methods of treatment, including chemotherapy, radiotherapy and immunotherapy, and so on. Therefore, this review summarizes the metabolic characteristics of glycolysis in GC cells and focuses on how abnormal lactate concentration can lead to immunosuppression through its effects on the differentiation, metabolism, and function of infiltrating immune cells, and how targeting this phenomenon may be a potential strategy to improve the therapeutic efficacy of GC. [ABSTRACT FROM AUTHOR]

Poly(ether ketone ketone) (PEKK) is a thermoplastic with excellent performance. To date, most PEKK copolymers are synthesized by a two-step method. However, in this work, a series of PEKK copolymers with diverse T/I (terephthaloyl/isophthaloyl) ratios were firstly synthesized by a facial one-step method. Then, the structure of PEKK copolymers was characterized and the crystallization and melting behavior were studied in detail. With the increase in meta isomers in the structure, the crystallization ability and melting point of copolymers reduced, as confirmed by non-isothermal and isothermal crystallization kinetics analysis. Furthermore, the double melting behavior of PEKK copolymers after isothermal annealing was researched employing differential scanning calorimetry (DSC) and temperature-modulated DSC (TMDSC). Unlike many other outcomes, our study demonstrate that the double melting behavior is mainly related to the superimposition of rigid amorphous devitrification and enthalpy relaxation. Finally, through the self-nucleation experiment of PEKK70 and PEKK80, the ideal self-nucleation temperatures (Ts,ideal) corresponding to the copolymers were determined, then the successive self-nucleation and annealing (SSA) technology was employed to analyze PEKK copolymers for the first time, and thermal classification was successfully achieved. [ABSTRACT FROM AUTHOR]

Cachexia affects approximately 50–80 % of advanced cancer patients, particularly those with gastric cancer (GC). Therefore, early detection of cachexia is essential to prevent its progression. Targeting the gut microbiota may be a promising approach for preventing and treating cachexia in patients with GC. Chemotherapy significantly reduced gut microbiota diversity in GC patients. Specifically, the abundance of bacterial genera such as Bacteroides , Streptococcus , and Prevotella was increased in the gut of patients postchemotherapy, which was closely associated with the development of cachexia. Serum metabolic analysis revealed a strong link between specific microbes and metabolite in patients with chemotherapy-induced GC cachexia. We further constructed a random forest model based on the top 6 genera in terms of abundance for the prediction of chemotherapy-related GC cachexia development; this model had an area under the receiver operating characteristic curve (AUC) of 93.5 % [95 % confidence interval (CI), 86.6 %-100 %], with a specificity and accuracy above 75 %. Additionally, we identified Enterotoxin Bacteroides fragilis (ETBF) as a key factor in chemotherapy-induced GC cachexia. In an in vivo GC model, the colonization of ETBF in the intestines of mice significantly accelerated the muscle and adipose tissue consumption induced by chemotherapy, resulting in cachexia symptoms. Furthermore, ETBF damaged the intestinal mucosal barrier by disrupting cell connections and attracting M1 macrophages, which advances GC cachexia. In conclusion, our findings indicate that gut microbiota imbalance is crucial in GC cachexia development, suggesting potential biomarkers for early diagnosis. Clinical trial registration: http://www.chictr.org.cn , Identification No: ChiCTR2200064547 [Display omitted] • Intestinal microbiota imbalance and metabolic disorders significantly contribute to cancer cachexia. • ETBF causes endotoxaemia by directly disrupting the intestinal mucosal barrier and indirectly releasing toxins. • ETBF promotes GC cachexia by recruiting intestinal macrophages to influence the intestinal immune microenvironment. • A random forest prediction model offers the possibility of predicting the potential clinical population of GC cachexia. [ABSTRACT FROM AUTHOR]

Purpose: Some studies were undertaken to evaluate the association between cigarette smoking and age-related macular degeneration (AMD). This meta-analysis summarized the risk estimate of smoking and AMD and provided robust evidence for the association. Methods: Relevant studies were identified by searching PubMed and MEDLINE (from 1966 to June 2007) and reviewing the reference lists of key articles. The summary relative risk ratio (RR) or odds ratio (OR) and 95% confidence interval (CI) were calculated. Study-specific risk estimates were pooled using a random-effects model. Results: Five prospective cohort and eight case-control studies met our inclusion criteria. Ever smoking was statistically significant associated with increased risk of AMD among cohort studies (RR, 1.61; 95% CI, 1.01–2.57) or case-control studies (RR, 1.76; 95% CI, 1.56–1.99). Current smokers were at higher risk of AMD than past smokers. Both geographic atrophy (GA) and neovascular AMD (NV) are subtypes of AMD. A significant relationship was found between smoking and GA risk. Smoking increased the risk of NV, with marginal nonsignificance (RR, 1.47; 95% CI, 0.92–2.37) in cohort studies and significance in case-control studies (RR, 1.96; 95% CI, 1.69–2.27). Conclusions: This meta-analysis indicated smoking, especially current smoking, was significantly associated with increased risks of AMD and its subtypes. [Copyright &y& Elsevier]

Abstract: Objective: Epidemiologic findings are inconsistent concerning the association of endometrial cancer risk with cigarette smoking. We conducted a meta-analysis of epidemiologic studies to examine this relation. Methods: A systematic literature search up to June of 2007 was performed in MEDLINE and EMBASE. Study-specific risk estimates were pooled using a random-effects model. Results: Ten prospective and 24 case-control studies were included in the analysis of the effect of ever smoking. Ever smoking was statistically significantly associated with a reduced risk of endometrial cancer among prospective studies (relative risk 0.81; 95% confidence interval [CI], 0.74-0.88) and case-control studies (odds ratio 0.72; 95% CI, 0.66-0.79). The inverse association was significant among current and former smokers. Six prospective and 6 case-control studies were included in the quantitative analysis. We noted that an increase in smoking of 20 cigarettes per day was statistically significantly associated with 16% and 27% reduced risks of endometrial cancer in prospective and case-control studies, respectively. We also found that cigarette smoking was significantly associated with a decreased risk of endometrial cancer among postmenopausal women (relative risk 0.71; 95% CI, 0.65-0.78) but not among premenopausal women. In addition, the risk reduction seemed to be stronger among hormone replacement therapy users than nonusers. Conclusion: Cigarette smoking was found to be significantly associated with a reduced risk of endometrial cancer, especially among postmenopausal women. [Copyright &y& Elsevier]

Sensor fault diagnosis is essential to guaranteeing the safety of lithium-ion batteries. To address the general drawbacks of the existing diagnosis methods, including the difficulty in determining the threshold, inability to handle multiple faulty sensors concurrently, and limited capacity in identifying fault modes, a multi-sensor multi-mode fault diagnosis method for lithium-ion battery packs is proposed. The proposed method utilizes time series and discriminative features to accomplish sensor-specific fault detection and fault mode identification. First, a total of 18 general time series features are extracted to characterize the measurements of each sensor during each charge–discharge cycle. Principal component analysis is then used to reduce the high-dimensional feature space to a two-dimensional space, such that fault detection can be carried out with the α -hull algorithm. For the detected faulty samples, a two-layer identification algorithm is designed based on three discriminative features, namely, correlation coefficient, impulse factor, and Hurst coefficient, to identify the specific fault modes. The diagnostics can decouple the information from different types of sensors so that the proposed method can effortlessly isolate current, voltage, and temperature sensors that are concurrently experiencing faults. Ultimately, experimental results from three scenarios, including simultaneous failure of multiple sensors, substantiate the effectiveness and feasibility of the proposed method. [Display omitted] • Sensor faults are detected without establishing models and setting thresholds. • Different types of sensors that malfunction simultaneously are effortlessly isolated. • The fault modes of the faulty samples can be accurately identified. • The proposed method can handle scenarios where multiple sensors fail simultaneously. • The diagnosis results in three scenarios prove the validity of the proposed method. [ABSTRACT FROM AUTHOR]

• Two functionalized polymers (PTPNHs) were synthesized by one-step modification. • The PTPNHs have remarkable morphology evolution from nanospheres to nanorods. • PTPNHs show enhanced CO 2 adsorption per unit surface area (0.281 mg/m2). • PTPNHs have exceptionally high ideal selectivity (CO 2 : N 2 = 123). The increasing carbon dioxide (CO 2) emissions from coal-fired power plants exacerbates the need for polymeric sorbents that can preferentially capture CO 2 over nitrogen (N 2). Herein we report two amine-functionalized microporous organic polymers (PTPNHs) through one-step facile modification of carboxyl-rich microporous organic polymers (PTPMA) that was prepared from a classic Friedel–Crafts coupling of commercially available monomers. The amidation chemistry enables an unprecedented morphology evolution of the microporous organic polymer from nanospheres to uniform nanorods and the choice of amidation agents allows a good control on the diameter and length of the as-made nanorods. More interestingly, the amine-appended PTPNHs show enhanced CO 2 adsorption per unit surface area (0.281 mg/m2, at 273 K/1.0 bar) and exceptionally high ideal selectivity (CO 2 : N 2 = 123) with high affinity towards CO 2 , despite of their decreased Brunauer–Emmett–Teller (BET) surface areas (554 m2 g−1). The CO 2 adsorption per unit surface area of the nanorods is about 1.6 folds of that of pristine PTPMA. This study constitutes a step on regulating channel surface polarity and morphology control, and offers the prospect for low-cost direct CO 2 capture technologies. [ABSTRACT FROM AUTHOR]

Jianpi Yangzheng decoction (JPYZ) possesses a potential anti-tumor activity in gastric cancer. However, potential effect of JPYZ on regulating tumor-associated macrophage (TAM)-derived exosomes to affect gastric cancer is still unclear. We aimed to clarify the role of tumor-associated macrophage derived exosomes (TAM-exos) in invasive and metastasis of gastric cancer and the mechanism of JPYZ regulate TAM-exos against gastric cancer. Flow cytometry was performed to demonstrate whether JPYZ involved in TAM polarization. After JPYZ treatment, TAM conditioned medium (TAM-CM)/TAM-exos were co-cultured with gastric cancer cells and were detected by wound healing and transwell assay. Transcriptome sequencing and bioinformatics analysis predicted the exosomal miRNA after JPYZ intervention in TAM. miRNA mimic and inhibitor were used to verify the effect of miRNA in exosomes on gastric cancer cells. Q-PCR and luciferase reporter assay were employed to clarify the targeting relationship between miRNA and target gene. Western blot assay detected the expression levels of epithelial-mesenchymal transition (EMT) markers and related signaling pathways proteins. We firstly demonstrated that TAM-CM intervened by JPYZ significantly inhibited the invasion and migration of gastric cancer. Furthermore, exosomes in TAM supernatants play a key role in migration of gastric cancer. Meanwhile, transcriptome sequencing and q-PCR revealed that miR-513b-5p expression was significantly reduced in TAM-exos intervened by JPYZ. And miR-513b-5p in TAM aggravated TAM-exos mediated invasion and migration of gastric cancer cells, the inhibitor of miR-513b-5p reversed TAM-exos mediated promotion. Bioinformatics analysis and luciferase reporter assay confirmed that PTEN was a direct target of miR-513b-5p in gastric cancer. MiR-513b-5p inhibited PTEN to activate AKT/mTOR signaling pathway thus promoting gastric cancer invasion and metastasis in vivo and in vitro. Importantly, JPYZ inhibited TAM derived exosomal miR-513b-5p, and alleviated AKT/mTOR activation by PTEN depended manner in gastric cancer. TAM-exos containing miR-513b-5p lead to gastric cancer invasion and migration. Our findings clarify a novel TAM-exos mechanism of JPYZ for inhibiting gastric cancer progression. [Display omitted] • JPYZ could inhibit the invasion and migration of gastric cancer through TAM-exos. • JPYZ reduced the level of miR-513 b-5p in TAM-exos and affected the progression of gastric cancer. • JPYZ inhibited the progress of gastric cancer by regulating TAM-exos miR-513 b-5p mediated PTEN/AKT signaling. [ABSTRACT FROM AUTHOR]

Developing complementary and effective drugs with less toxicity is urgent for gastric cancer (GC) therapy. Jianpi Yangzheng Decoction (JPYZ) is a curative medical plants formula against GC in clinic while its molecular mechanism remains to be further elucidated. To evaluate the in vitro and in vivo anticancer efficacy of JPYZ against GC and its potential mechanisms. The effect of JPYZ on regulating the candidate targets were screened and examined by RNA-Seq, qRT-PCR, luciferase reporter assay, and immunoblotting. Rescue experiment was conducted to authenticate the regulation of JPYZ on the target gene. Molecular interaction, intracellular localization and function of target genes were elucidated via Co-IP and cytoplasmic-nuclear fractionation. The impact of JPYZ on the abundance of target gene in clinical specimens of GC patients was evaluated by IHC. JPYZ treatment suppressed the proliferation and metastasis of GC cells. RNA seq revealed JPYZ significantly downregulated miR-448. A reporter plasmid containing CLDN18 3'-UTR WT exhibited significant decrease in luciferase activity when co-transfected with miR-448 mimic in GC cells. CLDN18.2 deficiency promoted the proliferation and metastasis of GC cells in vitro , as well as intensified the growth of GC xenograft in mice. JPYZ reduced the proliferation and metastasis of GC cells with CLDN18.2 abrogation. Mechanically, suppressed activities of transcriptional coactivator YAP/TAZ and its downstream targets were observed in GC cells with CLDN18.2 overexpression and those under JPYZ treatment, leading to cytoplasmic retention of phosphorylated YAP at site Ser-127. High abundance of CLDN18.2 was detected in more GC patients who received chemotherapy combined with JPYZ. JPYZ has an inhibitory effect on GC growth and metastasis partly by elevating CLDN18.2 abundance in GC cells, indicating more patients may benefit from combination therapy of JPYZ and the upcoming CLDN18.2 target agents. [Display omitted] • The multi-herb-combined JPYZ inhibits proliferation and metastasis of gastric cancer. • JPYZ remarkably elevates the abundance of CLDN18.2 in gastric cancer. • JPYZ-induced CLDN18.2 expression suppresses the activity of YAP/TAZ signaling. • JPYZ may improve the therapeutic effect of CLDN18.2 targeted therapy in gastric cancer. [ABSTRACT FROM AUTHOR]

[Display omitted] • An oral nano-antioxidant was constructed by encapsulating nanoceria and curcumin to mannose modified chitosan for the treatment of inflammatory bowel disease. • The oral nano-antioxidant targeted to macrophages and promoted M2 macrophage polarization to alleviate inflammation by scavenging excessive ROS. • The oral nano-antioxidant protected intestinal cells away from ferroptosis to enhance therapeutic efficacy of inflammatory bowel disease. • The oral nano-antioxidant effectively alleviates DSS-induced colitis in mice and maintain intestinal microecological balance. Inflammatory bowel disease (IBD) is a chronic inflammatory disease that characterized by excessive reactive oxygen species (ROS) and high ferroptosis. The ROS plays an essential role in macrophage polarization to maintain inflammation and the ferroptosis disrupts intestinal barrier for development of IBD. Herein, an oral nano-antioxidant (Ce-Cur@MCS) was developed by encapsulating nanoceria (CeO 2) and curcumin (Cur) to mannose modified chitosan (MCS). Due to the macrophage targeting property, the nano-antioxidant specially deliver to colonic inflammation site, especially to macrophages. It mimics both superoxide dismutase (SOD) and catalase (CAT) to eliminate ROS and scavenge hydroxyl radical in vitro. It can reduce the secretion of inflammatory factors of M1 and deficient M2 macrophage polarization. More important, it can also increase the expression of GSH and GPX4 to protect intestinal cells away from ferroptosis. The results in vivo further confirmed our formed oral nano-antioxidant can enhance therapeutic efficacy of IBD by suppressing macrophage induced inflammation and inhibiting ferroptosis of intestinal cells. In addition, it can increase the abundance and diversity of the gut microflora to maintain therapeutic efficacy of IBD. We envision that scavenging ROS including ferroptosis induced ROS is a viable therapeutic strategy for IBD and our formed oral nano-antioxidant has a promising application for clinical treatment of IBD. [ABSTRACT FROM AUTHOR]

The Dadu River Basin (DRB) is an important economic corridor on the Chuanxi Plateau. The DRB is located in the highly changeable terrain of the eastern Qinghai-Tibet Plateau and is often threatened by debris flows. To mitigate the damage of debris flow disasters to the construction and operation of large infrastructures such as railways, roads and hydropower stations in the DRB, it is necessary to evaluate debris flow susceptibility. The connectivity of potential material sources (CPMS), which proxies the possibility of potential material transfer from the source to the outlet, was calculated using an improved index of connectivity, excess topography and brittle fracture index to identify and quantify debris flow susceptibility. The results show that the IC and the gully scale have a Logartihmic function in the DRB, in which IC decreases as the catchment area increases. In 3967 gullies of the Dadu River and its tributaries, the total connectivity of potential material sources (TCPMS) could be used to distinguish between debris flow gullies and non-debris flow gullies (AUC = 0.748). The TCPMS and average connectivity of potential material sources (ACPMS) were used to classify the scale and activity intensity of the 2398 debris flow gullies into four levels. The moderate- and high-activity intensity and large- and extra large-scale debris flows are mainly distributed in Danba, Luding and Kangding. The results of this study provide reference and evidence for the identification and evaluation of debris flow susceptibility. • A new method for assessing debris flow susceptibility based on potential material sources and sediment connectivity. • The quantitative relationship between the scale of debris flow and conditioning factors. • The contribution of excess topography was considered. [ABSTRACT FROM AUTHOR]

Introduction: The C-31G polymorphism in the survivin promoter could de-repress the cell-cycle-dependent transcription of the human survivin gene, resulting in overexpression of survivin. This survivin mutation has only been studied on cervical carcinoma. However, no study has ever been conducted to evaluate the effect of the polymorphism on other cancers, including gastric cancer.Methods: In this hospital-based, case-control study, we investigated the association between the survivin C-31G polymorphism and risk of gastric cancer in a Chinese population using polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) protocols.Results: No statistically significant association was observed between gastric cancer risk and the variant genotype (GG + GC). However, the variant genotype (GG + GC) was either associated with risk of distal gastric cancer (odds ratios=0.50, 95% confidence interval=0.30-0.83) or with risk of well-differentiated tumor (odds ratios=0.46, 95% confidence interval=0.22-0.97).Conclusion: Our results demonstrate that the survivin C-31G polymorphism may be involved in distal gastric carcinogenesis and tumor differentiation in a Chinese population. [ABSTRACT FROM AUTHOR]

Abstract: A series of novel fluorinated poly(aryl ether)s containing phthalazinone moieties (FPPEs) have been prepared by a modified synthetic procedure for optical waveguide applications. The obtained random copolymers exhibited excellent solubility in polar organic solvents, high glass transition temperatures (T gs: 185–269°C), good thermal stabilities (the temperatures of 1% weight loss: 487–510°C) and good optical properties. By adjusting the feed ratio of the reactants, the refractive indices of TE and TM modes (at 1550nm) could be well controlled in the range of 1.575–1.498 and 1.552–1.484, respectively. The optical losses of the FPPEs exhibited relatively low values (less than 0.27dB/cm at 1310nm). Additionally, the thermo-optic coefficient (dn/dT) values of the FPPEs at 1310nm and 1550nm (TE mode) ranged from −0.97×10−4 °C to −1.33×10−4 °C and from −0.96×10−4 °C to −1.29×10−4 °C, respectively. [Copyright &y& Elsevier]

Abstract: To investigate the association between endothelin-converting enzyme-1b (ECE-1b) C-338A polymorphism and gastric cancer risk, we conducted a hospital-based case–control study of 256 gastric cancer cases and 256 controls matched on age and gender. The genotypes were identified by polymerase chain reaction-restriction fragment length polymorphism. We found that the genotype frequencies were significantly different (P =0.005) between cases and controls. Compared with the wild genotype CC, the variant genotypes (CA+AA) were associated with a 64% increased risk of gastric cancer [adjusted odds ratio (OR)=1.64, 95% confidence interval (CI) 1.15–2.33]. Further stratification analyses indicated that the increased risk was especially noteworthy in older subjects (age ⩾58) (adjusted OR=1.91, 95% CI 1.18–3.09), women (adjusted OR=2.30, 95% CI 1.11–4.79) and non-smokers (adjusted OR=1.79, 95% CI 1.19–2.67). Our results suggest that the ECE-1b C-338A polymorphism may be associated with increased risk of gastric cancer. [Copyright &y& Elsevier]

Abstract: Cross-linkable poly(phthalazinone ether ketone sulfone) bearing tetrafluorostyrene groups (PPEKS–FSt) has been prepared by copolycondensation reaction for optical waveguide applications. The resulting amorphous polymer exhibits good solubility in some common polar organic solvents (e.g., N,N′-dimethylacetamide, N-methyl-2-pyrrolidinone, chloroform) at room temperature, and can be easily spin-coated into thin films with good optical quality. The glass transition temperature (T g) and the temperature of 1% weight loss (1% T d) are 261°C and 494°C, respectively, which could be further increased by 31°C and 14°C upon thermal cross-linking. The cross-linked polymer thin films exhibit high refractive index (∼1.65, TE mode), high thermo-optic coefficient value (dn/dT) (−1.455×10−4/°C, TE mode), low optical loss (less than 0.24dB/cm at 1310nm) and relatively low birefringence (∼0.007). [Copyright &y& Elsevier]

Jian-pi-yang-zheng Decoction (JPYZ) is a traditional Chinese medicine that is used for the treatment of advanced gastric cancer, and it shows good efficacy in patients. A previous study indicated that JPYZ inhibited the progression of gastric cancer via the regulation of tumor-associated macrophages (TAMs), but the underlying molecular target of JPYZ regulation of TAMs has not been determined. The present study used modified-JPYZ (mJPYZ) to extend our investigation of gastric cancer. Our results showed that mJPYZ inhibited gastric cancer progression in vivo and in vitro. We found that mJPYZ decreased the activity of PI3-kinase γ (PI3Kγ) in TAMs, reduced the anti-inflammatory factor IL-10 and increased the expression of pro-inflammatory cytokines, such as TNF-α and IL-1β, which ultimately promoted the conversion of TAMs from M2 to M1. Our findings also indicated that mJPYZ inhibited the growth and metastasis of gastric cancer by alleviating the unfavorable differentiation of TAMs via the PI3Kγ signaling cascades. In conclusion, the present findings indicated that mJPYZ inhibited gastric cancer cell EMT via PI3Kγ-dependent TAM reprogramming, which eventually suppressed gastric cancer growth and metastasis. Our study provides an underlying mechanism of a Chinese medicine in the treatment of gastric cancer via PI3Kγ in macrophages. [ABSTRACT FROM AUTHOR]

Gastric cancer remains the second most common tumor in China. Modified-Bu-zhong-yi-qi decoction (mBYD) as an adjuvant therapy for gastric cancer patients after chemotherapy could significantly prolong the survival time of patients. However, the potential anticancer mechanism for mBYD has not been well characterized. Here, we conducted a comprehensive study of mBYD on a gastric cancer xenograft model with MFC cells in 615 mice and patients. Our results showed that the survival times of the 5-FU + mBYD and mBYD groups were significantly longer than that of the control group. Moreover, the 5-FU + mBYD group had a longer survival time than the 5-FU group. Flow cytometry revealed that the value of CD4+/CD8+ in the mBYD group increased and that the proportions of CD8+PD-1+ T cells and PD-1+Treg cells were decreased when compared to the control group. Compared with the 5-FU group, CD8+PD-1+ T cells and Treg cells were both decreased when 5-FU was combined with mBYD. Further analysis showed that mBYD inhibited PD-L1 expression by the PI3K/AKT pathway in gastric cancer. An in vitro study also showed that mBYD directly promoted the proliferation, activation and cytotoxicity of T lymphocytes. Meanwhile, mBYD reduced the upregulation of CD8+PD-1+ T cells induced by chemotherapy in patients with gastric cancer. In conclusion, mBYD could modulate peripheral immunity and suppress the immune escape of tumors, which may be a promising therapy for gastric cancer. [ABSTRACT FROM AUTHOR]