SUMMARY: We investigated Tweety Family Member 3 (TTYH3) level in lung adenocarcinoma (LUAD) and its relationship with immune infiltration in tumors by bioinformatics. Differential expressions of TTYH3 in lung cancer were analyzed with Oncomine, TIMER, GEO, UALCAN and HPA. Relationship of TTYH3 mRNA/protein levels with clinical parameters was analyzed by UALCAN. Co-expressed genes of TTYH3 in LUAD were analyzed using Cbioportal. Its relationship with LUAD prognosis was analyzed by Kaplan-Meier plotter. GO and KEGG analysis were performed. Correlation between TTYH3 and tumor immune infiltration were tested by TIMER, TISIDB and GEPIA. We found that TTYH3 was significantly increased in LUAD tissues. TTYH3 high expression was closely related to poor overall survival, post progression survival and first progression in LUAD patients. TTYH3 mRNA/protein levels were significantly associated with multiple pathways. Specifically, TTYH3 up-regulation was mostly related to biological regulation, metabolic process, protein blinding, extracellular matrix organization and pathways in cancer. Moreover, TTYH3 was positively associated with immune cell infiltration in LUAD. Finally, TTYH3 was highly expressed in LUAD as revealed by meta-analysis. TTYH3 is closely related to the prognosis of LUAD and immune cell infiltration, and it can be used as a prognostic biomarker for LUAD and immune infiltration.

RESUMEN: Investigamos por bioinformática el nivel de Tweety Family Member 3 (TTYH3) con adenocarcinoma de pulmón (LUAD) y su relación con la infiltración inmune en tumores. Las expresiones diferenciales de TTYH3 en cáncer de pulmón se analizaron con Oncomine, TIMER, GEO, UALCAN y HPA. Con UALCAN se analizó la relación de los niveles de ARNm/proteína de TTYH3 con los parámetros clínicos. Los genes coexpresados de TTYH3 en LUAD se analizaron utilizando Cbioportal. Su relación con el pronóstico LUAD se analizó mediante plotter de Kaplan- Meier. Se realizaron análisis GO y KEGG. TIMER, TISIDB y GEPIA probaron la correlación entre TTYH3 y la infiltración inmune tumoral. Encontramos que TTYH3 aumentó significativamente en los tejidos LUAD. La alta expresión de TTYH3 estuvo estrechamente relacionada con una supervivencia general deficiente, supervivencia posterior a la progresión y primera progresión en pacientes con LUAD. Los niveles de ARNm/ proteína de TTYH3 se asociaron significativamente con múltiples vías. Específicamente, la regulación positiva de TTYH3 se relacionó principalmente con la regulación biológica, el proceso metabólico, el cegamiento de proteínas, la organización de la matriz extracelular y las vías en el cáncer. Además, TTYH3 se asoció positivamente con la infiltración de células inmunitarias en LUAD. Finalmente, TTYH3 se expresó altamente en LUAD como lo reveló el metanálisis. TTYH3 está estrechamente relacionado con el pronóstico de LUAD y la infiltración de células inmunitarias, y se puede utilizar como biomarcador pronóstico para LUAD y la infiltración de células inmunitarias.

ABSTRACT Introduction: There are few circulating biomarkers for valvular heart disease. Angiopoietin (Ang) 1, Ang2, and vascular endothelial growth factor are important inflammation-associated cytokines. The aim of this study was to investigate the clinical significance and association of Ang1, Ang2, and vascular endothelial growth factor in valvular heart disease. Methods: This is a retrospective study; a total of 62 individuals (valvular heart disease patients [n=42] and healthy controls [n=20]) were included. Plasma levels of Ang1, Ang2, and vascular endothelial growth factor were detected by enzyme-linked immunosorbent assays. We retrospectively collected the baseline characteristics and short-term outcomes; logistic regression was performed to identify predictor for short-term mortality. Results: Ang2 was significantly decreased in the valvular heart disease group compared with the healthy control group (P=0.023), while no significant difference was observed in the Ang1 and vascular endothelial growth factor levels. The Ang2 level of New York Heart Association (NYHA) I/II patients — but not NYHA III/IV patients — was significantly decreased compared with that of healthy control individuals (NYHA I/II: P=0.017; NYHA III/IV: P=0.485). Univariable logistic regression analysis indicated that Ang2 was a significant independent predictor for short-term mortality (odds ratio 18.75, P=0.033, 95% confidence interval 8.08-102.33). Ang1 was negatively correlated with Ang2 (P=0.032, Pearson’s correlation coefficient =-0.317) and was positively correlated with vascular endothelial growth factor (P=0.019, Pearson’s correlation coefficient = 0.359). Conclusion: Ang2 might serve as a therapeutic and prognostic target for valvular heart disease.

Abstract To study the exact effect of purple wheat (PW) on dyslipidaemia in rats so as to lay the foundation of a dietary therapy for hyperlipidaemia. A total of 42 rats were randomly divided into two groups: normal control group (NC) consisting of 12 rats were fed with standard diet in the whole testing process, the other group rats were fed with high-fat diet to induce dyslipidaemia. The dyslipidaemic rats were averagely divided into three groups: dyslipidaemia control group (DC) with 60% common wheat flour, PW1 group with diet containing 60% purple wheat Jizimai1 flour, PW3 group with 60% purple wheat Jizimai3 flour. Six weeks later, the weight-gain-ratio of the rats in PW1 and PW3 groups were lower as compared to the rats in DC and NC groups. Further, we found that the levels of triglyceride, total cholesterol and low-density lipoprotein in the PW1 and PW3 groups were significantly reduced to almost that of normal levels. Finally, the results of hematoxylin and eosin staining showed that intaking of Jizimai1 and Jizimai3 could repair hepatocyte steatosis and kidney injury due to dyslipidaemia. Purple wheat diet therapy reduced lipid metabolism disorders and the liver tissue and renal injury in hyperlipidaemic rats.

Abstract To investigate the effect of corosolic acid treatment on erectile function in metabolic syndrome induced rat model. Fifty male 3-week-old SD rats were fed a high fat and high sugar diet. Six months later, metabolic variables were determined. Metabolic syndrome induced erectile function (MED) rats were confirmed by an apomorphine test. Then MED rats were treated with corosolic acid daily by oral gavage for 4 weeks. To evaluate erectile function, intracavernosal pressure (ICP)/mean arterial blood pressure (MAP) ratio was measured. Thiobarbituric acid reactive substances assay and dihydroethidium staining were used to assess reactive oxygen species (ROS) level. Protein expressions of gp91phox and eNOS were examined by western blotting and immunohistochemistry. Fasting blood glucose, body weight, total cholesterol and insulin were markedly increased in metabolic syndrome rats compared with those of the control rats (p < 0.05). The ratios of max ICP/MAP and area under curve (AUC)/MAP was markedly reduced in MED rats compared with the control rats (p < 0.05). The concentration of cyclic guanosine mono-phosphate (cGMP) and the expression of eNOS were significantly decreased in MED rats compared with the control group (p < 0.05). Moreover, ROS level and the expression of gp91phox were significantly increased in MED rats. Treatment with corosolic acid reversed these changes (each p < 0.05). Corosolic acid reduces the level of ROS, ameliorating endothelial dysfunction and improvement of erectile function in MED rats.

Abstract Adipocyte tissue inflammation orchestrates the occurrence and development of diseases induced by obesity. Here, the effects of Lagerstroemia speciosa (L.) Pers total flavonoids (LTF) on TNF-α-induced insulin resistance (IR) and inflammatory response in 3T3-L1 adipocytes and underlying mechanisms were studied. Cell glucose uptake test confirmed that TNF-α could induce IR in 3T3-L1 adipocytes. The sensitivity of 3T3-L1 adipocytes to insulin was increased by LTF treatment. The phosphorylation of IRS1 and Akt in TNF-α-treated 3T3-L1 adipocytes was markedly restored by LTF treatment. The results revealed that interleukin-6 (IL-6) and monocyte chemoattractant protein-1 (MCP-1) mRNA expression was elevated in TNF-α-administered 3T3-L1 adipocytes, whereas the mRNA expression of adiponectin (ADPN) was considerably decreased. When treated with 50 μg/mL LTF, the IL-6 and MCP-1 mRNA expression levels were drastically reduced, and the ADPN mRNA expression level was significantly raised. Moreover, the concentration of IL-6 in the supernatant of the medium was decreased after LTF treatment compared with the model group. Western blotting results showed that the phosphorylation of p38, JNK, and ERK of mitogen-activated protein kinase (MAPK) signaling pathways and IкB of NF-кB signaling pathway were inhibited. It suggested that LTF improves TNF-α-induced IR and inflammatory response in 3T3-L1 adipocytes via inhibiting MAPK and NF-кB signaling pathways.

Abstract This study investigated the hyperspectral reflectance response of time series generated during oven drying to changes in the moisture content of potato tubers. Seventeen preprocessing methods were used to eliminate the influence of spectral noise on the spectral characteristic curve. Algorithms such as CatBoost, LightGBM, and XGBoost are used to obtain the first 40 effective characteristic spectra of hyperspectral images, which reduces the redundancy of data and improves the prediction accuracy. The water content prediction model of potato tubers was established by using the selected characteristic bands. The results showed that the combined model based on Lasso and XGBoost algorithm had the strongest prediction ability. The best model is MF-Lasso-XGBoost, which has R2 value of 0.8908, Rmse of 0.0610, Mdae of 0.0389, and R2cv of 0.8448. This research can provide reference for the detection of potato moisture content and theoretical basis for the development of crop moisture detector.

Abstract The destruction of the pulmonary epithelial barrier in acute respiratory distress syndrome is caused by the damage of the alveolar epithelial cells. Oroxin A is an effective flavonoid component derived from the medicinal plant Oroxylum indicum (L.) Kurz. In this study, the oleic acid (OA)-induced A549 cell injury model was established in vitro to explore the protective mechanism of Oroxin A. The experiment was divided into the following groups: control, OA and OA + Oroxin A group. The OA-induced A549 cell injury was dose (time)-dependent and was detected by the CCK-8 assay. The protein and mRNA expression levels associated with pyroptosis are detected by Western blotting and RT-qPCR. After Oroxin A treatment, the levels of IL-1β, IL-18 and LDH released were significantly lower than the OA group. In terms of pyroptosis, Oroxin A can inhibit the expression of pyroptosis-related protein and mRNA. Significantly, the surfactant protein C (SPC) level in the OA + Oroxin A group was significantly higher than that in the OA group. The treatment with Oroxin A alleviates the OA-induced injury in the A549 cells, and its mechanism may be related to the inhibition of A549 cells pyroptosis and prevention of the degradation of the SPC.

Abstract To evaluate the effect of medical nutritional therapy (MNT) combined with low glycaemic index (LGI) formula at breakfast for 4 weeks on the glycaemic control of patients with type 2 diabetes mellitus (T2DM). Ninety-six participants were recruited and randomly equally divided into two groups. The intervention group was offered with 40g LGI formula at breakfast adjusted according to MNT, and the control group with regular MNT. After 4 weeks, fasting blood glucose, glycated albumin (GA), insulin, C-peptide levels and metabolic index were compared between the two groups. Compared to the intervention group, the total cholesterol (TC), low-density lipoprotein cholesterol (LDL-C), and the change of FBG (–0.64 ± 1.4 vs. 0.3 ± 2.2; p < 0.05) and 2h-PBG (–1.8 ± 3.6 vs.0.8 ± 3.2; p < 0.01) in the control group were significantly decreased. The LGI formulations, having a significant effect on controlling glucose and lipid metabolism, could be used as a non-pharmacological intervention for T2DM self-management.

Abstract Introduction: Atrial fibrillation (AF) is the most common sustained arrhythmia. Sorting nexin 10 (SNX10) has been reported to be an important regulator in embryonic development and human diseases, however, little is known about its role in cardiac disease. The aim of this study was to investigate the clinical significance of SNX10 expression in AF. Methods: Nineteen valvular heart disease patients with AF and nine valvular heart disease patients with sinus rhythm (SR) were enrolled. Atrial tissue samples from patients undergoing open heart surgery were examined. Atrial tissues of normal hearts were obtained from two cases’ autopsies. The SNX10 expression and its associations with the degree of fibrosis were analyzed by immunohistochemistry and Masson’s trichrome staining. Results: SNX10 expression was detected in the cytoplasm of cardiac cells in human myocardial tissue. The SNX10 expression level was higher in the SR group than in the AF group (P=0.023). SNX10 expression was negatively associated with the degree of fibrosis (P=0.017, Spearman rho=-0.447), the New York Heart Association degree (P=0.003, Spearman rho=-0.545), left atrial diameter (P=0.038, Spearman rho=-0.393), right atrial diameter (P=0.043, Spearman rho=-0.386), and the brain natriuretic peptide (BNP) level 24 hours after surgery (P=0.030, Spearman rho=-0.426), but not the BNP level before surgery and 72 hours after surgery. No statistical significance was observed between SNX10 and the level of troponin T and C-reactive protein. Conclusion: Decreased SNX10 might serve as a potential risk factor in AF of the valvular heart disease.

The goal of this study was to identify potential transcriptomic markers in pediatric septic shock prognosis by an integrative analysis of multiple public microarray datasets. Using the R software and bioconductor packages, we performed a statistical analysis to identify differentially expressed (DE) genes in pediatric septic shock non-survivors, and further performed functional interpretation (enrichment analysis and co-expression network construction) and classification quality evaluation of the DE genes identified. Four microarray datasets (3 training datasets and 1 testing dataset, 252 pediatric patients with septic shock in total) were collected for the integrative analysis. A total of 32 DE genes (18 upregulated genes; 14 downregulated genes) were identified in pediatric septic shock non-survivors. Enrichment analysis revealed that those DE genes were strongly associated with acute inflammatory response to antigenic stimulus, response to yeast, and defense response to bacterium. A support vector machine classifier (non-survivors vs survivors) was also trained based on DE genes. In conclusion, the DE genes identified in this study are suggested as candidate transcriptomic markers for pediatric septic shock prognosis and provide novel insights into the progression of pediatric septic shock.

Abstract Rock materials are often subjected to cyclic loads during construction. A full understanding of the deformation behavior of rock under cyclic loads is of great significance in engineering. In this study, by using the endochronic constitutive model proposed by Valanis, the reinforcement function form and constitutive parameters of the endochronic model are improved. An endochronic plasticity constitutive program for rock based on the finite element method is used to study the mechanical properties of rock under different cyclic loading conditions (of maximum loading stress, amplitude, and confining pressure), and through the use of red sandstone, marble, and basalt, experimental and simulation results are compared to verify the model. The results show that the theory can better simulate the hysteresis loop width and cumulative plastic strain of rock under cyclic loading and, under different loading conditions, the numerical simulation results are consistent with the actual rock experimental law. Therefore, the endochronic plasticity constitutive model in this study can be applied to investigate the influence of cyclic loading on the dynamic deformation behavior of rock.

Ischemia-reperfusion injury (IRI) has brought attention to flap failure in reconstructive surgery. To improve the prognosis of skin transplantation, we performed experimental IRI by surgical obstruction of blood flow and used sodium ferulate (SF) to prevent IRI in rats. After SF treatment, the morphological and histological changes of the skin flaps were observed by H&E and Masson's trichrome staining. We also detected the expression levels of COX-1, HO-1, and Ki67 by immunohistochemical and western blot analysis. Moreover, enzyme-linked immunosorbent assay was used to identify the content of tumor necrosis factor (TNF)-α, myeloperoxidase (MPO), malondialdehyde (MDA), and nitric oxide (NO) in peripheral blood and skin tissue. Compared with the model group, SF treatment significantly improved the recovered flap area (%) and promoted collagen synthesis. Cyclooxygenase-2 (COX-2) expression was significantly inhibited by heme oxygenase-1 (HO-1) induction after SF treatment. Furthermore, SF significantly inhibited the levels of TNF-α in peripheral blood, MPO and MDA in the skin tissue, and the increased synthesis of NO. Our results showed the protective effects of SF on IRI after flap transplantation and we believe that the protective effects of SF was closely related to the alleviation of the inflammatory response and the inhibition of the oxidative stress injury.

The objective of this study was to investigate the effect of Mycobacterium vaccae on Jagged 1 and gamma delta T17 (γδT17) cells in asthmatic mice. An asthma mouse model was established through immunization with ovalbumin (OVA). Gamma-secretase inhibitor (DAPT) was used to block the Notch signaling pathway. M. vaccae was used to treat asthma, and related indicators were measured. Blocking Notch signaling inhibited the production of γδT17 cells and secretion of cytokine interleukin (IL)-17, which was accompanied by a decrease in Jagged1 mRNA and protein expression in the treated asthma group compared with the untreated asthma group. Similarly, treatment with M. vaccae inhibited Jagged1 expression and γδT17 cell production, which was associated with decreased airway inflammation and reactivity. The Notch signaling pathway may play a role in the pathogenesis of asthma through the induction of Jagged1 receptor. On the other hand, the inhibitory effect of M. vaccae on Jagged1 receptor in γδT17 cells could be used for the prevention and treatment of asthma.

Abstract Purpose To analyze the plasma lipid spectrum between healthy control and patients with pancreatic cancer and to select differentially expressed tumor markers for early diagnosis. Methods In total, 20 patents were divided into case group and healthy control group according to surgical pathology. Of almost 1206 plasma lipid molecules harvested from 20 patients were measured by HILIC using the normal phase LC/MS. Heat map presented the relative levels of metabolites and lipids in the healthy control group and patients with pancreatic cancer. The PCA model was constructed to find out the difference in lipid metabolites. The principal components were drawn in a score plot and any clustering tendency could be observed. PLS-DA were performed to distinguish the healthy control group and pancreatic cancer according to the identified lipid profiling datasets. The volcano plot was used to visualize all variables with VIP>1 and presented the important variables with P<0.01 and |FC|>2. Results The upregulated lipid metabolites in patients with pancreatic cancer contained 9 lipids; however, the downregulated lipid metabolites contained 79 lipids. Conclusion There were lipid metabolomic differences in patients with pancreatic cancer, which could serve as potential tumor markers for pancreatic cancer.

ABSTRACT Macamides and Macaenes are the bioactive marker compounds in maca (Lepidium meyenii Walp., Brassicaceae) tuber. To simultaneously quantify these two types of compound, HPLC method was studied. To distinguish and group the growing regions of different maca samples, Hierarchical cluster analysis, a chemometric method, was applied to analyze the HPLC data. The calibration curves obtained using the HPLC method showed satisfactory linearity with determination coefficients >0.9998. The precision and repeatability relative standard deviation values were <4%, and the accuracy relative standard deviation value was <5%. The limits of detection was <0.1 µg/ml and the limit of quantification was <0.3 µg/ml. Our HPLC method was successfully used for the separation and determination of macamides and macaenes in Maca within 45 min, i.e., two macaenes (9-oxo-10E,12Z-octadecadienoic acid and 9-oxo-10E,12E-octadecadienoic acid) and five macamides (N-benzyl-9-oxo-10E,12Z-octadecadienamide, N-benzyl-9-oxo-10E,12E-octadecadienamide, N-benzyl-9Z,12Z,15Z-octadecatrienamide, N-benzyl-9Z,12Z-octadecadienamide and N-benzyl-hexadecanamide). The HPLC method was applied to analyze and quantify the seven compounds in thirty maca samples with different colors and origins. The origins of all the maca samples were distinguished and grouped using hierarchical cluster analysis of the HPLC data. Accordingly, the metabolism of macaenes and macamides in maca post-harvest processing has also been proposed. The HPLC method is efficient to simultaneously quantify the macamides and macaenes in maca. Analyzing the HPLC data using hierarchical cluster analysis can distinguish maca growing origins.