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To evaluate the in vitro and in vivo anti-metastasis efficacy of Jianpi Yangzheng (JPYZ) decoction against gastric cancer (GC) and its potential mechanisms. The distant metastasis of GC cells administered via tail vein injection was assessed using the pre-metastatic niche (PMN) model. 16S rRNA sequencing and GC–MS/MS were applied to determine the component of the gut microbiota and content of short-chain fatty acids (SCFAs) in feces of mice, respectively. The proportion of myeloid-derived suppressor cells (MDSCs) in the lung was evaluated by flow cytometry and immunofluorescence. Serum or tissue levels of inflammation factors including IL-6, IL-10 and TGF-β were determined by ELISA or Western blot respectively. Injecting GC cells into the tail vein of mice led to the development of lung metastases and also resulted in alterations in the composition of gut microbiota and the levels of SCFAs produced. Nevertheless, JPYZ treatment robustly impeded the effect of GC cells administration. Mechanically, JPYZ treatment not only prevented the alteration in gut microbiota structure, but also restored the SCFAs content induced by GC cells administration. Specifically, JPYZ treatment recovered the relative abundance of genera Moryella, Helicobacter, Lachnoclostridium, Streptococcus, Tuzzerella, GCA-900066575, uncultured_Lachnospiraceae, Rikenellaceae_RC9_gut_group and uncultured_bacterium_Muribaculaceae to near the normal control levels. In addition, JPYZ abrogated MDSCs accumulation in the lung tissue and blocked inflammation factors overproduction in the serum and lung tissues, which subsequently impede the formation of the immunosuppressive microenvironment. Correlation analysis revealed that the prevalence of Rikenellaceae in the model group exhibited a positive correlation with MDSCs proportion and inflammation factor levels. Conversely, the scarcity of Muribaculaceae in the model group showed a negative correlation with these parameters. This suggests that JPYZ might exert an influence on the gut microbiota and their metabolites, such as SCFAs, potentially regulating the formation of the PMN and consequently impacting the outcome of GC metastasis. These findings suggest that GC cells facilitate metastasis by altering the gut microbiota composition, affecting the production of SCFAs, and recruiting MDSCs to create a pro-inflammatory pre-metastatic niche. JPYZ decoction counteracts this process by reshaping the gut microbiota structure, enhancing SCFA production, and inhibiting the formation of the pre-metastatic microenvironment, thereby exerting an anti-metastatic effect. [Display omitted] [ABSTRACT FROM AUTHOR]

Autophagy could sense metabolic conditions and safeguard cells against nutrient deprivation, ultimately supporting the survival of cancer cells. Nobiletin (NOB) is a kind of bioactive component of the traditional Chinese medicine Citri Reticulatae Pericarpium and has been proven to induce GC cell death by reducing de novo fatty acid synthesis in our previous study. Nevertheless, the precise mechanisms by which NOB induces cell death in GC cells still need further elucidation. To examine the mechanism by which NOB inhibits gastric cancer progression through the regulation of autophagy under the condition of lipid metabolism inhibition. Proliferation was detected by the CCK-8 assay. RNA sequencing (RNA-seq) was used to examine signaling pathway changes. Electron microscopy and mRFP-GFP-LC3 lentiviral transfection were performed to observe autophagy in vitro. Western blot, plasmid transfection, immunofluorescence staining, and CUT & Tag-qPCR techniques were utilized to explore the mechanisms by which NOB affects GC cells. Molecular docking and molecular dynamics simulations were conducted to predict the binding mode of NOB and SREBP1. CETSA was adopted to verify the predicted of binding model. A patient-derived xenograft (PDX) model was employed to verify the therapeutic efficacy of NOB in vivo. We conducted functional studies and discovered that NOB inhibited the protective effect of autophagy via the PI3K/Akt/mTOR axis in GC cells. Based on previous research, we found that the overexpression of ACLY abrogated the NOB-induced autophagy-dependent cell death. In silico analysis predicted the formation of a stable complex between NOB and SREBP1. In vitro assays confirmed that NOB treatment increased the thermal stability of SREBP1 at the same temperature conditions. Moreover, CUT&TAG-qPCR analysis revealed that NOB could inhibit SREBP1 binding to the ACLY promoter. In the PDX model, NOB suppressed tumor growth, causing SREBP1 nuclear translocation inhibition, PI3K/Akt/mTOR inactivation, and autophagy-dependent cell death. NOB demonstrated the ability to directly bind to SREBP1, inhibiting its nuclear translocation and binding to the ACLY promoter, thereby inducing autophagy-dependent cell death via PI3K/Akt/mTOR pathway. [Display omitted] [ABSTRACT FROM AUTHOR]

Gastric cancer (GC) is a common malignant tumor with limited treatment options. The natural flavonoid nobiletin (NOB) is a beneficial antioxidant that possesses anticancer activity. However, the mechanisms by which NOB inhibits GC progression remain unclear. A CCK-8 assay was performed to determine cytotoxicity. Cell cycle and apoptosis analyses were performed by flow cytometry. RNA-seq was performed to detect differential gene expression after NOB treatment. RT‒qPCR, Western blot and immunofluorescence staining were used to examine the underlying mechanisms of NOB in GC. Xenograft tumor models were constructed to verify the effect of NOB and its specific biological mechanism in GC. NOB inhibited cell proliferation, caused cell cycle arrest and induced apoptosis in GC cells. KEGG classification identified that the inhibitory effect of NOB on GC cells mainly involved the lipid metabolism pathway. We further showed that NOB reduced de novo fatty acid (FA) synthesis, as evidenced by the decreased levels of neutral lipids and the expression levels of ACLY, ACACA and FASN, and ACLY abrogated the effect of NOB on lipid deposits in GC cells. In addition, we also found that NOB triggered endoplasmic reticulum (ER) stress by activating the IRE-1α/GRP78/CHOP axis, but overexpression of ACLY reversed ER stress. Mechanistically, inhibiting ACLY expression with NOB significantly reduced neutral lipid accumulation, thereby inducing apoptosis by activating IRE-1α-mediated ER stress and inhibiting GC cell progression. Finally, in vivo results also demonstrated that NOB inhibited tumor growth by decreasing de novo FA synthesis. NOB could inhibit the expression of ACLY to activate IRE-1α-induced ER stress, which ultimately led to GC cell apoptosis. Our results provide novel insight into the use of de novo FA synthesis for GC treatment and are the first to reveal that NOB inhibits GC progression by ACLY-dependent ER stress. [Display omitted] [ABSTRACT FROM AUTHOR]

Background: Modified Jianpi Yangzheng decoction (mJPYZ), as an empirical decoction of Traditional Chinese medicine has been shown significantly to prolong the survival of patients with advanced stage gastric cancer. Pyruvate kinase M2 (PKM2), has attracted attention for its important role on cellular aerobic glycolysis, however, few studies focus on PKM2 non-metabolic roles in tumor progression.Purpose: Our study aimed to investigate the potential role of gastric cancer exosomes containing PKM2 in regulating tumor-associated macrophages (TAM) and the mechanism of mJPYZ against gastric cancer.Methods: Colony Formation Assay, flow cytometry and TUNEL staining were employed to estimate the effect of mJPYZ on gastric cancer in tumor-bearing mice and cells. Western blot analyzed apoptosis-related protein expression changes. Network pharmacology and bioinformatics predicted potential exosomes modulation of mJPYZ in gastric cancer. Exosomes were isolated and co-cultured with TAM. Diff-Quik Staining observed the TAM morphological changes when incubating with gastric cancer cells exosomes. Flow cytometry and immunofluorescence were performed to demonstrate whether exosomes PKM2 involved in TAM polarization.Results: mJPYZ induced apoptosis of gastric cancer cells by targeting PKM2 and downregulating PI3K/Akt/mTOR axis in vivo and in vitro. Network pharmacology showed potential exosomes modulation of mJPYZ in gastric cancer. We extracted exosomes and found mJPYZ decreased the abundance of serum exosomes PKM2 in patients with advanced gastric cancer and xenograft tumor model. Additionally, we firstly detected and confirmed that PKM2 is a package protein of exosomes extracted from gastric cancer cells, and mJPYZ could diminish the content of exosomal PKM2 in gastric cancer cells. Importantly, mJPYZ reduced the delivery of exosomal PKM2 from tumor cells to macrophages, and alleviated exosomal PKM2-induced differentiation of M2-TAM in tumor microenvironment, eventually inhibited gastric cancer progression.Conclusion: Gastric cancer exosomes containing PKM2 could lead to M2 macrophages differentiation, thereby promoting gastric cancer progression. Our findings provide a rationale for potential application of mJPYZ in the treatment of gastric cancer via PKM2. [ABSTRACT FROM AUTHOR]

Low-cycle fatigue properties of 30Cr1Mo1 V steam turbine rotor steel were studied by RDL05 electronic creep fatigue test machine at 0.1%.s -1 , 0.3%.s -1 , 0.5%.s -1 loading rates applied the total strain controlled method. The results involve that with the loading rate increases at 538 °C, cyclic stress of the rotor steel increases, and low-cycle fatigue life increases too; in the same strain range values, the increasing loading rate leads to the greater stress amplitude; with the increase of the strain range values, the stress increases and the low-cycle fatigue life decreases. The relationship of stress-strain and the loading rate is , the relationship of low-cycle fatigue life and the loading rate is . [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]

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]

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]

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]