Overexpression of COX7A1 Promotes the Resistance of Gastric Cancer to Oxaliplatin and Weakens the Efficacy of Immunotherapy.

Gastric cancer (GC) is one of the most common clinical malignant tumors worldwide, with high morbidity and mortality. Presently, the overall response rate to immunotherapy is low, and current methods for predicting the prognosis of GC are not optimal. Therefore, novel biomarkers with accuracy, efficiency, stability, performance ratio, and wide clinical application are needed. Based on public data sets, the chemotherapy cohort and immunotherapy cohort from Sun Yat-sen University Cancer Center, a series of bioinformatics analyses, such as differential expression analysis, survival analysis, drug sensitivity prediction, enrichment analysis, tumor immune dysfunction and exclusion analysis, single-sample gene set enrichment analysis, stemness index calculation, and immune cell infiltration analysis, were performed for screening and preliminary exploration. Immunohistochemical staining and in vitro experiments were performed for further verification. Overexpression of COX7A1 promoted the resistance of GC cells to Oxaliplatin. COX7A1 may induce immune escape by regulating the number of fibroblasts and their cellular communication with immune cells. In summary, measuring the expression levels of COX7A1 in the clinic may be useful in predicting the prognosis of GC patients, the degree of chemotherapy resistance, and the efficacy of immunotherapy.

Construction of a gene model related to the prognosis of patients with gastric cancer receiving immunotherapy and exploration of COX7A1 gene function.

BACKGROUND: GC is a highly heterogeneous tumor with different responses to immunotherapy, and the positive response depends on the unique interaction between the tumor and the tumor microenvironment (TME). However, the currently available methods for prognostic prediction are not satisfactory. Therefore, this study aims to construct a novel model that integrates relevant gene sets to predict the clinical efficacy of immunotherapy and the prognosis of GC patients based on machine learning. METHODS: Seven GC datasets were collected from the Gene Expression Omnibus (GEO) database, The Cancer Genome Atlas (TCGA) database and literature sources. Based on the immunotherapy cohort, we first obtained a list of immunotherapy related genes through differential expression analysis. Then, Cox regression analysis was applied to divide these genes with prognostic significancy into protective and risky types. Then, the Single Sample Gene Set Enrichment Analysis (ssGSEA) algorithm was used to score the two categories of gene sets separately, and the scores differences between the two gene sets were used as the basis for constructing the prognostic model. Subsequently, Weighted Correlation Network Analysis (WGCNA) and Cytoscape were applied to further screen the gene sets of the constructed model, and finally COX7A1 was selected for the exploration and prediction of the relationship between the clinical efficacy of immunotherapy for GC. The correlation between COX7A1 and immune cell infiltration, drug sensitivity scoring, and immunohistochemical staining were performed to initially understand the potential role of COX7A1 in the development and progression of GC. Finally, the differential expression of COX7A1 was verified in those GC patients receiving immunotherapy. RESULTS: First, 47 protective genes and 408 risky genes were obtained, and the ssGSEA algorithm was applied for model construction, showing good prognostic discrimination ability. In addition, the patients with high model scores showed higher TMB and MSI levels, and lower tumor heterogeneity scores. Then, it is found that the COX7A1 expressions in GC tissues were significantly lower than those in their corresponding paracancerous tissues. Meanwhile, the patients with high COX7A1 expression showed higher probability of cancer invasion, worse clinical efficacy of immunotherapy, worse overall survival (OS) and worse disease-free survival (DFS). CONCLUSIONS: The ssGSEA score we constructed can serve as a biomarker for GC patients and provide important guidance for individualized treatment. In addition, the COX7A1 gene can accurately distinguish the prognosis of GC patients and predict the clinical efficacy of immunotherapy for GC patients.

A system for fluid pumping by liquid metal multi-droplets.

The transportation and control of microfluidics have an important influence on the fields of biology, chemistry, and medicine. Pump systems based on the electrocapillary effect and room-temperature liquid metal droplets have attracted extensive attention. Flow rate is an important parameter that reflects the delivery performance of the pump systems. In the systems of previous studies, cylindrical structures are mostly used to constrain the droplet. The analysis and quantitative description of the influence of voltage frequency, alternating voltage, direct current voltage bias, and solution concentration on the flow rate are not yet comprehensive. Furthermore, the systems are driven by only one droplet, which limits the increase in flow rate. Therefore, a pump with a cuboid structure is designed and the droplet is bound by pillars, and the flow rate of the pump is increased by more than 200% compared with the cylindrical pump. For this structure, the mechanism of various factors on the flow rate is analyzed. To further enhance the flow rate, a pump system with multi-droplets is proposed. Moreover, the expression of flow velocity of the solution on the surface of each droplet and the relationship between the flow rate, alternating voltage, and the number of droplets are deduced. Finally, the potential of applying the multi-droplet cuboid pump system in drug delivery and analytical chemistry is demonstrated. Additionally, the core of the pump, the droplet area, is modularized, which breaks the overall structural limitations of the liquid metal pump and provides ideas for pump design.

Coalescence-Induced Droplet Jumping on Superhydrophobic Surfaces with Annular Wedge-Shaped Micropillar Arrays.

The coalescence-induced droplet jumping on superhydrophobic surfaces has extensive application potential in water harvesting, thermal management of electronic devices, and microfluidics. The rational design of the surface structure can influence the interaction between the droplet and the surface, thereby controlling the velocity and direction of the droplet's jumping. In this study, we fabricate the superhydrophobic surface with annular wedge-shaped micropillar arrays, examine the dynamic behavior of condensate droplets on the surface, and measure the temporal and spatial variations of droplet density, average radius, and surface coverage with wedge-shaped micropillars of varying sizes. In addition, the energy analysis of the coalescence-induced droplet jumping reveals that the two primary factors influencing the jumping are the relative size and position of the droplets and micropillars. Further numerical simulations find that the wedge-shaped micropillars cause an asymmetric distribution of pressure within the droplet and at the solid-liquid contact surface, which generates an unbalanced force driving the droplet in the gradient direction of the wedge-shaped micropillar, causing the droplet to jump off the surface with both vertical and gradient-direction velocities. The capacity of the wedge-shaped micropillar surface to transport droplets in the gradient direction increases and then decreases as the relative size of the droplets and micropillars increases. The relative position of the droplet center-of-mass line perpendicular to the bottom edge of the wedge micropillars' trapezoidal shape is more favorable for droplet transport. This work reveals the influence mechanism of surface structure on the velocity and direction of droplet jumping, and the results can guide the microstructure design of superhydrophobic surfaces, which has significant implications for the application of droplet jumping.

An Oscillation System Based on a Liquid Metal Droplet and Pillars under a Direct Current Electric Field.

Gallium-based liquid metal is a new class of material that has attracted extensive attention due to its excellent deformation characteristics and great potential in applications. Based on the deformation characteristics of liquid metal droplets, researchers have developed many oscillation systems composed of gallium indium tin alloy (GaInSn) droplet and graphite, or aluminum-doped gallium indium alloy (Al-GaIn24.5) droplet and iron, and so on. Rather than the oxidation and deoxidation mechanisms used in previous systems, an oscillation system that can achieve gallium indium alloy (EGaIn) droplet oscillation with the frequency of 0-29 Hz is designed depending on the interactions between the electric field, pillars, sodium hydroxide, and the droplet. The forces on the droplet are analyzed specifically, which have a great influence on droplet deformation. Additionally, the effects of factors such as voltage, the concentration of sodium hydroxide (NaOH) solution, and droplet size on the droplet oscillation are elucidated based on the force analysis, enabling the flexible control of the oscillation frequency and amplitude of the droplet. This work provides a new perspective on the design of oscillation systems and further enhances our understanding of the deformation of gallium-based liquid metal droplets.

High-speed directional transport of condensate droplets on superhydrophobic saw-tooth surfaces.

HYPOTHESIS: Most droplets on high-efficiency condensing surfaces have radii of less than 100 µm, but conventional droplet transport methods (such as wettability-gradient surfaces and structural-curvature-gradient surfaces) that rely on the unbalanced force of three-phase lines can only transport millimeter-sized droplets efficiently. Regulating high-speed directional transport of condensate droplets is still challenging. Therefore, we present a method for condensate droplet transportation, based on the reaction force of the superhydrophobic saw-tooth surfaces to the liquid bridge, the condensate droplets could be transported at high speed and over long distances. EXPERIMENTS: The superhydrophobic saw-tooth surfaces are fabricated by femtosecond laser ablation and chemical etching. Condensation experiments and luminescent particle characterization experiments on different surfaces are conducted. Aided by the theoretical analysis, we illustrate the remarkable performance of condensate droplet transportation on saw-tooth surfaces. FINDINGS: Compared with conventional methods, our method improves the transport velocity and relative transport distance by 1-2 orders of magnitude and achieves directional transport of the smallest condensate droplet of about 2 µm. Furthermore, the superhydrophobic saw-tooth surfaces enable multi-hop directional jumping of condensate droplets, leading to cross-scale increases in transport distances from microns to decimeters.

Upregulation of SOCS2 causes mitochondrial dysfunction and promotes ferroptosis in pancreatic cancer cells.

SOCS2 exerts oncogenic effects in a variety of tumors, but its role in pancreatic cancer has not been studied. The purpose of this study was to explore the role of SOCS2 in pancreatic cancer. The expression level of SOCS2 and the content of mitochondrial DNA (mtDNA) in the cells were detected by real-time PCR (qRT-PCR), and SOCS2 was overexpressed in PANC-1 and Capan-2 cells by transfection with pcDNA3.2-SOCS2. CCK-8, cell colony formation assay, and flow cytometry were used respectively to detect the cell proliferation rate, cell colony formation ability, and the level of ROS in the cells. The ATP level, glucose consumption level, and Fe2 + level in the cells were assessed by biochemical assays. And Western blot determined the protein expression levels of SOCS2 as well as ferroptosis-related proteins, namely, SLC7A11, DMT1, TFRC, and FTH. We found that SOCS2 was significantly down-regulated in pancreatic cancer cells. Overexpression of SOCS2 significantly decreased the viability of PANC-1 and Capan-2 cells, reduced the content of mtDNA and the level of ATP, and caused mitochondrial dysfunction with an accumulation of ROS. Aside from these effects, up-regulation of SOCS2 raised the levels of Fe2 +, DMT1 and TFRC, and decreased the level of SLC7A11 and FTH in PANC-1 and Capan-2 cells, thereby inducing the occurrence of ferroptosis. In conclusion, up-regulated SOCS2 may enhance mitochondrial dysfunction and ferroptosis in pancreatic cancer cells, which can be used as a molecular target for the diagnosis and treatment of pancreatic carcinoma.

Identification and Analysis of Crucial Genes in H. pylori-Associated Gastric Cancer Using an Integrated Bioinformatics Approach.

Background: The relationship between H. pylori infection and gastric cancer (GC) has been widely studied, and H. pylori is considered as the main factor. Utilizing bioinformatics analysis, this study examined gene signatures related to progressing H. pylori-associated GC. Materials and Methods: The dataset GSE13195 was chosen to search for abnormally expressed genes in H. pylori-associated GC and normal tissues. The TCGA-STAD database was chosen to verify the expression of key genes in GC and normal tissues. Results: In GSE13195, a total of 332 differential expression genes (DEGs) were screened. The results of weighted gene co-expression network analysis showed that the light cyan, plum2, black, and magenta4 modules were associated with stages (T3, T2, and T4), while the orangered4, salmon2, pink, and navajowhite2 modules were correlated with lymph node metastasis (N3, N2, and N0). Based on the results of DEGs and hub genes, a total of 7 key genes (ADAM28, FCER1G, MRPL14, SOSTDC1, TYROBP, C1QC, and C3) were screened out. These gene mRNA levels were able to distinguish between normal and H. pylori-associated GC tissue using receiver operating characteristic curves. After transcriptional level verification and survival analysis, ADAM28 and C1QC were excluded. An immune infiltration study revealed that key genes were involved in regulating the infiltration levels of cells associated with innate immune response, antigen presentation process, humoral immune response, or Tcell-mediated immune response. In addition, drugs targeting FCER1G and TYROBP have been approved and are under investigation. Conclusion: Our study identified five key genes involved in H. pylori-associated GC tumorigenesis. Patients with higher levels of C3 expression had a poorer prognosis than those with lower levels. In addition, these key genes may serve as biomarkers and therapeutic targets for H. pylori-associated GC diagnosis, targeted therapy, and immunotherapy in the future.

A multicenter, randomized, double-blind, placebo-controlled, phase 3 trial of olanzapine plus triple antiemetic regimen for the prevention of multiday highly emetogenic chemotherapy-induced nausea and vomiting (OFFER study).

Background: Evidence supports prophylactic use of olanzapine for the treatment of chemotherapy-induced nausea and vomiting (CINV). However, most studies to date have focused on patients with single-day highly emetogenic chemotherapy (HEC). Currently, administration of antiemetic therapies for nausea and vomiting induced by multiday chemotherapy regimens remains a challenge. In this study, we evaluated the efficacy of olanzapine combined with triple antiemetic therapy for the prevention of CINV in patients receiving multiday chemotherapy. Methods: We performed a randomized, double-blind, placebo-controlled phase 3 trial in 22 hospitals. Eligible patients were between 18 and 75 years old, were diagnosed with malignant solid tumors, and they had an Eastern Cooperative Oncology Group (ECOG) performance status of 0-2. All the study participants were scheduled to be treated with chemotherapy regimens containing 3-day cisplatin (3-day total dose ≥75 mg/m2). Randomization was computer generated and stratified by gender and chemotherapy treatment history. Allocation was done via an interactive web response system. Enrolled patients were randomly assigned 1:1 to receive either 5 mg olanzapine or placebo orally before bedtime for 5 days combined with intravenous fosaprepitant (150 mg) 1 h before the administration of cisplatin on day 1, ondansetron hydrochloride intravenously, and dexamethasone orally 30 min before cisplatin from days 1 to 3. Dexamethasone was also administered at the same time on days 4 and 5. The primary endpoint was the proportion of subjects with complete response (no vomiting and no rescue therapy) within the overall phase (days 1-8) after starting chemotherapy. Baseline plasma concentrations of P-substance and 5-HT were measured for exploratory analysis. This study was registered at ClinicalTrials.gov, number NCT04536558. Findings: Between December 2020 and September 2021, 349 patients with malignant solid tumors were enrolled in the study, with 175 participants randomly assigned to receive olanzapine and 174 participants assigned to receive placebo. The proportion of patients who achieved a complete response in the overall phase was significantly higher in the olanzapine group than in the placebo group (69% vs. 58%, P = 0.031). A complete response benefit was observed in the olanzapine group versus the placebo group in almost all the subgroups. Four factors were considered significantly associated with complete response in multivariable analysis: treatment group, gender, baseline plasma concentration of 5-HT, and prior radiotherapy. All the reported adverse events associated with olanzapine administration were grades 1 and 2. Interpretation: Olanzapine (5 mg) combined with fosaprepitant, ondansetron, and dexamethasone was better than triple antiemetic therapy alone for patients receiving multiday chemotherapy regimens. Based on these results, the four-drug combination should be recommended as the best antiemetic regimen given to patients receiving multiday cisplatin-based chemotherapy and baseline plasma concentration of 5-HT may be used to identify individuals who are prone to CINV. However, all these findings need to be further validated in future studies. Funding: Jiangsu Hansoh Pharmaceutical Group Co., Ltd. provided research grant and study drugs for this investigator-initiated study.

A new acidic microenvironment related lncRNA signature predicts the prognosis of liver cancer patients.

Background: The acidic microenvironment (AME), like hypoxia, inflammation, or immunoreaction, is a hallmark of the tumor microenvironment (TME). This work aimed to develop a prediction signature dependent on AME-associated lncRNAs in order to predict the prognosis of LC individuals. Methods: We downloaded RNA-seq information and the corresponding clinical and predictive data from The Cancer Genome Atlas (TCGA) dataset and conducted univariate and multivariate Cox regression analyses to identify AME-associated lncRNAs for the construction of a prediction signature The Kaplan-Meier technique was utilized to determine the overall survival (OS) rate of the high (H)-risk and low (L)-risk groups. Using gene set enrichment analysis (GSEA) the functional variations between the H- and L-risk groups were investigated. The association between the prediction signature and immunological state was investigated using single-sample GSEA (ssGSEA). Additionally, the association between the predicted signature and the therapeutic response of LC individuals was evaluated. Lastly, quantitative reverse transcription polymerase chain reaction (qRT-PCR) was performed to verify the risk model. Results: We generated a signature comprised of seven AME-associated lncRNAs (LINC01116, AC002511.2, LINC00426, ARHGAP31-AS1, LINC01060, TMCC1-AS1, AC012065.1). The H-risk group had a worse prognosis than the L- risk group. The AME-associated lncRNA signature might determine the prognosis of individuals with LC independently. The AME-related lncRNA signature shows a greater predictive effectiveness than clinic-pathological factors, with an area under the receiver operating characteristic (ROC) curve of 0.806%. When participants were categorized based on several clinico-pathological characteristics, the OS of high-risk individuals was shorter compared to low-risk patients. GSEA demonstrated that the metabolism of different acids and the PPAR signaling pathway are closely associated with low-risk individuals. The prognostic signature was substantially associated with the immunological status of LC individuals, as determined by ssGSEA. High risk individuals were more sensitive to some immunotherapies (including anti-TNFSF4 anti-SIRPA, anti-CD276 and anti-TNFSF15) and some conventional chemotherapy drugs (including lapatinib and paclitaxel). Finally, the expression levels of the seven lncRNAs comprising the signature were tested by qRT-PCR. Conclusions: A basis for the mechanism of AME-associated lncRNAs in LC is provided by the prediction signature, which also offers clinical therapeutic recommendations for LC individuals.

A novel difficulty scoring system of laparoscopic liver resection for liver tumor.

Objectives: To develop a novel difficulty scoring system (NDSS) to predict the surgical difficulty of laparoscopic hepatectomy. Patients and methods: A total of 138 patients with liver tumors performed liver resection (LLR) between March 2017 to June 2022 were selected from Affiliated Hospital of Jiangnan University and Wujin Hospital Affiliated with Jiangsu University.Patient demographics, laboratory tests, intraoperative variables, pathological characteristics were assessed. We also assessed the Child Pugh score and the DSS-B score. Results: Patients were divided into training and testing cohort according to their hospital. Patients in training cohort were divided into high and low difficult groups based on operation time, blood loss and conversion. Higher percentage of patients with malignant liver tumor (87.0% vs. 58.1%; P = 0.003) or history of hepatobiliary surgery (24.1% vs. 7.0%; P = 0.043) in high difficult group than in low difficult group. To improve the difficulty scoring system, we incorporated the history of hepatobiliary surgery and nature of the tumor. A novel difficulty scoring system was established. The results showed that the operation time (P < 0.001), blood loss (P < 0.001), ALT (P < 0.001) and AST (P = 0.001) were associated with the novel difficulty score significantly. Compared with DSS-B, the NDSS has a higher area under the receiver operating characteristic (AUROC) (0.838 vs. 0.814). The nomogram was established according to the NDSS. The AUROCs of the nomogram in training and testing cohort were 0.833 and 0.767. The calibration curves for the probability of adverse event showed optimal agreement between the probability as predicted by the nomogram and the actual probability. Conclusions: We developed a nomogram with the NDSS that can predict the difficulty of LLR. This system could more accurately reflect the difficulty of surgery and help liver surgeons to make the surgical plan and ensure the safety of the operation.

Identification of Key Genes in the HBV-Related HCC Immune Microenvironment Using Integrated Bioinformatics Analysis.

Purpose: Hepatocellular carcinoma (HCC) has poor prognosis and high mortality among gastrointestinal tumors because of its insidious onset and strong invasiveness. However, there was little understanding of their pathogenesis. The purpose of this study was to use bioinformatics analysis to identify genes associated with the immune microenvironment in HBV-related HCC and to develop new therapeutic targets to prevent and treat cancer. Methods: RNA-seq data of HBV-related HCC cases were downloaded from TCGA-LIHC database. ESTIMATE and Deseq2 algorithms were used to screen out differentially expressed genes (DEGs). WGCNA was used to construct gene coexpression networks. In key modules, functional enrichment analysis was performed. Protein-protein interaction (PPI) was used to screen hub genes, and survival analysis was conducted to assess their prognostic significance. Following, we search for key genes differentially expressed between cancerous and paracancerous tissues in GSE136247 and GSE121248 datasets. Reveal the potential links between key genes in immune infiltration by using TIMER. Finally, in TCGA-LIHC database, integration of key genes with clinical data were used to further validate their correlation with prognosis. Results: In the cohort of HBV-related HCC patients, immune/stromal/ESTIMATE scores were not significantly associated with patient prognosis. After bioinformatics analysis, screening out five key genes was significantly related to the prognosis of HBV-related HCC. Downregulation of SLAMF1 and TRAF3IP3 suggested poor prognosis and was related to a variety of immune cell infiltration. Furthermore, compared with adjacent nontumor tissues, TRAF3IP3 and SLAMF1 were highly expressed in tumor tissues and were linked to tumor recurrences. Conclusion: In conclusion, SLAMF1 and TRAF3IP3 were identified with higher expression in tumor tissues and associated with tumor recurrence. It will be a new research direction of tumor progress and treatment.

Condensation droplet sieve.

Large droplets emerging during dropwise condensation impair surface properties such as anti-fogging/frosting ability and heat transfer efficiency. How to spontaneously detach massive randomly distributed droplets with controlled sizes has remained a challenge. Herein, we present a solution called condensation droplet sieve, through fabricating microscale thin-walled lattice structures coated with a superhydrophobic layer. Growing droplets were observed to jump off this surface once becoming slightly larger than the lattices. The maximum radius and residual volume of droplets were strictly confined to 16 µm and 3.2 nl/mm2 respectively. We reveal that this droplet radius cut off is attributed to the large tolerance of coalescence mismatch for jumping and effective isolation of droplets between neighboring lattices. Our work brings forth a strategy for the design and fabrication of high-performance anti-dew materials.

Metformin Improves the Senescence of Renal Tubular Epithelial Cells in a High-Glucose State Through E2F1.

Diabetic kidney disease is a major cause of chronic kidney condition and the most common complication of diabetes. The cellular senescence participates in the process of diabetic kidney disease, but the specific mechanism is not yet clear. Cell cycle-related protein E2F transcription factor 1 (E2F1) is a member of the E2F transcription factor family, it plays a key role in cellular damage under HG conditions. In this study, we explored whether metformin improves a high-glucose-induced senescence and fibrosis of renal tubular epithelial cells through cell cycle-related protein E2F1. In the in vivo experiments, the recombinant adeno-associated virus (AAV-shE2F1) knockdown E2F1 gene was injected into the tail vein of 16-weeks-old db/db mice for 8 weeks. The 16-week-old db/db mice were administered metformin (260 mg/kg/d) continuously for 8 weeks. The normal control group (NC) and diabetic model group (DM) were set up simultaneously. Mice renal tubular epithelial cells (mRTECs) were cultured in vitro. The cells were randomly divided into the following groups: normal glucose (NG, containing 5.5 mmol/L glucose), high glucose group (HG, containing 30 mmol/L glucose), NG/HG metformin intervention group (NG/HG + Met), NG/HG negative control siRNA transfection group (NG/HG + Control), NG/HG E2F1 siRNA transfection group (NG/HG + siRNA E2F1), HG metformin intervention and overexpression E2F1 plasmid transfection group (HG + Met + overexpress-E2F1). The expression of related indexes were detected by Western blot, real-time polymerase chain reaction (PCR), immunohistochemistry, and immunofluorescence. The results showed that E2F1 knockdown or metformin reduces the degree of renal fibrosis, DNA damage, and cellular senescence in the DM group; metformin also reduced the expression of E2F1. If E2F1 was overexpressed, the effects of metformin in delaying fibrosis and reducing DNA damage and cellular senescence could be weakened. Thus, metformin alleviates high-glucose-induced senescence and fibrosis of renal tubular epithelial cells by downregulating the expression of E2F1.

BMP-7 Upregulates Id2 Through the MAPK Signaling Pathway to Improve Diabetic Tubulointerstitial Fibrosis and the Intervention of Oxymatrine.

Diabetic kidney disease is one of the most serious microvascular complications of diabetes. It progresses irreversibly to end-stage renal disease if left untreated. Bone morphogenetic protein (BMP)-7 is a negative regulator of organ fibrosis and may also play an essential role in tubulointerstitial fibrosis. This study aimed to investigate the precise role and potential molecular mechanisms of BMP-7 in the progression of diabetic nephropathy. In this study, BMP-7 was overexpressed in vivo after the replication of the diabetic rat model using streptozotocin. The results showed that BMP-7 inhibited the phosphorylation of related mitogen-activated protein kinase (MAPK) pathways while upregulating the inhibitor of differentiation (Id2) expression and effectively ameliorated pathological renal injury. Further in vitro validation showed that the inhibition of the phosphorylation of MAPKs at a high glucose concentration in renal tubular epithelial cells was followed by the upregulation of Id2 protein expression, suggesting that BMP-7 could improve diabetic nephropathy by upregulating Id2 protein levels through the BMP-7-MAPK signaling pathway. Previous laboratory studies found that oxymatrine improved renal fibrotic lesions. However, the exact mechanism is unclear. The present study showed that oxymatrine treatment in a diabetic rat model upregulated BMP-7 protein expression and inhibited MAPK pathway protein phosphorylation levels. These results suggested that oxymatrine improved the epithelial-to-mesenchymal transition process in the early stage of diabetic kidney disease by regulating the BMP-7-MAPK pathway and ameliorated renal tubulointerstitial fibrosis.

The relationship between occupational physical activity and dyslipidaemia in farmers with varying working modes in southwest China: the China multi-ethnic cohort study.

BACKGROUND: Farmers are the integral members of rural communities. In the present study, we determined the association between occupational physical activity (OPA) of farmers and dyslipidaemia. METHODS: We included 7649 farmers from The China Multi-Ethnic Cohort (CMEC) Study. The working modes of all farmers were divided into four types according to their self-reported seasonal changes in farming work and/or other job changes (1: no change; 2: changing job; 3: seasonal changes; and 4: seasonal and job changes). OPA was self-reported, and the OPA levels in the four groups were classified as Q1, Q2-Q3, and Q4 by quantile. Dyslipidaemia was defined as the presence of abnormalities in lipid indicators. Binary logistic regression was used to estimate the association between OPA and dyslipidaemia. RESULTS: Compared with those in the no change group, the participants in other three groups were younger with lower level of education, annual income, and leisure-time physical activity (LTPA). Active OPA could reduce the risk of dyslipidaemia in the no change [men: odds ratios (OR) = 0.21, 95% confidence intervals (CI): 0.07-0.64; women: OR = 0.43, 95% CI: 0.20-0.93] and seasonal change (men: OR = 0.46, 95% CI: 0.27-0.77; women: OR = 0.59, 95% CI: 0.41-0.86) groups. However, in the seasonal and job change group (men: OR = 3.23, 95% CI: 1.06-9.80; women: OR = 3.24, 95% CI: 1.42-7.41), active OPA increased the risk of dyslipidaemia. CONCLUSIONS: Different OPA levels might lead to differences in association with blood lipid levels. Thus, OPA guidelines must be developed for farmers, especially for those who experience seasonal changes in farming work and job changes.

Patterns and demographic correlates of domain-specific physical activities and their associations with dyslipidaemia in China: a multiethnic cohort study.

OBJECTIVE: To evaluate the patterns and demographic correlates of domain-specific physical activities (PAs) and their associations with dyslipidaemia among ethnic minorities in China. DESIGN: Cross-sectional. PARTICIPANTS: In total, 17 081 individuals were included. PRIMARY AND SECONDARY OUTCOME MEASURES: Domain-specific PAs were assessed using a questionnaire related to occupational, transportation, housework and leisure-time PAs. Dyslipidaemia was measured using an automatic biochemical instrument. Demographic variables were self-reported. RESULTS: Housework accounted for most PAs in the study. Elderly people were more likely to participate in housework and leisure-time PA, whereas the mean level of PA in people with low education level and household income was high. With G3-G4 levels of occupational PA, Dong men (G4: OR=0.530, 95% CI 0.349 to 0.806), Miao women (G3: OR=0.698, 95% CI 0.524 to 0.931; G4: OR=0.611, 95% CI 0.439 to 0.850) and Bouyei women (G3: OR=0.745, 95% CI 0.566 to 0.981; G4: OR=0.615, 95% CI 0.440 to 0.860) tended to have a low risk of dyslipidaemia. With G2 levels of transportation, PA could reduce the risk of dyslipidaemia in Bouyei women (G2: OR=0.747, 95% CI 0.580 to 0.962). G2-G3 levels of leisure-time PA could reduce the risk of dyslipidaemia in Miao men (G2: OR=0.645, 95% CI 0.446 to 0.933; G3: OR=0.700, 95% CI 0.513 to 0.954). However, a high risk of dyslipidaemia was observed with G4 levels of leisure-time PA among Bouyei women (G4: OR=.353, 95% CI 1.001 to 1.905) and with transportation PA among Dong men (G4: OR=1.591, 95% CI 1.130 to 2.240). CONCLUSION: The main PA of the ethnic minorities in Guizhou Province involved housework. Domain-specific PAs varied with demographic factors, and active domain-specific PAs were associated with a reduced risk of dyslipidaemia.

Evaluation of anthropometric indices as a predictor of diabetes in Dong and Miao ethnicities in China: A cross-sectional analysis of China Multi-Ethnic Cohort Study.

BACKGROUND: Although it is known that obesity is inseparable from diabetes, many anthropometric indices are used for determining obesity. At the same time, research on the predictive indices of diabetes in Chinese minority populations is lacking. Therefore, this study determines the relationship between different anthropometric indices and diabetes, and identifies the best index and best cut-off values for predicting diabetes. METHOD: In total, 11,035 Dong and Miao ethnic participants (age: 30-79 years) from the China Multi-Ethnic Cohort study were included. The logistic regression model was used to examine the relationship between the different anthropometric indices and diabetes risk. The receiver operating characteristic curve and the area under the curve (AUC) were used to identify the best predictor of diabetes. RESULTS: In multivariate adjusted logistic regression models, body mass index (BMI), waist circumference (WC), waist-to-hip ratio (WHR), waist-to-height ratio (WHtR), a body shape index (ABSI), body roundness index (BRI), and visceral adiposity index (VAI) were positively correlated with diabetes risk. Among Chinese Dong men and women and Miao men, WHR had the largest AUC (0.654/0.719/0.651). Among Miao women, VAI had the largest AUC(0.701). The best cut-off values of WHR for Dong men and women and Miao men were 0.94, 0.92, and 0.91, respectively. The best cut-off value of VAI for Miao women was 2.20. CONCLUSION: Obesity indicators better predict diabetes in women than men. WHR may be the best predictor of diabetes risk in both sex of Dong ethnicity and Miao men, and VAI may be the best predictor of diabetes risk in Miao women.

Axial spreading of droplet impact on ridged superhydrophobic surfaces.

HYPOTHESIS: Due to the complex hydrodynamics of droplet impact on ridged superhydrophobic surfaces, quantitative droplet spreading characteristics are unrevealed, limiting the practical applications of ridged superhydrophobic surfaces. During droplet impacting, the size ratio (the ratio of the ridge diameter to the droplet diameter) is an important factor that affects droplet spreading dynamics. EXPERIMENTS: We fabricated ridged superhydrophobic surfaces with size ratios ranging from zero to one, and conduct water droplet impact experiments on these surfaces at varied Weber numbers. Aided by the numerical simulations and theoretical analysis, we illustrate the droplet spreading dynamics and reveal the law on the maximum axial spreading coefficient. FINDS: The results show that the droplet spreading and retraction dynamics on ridged superhydrophobic surfaces are significantly asymmetric in the axial and spanwise directions. Focusing on the maximum axial spreading coefficient, we find it decreases first and then increases with increasing size ratios, indicating the existence of the critical size ratio. The maximum axial spreading coefficient can be reduced by 25-40% at the critical size ratio compared with that on flat surfaces. To predict the maximum axial spreading coefficient, two theoretical models are proposed respectively for size ratios smaller and larger than the critical size ratio.

Ultimate jumping of coalesced droplets on superhydrophobic surfaces.

HYPOTHESIS: Jumping of coalesced droplets on superhydrophobic surfaces (SHSs) is widely used for enhanced condensation, anti-icing/frosting, and self-cleaning due to its superior droplet transport capability. However, because only a tiny fraction (about 5%) of the released excess surface energy during coalescence can be transformed into jumping kinetic energy, the jumping is very weak, limiting its application. METHODS: We experimentally propose enhanced jumping methods, use machine learning to design structures that achieve ultimate jumping, and finally combine experiments and simulations to investigate the mechanism of the enhanced jumping. FINDING: We find that a more orderly flow inside the droplets through the structure is the key to improve energy transfer efficiency and that the egg tray-like structure enables the droplet to jump with an energy transfer efficiency 10.6 times higher than that of jumping on flat surfaces. This energy transfer efficiency is very close to the theoretical limit, i.e., almost all the released excess surface energy is transformed into jumping kinetic energy after overcoming viscous dissipation. The ultimate jumping enhances the application of water droplet jumping and enables other low surface energy fluid such as R22, R134a, Gasoline, and Ethanol, which cannot jump on a flat surface, to jump.