Parecoxib inhibits tumorigenesis and angiogenesis in hepatocellular carcinoma through ERK-VEGF/MMPs signaling pathway.

Parecoxib, a well-recognized nonsteroidal anti-inflammatory drug, has been reported to possess anticancer properties in various tumor types. In this work, we aimed to investigate the potential anticancer effects of parecoxib on hepatocellular carcinoma (HCC) cells. To assess the impact of parecoxib on HCC cell proliferation, we employed Cell Counting Kit-8, colony formation, and 5-ethynyl-2'-deoxyuridine assays. Hoechst/propidium iodide (PI) double staining and flow cytometry were performed to evaluate apoptosis and cell cycle analysis. Wound healing and transwell assays were utilized to assess cell migration and invasion. Tube formation assay was employed to analyze angiogenesis. Protein levels were determined using western blotting, and mRNA expression levels were assessed using quantitative real-time polymerase chain reaction (PCR). A xenograft mouse model was used to confirm the antitumor effects of parecoxib on HCC tumors in vivo. Our data demonstrated that parecoxib effectively inhibited the proliferation of HCC cells in a dose- and time-dependent manner. In addition, parecoxib induced cell cycle arrest in the G2 phase and promoted apoptosis. Moreover, parecoxib hindered tumor migration and invasion by impeding the epithelial-mesenchymal transition process. Further investigation showed that parecoxib could significantly suppress angiogenesis through the inhibition of extracellular signal-regulated kinase (ERK)-vascular endothelial growth factor (VEGF) axis. Notably, treatment with the ERK activator phorbol myristate acetate upregulated the expression of matrix metalloproteinase (MMP)-2, MMP-9, and VEGF and reversed the function of parecoxib in HCC cells. Besides, parecoxib displayed its antitumor efficacy in vivo. Collectively, our results suggest that parecoxib ameliorates HCC progression by regulating proliferation, cell cycle, apoptosis, migration, invasion, and angiogenesis through the ERK-VEGF/MMPs signaling pathway.

Immune cell signatures and causal association with irritable bowel syndrome: A mendelian randomization study.

BACKGROUND: The mucosal barrier's immune-brain interactions, pivotal for neural development and function, are increasingly recognized for their potential causal and therapeutic relevance to irritable bowel syndrome (IBS). Prior studies linking immune inflammation with IBS have been inconsistent. To further elucidate this relationship, we conducted a Mendelian randomization (MR) analysis of 731 immune cell markers to dissect the influence of various immune phenotypes on IBS. Our goal was to deepen our understanding of the disrupted brain-gut axis in IBS and to identify novel therapeutic targets. AIM: To leverage publicly available data to perform MR analysis on 731 immune cell markers and explore their impact on IBS. We aimed to uncover immunophenotypic associations with IBS that could inform future drug development and therapeutic strategies. METHODS: We performed a comprehensive two-sample MR analysis to evaluate the causal relationship between immune cell markers and IBS. By utilizing genetic data from public databases, we examined the causal associations between 731 immune cell markers, encompassing median fluorescence intensity, relative cell abundance, absolute cell count, and morphological parameters, with IBS susceptibility. Sensitivity analyses were conducted to validate our findings and address potential heterogeneity and pleiotropy. RESULTS: Bidirectional false discovery rate correction indicated no significant influence of IBS on immunophenotypes. However, our analysis revealed a causal impact of IBS on 30 out of 731 immune phenotypes (P < 0.05). Nine immune phenotypes demonstrated a protective effect against IBS [inverse variance weighting (IVW) < 0.05, odd ratio (OR) < 1], while 21 others were associated with an increased risk of IBS onset (IVW ≥ 0.05, OR ≥ 1). CONCLUSION: Our findings underscore a substantial genetic correlation between immune cell phenotypes and IBS, providing valuable insights into the pathophysiology of the condition. These results pave the way for the development of more precise biomarkers and targeted therapies for IBS. Furthermore, this research enriches our comprehension of immune cell roles in IBS pathogenesis, offering a foundation for more effective, personalized treatment approaches. These advancements hold promise for improving IBS patient quality of life and reducing the disease burden on individuals and their families.

Overexpressing S100A9 ameliorates NK cell dysfunction in estrogen receptor-positive breast cancer.

BACKGROUND: Estrogen receptor (ER) positive human epidermal growth factor receptor 2 (HER2) negative breast cancer (ER+/HER2-BC) and triple-negative breast cancer (TNBC) are two distinct breast cancer molecular subtypes, especially in tumor immune microenvironment (TIME). The TIME of TNBC is considered to be more inflammatory than that of ER+/HER2-BC. Natural killer (NK) cells are innate lymphocytes that play an important role of tumor eradication in TME. However, studies focusing on the different cell states of NK cells in breast cancer subtypes are still inadequate. METHODS: In this study, single-cell mRNA sequencing (scRNA-seq) and bulk mRNA sequencing data from ER+/HER2-BC and TNBC were analyzed. Key regulator of NK cell suppression in ER+/HER2-BC, S100A9, was quantified by qPCR and ELISA in MCF-7, T47D, MDA-MB-468 and MDA-MB-231 cell lines. The prognosis predictability of S100A9 and NK activation markers was evaluated by Kaplan-Meier analyses using TCGA-BRAC data. The phenotype changes of NK cells in ER+/HER2-BC after overexpressing S100A9 in cancer cells were evaluated by the production levels of IFN-gamma, perforin and granzyme B and cytotoxicity assay. RESULTS: By analyzing scRNA-seq data, we found that multiple genes involved in cellular stress response were upregulated in ER+/HER2-BC compared with TNBC. Moreover, TLR regulation pathway was significantly enriched using differentially expressed genes (DEGs) from comparing the transcriptome data of ER+/HER2-BC and TNBC cancer cells, and NK cell infiltration high/low groups. Among the DEGs, S100A9 was identified as a key regulator. Patients with higher expression levels of S100A9 and NK cell activation markers had better overall survival. Furthermore, we proved that overexpression of S100A9 in ER+/HER2-cells could improve cocultured NK cell function. CONCLUSION: In conclusion, the study we presented demonstrated that NK cells in ER+/HER2-BC were hypofunctional, and S100A9 was an important regulator of NK cell function in ER+BC. Our work contributes to elucidate the regulatory networks between cancer cells and NK cells and may provide theoretical basis for novel drug development.

Comparing survival outcomes between neoadjuvant and adjuvant chemotherapy within T2N1M0 stage hormone receptor-positive, HER2-negative breast cancer: a retrospective cohort study based on SEER database.

BACKGROUND: Guideline recommendations for the application of neoadjuvant chemotherapy (NACT) in T2N1M0 stage hormone receptor-positive, HER2-negative (HR + /HER2-) breast cancer are ambiguous. The debate continues regarding whether NACT or adjuvant chemotherapy (ACT) offers superior survival outcomes for these patients. MATERIALS AND METHODS: Female patients diagnosed with HR + /HER2- breast cancer at T2N1M0 stage between 2010 and 2020, were identified from the Surveillance, Epidemiology, and End Results database and divided into two groups, the NACT group and the ACT group. Propensity score matching (PSM) was utilized to establish balanced cohorts between groups, considering baseline features. Kaplan-Meier (K-M) analysis and the Cox proportional hazards model were executed to assess the efficacy of both NACT and ACT in terms of overall survival (OS) and breast cancer-specific survival (BCSS). A logistic regression model was employed to examine the association between predictive variables and response to NACT. RESULTS: After PSM, 4,682 patients were finally included. K-M curves showed that patients receiving NACT exhibited significantly worse OS and BCSS when compared with patients undergoing ACT. Multivariable Cox analysis indicated that not achieving pathologic complete response (non-pCR) after NACT (versus ACT), was identified as an adverse prognostic factor for OS (HR 1.58, 95% CI 1.36-1.83) and BCSS (HR 1.70, 95% CI 1.44-2. 02). The logistic regression model revealed that low tumor grade independently predicted non-pCR. CONCLUSION: Among T2N1M0 stage HR + /HER2- patients, OS and BCSS of NACT were inferior to ACT. Patients who attained non-pCR after NACT demonstrated significantly worse survival outcomes compared with those who received ACT.

Effects of isorhamnetin on liver injury in heat stroke-affected rats under dry-heat environments via oxidative stress and inflammatory response.

Isorhamnetin is a natural flavonoid compound, rich in brass, alkaloids, and sterols with a high medicinal value. This study investigated the effects of isorhamnetin on liver injury and oxidative and inflammatory responses in heat-stroke-affected rats in a dry-heat environment. Fifty Sprague Dawley rats were randomly divided into five groups: normal temperature control (NC, saline), dry-heat control (DHC, saline), low-dose isorhamnetin-pretreated (L-AS, 25 mg/Kg), medium-dose isorhamnetin-pretreated (M-AS, 50 mg/Kg), and high-dose isorhamnetin-pretreated (H-AS, 100 mg/Kg) group. Saline was administered to the NC and DHC groups and corresponding concentrations of isorhamnetin were administered to the remaining three groups for 1 week. Blood and liver tissue were analyzed for oxidative stress and inflammation. The liver histopathological injury score, serum liver enzyme (alanine transaminase, aspartate transaminase, and lactate dehydrogenase), liver oxidative stress index (superoxide dismutase [SOD], catalase [CAT], and malondialdehyde), and inflammation index (tumor necrosis factor α [TNF-α], interleukin [IL]-1ß, IL-6, and lipopolysaccharides) were significantly higher in the DHC group than in the NC group (P < 0.05). These index values in the L-AS, M-AS, and H-AS groups were significantly lower than those in the DHC group (P < 0.05). The index values decreased significantly with an increase in the concentration of isorhamnetin (P < 0.05), while the index values of CAT and SOD showed the opposite tendency (P < 0.05). The expression of liver tissue nuclear factor kappa B (NF-κB), caspase-3, and heat shock protein (HSP-70) was higher in the DHC group than in the NC group (P < 0.05). Comparison between the isorhamnetin and DHC groups revealed that the expression of NF-кB and caspase-3 was decreased, while that of HSP-70 continued to increase (P < 0.05). The difference was significant for HSP-70 among all the isorhamnetin groups (P < 0.05); however, the NF-кB and caspase-3 values in the L-AS and H-AS groups did not differ. In summary, isorhamnetin has protective effects against liver injury in heat-stroke-affected rats. This protective effect may be related to its activities concerning antioxidative stress, anti-inflammatory response, inhibition of NF-кB and caspase-3 expression, and enhancement of HSP-70 expression.

Using Redox-Switchable Polymerization Catalysis to Synthesize a Chemically Recyclable Thermoplastic Elastomer.

In an effort to synthesize chemically recyclable thermoplastic elastomers, a redox-switchable catalytic system was developed to synthesize triblock copolymers containing stiff poly(lactic acid) (PLA) end blocks and a flexible poly(tetrahydrofuran-co-cyclohexene oxide) (poly(THF-co-CHO) copolymer as the mid-block. The orthogonal reactivity induced by changing the oxidation state of the iron-based catalyst enabled the synthesis of the triblock copolymers in a single reaction flask from a mixture of monomers. The triblock copolymers demonstrated improved flexibility compared to poly(l-lactic acid) (PLLA) and thermomechanical properties that resemble thermoplastic elastomers, including a rubbery plateau in the range of -60 to 40 °C. The triblock copolymers containing a higher percentage of THF versus CHO were more flexible, and a blend of triblock copolymers containing PLLA and poly(d-lactic acid) (PDLA) end-blocks resulted in a stereocomplex that further increased polymer flexibility. Besides the low cost of lactide and THF, the sustainability of this new class of triblock copolymers was also supported by their depolymerization, which was achieved by exposing the copolymers sequentially to FeCl3 and ZnCl2 /PEG under reactive distillation conditions.

Nanocurcumin attenuates pyroptosis and inflammation through inhibiting NF-κB/GSDMD signal in high altitude-associated acute liver injury.

Exposure to a hypobaric hypoxic environment at high altitudes can lead to liver injury, and mounting evidence indicates that pyroptosis and inflammation play important roles in liver injury. Curcumin (Cur) can inhibit pyroptosis and inflammation. Therefore, our purpose here was to clarify the mechanism underlying the protective effect of nanocurcumin (Ncur) and Cur in a rat model of high altitude-associated acute liver injury. Eighty healthy rats were selected and exposed to different altitudes (6000 or 7000 m) for 0, 24, 48, or 72 h. Fifty normal healthy rats were divided into normal control, high-altitude control, salidroside (40 mg/kg [Sal-40]), Cur (200 mg/kg [Cur-200]), and Ncur (25 mg/kg [Ncur-25]) groups and exposed to a high-altitude hypobaric hypoxic environment (48 h, 7000 m). Serum-liver enzyme activities (alanine transaminase, aspartate transaminase, and lactate dehydrogenase were detected and histopathology of liver injury was evaluated by hematoxylin and eosin staining, and inflammatory factors were detected in liver tissues by enzyme-linked immunosorbent assays. Pyroptosis-associated proteins (gasdermin D, gasdermin D N-terminal [GSDMD-N], pro-Caspase-1, and cleaved-Caspase-1 [cleaved-Casp1]) and inflammation-associated proteins (nuclear factor-κB [NF-κB], phospho-NF-κB [P-NF-κB], and high-mobility group protein B1 [HMGB1]) levels were analyzed by immunoblotting. Ncur and Cur inhibited increased serum-liver enzyme activities, alleviated liver injury in rats caused by high-altitude hypobaric hypoxic exposure, and downregulated inflammatory factors, including tumor necrosis factor-α, interleukin (IL)-1ß, IL-6, and IL-18, in rat liver tissues. The level of P-NF-κB, GSDMD-N, cleaved-Casp1, and HMGB1 in rat liver tissues increased significantly after high-altitude exposure. Ncur and Cur downregulated P-NF-κB, GSDMD-N, cleaved-Casp-1, and HMGB1. Ncur and Cur may inhibit inflammatory responses and pyroptosis in a rat model of high altitude-associated acute liver injury.

Advances in the Field of Two-Dimensional Crystal-Based Photodetectors.

Two-dimensional (2D) materials have sparked intense interest among the scientific community owing to their extraordinary mechanical, optical, electronic, and thermal properties. In particular, the outstanding electronic and optical properties of 2D materials make them show great application potential in high-performance photodetectors (PDs), which can be applied in many fields such as high-frequency communication, novel biomedical imaging, national security, and so on. Here, the recent research progress of PDs based on 2D materials including graphene, transition metal carbides, transition-metal dichalcogenides, black phosphorus, and hexagonal boron nitride is comprehensively and systematically reviewed. First, the primary detection mechanism of 2D material-based PDs is introduced. Second, the structure and optical properties of 2D materials, as well as their applications in PDs, are heavily discussed. Finally, the opportunities and challenges of 2D material-based PDs are summarized and prospected. This review will provide a reference for the further application of 2D crystal-based PDs.

Experimental Formation and Mechanism Study for Super-High Dielectric Constant AlOx/TiOy Nanolaminates.

Super-high dielectric constant (k) AlOx/TiOy nanolaminates (ATO NLs) are deposited by an atomic layer deposition technique for application in next-generation electronics. Individual multilayers with uniform thicknesses are formed for the ATO NLs. With an increase in AlOx content in each ATO sublayer, the shape of the Raman spectrum has a tendency to approach that of a single AlOx layer. The effects of ATO NL deposition conditions on the electrical properties of the metal/ATO NL/metal capacitors were investigated. A lower deposition temperature, thicker ATO NL, and lower TiOy content in each ATO sublayer can lead to a lower leakage current and smaller loss tangent at 1 kHz for the capacitors. A higher deposition temperature, larger number of ATO interfaces, and higher TiOy content in each ATO sublayer are important for obtaining higher k values for the ATO NLs. With an increase in resistance in the capacitors, the ATO NLs vary from semiconductors to insulators and their k values have a tendency to decrease. For most of the capacitors, the capacitances reduce with increments in absolute measurement voltage. There are semi-circular shapes for the impedance spectra of the capacitors. By fitting them with the equivalent circuit, it is observed that with the increase in absolute voltage, both parallel resistance and capacitance decrease. The variation in the capacitance is explained well by a novel double-Schottky electrode contact model. The formation of super-high k values for the semiconducting ATO NLs is possibly attributed to the accumulation of charges.

CEO's functional experience and firm performance based on text mining.

The impact of a chief executive officer's (CEO's) functional experience on firm performance has gained the attention of many scholars. However, the measurement of functional experience is rarely disclosed in the public database. Few studies have been conducted on the comprehensive functional experience of CEOs. This paper used the upper echelons theory and obtained deep-level curricula vitae (CVs) data through the named entity recognition technique. First, we mined 15 consecutive years of CEOs' CVs from 2006 to 2020 from Chinese listed companies. Second, we extracted information throughout their careers and automatically classified their functional hierarchy. Finally, we constructed breadth (functional breadth: functional experience richness) and depth (functional depth: average tenure and the hierarchy of function) for empirical analysis. We found that a CEO's breadth is significantly negatively related to firm performance, and the quadratic term is significantly positive. A CEO's depth is significantly positively related to firm performance, and the quadratic term is significantly negative. The research results indicate a u-shaped relationship between a CEO's breadth and firm performance and an inverted u-shaped relationship between their depth and firm performance. The study's findings extend the literature on factors influencing firm performance and CEOs' functional experience. The study expands from the horizontal macro to the vertical micro level, providing new evidence to support the recruitment and selection of high-level corporate talent.

Ferulic Acid Protects Endothelial Cells from Hypoxia-Induced Injury by Regulating MicroRNA-92a.

Materials and Methods: CCK-8 (cell counting kit-8), Western blotting and Annexin V-FITC/PI staining were used to detect cell viability and apoptosis after hypoxia stimulation. The level of microRNA-92 a (miR-92 a) was detected by qRT-PCR.. Then, the assays of flow cytometry and the annexin V/PI staining kit were applied to value the impact of FA on hypoxia-induced cell proliferation, cell cycle distribution, and apoptosis. Furthermore, the inhibitor and mimic of miR-92a were also administrated to explore the role of miR-92a in this process. Student's t-test was used to explore the differences between two groups, while one-way analysis of variance (ANOVA) was used to explore the differences between more than two groups. Results: The results showed that hypoxia stimulation significantly inhibited HUVEC viability and proliferation, such as remarkably decreasing the expression of CDK2, CDK4, and cyclin D1 in HUVECs. The results of annexin V-FITC/PI apoptosis detection showed that hypoxia culture significantly induced HUVEC apoptosis, which indicated that hypoxia stimulation significantly inhibited viability and proliferation of HUVECs but caused cell apoptosis and the expression of miR-92a. Meanwhile, FA remarkably protected HUVECs from hypoxia-induced inhibition of viability and proliferation, as well as the enhancement of apoptosis and miR-92a expression. Furthermore, suppression of miR-92a enhanced the protective effects of FA on hypoxia-induced HUVECs, while activation of miR-92a reversed those effects. Conclusion: Our study reported that FA preserved HUVECs from hypoxia-induced injury via regulating miR-92a, which facilitated the understanding of the protective capacity of FA in hypoxia-caused HUVEC injury.

Solid fuel production from co-hydrothermal carbonization of polyvinyl chloride and corncob: Higher dechlorination efficiency and process water recycling.

The hydrothermal carbonization (HTC) of polyvinyl chloride (PVC) and wet herbal agricultural wastes for solid fuel production remains bleak economics and sustainability because of high chloride residual, wastewater burden and low production capacity. In this study, the HTC dechlorination was investigated using the first-order reaction kinetic analysis. We found that the co-hydrothermal carbonization (co-HTC) of PVC and the typical biomass (corncob) achieved a staggering drop of dechlorination activation energy from 189.95 kJ/mol to 110.04 kJ/mol. The co-HTC process achieved rapid dechlorination and carbonization due to synergistic effect, to suppress the chlorine content in bituminous-coal-like hydrochar less than 0.05 %. The process wastewater (process water) from co-HTC was recycled four times to evaluate the reusability and chemical evolution. The organics in co-HTC environment enhanced the carbonization which was confirmed by the improved heating value (30.06 to 32.42 MJ·kg-1), hydrochar yield (33.33 % to 36.47 %) and energy recovery efficiency (57.73 % to 68.13 %). The Fourier transform infrared spectroscopy (FTIR) and scanning electron microscopy (SEM) evidenced the process water recirculation maintained high chloride removal. Moreover, the possible formation pathways of two kinds of hydrochars were discussed through the chemical composition of the aqueous phase and the characteristic structures of hydrochar. The co-HTC and process water recycling strategies provide a more promising prospect to convert PVC and biomass wastes into solid fuels.

Anti-Inflammatory and Anti-Oxidative Effects of Isorhamnetin for Protection Against Lung Injury in a Rat Model of Heatstroke in a Dry-Heat Environment.

BACKGROUND Isorhamnetin is a natural flavonoid compound with anti-inflammatory and antioxidant properties. However, its roles in alleviating lung injury associated with heatstroke remain unclear. Therefore, this study aimed to evaluate the protective effects of different isorhamnetin doses on lung injury in heatstroke rat models exposed to a dry-heat environment. MATERIAL AND METHODS Fifty Sprague-Dawley rats were randomly divided into 5 groups: normal control (0.9% saline), heatstroke (0.5% CMCNa), and isorhamnetin (25, 50, and 100 mg/kg) groups; treatments were administered by gavage daily for 7 days. All rats, except those in the control group, were exposed to a dry-heat environment (41±1°C, 10±2% relative humidity) for 150 min to induce heatstroke. Pathological changes, ultrastructure, edema, inflammation, and oxidative stress in the lungs were assessed. RESULTS Compared with the heatstroke group, rats treated with 100 mg/kg isorhamnetin showed amelioration of histopathological and ultrastructural changes in the lungs; decreased lung injury scores (P<0.05) and wet/dry weight ratios (P<0.01); lower levels of phospho-nuclear factor-kappaB (P<0.05), high-mobility group box 1 (P<0.01), tumor necrosis factor-alpha (P<0.01), interleukin (IL)-1ß (P<0.01), and IL-6 (P<0.01); lower malondialdehyde contents (P<0.01); and higher superoxide dismutase (P<0.01) and catalase activities (P<0.05). CONCLUSIONS In a dry-heat environment, isorhamnetin protected against lung injury in heatstroke rat models via anti-inflammatory and anti-oxidative mechanisms.

Graphene-Oxide-Based Fluoro- and Chromo-Genic Materials and Their Applications.

Composite materials and their applications constitute a hot field of research nowadays due to the fact that they comprise a combination of the unique properties of each component of which they consist. Very often, they exhibit better performance and properties compared to their combined building blocks. Graphene oxide (GO), as the most widely used derivative of graphene, has attracted widespread attention because of its excellent properties. Abundant oxygen-containing functional groups on GO can provide various reactive sites for chemical modification or functionalization of GO, which in turn can be used to develop novel GO-based composites. This review outlines the most recent advances in the field of novel dyes and pigments encompassing GO as a key ingredient or as an important cofactor. The interactions of graphene with other materials/compounds are highlighted. The special structure and unique properties of GO have a great effect on the performance of fabricated hybrid dyes and pigments by enhancing the color performance of dyes, the anticorrosion properties of pigments, the viscosity and rheology of inks, etc., which further expands the applications of dyes and pigments in dyeing, optical elements, solar-thermal energy storage, sensing, coatings, and microelectronics devices. Finally, challenges in the current development as well as the future prospects of GO-based dyes and pigments are also discussed. This review provides a reference for the further exploration of novel dyes and pigments.

Charging effect induced by electron beam irradiation: a review.

Charging effect frequently occurs when characterizing nonconductive materials using electrons as probes and/or signals and can impede the acquisition of useful information about the material under investigation. It is not adequate to investigate it merely by experiments, but theoretical investigations, for which the Monte Carlo method is a suitable tool, are also necessary. In this paper we review Monte Carlo simulations and selected experiments, intending to provide general insight into the charging effects induced by electron beam irradiation. We will introduce categories of the charging effect, the theoretical framework that is adopted in Monte Carlo modeling of the charging effect and present some typical simulation results. At last, with the knowledge on charging effect imparted by the above contents, we will discuss the measures that can be used for minimizing it.

Network analysis of potential risk genes for psoriasis.

BACKGROUND: Psoriasis is a complex chronic inflammatory skin disease. The aim of this study was to analyze potential risk genes and molecular mechanisms associated with psoriasis. METHODS: GSE54456, GSE114286, and GSE121212 were collected from gene expression omnibus (GEO) database. Differentially expressed genes (DEGs) between psoriasis and controls were screened respectively in three datasets and common DEGs were obtained. The biological role of common DEGs were identified by enrichment analysis. Hub genes were identified using protein-protein interaction (PPI) networks and their risk for psoriasis was evaluated through logistic regression analysis. Moreover, differentially methylated positions (DMPs) between psoriasis and controls were obtained in the GSE115797 dataset. Methylation markers were identified after comparison with the common genes. RESULTS: A total of 118 common DEGs were identified, which were mainly involved in keratinocyte differentiation and IL-17 signaling pathway. Through PPI network, we identified top 10 degrees as hub genes. Among them, high expression of CXCL9 and SPRR1B may be risk factors for psoriasis. In addition, we selected 10 methylation-modified genes with the higher area under receiver operating characteristic curve (AUC) value as methylation markers. Nomogram showed that TGM6 and S100A9 may be associated with an increased risk of psoriasis. CONCLUSION: This suggests that immune and inflammatory responses are active in keratinocytes of psoriatic skin. CXCL9, SPRR1B, TGM6 and S100A9 may be potential targets for the diagnosis and treatment of psoriasis.

Epidemiological survey to determine the prevalence of cholecystolithiasis in Uyghur, Kazakh, and Han Ethnic Groups in the Xinjiang Uyghur Autonomous Region of China: cross-sectional studies.

BACKGROUND: This study was performed to understand the prevalence of and possible risk factors for cholecystolithiasis in Uyghur, Kazakh, Han, and other ethnic groups in the Xinjiang Uyghur autonomous region of China. METHODS: Subjects were enrolled using typical case sampling and multistage stratified random sampling. We collected epidemiological data regarding cholecystolithiasis using a standard questionnaire of risk factors for gallbladder disease in Xinjiang. The subjects completed the questionnaire and underwent an abdominal ultrasound examination of the liver and gallbladder. RESULTS: This study included 5454 Xinjiang residents aged ≥ 18 years. The prevalence of cholecystolithiasis was 15% (11.3% in men and 17.1% in women), and the sex difference was statistically significant (male-to-female odds ratio [OR] 1.867; p < 0.001). The cholecystolithiasis prevalence was also significantly different among the Han, Uyghur, Kazakh, and other ethnic groups (13.1%, 20.8%, 11.5%, and 16.8%, respectively; p < 0.001). The prevalence of cholecystolithiasis in northern Xinjiang was 13.5% and that in southern Xinjiang was 17.5%; this difference was also statistically significant (OR 1.599; p < 0.001). Across all ethnic groups, the cholecystolithiasis prevalence significantly increased with age (all p < 0.01) and body mass index (BMI) (all p < 0.01). A multivariate logistic regression analysis indicated that cholecystolithiasis prevalence was associated with sex, age, BMI, smoking, diabetes, fatty liver disease, and geographical differences between northern and southern Xinjiang. CONCLUSIONS: The prevalence of cholecystolithiasis was significantly higher in the Uyghur ethnic group than in the Han, Kazakh, and other ethnic groups; in women than in men; in southern Xinjiang than in northern Xinjiang; in patients with fatty liver disease; and increased with age and BMI. Our findings could provide a theoretical basis for the formulation of control measures for cholecystolithiasis.

Swine hemorrhagic shock model and pathophysiological changes in a desert dry-heat environment.

BACKGROUND: This study aimed to establish a traumatic hemorrhagic shock (THS) model in swine and examine pathophysiological characteristics in a dry-heat environment. METHODS: Forty domestic Landrace piglets were randomly assigned to four study groups: normal temperature non-shock (NS), normal temperature THS (NTHS), desert dry-heat non-shock (DS), and desert dry-hot THS (DTHS) groups. The groups were exposed to either normal temperature (25°C) or dry heat (40.5°C) for 3 h. To induce THS, anesthetized piglets in the NTHS and DTHS groups were subjected to liver trauma and hypovolemic shock until death, and piglets in the NS and DS groups were euthanized at 11 h and 4 h, respectively. Body temperature, blood gas, cytokine production, and organ function were assessed before and after environmental exposure at 0 h and at every 30 min after shock to death. Hemodynamics was measured post exposure and post-shock at 0 h and at every 30 min after shock to death. RESULTS: Survival, body temperature, oxygen delivery, oxygen consumption, and cardiac output were significantly different for traumatic hemorrhagic shock in the dry-heat groups compared to those in the normal temperature groups. Lactic acid and IL-6 had a marked increase at 0.5 h, followed by a progressive and rapid increase in the DTHS group. CONCLUSIONS: Our findings suggest that the combined action of a dry-heat environment and THS leads to higher oxygen metabolism, poorer hemodynamic stability, and earlier and more severe inflammatory response with higher mortality.

Curcumin prevents renal cell apoptosis in acute kidney injury in a rat model of dry-heat environment heatstroke via inhibition of the mitochondrial apoptotic pathway.

Heatstroke is a life-threatening illness that is characterised by a core body temperature >40°C and central nervous system dysfunction. Acute kidney injury (AKI) is a common complication of heatstroke, and the mitochondrial apoptotic pathway has been demonstrated to be one of the leading causes of tissue damage and cell death in AKI. Curcumin is a phenol that is extracted from turmeric and demonstrates anti-apoptotic properties. To test if curcumin can protect the kidney from injury caused by heat stress, the effect of curcumin administration on renal injury and apoptosis of renal tissue was examined in a rat model of dry-heat environment. A total of 50 Sprague-Dawley rats were randomly divided into five groups (n=10): Standard temperature control, dry-heat control and curcumin treatment groups (50, 100 and 200 mg/kg groups). After exposure to a dry-heat environment for 150 min, the rats were anesthetized and euthanized. Blood, urine and renal tissue were collected to quantify the expression of specific mitochondrial apoptosis-related molecules. Curcumin pre-treatment decreased blood urea nitrogen and serum creatinine, urinary kidney injury molecule-1, and neutrophil gelatinase-associated lipocalin levels compared with the dry-heat control group. Curcumin was also revealed to downregulate c-Jun N-terminal kinases (JNK), cytochrome c, caspase-3 and caspase-9 expression upon treatment with 100 and 200 mg/kg curcumin, which may result in inhibition of the mitochondrial apoptotic pathway in renal cells. The current study revealed that Curcumin may to have potential for preventing heatstroke-induced AKI.

Curcumin alleviates acute kidney injury in a dry-heat environment by reducing oxidative stress and inflammation in a rat model.

Curcumin exhibits anti-inflammatory and antioxidant activities. We investigated the protective effects of curcumin in a renal injury rat model under dry-heat conditions. We divided Sprague-Dawley rats into four groups: dry-heat 0- (normal temperature control group), 50-, 100-, and 150-minute groups. Each group was divided into five subgroups (n = 10): normal saline (NS), sodium carboxymethylcellulose (CMCNa), and curcumin pretreated low, medium, and high-dose (50, 100, and 200 mg/kg, respectively) groups. Compared to the normal temperature group, serum creatinine, blood urea nitrogen, urinary kidney injury molecule-1, and neutrophil gelatinase-associated load changes in lipoprotein (NGAL) levels were significantly increased in the dry-heat environment group (P < .05); inducible nitric oxide synthase (iNOS) and cyclooxygenase-2 (COX-2) expression and malondialdehyde (MDA) and related inflammatory factor levels were increased in the kidney tissue. Superoxide dismutase (SOD) and catalase (CAT) levels were decreased. However, following all curcumin pretreatment, the serum levels of kidney injury indicators and NGAL were decreased in the urine compared to those in the NS and CMCNa groups (P < .05), whereas renal SOD and CAT activities were increased and MDA was decreased (P < .05). Renal tissues of the 150-minute group showed obvious pathological changes. Compared to the NS group, pathological changes in the renal tissues of the 100- and 200-mg/kg curcumin groups were significantly reduced. Furthermore, iNOS and COX-2 expression and inflammatory factor levels were decreased after curcumin treatment. Curcumin exerted renoprotective effects that were likely mediated by its antioxidant and anti-inflammatory effects in a dry-heat environment rat model.