Search

Background/Aims: Low educational attainment is a well-established risk factor for nonalcoholic fatty liver disease (NAFLD) in developed areas. However, the association between educational attainment and the risk of NAFLD is less clear in China. Methods: A cross-sectional study including over 200,000 Chinese adults across mainland China was conducted. Information on education level and lifestyle factors were obtained through standard questionnaires, while NAFLD and advanced fibrosis were diagnosed using validated formulas. Outcomes included the risk of NAFLD in the general population and high probability of fibrosis among patients with NAFLD. Logistic regression analysis was employed to estimate the risk of NAFLD and fibrosis across education levels. A causal mediation model was used to explore the potential mediators. Results: Comparing with those receiving primary school education, the multi-adjusted odds ratios (95% confidence intervals) for NAFLD were 1.28 (1.16 to 1.41) for men and 0.94 (0.89 to 0.99) for women with college education after accounting for body mass index. When considering waist circumference, the odds ratios (95% CIs) were 0.94 (0.86 to 1.04) for men and 0.88 (0.80 to 0.97) for women, respectively. The proportions mediated by general and central obesity were 51.00% and 68.04% for men, while for women the proportions were 48.58% and 32.58%, respectively. Furthermore, NAFLD patients with lower educational attainment showed an incremental increased risk of advanced fibrosis in both genders. Conclusion : s: In China, a low education level was associated with a higher risk of prevalent NAFLD in women, as well as high probability of fibrosis in both genders.

Abstract Deregulation of circular RNAs (circRNAs) is widely recognized in cancer progression. Our study aims to investigate the role of circ_0020460 in the development of cervical cancer (CC) and its potential mechanism of action. Quantitative real-time polymerase chain reaction (qRT-PCR) and western blot assays were used to detect the expression levels of circ_0020460, miR-485-3p and C-X-C motif chemokine ligand 1 (CXCL1). The roles of circ_0020460 on cell proliferation, cell migration, cell invasion, cell apoptosis, and angiogenesis were investigated using cell counting kit-8 (CCK-8) and Ethynyl deoxyuridine (Edu) assay, wound healing assay, transwell assay, flow cytometry assay, and tube formation assay, respectively. The putative relationship predicted by bioinformatics analysis was verified by dual-luciferase reporter assay and RNA immunoprecipitation (RIP) assay. Xenograft models were constructed to explore the role of circ_0020460 in vivo. The expression of circ_0020460 and CXCL1 expression were increased, while miR-485-3p expression was declined in CC tissues and cells. Circ_0020460 knockdown suppressed CC cell proliferation, cell migration, cell invasion, angiogenesis, and promoted cell apoptosis. Circ_0020460 functioned as a miR-485-3p sponge to inhibit miR-485-3p level, and the anti-cancer effects mediated by circ_0020460 knockdown were reversed by miR-485-3p inhibitor. MiR-485-3p bound to CXCL1 3ʹ untranslated region (3ʹUTR) to degrade CXCL1 expression, and the anti-cancer effects of miR-485-3p restoration were impaired by CXCL1 overexpression. Circ_0020460 downregulation inhibited CC xenograft tumor growth. These results suggest that circ_0020460 promoted the malignant behavior of CC cells by modulating the miR-485-3p/CXCL1 axis.

Abstract Aims Primary mucoepidermoid carcinomas (MECs) of the sinonasal tract and nasopharynx are rare entities that represent a diagnostic challenge, especially in biopsy samples. Herein, we present a case series of MECs of the sinonasal and skull base and its mimics to evaluate the clinicopathological and molecular characteristics in order to avoid misdiagnosis. Methods We reviewed the pathology records of patients diagnosed from 2014 to 2022. Thirty MECs were consecutively diagnosed during that period. Results Based on morphological and fluorescence in situ hybridization (FISH) analyses, 30 tumors originally diagnosed as MECs were separated into MAML2 fusion-positive (7 cases) and MAML2 fusion-negative groups (23 cases), in which 14 tumors were positive for the EWSR1::ATF1 fusion; these tumors were reclassified to have hyalinizing clear cell carcinoma (HCCC). The remaining nine MAML2 FISH negative cases were reconfirmed as squamous cell carcinoma (SCC, 3 cases) which showed keratinization and high Ki-67 expression; DEK::AFF2 carcinomas (2 cases), in which DEK gene rearrangement was detected by FISH; and MECs as previously described (4 cases) with typical morphological features. Including 7 MAML2 rearrangements tumors, 11 MEC cases had a male-to-female ratio of 4.5:1, and 6 tumors arose from the nasopharyngeal region, while 5 tumors arose from the sinonasal region. The prognosis of this series of salivary gland-type MECs was favorable. Conclusions Our study confirmed that HCCC runs the risk of being misdiagnosed as MEC in the sinonasal tract and nasopharynx, particularly with biopsy specimens. Careful histological evaluation with supporting molecular testing can facilitate pathological diagnoses.

Abstract Epidemiological studies suggested an association between omega-3 fatty acids and cognitive function. However, the causal role of the fatty acid desaturase (FADS) gene, which play a key role in regulating omega-3 fatty acids biosynthesis, on cognitive function is unclear. Hence, we used two-sample Mendelian randomization (MR) to estimate the gene-specific causal effect of omega-3 fatty acids (N = 114,999) on cognitive function (N = 300,486). Tissue- and cell type-specific effects of FADS1/FADS2 expression on cognitive function were estimated using brain tissue cis-expression quantitative trait loci (cis-eQTL) datasets (GTEx, N ≤ 209; MetaBrain, N ≤ 8,613) and single cell cis-eQTL data (N = 373), respectively. These causal effects were further evaluated in whole blood cis-eQTL data (N ≤ 31,684). A series of sensitivity analyses were conducted to validate MR assumptions. Leave-one-out MR showed a FADS gene-specific effect of omega-3 fatty acids on cognitive function [β = −1.3 × 10−2, 95% confidence interval (CI) (−2.2 × 10−2, −5 × 10−3), P = 2 × 10−3]. Tissue-specific MR showed an effect of increased FADS1 expression in cerebellar hemisphere and FADS2 expression in nucleus accumbens basal ganglia on maintaining cognitive function, while decreased FADS1 expression in nine brain tissues on maintaining cognitive function [colocalization probability (PP.H4) ranged from 71.7% to 100.0%]. Cell type-specific MR showed decreased FADS1/FADS2 expression in oligodendrocyte was associated with maintaining cognitive function (PP.H4 = 82.3%, respectively). Increased FADS1/FADS2 expression in whole blood showed an effect on cognitive function maintenance (PP.H4 = 86.6% and 88.4%, respectively). This study revealed putative causal effect of FADS1/FADS2 expression in brain tissues and blood on cognitive function. These findings provided evidence to prioritize FADS gene as potential target gene for maintenance of cognitive function.

BackgroundThe triglyceride glucose (TyG) index has been associated with an increased risk in breast cancer. However, this association remains unclear among the Chinese population. This study aimed to investigate whether the TyG index is associated with the risk of prevalent breast cancer in Chinese women.MethodsThis cross-sectional study included 142,184 women from the REACTION (Risk Evaluation of Cancers in Chinese Diabetic Individuals: A Longitudinal) Study, which recruited adults aged 40 years or older from 25 centers across mainland China between 2011 and 2012. The TyG index was calculated according to the formula: Ln (fasting triglycerides [mg/dL] × fasting glucose [mg/dL]/2). Multivariable-adjusted logistic regression models were used to evaluate odds ratios (ORs) and 95% confidence intervals (CIs) regarding the associations between the TyG index and breast cancer.ResultsMultivariable-adjusted logistic regression analysis showed that compared with the lowest quartile of the TyG index, the highest quartile of the TyG index was significantly associated with an increased risk of prevalent breast cancer, with an OR (95% CI) of 1.61 (1.19–2.17). In the stratified analysis, the association of each 1 SD increase in the TyG index with risk of prevalent breast cancer was more dominant in individuals with menarche at age 13–17, those who were postmenopausal, those with a history of breastfeeding, and those who had two to four children, with the ORs (95% CIs) of 1.35 (1.09–1.68), 1.27 (1.05–1.54), 1.26 (1.05–1.52), and 1.32 (1.08–1.62), respectively. Moreover, among those without discernible insulin resistance (homeostatic model assessment-insulin resistance [HOMA-IR] ≥2.5), hyperglycemia and dyslipidemia, each 1 SD increase in the TyG index was associated with a 1.36-fold increase in breast cancer risk, with an OR (95% CI) of 2.36 (1.44–3.87).ConclusionThe TyG index is significantly associated with the prevalent breast cancer risk among middle-aged and elderly Chinese women.

Grass damage has become an important factor restricting foxtail millet production; chemical weeding can help resolve this issue. However, special herbicides in foxtail millet fields are lacking. Penoxsulam has a broad weed control spectrum and a good control effect. In this project, Jingu 21 was used as the test material, and five different concentrations of penoxsulam were used for spraying test in the three–five leaf stage. In this experiment, the effects on the growth of foxtail millet were discussed by measuring the agronomic characters and antioxidant capacity of foxtail millet after spraying penoxsulam. The results showed that: (1) penoxsulam is particularly effective in controlling Amaranthus retroflexus L. (A. retroflexus) and Echinochloa crus-galli (L.) Beauv. (E. crus-galli), but is ineffective in controlling Chenopodium album L. (C. album) and Digitaria sanguinalis (L.) Scop. (D. sanguinalis); (2) the stem diameter, fresh weight, and dry weight of the above-ground parts decreased with the increase in spraying amount; (3) as the spraying dosage increased, the superoxide (SOD), peroxidase (POD), and catalase (CAT) activities in the foxtail millet initially increased and subsequently decreased; the malonaldehyde (MDA) content increased. Our experiment found that 1/2X and 1X spraying dosages had certain application value in controlling gramineous weeds in foxtail millet field. Other spraying dosages are not recommended as they may harm the crops. Our findings provide reference for identifying new herbicides in the foxtail millet field.

Monolepta signata is a polyphagous and highly destructive agricultural pest, currently only distributed in Asia. In its place of origin, it poses a serious threat to important economic crops, for instance, maize (Zea mays L.) and cotton (Gossypium hirsutum L.). Based on morphological and molecular data research, it has been found that M. quadriguttata (Motschulsky), M. hieroglyphica (Motschulsky), and M. signata are actually the same species. This discovery means that the range of this pest will expand, and it also increases the risk of it spreading to non-native areas worldwide. It is crucial for global agricultural production to understand which countries and regions are susceptible to invasion by M. signata and to formulate corresponding prevention, control, and monitoring strategies. This study uses the maximum entropy model, combined with bioclimatic variables and elevation, to predict the potentially suitable areas and diffusion patterns of M. signata worldwide. The results indicate that in its suitable area, M. signata is mainly affected by three key climatic factors: Precipitation of Wettest Month (bio13), Mean Temperature of Warmest Quarter (bio10), and Temperature Seasonality (bio4). Under the current status, the total suitable region of M. signata is 252,276.71 × 104 km2. In addition to its native Asia, this pest has potentially suitable areas in Oceania, South America, North America, and Africa. In the future, with climate change, the suitable area of M. signata will expand to high-latitude areas and inland areas. This study found that by the 2070s, under the SSP5-8.5 climate scenario, the change in the potentially suitable area of this insect is the largest. By identifying the potentially suitable areas and key climatic factors of M. signata, we can provide theoretical and technical support to the government, enabling them to more effectively formulate strategies to deal with the spread, outbreak, and invasion of M. signata.

Straw covering is a protective tillage measure in agricultural production, but there is relatively little research on the allelopathic effects of corn straw on weeds and foxtail millet. This experiment studied the allelopathic effects of corn straw on four weeds (Chenopodium album, Setaria viridis, Echinochloa crus-galli and Amaranthus retroflexus) in foxtail millet fields, and also measured the growth indicators of foxtail millet. The study consisted of Petri dish and field experiments. Five treatments were used in the Petri dish experiment: clear water as control (0 g/L, TCK) and four types of corn straw water extracts. They were, respectively, the stock solution (100 g/L, T1), 10 X dilution (10 g/L, T2), 50 X dilution (2 g/L, T3), and 100 X dilution (1 g/L, T4) of corn straw water extracts. Additionally, seven treatments were set up in the field experiment, consisting of three corn straw covering treatments, with covering amounts of 3000 (Z1), 6000 (Z2) and 12,000 kg/ha (Z3), and four control treatments—one treatment with no corn straw cover (CK) and three treatments involving the use of a black film to create the same shading area as the corn straw covered area, with black film coverage areas of 50% (PZ1), 70% (PZ2), and 100% (PZ3), respectively. The results showed that the corn straw water extract reduced the germination rate of the seeds of the four weeds. The T1 treatment resulted in the allelopathic promotion of C. album growth but the inhibition of S. viridis, E. crus-galli, and A. retroflexus growth. Treatments T2, T3, and T4 all induced the allelopathic promotion of the growth of the four weeds. The order of the effects of the corn straw water extracts on the comprehensive allelopathy index of the four weed seeds was as follows: C. album > S. viridis > A. retroflexus > E. crus-galli. With an increase in the corn straw mulching amount, the density and total coverage of the four weeds showed a gradual downward trend, whereas the plant control effect and fresh weight control effect showed a gradual upward trend. All indices showed the best results under 12,000 kg/ha of mulching and returning to the field. Overall, corn straw coverage significantly impacted the net photosynthetic rate and transpiration rate of foxtail millet and increased the yield of foxtail millet. Under coverages of 6000 and 12,000 kg/ha, the growth of foxtail millet is better. Based on our findings, we recommend a corn straw coverage of 12,000 kg/ha for the allelopathic control of weeds in foxtail millet fields.

Abstract Background Observational studies and conventional Mendelian randomization (MR) studies showed inconclusive evidence to support the association between omega-3 fatty acids and type 2 diabetes. We aim to evaluate the causal effect of omega-3 fatty acids on type 2 diabetes mellitus (T2DM), and the distinct intermediate phenotypes linking the two. Methods Two-sample MR was performed using genetic instruments derived from a recent genome-wide association study (GWAS) of omega-3 fatty acids (N = 114,999) from UK Biobank and outcome data obtained from a large-scale T2DM GWAS (62,892 cases and 596,424 controls) in European ancestry. MR-Clust was applied to determine clustered genetic instruments of omega-3 fatty acids that influences T2DM. Two-step MR analysis was used to identify potential intermediate phenotypes (e.g. glycemic traits) that linking omega-3 fatty acids with T2DM. Results Univariate MR showed heterogenous effect of omega-3 fatty acids on T2DM. At least two pleiotropic effects between omega-3 fatty acids and T2DM were identified using MR-Clust. For cluster 1 with seven instruments, increasing omega-3 fatty acids reduced T2DM risk (OR: 0.52, 95%CI 0.45–0.59), and decreased HOMA-IR (β = − 0.13, SE = 0.05, P = 0.02). On the contrary, MR analysis using 10 instruments in cluster 2 showed that increasing omega-3 fatty acids increased T2DM risk (OR:1.10; 95%CI 1.06–1.15), and decreased HOMA-B (β = − 0.04, SE = 0.01, P = 4.52 × 10–5). Two-step MR indicated that increasing omega-3 fatty acid levels decreased T2DM risk via decreasing HOMA-IR in cluster 1, while increased T2DM risk via decreasing HOMA-B in cluster 2. Conclusions This study provides evidence to support two distinct pleiotropic effects of omega-3 fatty acids on T2DM risk influenced by different gene clusters, which could be partially explained by distinct effects of omega-3 fatty acids on insulin resistance and beta cell dysfunction. The pleiotropic feature of omega-3 fatty acids variants and its complex relationships with T2DM need to be carefully considered in future genetic and clinical studies.

Abstract Purpose To evaluate prognostic significance of human papillomavirus (HPV) in hypopharyngeal squamous cell carcinoma patients, and to investigate the effect of p53 and TP53 mutations on the prognosis of patients. Methods A total of 111 patients were enrolled in our retrospective study. HPV infection status was detected in formalin-fixed paraffin-embedded tissue by real-time multiplex PCR test. p53 expression was evaluate by immunohistochemical staining. TP53 exon mutations were analyzed by PCR amplification and Sanger sequencing. HPV infection status, p53 expression and TP53 mutation were compared with clinical outcome including overall survival and recurrence-free survival by Kaplan-Meier method and Log-rank test. Results Of the 111 investigated patients, 18 (16.22%) were positive for HPV infection. HPV(-) patients have a worse clinical outcome than HPV(+) patients. TP53 mutations have similar mutation rates in patients with and without HPV (55.56% vs. 41.94%). p53 and TP53 mutation were not associated with prognosis of patients in HPV(-) patients. TP53 disruptive mutations were found both in patients with or without HPV infection. Furthermore, TP53 non-disruptive mutation had a significantly better clinical outcome than those with disruptive mutation in HPV(-) patients. Conclusion Our results showed that HPV infection status is a strong prognostic indicator of survival. p53 and TP53 mutations do not appear to significantly impact survival in HPV(-) patients. TP53 disruptive mutation is associated with reduced survival in HPV(-)/TP53 mutation patients.

Summary: Background: Metformin shows beneficial effects on cardiometabolic health in diabetic individuals. However, the beneficial effects in the general population, especially in non-diabetic individuals are unclear. We aim to estimate the effects of perturbation of seven metformin targets on cardiometabolic health using Mendelian randomization (MR). Methods: Genetic variants close to metformin-targeted genes associated with expression of the corresponding genes and glycated haemoglobin (HbA1c) level were used to proxy therapeutic effects of seven metformin-related drug targets. Eight cardiometabolic phenotypes under metformin trials were selected as outcomes (average N = 466,947). MR estimates representing the weighted average effects of the seven effects of metformin targets on the eight outcomes were generated. One-sample MR was applied to estimate the averaged and target-specific effects in 338,425 non-diabetic individuals in UK Biobank. Findings: Genetically proxied averaged effects of five metformin targets, equivalent to a 0.62% reduction of HbA1c level, was associated with 37.8% lower risk of coronary artery disease (CAD) (odds ratio [OR] = 0.62, 95% confidence interval [CI] = 0.46–0.84), lower levels of body mass index (BMI) (β = −0.22, 95% CI = −0.35 to −0.09), systolic blood pressure (SBP) (β = −0.19, 95% CI = −0.28 to −0.09) and diastolic blood pressure (DBP) levels (β = −0.29, 95% CI = −0.39 to −0.19). One-sample MR suggested that the seven metformin targets showed averaged and target-specific beneficial effects on BMI, SBP and DBP in non-diabetic individuals. Interpretation: This study showed that perturbation of seven metformin targets has beneficial effects on BMI and blood pressure in non-diabetic individuals. Clinical trials are needed to investigate whether similar effects can be achieved with metformin medications. Funding: Funding information is provided in the Acknowledgements.

Abstract Background Bile acids (BAs) are closely related to nutrient supply and modified by gut microbiota. Gut microbiota perturbations shape BA composition, which further affects host metabolism. Methods We investigated BA profiles in plasma, feces, and liver of mice fed ad libitum, fasted for 24 h, fasted for 24 h and then refed for 24 h using ultraperformance liquid chromatography coupled to tandem mass spectrometry. Gut microbiota was measured by 16S rRNA gene sequencing. Expressions of BA biosynthesis‐related genes in the liver and BA reabsorption‐related genes in the ileum were analyzed. Findings Compared with the controls, unconjugated primary BAs (PBAs) and unconjugated secondary BAs (SBAs) in plasma were decreased whereas conjugated SBAs in plasma, unconjugated PBAs, unconjugated SBAs and conjugated SBAs in feces, and unconjugated SBAs in liver were increased in the fasting mice. The expression of BA biosynthesis‐related genes in the liver and BA reabsorption‐related genes in the ileum were decreased in the fasting mice compared with the controls. Compared with the controls, Akkermansia, Parabacteroides, Muribaculum, Eubacterium_coprostanoligenes and Muribaculaceae were increased in the fasting mice whereas Lactobacillus and Bifidobacterium were decreased. All these changes in BAs and gut microbiota were recovered under refeeding. Akkermansia was negatively correlated with plasma levels of unconjugated PBAs, unconjugated SBAs and glucose, whereas it was positively correlated with plasma conjugated SBAs, fecal unconjugated PBAs, and fecal unconjugated SBAs. Conclusions We characterized the BA profiles, gut microbiota, and gene expression responsible for BA biosynthesis and intestinal reabsorption to explore their rapid changes in response to food availability. Our study highlighted the rapid effect of nutrient supply on BAs and gut microbiota.

Foxtail millet planting has a long history and profound role in agricultural civilization. However, weeds have become one of the obstacles restricting the development of the foxtail millet industry. Penoxsulam, as an early post-emergence herbicide for controlling gramineous weeds in paddy fields, is effective for some broadleaf weeds. In this study, six different doses (CK, 0.5X, 1X, 2X, 3X, 4X) of penoxsulam were sprayed at the 3–5 leaf stage of the conventional variety Jingu 21 to study its effect on the growth and development of foxtail millet, in order to screen out the appropriate spraying concentration. The main results are as follows: Within 15 days after spraying penoxsulam, the plant height and leaf area of foxtail millet decreased with the increase in spraying dose, and gradually recovered 15–25 days after spraying, but there were still significant differences compared with CK. The photosynthetic pigment content, net photosynthetic rate (Pn), transpiration rate (Tr), stomatal conductance (Gs), the maximum photochemical efficiency (Fv/Fm), photosynthetic system II actual photochemical efficiency (Y(II)), and photochemical quenching coefficient (qP) of foxtail millet decreased with an increase in the penoxsulam spraying dose, while the intercellular CO2 concentration (Ci) and non-photochemical quenching coefficient (NPQ) showed an upward trend. There was almost no significant difference in each index between the spraying dose of 0.5X and 1X and CK, but the photosynthesis of foxtail millet leaves was still significantly inhibited under a spraying dose of 3X and 4X. Penoxsulam had certain growth-inhibiting effects on Echinochloa crus-galli (L.) Beauv. (E. crus-galli), Digitaria sanguinalis (L.) Scop. (D. sanguinalis), Chenopodium album L. (C. album), and Amaranthus retroflexus L. (A. retroflexus) which increased as the spraying dosage increased. Our study found that spraying dose groups of 0.5X and 1X penoxsulam were safe for foxtail millet growth and could be used to control gramineous weeds in fields. Other spraying doses are not recommended in the field due to their serious phytotoxicity to foxtail millet, which provides a new measure for weed control in foxtail millet fields.

Thermoacoustic oscillation is indeed a phenomenon characterized by the symmetric coupling of thermal and acoustic waves. This paper introduces a novel approach for monitoring and predicting thermoacoustic combustion instability using a combination of recurrence quantification analysis (RQA) and an optimized deep belief network (DBN). Six samples of combustion state data were collected using two distinct types of burners to facilitate the training and validation of GA-DBN. The proposed methodology leverages RQA to extract intricate patterns and dynamic features from time series data representing combustion behavior. By quantifying the recurrence plot of specific patterns, the analysis provides valuable insights into the underlying thermoacoustic dynamics. Among three different feature extraction methods, RQA stands out remarkably in performance. These RQA-derived features serve as input to a carefully tuned DBN, which is trained to learn the complex relationships within the combustion process. The classification accuracy of deep belief network optimized by genetic algorithm (GA-DBN) reached an impressive 99.8%. Subsequent multiple comparisons were conducted between GA-DBN, DBN, and support vector machine (SVM), revealing that GA-DBN consistently demonstrated satisfactory classification results. This method holds significant importance in monitoring intricate combustion states.

Accurate prediction of thermoacoustic instability is a prerequisite for thermoacoustic control to avoid the damage of combustion chamber, however, this problem has not been completely solved yet. This paper proposes a data-driven method based on the Elman neural network (ENN) to predict the value of acoustic pressure of combustion instability. As a comparison, a model based on support vector machine (SVM) was built. It is proved that ENN has better prediction performance with a certain predicted time horizon compared to the SVM method. What is more, the prediction model based on ENN can adapt to time-varying characteristics of the transition scenario which is characterized by amplitude modulation, multiple frequencies, and irregular bursts. ENN model still maintains enough prediction accuracy for various input training sets, indicating that ENN can fully mine the features of data and has a strong feature extraction ability in combustion oscillation prediction. Hence, it is demonstrated that ENN is a promising prediction tool for thermoacoustic instability under various combustion conditions. These findings are of great significance for the accurate prediction and control of thermoacoustic instability.

Objective: Seseli mairei Wolff extracts (SMWE) are widely used to treat psoriasis as a Chinese medicine, but their effect and mechanism are unclear. This study verified the effect of SMWE on psoriasis by regulating Th17 cells. Methods: HaCaT cells were treated with IL-17A in vitro to evaluate the effect of SMWE on psoriasis. In vivo, the mice psoriasis model was established using imiquimod (IMQ, 62.5 mg/d), and intragastrically treated with the different drugs for six days. The severity of skin inflammation was evaluated with Psoriasis Area and Severity Index (PASI) scores and pathology. The levels of inflammation cytokines were assessed with immunofluorescence, immunochemistry, ELISA, and real-time PCR. The number of Th17 cells was determined with flows. Results: SMWE inhibited the proliferation of HaCaT cells and reduced the IL-17A-induced IL-6 production in vitro. In vivo, SMWE deduced the levels of IL-1β, IL-6, IL-8, IL-17A, IL-17F, IL-22, IL-23, and TNF-α, while increasing the level of IL-10 compared to the model group. SMWE also inhibited the levels of NF-κB, JAK2, and STAT3 proteins, while declining the expressions of Gr-1, and MPO. Interestingly, SMWE significantly decreased the number of Th17 cells. Conclusion: SMWE inhibited the proliferation of HaCaT cells and attenuated the development of psoriasis lesions by inhibiting Th17 cells to regulate the levels of inflammation cytokines.

Abstract Objective To investigate the effect of modified colonoscopy nursing pads in colonoscopy. Methods A total of 262 subjects who underwent colonoscopy at our endoscopy center between September 1, 2021 and February 28, 2022 were selected and randomly divided into a control group and an experimental group, with 131 cases in each group. The control group used conventional nursing pads, while the experimental group used modified nursing pads. The success rate of the first correct position, the time spent by the nurse to guide the correct position, the bed unit contamination rate, the contamination rate of the operator's protective equipment, the privacy protection of the examinees and the satisfaction degree after the examination were compared between the two groups. Results The success rate of the first correct position of the examinees in the experimental group was significantly higher than that of the control group (P

Abstract Background Evidence regarding the impact of education on diabetes risk is scarce in developing countries. We aimed to explore the association between education and diabetes within a large population in China and to identify the possible mediators between them. Methods Information on educational level and lifestyle factors was collected through questionnaires. Diabetes was diagnosed from self‐report and biochemical measurements. A structural equation model was constructed to quantify the mediation effect of each mediator. Results Compared with their least educated counterparts, men with college education had a higher risk of diabetes (odds ratio [OR] 1.19; 95% confidence interval [CI], 1.12–1.27), while college‐educated women were less likely to have diabetes (OR 0.77; 95% CI, 0.73–0.82). Obesity was the strongest mediator in both genders (proportion of mediation: 11.6% in men and 23.9% in women), and its association with education was positive in men (β[SE] 0.0387 [0.0037]) and negative in women (β[SE] −0.0824 [0.0030]). Taken together, all behavioral factors explained 12.4% of the excess risk of diabetes in men and 33.3% in women. Conclusions In a general Chinese population, the association between education level and diabetes was positive in men but negative in women. Obesity was the major mediator underlying the education disparities of diabetes risk, with a stronger mediation effect among women.

Natural cellulose fibers with high cellulose and lignin content and elongation as high as 45% similar to that of coir were extracted from the shells of Areca cathechu for potential use for composite, textile and other applications. Areca shells are removed to obtain the nuts and are disposed as waste with no significant value. The shells are lignocellulosic in nature and have antioxidant properties and usefulfor medical applications. Some attempts have been made to utilize the shells as reinforcement for composites, conversion into carbon etc. In this research, we have subject areca shells to extensive alkali treatment to obtain cellulose rich fibers. Alkali treatment resulted in compositional, structural and morphological changes to the fibers depending on the concentration of alkali and treatment time. Tensile strength increased from 23 to 59 MPa and elongation from 34% to 45%. Although, there was no major change in the composition of the fibers, the diameter of the fibers decreased by about 50% and thermal stability showed substantial improvement. Morphological changes included increase in pores and surface appearance. Fibers obtained in this research show potential for composite and other applications. Using areca nut shells for fibrous applications could lead to substantial value addition and eventual use of the shells as sustainable sources for materials and products.

Abstract Background Previous studies reported that famine exposure had an effect on metabolic syndrome (MetS). However, there is an inadequacy of study regarding the association between famine exposure, adulthood general obesity, and the risk of MetS. Methods A total of 8883 subjects aged ≥40 years from Jiading community in Shanghai were included. We defined famine exposure subgroups as nonexposed (1963–1974), fetal exposed (1959–1962), childhood exposed (1949–1958), and adolescence exposed (1941–1948). MetS was defined based on the National Cholesterol Education Program Adult Treatment Panel III (NCEP‐ATP III) criteria. Results Compared with the nonexposed group, the risks of MetS were increased in the fetal‐, childhood‐, and adolescence‐exposed groups with odds ratios (OR) and 95% confidence intervals (CI) of 1.48 (1.23–1.78), 1.89 (1.63–2.20), and 2.34 (1.99–2.74), respectively. After adjusting for sex, age, smoking status, drinking status, education, body mass index (BMI), and physical activity, the increased risk of MetS related to the fetal‐exposed and childhood‐exposed groups with OR and 95% CI of 1.42 (1.04–1.94) and 1.50 (1.02–2.21), respectively, were observed only in women. Famine exposure was significantly associated with MetS among individuals with a BMI

Abstract Background The triglyceride glucose (TyG) index is closely associated with subclinical atherosclerosis. However, the association remains inconclusive among obese and nonobese individuals. Methods This prospective study was conducted in 5751 adults with normal carotid intima‐media thickness (CIMT) at baseline. We divided the population into four groups based on the TyG index, which was calculated by the following formula: Ln (fasting triglycerides [mg/dL] × fasting glucose [mg/dL]/2). Information on CIMT was acquired by ultrasonography. Incident elevated CIMT was defined as IMT values greater than 0.9 mm at follow‐up. Odds ratios (ORs) and 95% confidence intervals (CIs) of the associations between TyG index and elevated CIMT were estimated using multivariable logistic regression models. Results After a median follow‐up of 4.3 years, 722 (12.6%) individuals had progressed to elevated CIMT. Compared with the second quartile of the TyG index, the first and fourth quartile both conferred higher risks of elevated CIMT after adjusting for potential confounders. In the total population, the ORs for the first and fourth quartile were 1.29 (95% CI, 1.00‐1.66) and 1.42 (95% CI, 1.11‐1.83), respectively. Restricted cubic splines demonstrated an approximately U‐shaped association between TyG index and elevated CIMT among the total and nonobese adults (P for nonlinearity

Abstract Purpose To investigate the expression and prognostic value of c-Jun in hypopharyngeal squamous cell carcinoma (HPSCC). Methods A retrospective study was performed on a cohort of 99 HPSCC patients. The expression of c-Jun and phosphorylated-c-Jun (p-c-Jun) was evaluated via immunohistochemistry (IHC) staining. Overall survival (OS) and progression-free survival (PFS) were assessed using Kaplan–Meier method and multivariate Cox regression analysis. Results The high expression of c-Jun and p-c-Jun in HPSCC accounted for 60.61% and 16.16%, respectively. High expression of c-Jun was closely associated with cT stage (p = 0.0401), tumor size (p = 0.0276), number of lymph node metastases (p = 0.0205) and pathological differentiation (p = 0.0108). The expression of c-Junhigh (p = 0.0043), p-c-Junhigh (p = 0.0376) and c-Junhigh/p-c-Junhigh were closely associated with poor OS. The Cox proportional multivariate hazard model revealed that lymphovascular invasion and c-Jun expression were independent influencing factors of OS in HPSCC patients. Conclusion Our findings suggest that c-Jun is a reliable prognostic factors in HPSCC patients.

Summary: Liquid-chromatography-mass-spectrometry-based metabolomics is widely used in prospective case-control studies for disease prediction. Given the large amount of clinical and metabolomics data involved, data integration and analyses are crucial to provide an accurate understanding of the disease. We provide a comprehensive analysis approach to explore associations among clinical risk factors, metabolites, and disease. We describe steps for performing Spearman correlation, conditional logistic regression, casual mediation, and variance partitioning to investigate the potential effects of metabolites on disease.For complete details on the use and execution of this protocol, please refer to Wang et al. (2022).1 : Publisher’s note: Undertaking any experimental protocol requires adherence to local institutional guidelines for laboratory safety and ethics.

The progress devoted to improving the performance of neural networks has come at a high price in terms of cost and experience. Fortunately, the emergence of Neural Architecture Search improves the speed of network design, but most excellent works only optimize for high accuracy without penalizing the model complexity. In this paper, we propose an efficient CNN architecture search framework, MOO-DNAS, with multi-objective optimization based on differentiable neural architecture search. The main goal is to trade off two competing objectives, classification accuracy and network latency, so that the search algorithm is able to discover an efficient model while maintaining high accuracy. In order to achieve a better implementation, we construct a novel factorized hierarchical search space to support layer variety and hardware friendliness. Furthermore, a robust sampling strategy named “hard-sampling” is proposed to obtain final structures with higher average performance by keeping the highest scoring operator. Experimental results on the benchmark datasets MINST, CIFAR10 and CIFAR100 demonstrate the effectiveness of the proposed method. The searched architectures, MOO-DNAS-Nets, achieve advanced accuracy with fewer parameters and FLOPs, and the search cost is less than one GPU-day.

Epidemiological evidence regarding the effect of omega-3 polyunsaturated fatty acid (PUFA) supplementation on inflammatory bowel disease (IBD) is conflicting. Additionally, little evidence exists regarding the effects of specific omega-3 components on IBD risk. We applied two-sample Mendelian randomization (MR) to disentangle the effects of omega-3 PUFAs (including total omega-3, α-linolenic acid, eicosapentaenoic acid (EPA), or docosahexaenoic acid (DHA)) on the risk of IBD, Crohn’s disease (CD) and ulcerative colitis (UC). Our findings indicated that genetically predicted increased EPA concentrations were associated with decreased risk of IBD (odds ratio 0.78 (95% CI 0.63–0.98)). This effect was found to be mediated through lower levels of linoleic acid and histidine metabolites. However, we found limited evidence to support the effects of total omega-3, α-linolenic acid, and DHA on the risks of IBD. In the fatty acid desaturase 2 (FADS2) region, robust colocalization evidence was observed, suggesting the primary role of the FADS2 gene in mediating the effects of omega-3 PUFAs on IBD. Therefore, the present MR study highlights EPA as the predominant active component of omega-3 fatty acids in relation to decreased risk of IBD, potentially via its interaction with linoleic acid and histidine metabolites. Additionally, the FADS2 gene likely mediates the effects of omega-3 PUFAs on IBD risk.

Abstract Background Tumor migration and invasion is a complex and diverse process that involves the epithelial–mesenchymal transition (EMT) of tumor cells and degradation of the extracellular matrix by matrix metalloproteases (MMPs). Mortalin is an important oncogene. It has been reported to play an important role in tumor migration and invasion through various signaling pathways, but the underlying mechanism is not fully understood. Methods Here, we investigated the role of mortalin in the migration of the hepatocellular carcinoma (HCC) cell lines HepG2 and HCCLM3. Results The overexpression of mortalin in HepG2 cells decreased the protein level of reversion-inducing cysteine-rich protein with Kazal motifs (RECK) and activated the phosphorylation and acetylation of STAT3, thereby up-regulating matrix metalloproteinase 9 (MMP9) and promoting cell migration and invasion. In contrast, in HCCLM3 cells, mortalin knockdown increased the expression of RECK, inhibited the STAT3 pathway and the activity of MMP9, and inhibited cell migration and invasion. Furthermore, we found that salvianolic acid B, a caffeic acid phenethyl ester analog, specifically bound to mortalin and increased the degradation of mortalin proteasomes through ubiquitination, thereby up-regulating RECK, inhibiting STAT3, and finally inhibiting the migration and invasion of HCC cells. Conclusion Our work suggested that mortalin is a potential therapeutic target for hepatocellular carcinoma.

Abstract Background Circular RNAs (circRNAs) are increasingly recognized as important regulators in cancer including ovarian cancer (OC). This work focuses on the effects of circ_0000745 on the OC development of and molecules involved. Methods Expression of circ_0000745 in collected OC tissues and the acquired OC cell lines was examined by RT-qPCR. The stability of circ_0000745 in cells was examined by RNase R treatment. The target transcripts interacted with circ_0000745 were predicted using bioinformatic systems. Gain- and loss-of-function studies of circ_0000745, microRNA (miR)-3187-3p and erb-b2 receptor tyrosine kinase 4 (ERBB4) were conducted to determine their functions on proliferation, migration, invasion and stem cell property of OC cells. Results Circ_0000745 and ERBB4 were abundantly expressed while miR-3187-3p was poorly expressed in OC tissues and cells. Circ_0000745 sequestered miR-3187-3p and blocked its repressive effect on ERBB4. Downregulation of circ_0000745 reduced proliferation, aggressiveness, epithelial-mesenchymal transition, and stemness of SK-OV-3 cells, but this reduction was blocked upon miR-3187-3p inhibition or ERBB4 upregulation. By contrast, artificial induction of circ_0000745 upregulation, miR-3187-3p upregulation and ERBB4 downregulation led to inverse trends in ES-2 cells. ERBB4 promoted the phosphorylation of the PI3K/AKT signaling pathway. An RNA binding protein IGF2BP2 was found to circ_0000745 bind to and promote its expression and stability. Conclusion This study demonstrated that circ_0000745 upregulated by IGF2BP2 promotes aggressiveness and stemness of OC cells through a miR-3187-3p/ERBB4/PI3K/AKT axis. Circ_0000745 may serve as a promising target for OC treatment.

Photocatalysis for water treatment has attracted the attention of many scientists. MXenes, as a new environmental green material, exhibits a good application prospect in the field of photocatalysis because of its ability to promote the generation of photogenerated carriers and the transport of electron-hole pairs in a short time. However, there are relatively limited studies using this material for water resources treatment and there is a lack of systematic reviews to summarize the current research status. This manuscript mainly focuses on the advantages of MXenes materials used in photocatalysis companies with the application examples of MXenes materials in various methods of water treatment. Finally, the application defects and development directions of MXenes materials in water treatment for application prospects are summarized. This review can provide a theoretical basis for the related research on photocatalytic water treatment of MXenes materials and gain a step forward for high-efficient production within the water industry.

ObjectivesRecent studies found that secreted protein acidic and rich in cysteine-like protein 1 (Sparcl1) could inhibit lipid droplets accumulation by peroxisome proliferator-activated receptor-gamma (PPARγ) signal pathway. However, the associations of serum Sparcl1 level with lipids profiles and other metabolic phenotypes remain unknown in human population study.MethodsWe determined serum Sparcl1 using sandwich enzyme-linked immunosorbent assays among 1750 adults aged 40 years and older from a community in Shanghai, China. Generalized linear regression models were used to evaluate the association between Sparcl1 and metabolic measures. Multivariable-adjusted logistic regression analyses were performed to evaluate the relationship of serum Sparcl1 with prevalent dyslipidemia.ResultsWith the increment of serum Sparcl1, participants tended to have lower level of triglycerides, and higher level of high-density lipoprotein cholesterol (all P for trend < 0.01). No significant associations between serum Sparcl1 and glucose, blood pressure, or body size were observed. The generalized linear regression models suggested that per standard deviation (SD) increment of serum Sparcl1 was significantly inversely associated with triglycerides (β= -0.06, P=0.02). The prevalence of dyslipidemia decreased across the sparcl1 quartiles (P for trend 0.05).ConclusionSerum Sparcl1 was significantly associated with decreased risk of prevalent dyslipidemia in Chinese population. Further studies are warranted to confirm this association.

Rheumatoid arthritis (RA) is an autoimmune disease involving joints, with clinical manifestations of joint inflammation, bone damage and cartilage destruction, joint dysfunction and deformity, and extra-articular organ damage. As an important source of new drug molecules, natural medicines have many advantages, such as a wide range of biological effects and small toxic and side effects. They have become a hot spot for the vast number of researchers to study various diseases and develop therapeutic drugs. In recent years, the research of natural medicines in the treatment of RA has made remarkable achievements. These natural medicines mainly include flavonoids, polyphenols, alkaloids, glycosides and terpenes. Among them, resveratrol, icariin, epigallocatechin-3-gallate, ginsenoside, sinomenine, paeoniflorin, triptolide and paeoniflorin are star natural medicines for the treatment of RA. Its mechanism of treating RA mainly involves these aspects: anti-inflammation, anti-oxidation, immune regulation, pro-apoptosis, inhibition of angiogenesis, inhibition of osteoclastogenesis, inhibition of fibroblast-like synovial cell proliferation, migration and invasion. This review summarizes natural medicines with potential therapeutic effects on RA and briefly discusses their mechanisms of action against RA.

The innate immune pathway serves as the first line of defense against viral infections and plays a crucial role in the host’s immune response in clearing viruses. Prior research has indicated that the influenza A virus has developed various strategies to avoid host immune responses. Nevertheless, the role of the NS1 protein of the canine influenza virus (CIV) in the innate immune pathway remains unclear. In this study, eukaryotic plasmids of NS1, NP, PA, PB1, and PB2 were constructed, and it was found that these proteins interact with melanoma differentiation-associated gene 5 (MDA5) and antagonize the activation of IFN-β promoters by MDA5. We selected the NS1 protein for further study and found that NS1 does not affect the interaction between the viral ribonucleoprotein (RNP) subunit and MDA5, but that it downregulates the expression of the laboratory of genetics and physiology 2 (LGP2) and retinoic acid-inducible gene-I (RIG-I) receptors in the RIG-I pathway. Additionally, NS1 was found to inhibit the expression of several antiviral proteins and cytokines, including MX dynamin like GTPase 1 (MX1), 2′-5′oligoadenylate synthetase (OAS), Signal Transducers and Activators of Transcription (STAT1), tripartite motif 25 (TRIM25), interleukin-2 (IL-2), IFN, IL-8, and IL-1β. To further investigate the role of NS1, a recombinant H3N2 virus strain (rH3N2) and an NS1-null virus (rH3N2ΔNS1) were rescued using reverse-genetic technology. The rH3N2ΔNS1 virus exhibited lower viral titers compared to rH3N2, but had a stronger activation effect on the receptors LGP2 and RIG-I. Furthermore, when compared to rH3N2, rH3N2ΔNS1 exhibited a more pronounced activation of antiviral proteins such as MX1, OAS, STAT1, and TRIM25, as well as antiviral cytokines such as IL-6, IFN-β, and IL-1β. These findings suggest a new mechanism by which NS1, a nonstructural protein of CIV, facilitates innate immune signaling and provides new avenues for the development of antiviral strategies.

In this research, tulsi (wild type) stalks were treated with NaOH to obtain natural cellulosic fibers. X-ray diffractions showed typical cellulose diffraction peak at 22.7°. The fibers had a tensile strength of 445 MPa, higher than fibers obtained from other agricultural residues. The fibers also displayed good thermal stability up to 300℃ making it suitable for a wide range of applications. The fibers inherited the antimicrobial properties from the stalks and showed high activities against both Gram positive and Gram negative bacteria. The extracted fibers could be used in composites and manufacturing tents and canvas.

BackgroundMetabolic dysfunction is known to be associated with arterial stiffness. However, the risks of metabolic syndrome and diabetes due to arterial stiffness and the potential mechanism remain unclear. We aimed to investigate the association of arterial stiffness with the risk of metabolic syndrome and diabetes, and determine whether this association is mediated by liver fat.MethodsA prospective study was conducted with 4,139 Chinese adults who were metabolically healthy at baseline. Arterial stiffness was measured by brachial–ankle pulse wave velocity (baPWV). Obesity was defined as body mass index ≥25 kg/m2. The primary outcomes were incident metabolic syndrome and diabetes.ResultsDuring a median follow-up of 4.4 years, 1,022 (24.7%) and 354 (9.5%) participants developed metabolic syndrome and diabetes, respectively. Compared with those in the lowest quartile of baPWV, participants in the highest quartile had 85 and 91% higher risks of metabolic syndrome and diabetes [risk ratio (RR) 1.85, 95% confidence interval (CI) 1.41, 2.42 for metabolic syndrome; RR 1.91, 95% CI 1.16, 3.15 for diabetes]. Mediation analyses indicated that fatty liver significantly mediated the association of arterial stiffness with metabolic syndrome and diabetes risk. Specifically, 18.4% of metabolic syndrome and 12.6% of diabetes risk due to arterial stiffness were mediated through fatty liver.ConclusionsArterial stiffness was associated with higher risks of metabolic syndrome and diabetes in individuals with obesity. This association may be partially mediated by fatty liver.

BackgroundApolipoprotein B (apoB) and non-high-density lipoprotein cholesterol (non-HDL-C) have been shown to predict cardiovascular disease (CVD) even in the case of low levels of low-density lipoprotein cholesterol (LDL-C). We aimed to investigate whether the discordance between LDL-C and apoB or non-HDL-C was associated with arterial stiffness and elevated carotid intima-media thickness (CIMT) in middle-aged and elderly adults.MethodsA total of 5,279 Chinese adults free of CVD at baseline were included and followed with a mean follow-up of 4.3 years. Arterial stiffness was measured by brachial-ankle pulse wave velocity (baPWV) and pulse pressure (PP). The associations of apoB, non-HDL-C, and LDL-C with arterial stiffness or elevated CIMT were examined with logistic regression models using either continuous scales by restricted cubic splines or categories of concordant and discordant values defined by medians.ResultsHigh apoB but not LDL-C was associated with elevated baPWV or PP. High apoB, non-HDL-C, and LDL-C were all associated with elevated CIMT (p < 0.05). Individuals with low levels of LDL-C and discordantly high apoB or non-HDL-C compared to those with concordantly low apoB or non-HDL-C demonstrated higher risks of elevated baPWV [ORs (95% CI) of 1.40 (1.03–1.91) and 1.56 (1.12–2.18), respectively] and elevated PP [ORs (95% CI) of 1.61 (1.19–2.18) and 1.55 (1.12–2.15), respectively]. While, discordant high LDL-C with low apoB was associated with an increased risk of elevated CIMT (OR, 1.74; 95% CI, 1.13–2.69).ConclusionDiscordance analysis revealed that elevated apoB or non-HDL-C was a better predictor of risk of arterial stiffness, whereas LDL-C for elevated CIMT.

Recently, deep reinforcement learning (RL) has been a hot topic due to its high capability in solving complex decision-making tasks. Although deep RL has achieved remarkable results in many fields, efficient exploration remains one of its most challenging issues. Conventional exploration heuristic methods, such as random exploration, have proven to be not suitable for complex RL tasks along with high-dimensional states and large action spaces. In this paper, we propose a novel lightweight and general neural network module for effective global exploration, called the Noisy Attention Exploration Module (NAEM), of which the key insight is to introduce parametric and learnable Gaussian noise into the attention mechanism for global exploration. NAEM is a general structure based on the Convolutional Block Attention Module (CBAM), which retains the ability of attention to enhance feature representation for any CNNs. In order to evaluate our module, we embed it into both value-based and actor-critic RL algorithms to test their performance improvement over related agents. The experimental results show that both of the modified agents achieve a performance improvement of more than 130% on most Atari games when compared with their original versions. In addition, for the NoisyNet agents, the training time can be reduced by about 30% through using NAEM as an alternative exploration.

Complex aluminum hydrides with high hydrogen capacity are among the most promising solid-state hydrogen storage materials. The present study determines the thermal stability, hydrogen dissociation energy, and electronic structures of alkali metal aluminum hydrides, MAlH4 (M = Li, Na, K, and Cs), using first-principles density functional theory calculations in an attempt to gain insight into the dehydrogenation mechanism of these hydrides. The results show that the hydrogen dissociation energy (Ed-H2) of MAlH4 (M = Li, Na, K, and Cs) correlates with the Pauling electronegativity of cation M (χP); that is, the Ed-H2 (average value) decreases, i.e., 1.211 eV (LiAlH4) < 1.281 eV (NaAlH4) < 1.291 eV (KAlH4) < 1.361 eV (CsAlH4), with the increasing χP value, i.e., 0.98 (Li) > 0.93 (Na) > 0.82 (K) > 0.79 (Cs). The main reason for this finding is that alkali alanate MAlH4 at higher cation electronegativity is thermally less stable and held by weaker Al-H covalent and H-H ionic interactions. Our work contributes to the design of alkali metal aluminum hydrides with a favorable dehydrogenation, which is useful for on-board hydrogen storage.

Purpose: To investigate whether asiatic acid (AA) can improve the quantity and function of retinal ganglion cells (RGCs), as well as how AA regulates synaptic pathways in rat models with chronic glaucoma. Methods: In our study, a rat model of chronic glaucoma was prepared via the electrocoagulation of the episcleral veins. The numbers of surviving RGCs were counted via retrograde Fluorogold labeling, and a whole-cell patch clamp was used to clamp RGCs in normal retinal sections and in retinal sections 4 weeks after glaucoma induction. Results: Retrograde-Fluorogold-labeled RGC loss caused by persistent glaucoma was decreased by AA. Additionally, AA reduced the postsynaptic current produced by N-methyl-D-aspartate (NMDA) and diminished miniature glutamatergic excitatory neurotransmission to RGCs. On the other hand, AA increased miniature gamma-aminobutyric acid (GABA)-ergic inhibitory neurotransmission to RGCs and enhanced the GABA-induced postsynaptic current. The excitability of the RGC itself was also decreased by AA. RGCs in glaucomatous slices were less excitable because AA decreased their spontaneous action potential frequency and membrane potential, which led to a hyperpolarized condition. Conclusions: AA directly protected RGCs in a chronic glaucoma rat model by lowering their hyperexcitability. To enhance RGCs’ survival and function in glaucoma, AA may be a viable therapeutic drug.

Abstract Loss of nephron primary cilia due to disruption of the Ift88 gene results in sex‐ and age‐specific phenotypes involving renal cystogenesis, blood pressure (BP) and urinary Na+ excretion. Previous studies demonstrated that male mice undergoing induction of nephron‐specific Ift88 gene disruption at 2 months of age developed reduced BP and increased salt‐induced natriuresis when pre‐cystic (2 months post‐induction) and became hypertensive associated with frankly cystic kidneys by 9 months post‐induction; in contrast, female Ift88 KO mice manifested no unique phenotype 2 months post‐induction and had mildly reduced BP 9 months post‐induction. The current study utilized these Ift88 KO mice to investigate associated changes in renal Na+ transporter and channel protein expression. At 2 months post‐induction, pre‐cystic male Ift88 KO mice had reduced high salt diet associated total NKCC2 levels while female mice had no alterations in Na+ transporters or channels. At 9 months post‐induction, cystic male Ift88 KO mice had increased total and phosphorylated NHE3 levels together with reduced NKCC2, phosphorylated and/or total NCC, and ENaC‐α expression on normal and high salt diets. In contrast, female Ift88 KO mice at 9 months post‐induction had no changes in Na+ transporters or channels beyond an increase in phosphorylated‐NCC during high salt intake. Thus, reduced BP in pre‐cystic, and elevated BP in renal cystic, male Ift88 KO mice are associated with unique sex‐dependent changes in nephron Na+ transporter/channel expression.

Background. This study is aimed at investigating the expressions and prognostic values of secreted or membrane-located proteins (SMPs) in laryngeal squamous cell carcinoma (LSCC). The correlations between the expressions of SMPs and immune cells’ infiltrations were also investigated. Methods. The expression data of normal laryngeal and LSCC samples were obtained from the TCGA and GEO datasets. The differentially expressed SMPs were identified, and their prognostic values were analyzed. The biological functions of differentially expressed and worse-survival-related SMPs were explored. LASSO regression, Cox multivariate analysis, and nomogram were used to construct a model to predict the survival. Then, the infiltrations of the 24 immune cell populations were calculated using the GSVA method, and the correlations between the expression of SMPs and the immune infiltration were investigated. Results. 122 samples (12 normal and 120 LSCC) of the TCGA database and 114 samples (57 normal and 57 LSCC) of GSE127165 were included. We identified that 138 SMPs were significantly upregulated in LSCC samples of both the TCGA and GEO datasets, among which 52 SMPs were significantly correlated with worse survival. GO and KEGG analyses revealed those 52 SMPs significantly participate in tumor microenvironment and immune cells’ communication. Nine of 52 SMPs (ABCC5, ATP1B3, CLEC11A, FLNA, FSTL3, MMP1, NME1, OAS3, and PHLDB2) were included in the nomogram to effectively and accurately predict the LSCC patients’ survival. The expressions of most SMPs, such as MMP1 and FSTL3, were significantly positively correlated with the immune infiltration of LSCC. Conclusions. In this study, the expression, prognostic values, and correlations with immune infiltration of SMPs were analyzed in LSCC samples. Our analyses identified several significant SMPs differentially expressed between normal laryngeal and LSCC samples, correlated with worse survival, and related to the immune infiltration.

To model the car-following behavior more accurately, we carried out the molecular similarity analysis between the vehicles on the road and the inert gas system, comparing vehicles with microscopic particles in long and narrow pipes. The complex car-following interaction behavior is simplified into a dynamic process of the follower car that is constantly seeking to maintain the required safety distance from the leading vehicle. Through mathematical derivation of the Lennard–Jones potential function suitable for thermodynamic analysis of inert gas systems, the influence of each variable on the potential energy is clarified, and the existing problems of the existing molecular car-following model are analyzed, referring to the general Lennard–Jones potential function to build the vehicle interaction potential function. Considering the impact of the road wall potential generated by the lane boundary, a car-following model based on Lennard–Jones interaction potential is presented. The simulation test results show that compared with the existing molecular car-following model and IDM model, the average absolute error and root mean square error of the vehicle acceleration results obtained by this model and the actual data are lower, which proves that the vehicle is based on the Lennard–Jones interaction potential. The vehicle-following model based on Lennard–Jones interaction potential has a better fitting effect on the real vehicle-following behavior.

Abstract Background Cancer cells induce the infiltration of various immune cells that are located or distributed in different sites and play multiple roles, which have recently been proposed to predict clinical outcomes. We therefore studied the prognostic significance of the presence of tumour-infiltrating lymphocytes (TILs) and the ratios between different types of immune cells in hypopharyngeal squamous cell carcinoma (HPSCC). Methods We retrospectively analysed 132 consecutive patients diagnosed with advanced HPSCC in 2013–2017. Tumoural parenchyma was immunohistochemically counted manually for the number of CD8, CD4 and Foxp3 cells. The ratios of CD8/Foxp3 and CD8/CD4 ratios were calculated for each specimen and analyzed with respect to patient clinicopathological variables and prognosis. Results HPSCC patients with high levels of TILs showed evident correlations with well differentiated tumors (P

Abstract Background Information on HPV-associated sinonasal squamous cell carcinoma (SNSCC) is very limited in China. The aim of this study was to determine the prevalence of HPV in a large cohort of SNSCC patients in China. Methods Clinical records and formalin-fixed and paraffin-embedded tumor specimens from 30 SNSCC patients with associated inverted papilloma (IP-SNSCC) and 84 de novo SNSCC (DN-SNSCC) patients were retrieved between 2010 and 2017. HPV status was determined for each specimen using a combination of p16 immunohistochemistry and GP5+/6+ PCR. Results Immunohistochemistry for p16 was positive in two IP-SNSCC patients (2/30, 6.7%) and in 16 DN-SNSCC patients (16/84, 19.0%). HPV DNA was detected in six IP-SNSCC patients (6/30, 20%) and in three DN-SNSCC patients (3/84, 3.8%). Expression of p16 was not correlated with the presence of HPV DNA (p = 0.150). Among 18 p16-positive SNSCC patients, only three were HPV DNA-positive. Furthermore, only three of nine HPV DNA-positive tumors exhibited high p16 expression. In IP-SNSCC patients, only one of six HPV DNA-positive tumors exhibited high p16 expression. In DN-SNSCC patients, two of three HPV DNA-positive tumors exhibited high p16 expression. The positive rates for both HPV DNA and p16 in IP-SNSCC patients and DN-SNSCC patients were 3.3 and 2.4%, respectively. Conclusions Immunostaining for p16 is not a reliable surrogate marker of HPV status in SNSCC. The presence of HPV is rarely detected in DN-SNSCC patients in Eastern China. IP-SNSCC patients frequently lack of p16 overexpression despite the presence of high-risk HPV DNA.

Objective: The endothelial to mesenchymal transition (EndMT) plays a major role in cancer metastasis by regulating the complexity of the tumor microenvironment (TME). Here, we investigated whether 27-hydroxycholesterol (27HC) induces EndMT in endothelial cells (ECs). Methods: EndMT markers in the human microvascular endothelial cell-1 (HMEC-1) cell line and human umbilical vein endothelial cells (HUVECs) stimulated with 27HC were evaluated with Western blot. Epithelial to mesenchymal transition (EMT) markers in breast cancer (BC) cells cultured in conditioned medium were investigated with quantitative real time polymerase chain reaction (qRT-PCR). The MMP-2 and MMP-9 mRNA expression and activity were detected with qRT-PCR and gelatin zymography assays, respectively. The effect of activated STAT3 on 27HC-induced EndMT was validated by Western blot, immunofluorescence staining, and cell transfection assays. The migration ability of BC cells was evaluated with Transwell assays. Results: We found that 27HC induced EndMT in HMEC-1 and HUVECs, and 27HC-induced EndMT facilitated EMT and BC cell migration. The 27HC-induced EMT of BC cells also promoted EndMT and HUVEC migration. Investigation of the underlying molecular mechanisms revealed that STAT3 knockdown repressed EndMT in HUVECs as well as migration in BC cells induced with 27HC. In addition, C646 and resveratrol, inhibitors of STAT3 acetylation, repressed the expression of Ac-STAT3, p-STAT3, and EndMT markers in HUVECs exposed to 27HC; these HUVECs in turn attenuated the migration ability of BC cells in 27HC-induced EndMT. Conclusions: Cross-talk between 27HC-induced EndMT and EMT was observed in the TME. Moreover, activation of STAT3 signaling was found to be involved in 27HC-induced EndMT.

Abstract Background Mounting evidence suggests that complement components promote tumor progression via modulating immune suppression, angiogenesis, or tumor cell proliferation. However, the role of C3a-C3aR signaling in regulating lung metastasis of breast cancer remains unknown. Methods We performed various ex-vivo and in-vivo assays. Genetic and pharmacological C3aR blockade models were applied to investigate the role of C3a-C3aR in metastasis of breast cancer. Results C3a-C3aR signaling in CAFs facilitates the metastasis of breast cancer. Mechanically, C3a-C3aR signaling augments pro-metastatic cytokine secretion and extracellular matrix components expression of CAFs via the activation of PI3K-AKT signaling. Genetic or pharmacological blockade of C3aR signaling effectively inhibited lung metastasis of breast cancer in mouse models. Conclusions C3a-C3aR signaling in CAFs facilitates the metastasis of breast cancer. Targeting C3aR signaling is a potential anti-metastasis strategy for breast cancer therapy.

In recent times, Gold nanoparticles (AuNPs) synthesized from plant extracts and their anticancer activity have attracted significant attention. We report the green approach for the synthesis of AuNPs using extract from Abies spectabilis plant. In this study, the reaction parameters were optimized to control the size of the nanoparticle, which was confirmed by Transmission Electron microscopy (TEM). Various characterization technique such as SAED pattern, UV visible spectroscopy, EDX, FTIR, and AFM were employed to analyze the synthesized AuNPs obtained from A. spectabilis plant extract. Furthermore, we investigated the anticancer activities using T24 cell lines. Interestingly, the results of extensive screening on the applications of newly synthesized AuNPs were tested for their cytotoxicity effects on anticancer activity against T24 cells by MTT assay. The cell apoptosis was studied using TUNEL, DAPI, caspase activity, cell invasion and migration. Nanoparticles at different concentrations ranging from 1 to 25 μg/ml exhibited a dose dependent cytotoxicity for 24 h. Condensation and DNA fragmentation are characteristic of apoptosis by DAPI, TUNEL staining, and the significant up regulations of Beclin-1, Bax and caspase 3, whereas the expressions of anti-apoptotic Bcl-2 and Bid were down regulated. However, this study, therefore attempts to report the synthesis, characterization, and anticancer activity of gold nanoparticles of A. spectabilis plant extract beneficial for cancer therapeutics.

ObjectivesNationwide studies focusing on the impact of early-onset type 2 diabetes and obesity on the development of cardiovascular diseases (CVD) are limited in China. We aimed to investigate the association between age at diagnosis of type 2 diabetes and the risk of CVD, and to further examine the modifying effect of obesity on this association among Chinese adults.MethodsThis study included 23,961 participants with previously diagnosed diabetes from a large nationwide population-based cohort study across mainland China. With an interviewer-assisted questionnaire, we collected detailed information on CVDs. Logistic regression analysis was used to evaluate the risk of CVDs associated with age at diagnosis of diabetes.ResultsCompared with patients with late-onset diabetes (≥60 years), those with earlier-onset diabetes had increased risks for CVD, with adjusted ORs (95% CIs) of 1.72 (1.36-2.17), 1.52 (1.31-1.75) and 1.33 (1.19-1.48) for patients diagnosed aged

Energy limitation is one of the intrinsic shortcomings of wireless sensor networks (WSNs), although it has been widely applied in disaster response, battlefield surveillance, wildfire monitoring, radioactivity detection, etc. Due to the large amount of energy consumed for data transmission, how to prolong the network lifespan by designing various hierarchical routing protocols has attracted more and more attention. As a result, numerous achievements have emerged successively. However, these presented mechanisms can rarely guarantee the satisfactory quality of service (QoS), while lowering the energy cost level of WSNs. Meanwhile, invulnerability is undoubtedly an excellent quantitative index to assess QoS. Therefore, it is critical to develop a practical routing method to optimize network lifetime by considering both invulnerability and energy efficiency. Game theory is suitable for such a critical problem as it can be used in node or at network level to encourage the decision-making capabilities of WSNs. In this paper, a novel invulnerability-aware clustering routing algorithm (IACRA) using game-theoretic method is proposed to solve the predicament. The core features of the addressed game-theory-based routing protocol include integral invulnerability awareness, optimal cluster head selection in hierarchical routing, distance-aware cluster head discovery, and cluster rotation update mechanism for lifetime optimization. Particularly, the integral network invulnerability based on weighted fusion is constructed for further defining the profit model by combining the invulnerability indicators used to evaluate the local and whole network. Meanwhile, the optimal probability function of every node elected as CH in per cluster is established through the game between invulnerability and node energy consumption. In addition, the cluster update mechanism base on cluster rotation is proposed to avoid the rapid death of nodes with large energy consumption for maximizing network lifetime. The experimental results indicated a significant improvement in energy balance as well as in invulnerability compared with the other three kinds of well-known clustering routing protocols including GEEC (Game-theory-based energy efficient clustering routing protocol), HGTD (Hybrid, game-theory-based distributed clustering protocol), and EEGC (Efficient energy-aware and game-theory-based clustering protocol). Concretely, at the 400 communication rounds, the invulnerability of IACRA was higher than that of GEEC, HGTD, and EEGC by 77.56%, 29.45% and 15.90%, respectively, and the average residual energy of IACRA was 8.61%, 18.35% and 6.36% larger than that of GEEC, HGTD, and EEGC, respectively. Based on these results, the proposed protocol can be utilized to increase the capability of WSNs against deterioration of QoS and energy constraints.

With the promising potential application of Ag/graphene-based nanomaterials in medicine and engineering materials, the large-scale production has attracted great interest of researchers on the basis of green synthesis. In this study, water-soluble silver/graphene oxide (Ag/GO) nanomaterials were synthesized under ultrasound-assisted conditions. The structural characteristics of Ag/GO were confirmed by Fourier transform infrared spectroscopy, X-ray diffraction, transmission electron microscopy, scanning electron microscopy and energy dispersion spectroscopy, respectively. The results showed the silver particles (AgNPs) obtained by reduction were attached to the surface of GO, and there was a strong interaction between AgNPs and GO. The antibacterial activity was primarily evaluated by the plate method and hole punching method. Antibacterial tests indicated that Ag/GO could inhibit the growth of Gram-negative and Gram-positive bacteria, special for the Staphylococcus aureus.

Recently, with the popularization of camera tools such as mobile phones and the rise of various short video platforms, a lot of videos are being uploaded to the Internet at all times, for which a video retrieval system with fast retrieval speed and high precision is very necessary. Therefore, content-based video retrieval (CBVR) has aroused the interest of many researchers. A typical CBVR system mainly contains the following two essential parts: video feature extraction and similarity comparison. Feature extraction of video is very challenging, previous video retrieval methods are mostly based on extracting features from single video frames, while resulting the loss of temporal information in the videos. Hashing methods are extensively used in multimedia information retrieval due to its retrieval efficiency, but most of them are currently only applied to image retrieval. In order to solve these problems in video retrieval, we build an end-to-end framework called deep supervised video hashing (DSVH), which employs a 3D convolutional neural network (CNN) to obtain spatial-temporal features of videos, then train a set of hash functions by supervised hashing to transfer the video features into binary space and get the compact binary codes of videos. Finally, we use triplet loss for network training. We conduct a lot of experiments on three public video datasets UCF-101, JHMDB and HMDB-51, and the results show that the proposed method has advantages over many state-of-the-art video retrieval methods. Compared with the DVH method, the mAP value of UCF-101 dataset is improved by 9.3%, and the minimum improvement on JHMDB dataset is also increased by 0.3%. At the same time, we also demonstrate the stability of the algorithm in the HMDB-51 dataset.