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Abstract This study aimed to explore the potential association between Endothelin type A receptor (EDNRA) genetic polymorphisms and susceptibility to large artery atherosclerotic stroke (LAA), as well as the involvement of inflammation mechanisms. We recruited Han Chinese patients with LAA and age- and sex-matched controls. The distribution of alleles and genotypes for 16 single nucleotide polymorphisms (SNPs) in EDNRA was analyzed using dominant, recessive, and co-dominant genetic models between cases and controls. We quantified the mRNA and protein levels of EDNRA and NLRP3 genes, and concentrations of inflammatory factors (TNFα, IL-1β, IL-6, IL-8, IL-10, IL-18, and CCL18) in peripheral blood samples randomly selected from cases and controls. We also investigated the relationship between these SNPs, gene expression patterns and inflammatory factor levels. A total of 428 LAA cases and 434 controls were enrolled in this study. The results showed that rs5343 TT genotype of EDNRA was significantly associated with an increased risk of LAA (OR = 3.243, 95%CI = 1.608–6.542, P = 0.001). It also demonstrated a significant upregulation level of NLRP3 as well as higher concentrations of IL-10, IL-18, and CCL-18 in cases compared to controls. Besides, we discovered that the EDNRA polymorphisms were linked to NLRP3, IL-6, IL-10, and IL-18 levels in cases. There existed a positive correlation between EDNRA transcription levels and both NLRP3 transcript levels (r = 0.437, p

Abstract Cardiovascular disease (CVD) is a major chronic disease worldwide and its risk factors have long been investigating in epidemiological studies. Our study aims to develop a body composition-based risk score and integrate it into the Framingham Risk Score (FRS) to improve CVD prediction among well-functioning older adults. We included 1882 older adults from the Health, Aging and Body Composition (Health ABC) study to screen body composition variables obtained from the Dual-energy X-ray absorptiometry (DXA). Three models were developed and compared: the 4-DXA model, the refit FRS, and the refit FRS plus 4-DXA model. C-statistics were 0.62 (95% CI: 0.59, 0.65) for the refit FRS, 0.58 (95% CI: 0.55, 0.61) for the 4-DXA model, and 0.63 (95% CI: 0.60, 0.66) for the refit FRS plus 4-DXA model. Compared to the refit FRS, the refit FRS plus 4-DXA model slightly improved CVD outcome prediction as the discrimination slope, net reclassification index, and the integrated discrimination index were 0.053 (95% CI: 0.041, 0.066), 0.098 (95% CI = – 0.0033, 0.20) and 0.013 (95% CI: 0.0069–0.019). This study provides a model for more accurate risk stratification and draws more attention on DXA-based indices in the clinical setting. It also encourages further research in validating the developed risk score in more diverse population and in investigating a broader range of CVD risk factors.

Abstract Reactor pressure vessel (RPV) studs are key components of nuclear reactors, and their connection with flange ensures the sealing of the RPV under high-pressure and high-temperature conditions. In the present work, the external threads of the RPV stud were prepared by triaxial rolling, and the texture evolution of the external thread root material of an RPV stud was predicted by finite element analysis coupled with viscoplastic self-consistent simulations. The microstructure of the external thread root material of RPV stud was characterized by scanning electron microscope and electron back-scattered diffraction. The installation characteristics of the turned and rolled parts of the RPV stud were tested by installation and pretightening tests. It was found that the dynamic recrystallization at the external thread root formed ultrafine tempered sorbite grains, high-angle grain boundaries (47%), and strong {111} and {111} textures. In the installation and pretightening test, the residual elongation of rolled parts was reduced by 6% under the same loading pressure. The triaxial rolling process distributed the microstructure of the external thread root of the RPV stud in a gradient manner, resulting in improved stud installation characteristics.

Abstract Evidence from previous studies have demonstrated that gut microbiota are closely associated with occurrence of interstitial cystitis/bladder pain syndrome (IC/BPS), yet the causal link between the two is not well known. In this study, we performed a two-sample Mendelian randomization (MR) analysis to determine the possible causal association between gut microbiota with IC/BPS. Gut microbiota summary level data were derived from the genome-wide association study (GWAS) conducted by MiBioGen and the IC/BPS GWAS summary level data were obtained from the GWAS Catalog. Next, we performed an MR study to investigate the causal link between gut microbiota and IC/BPS. The primary method for causal analysis was the inverse variance weighted (IVW), and the MR results were validated through multiple sensitivity analyses. A positive association was found between IC/BPS and eight gut microbial taxa, including genus Bacteroides, genus Haemophilus, genus Veillonella, genus Coprococcus1, genus Butyricimonas, family Bacteroidaceae, family Christensenellaceae, and order Lactobacillales. Sensitivity analysis revealed lack of significant pleiotropy or heterogeneity in the obtained results. This MR analysis reveals that a causal association exists between some gut microbiota with IC/BPS. This finding may is expected to guide future research and development of IC/BPS preventions and treatments based on the bladder-gut axis. However, given the clinical complexity and diagnostic challenges of IC/BPS, along with the limitations of using large-scale GWAS summary data for analysis, our MR results require further validation through additional research.

Abstract Since the Qin terracotta warriors were unearthed, polyamide 650 cross-linked E-44 epoxy resin binder has been employed to bond and restore them. In this paper, the chemical aging of the binders service in indoor natural environment during the past 30 years in the terracotta warriors was studied by means of infrared spectroscopy, X-ray photoelectron spectroscopy and thermogravimetric analysis. The results indicated that the binders did not emerge the characteristic peak of carbonyl stretching vibration at 1700 cm−1 in the IR spectra of all determined binders, and their thermal decomposition curves did not emerge any abnormal changes, and the thermal decomposition mainly occurred above 300 °C. There are evident ceramic grains attached to the surface of the binders being peeled off for sampling. These results that the binders service in the Qin terracotta warriors did not exhibit an observable chemical aging and still has strong adhesion. Generally, discrepancies were observed between natural aging and accelerated artificial aging due to the ineffectiveness of the latter to reproduce the effects of complex weather conditions. Compared to artificially accelerated aging, the evaluation results in a long-term natural aging of the binder which is used for restoration of the life-size Qin terracotta warriors, providing in the present investigation, are more reliable in terms of predicting the safety of restored terracotta warriors.

Abstract The triglyceride-glucose (TyG) index is a novel marker of insulin resistance that has been strongly associated with many diseases related to metabolic disorders, such as diabetes, coronary heart disease, myocardial infarction, obesity, nonalcoholic fatty liver disease, and stroke. However, whether the TyG index is associated with the prevalence of gallstones has not been determined. Therefore, the purpose of this study was to evaluate the relationship between the TyG index and the prevalence of gallstones in American adults, as well as the age at which adults in America undergo their first gallstone surgery. We selected individuals from the National Health and Nutrition Examination Survey (NHANES) database from 2017 to March 2020. Based on the goal of our study, comprehensive inclusion and exclusion criteria were created. A logistic regression analysis, dose–response curve, and subgroup analysis were computed to assess the relationship between the TyG index and gallstone prevalence and age at first surgery for gallstone. A total of 3905 participants aged > 20 years were included in our study, of whom 421 had a self-reported history of gallstones. A total of 1884 (48.2%) males and 2021 (51.8%) females were included. After confounders adjustment, it was found single-unit increases in the TyG index were linked with a 25.0% increase in gallstone prevalence (odds ratio [OR] = 1.25, 95% confidence interval [95%CI]: 1.04, 1.51). After conversion of the TyG index values from continuous to categorical variables with tertiles, a marked 48% increase in gallstone incidence was found in tertile 3 relative to tertile 1 (OR = 1.48, 95% CI: 1.09, 1.99). The dose–response curve results indicated positive associations between gallstone prevalence and the TyG index, while the latter was negatively associated with age at first gallstone surgery. Based on subgroup analysis, the positive association between TyG index and high-incidence of gallstones was more significant in females (OR = 1.39, 95% CI: 1.09, 1.77), age

Abstract Protein induced by vitamin K absence or antagonist II (PIVKA-II) plays a critical role in the diagnosis of hepatocellular carcinoma (HCC), however, studies on its efficacy in diagnosing recurrent HCC were rarely found. A multicenter, retrospective, and observational study was conducted. During the overall follow-up of 5 years, HCC patients who had curative resection were monitored every 3 months in the first year post-surgery and every 6 months thereafter if no recurrence occurred. Tumor markers were collected at the diagnosis of recurrence for those with recurrence and at the last follow-up for those without recurrence. The median serum levels of PIVKA-II and AFP in the recurrence group were significantly higher than those in the non-recurrence group (PIVKA-II: 84.62 vs. 18.76 mAU/ml, p

Abstract Disc cutters are essential for full-section hard-rock tunnel boring machines. The performance of these devices directly affects tunnel engineering costs and duration. This paper proposes a sinusoidal variable cross-section (VCS) cutter ring and design method and establishes a digital model. Rock-like materials are simulated with a finite element model, and the model validity is verified via rock simulation mechanics tests. A disc cutter rolling rock simulation model for a linear cutting machine is also established, and simulation tests are performed for single- and three-cutter rolling using sinusoidal VCSs and constant cross-section (CCS) cutter models, respectively. The stress and energy changes for the cutters and rock-like material damage area were compared via simulation, confirming that some sinusoidal VCS cutter rings do less work on rock-like materials and cause larger crushing areas under the same engineering parameters; therefore, these cutter rings have smaller specific energies. The sinusoidal VCS cutter ring performance is 7% greater than that of CCS on average under single-cutter simulation, and the intermediate cutter performance of the intermediate cutter is 9% greater than that of CCS on average under three-cutter simulation. Thus, sinusoidal VCS cutter rings offer improved rock damage performance, and further research and application of this technology will improve the working efficiency of tunnel boring machines.

Abstract Freeze–thaw failure of frozen rock slope often occurs during engineering construction and mining in cold area, which poses a great threat to engineering construction and people's life safety. The properties of rock mass in cold region will change with the periodic change of temperature, which makes it difficult to accurately evaluate the stability of slope under the action of freeze–thaw cycle by conventional methods. Based on field investigation and literature review, this paper discusses the characteristics of frozen rock mass and the failure mechanism of frozen rock slope, and gives the types and failure modes of frozen rock slope. Then, the research status of frozen rock slope is analyzed. It is pointed out that the failure of frozen rock slope is the result of thermo-hydro-mechanical (THM) coupling. It is considered that freeze–thaw cycle, rainfall infiltration and fracture propagation have significant effects on the stability of frozen rock slope, and numerical simulation is used to demonstrate. The research shows that the safety factor of frozen rock slope changes dynamically with the surface temperature, and the safety factor of slope decreases year by year with the increase of freeze–thaw cycles, and the fracture expansion will significantly reduce the safety factor. Based on the above knowledge, a time-varying evaluation method of frozen rock slope stability based on THM coupling theory is proposed. This paper can deepen scholars' understanding of rock fracture slope in cold area and promote related research work.

Abstract To investigate the short-term effects and differences between exercise alone and exercise combined with self-mobilization training on chronic non-specific neck pain (CNSNP). Thirty subjects who met the criteria were recruited and randomly assigned to the exercise training group, the exercise combined with cervical self-mobilization training group (ECCM), and the exercise combined with cervicothoracic self-mobilization training group (ECCTM). The exercise training group received 6 weeks of deep neck flexor under biofeedback and scapular stability training, and the other two groups received 6 weeks of cervical self-mobilization and cervicothoracic self-mobilization, respectively, in addition to exercise training. Neck pain, cervical range of motion (ROM), neck disability, strength and endurance of deep neck flexor and quality of life were assessed before and after 6 weeks of training. The study results showed that all the three training programs for 6 weeks increased the strength and endurance of deep neck flexor, increased cervical ROM, reduced pain, and improved neck function (P

Abstract Melanoma is a malignant skin tumor. This study aimed to explore and assess the effect of novel biomarkers on the progression of melanoma. Differently expressed genes (DEGs) were screened from GSE3189 and GSE46517 datasets of Gene Expression Omnibus database using GEO2R. Gene Ontology and Kyoto Encyclopedia of Genes and Genomes pathway analyses were conducted based on the identified DEGs. Hub genes were identified and assessed using protein–protein interaction networks, principal component analysis, and receiver operating characteristic curves. Quantitative real-time polymerase chain reaction was employed to measure the mRNA expression levels. TIMER revealed the association between aldehyde dehydrogenase 2 (ALDH2) and tumor immune microenvironment. The viability, proliferation, migration, and invasion were detected by cell counting kit-8, 5-ethynyl-2′-deoxyuridine, wound healing, and transwell assays. Total 241 common DEGs were screened out from GSE3189 and GSE46517 datasets. We determined 6 hub genes with high prediction values for melanoma, which could distinguish tumor samples from normal samples. ALDH2, ADH1B, ALDH3A2, DPT, EPHX2, and GATM were down-regulated in A375 and SK-MEL-2 cells, compared with the human normal melanin cell line (PIG1 cells). ALDH2 was selected as the candidate gene in this research, presenting a high diagnostic and predictive value for melanoma. ALDH2 had a positive correlation with the infiltrating levels of immune cells in melanoma microenvironment. Overexpression of ALDH2 inhibited cell viability, proliferation, migration, and invasion of A375/SK-MEL-2 cells. ALDH2 is a new gene biomarker of melanoma, which exerts an inhibitory effect on melanoma.

Abstract Disulfidptosis is a condition where dysregulated NAPDH levels and abnormal accumulation of cystine and other disulfides occur in cells with high SLC7A11 expression under glucose deficiency. This disrupts normal formation of disulfide bonds among cytoskeletal proteins, leading to histone skeleton collapse and triggering cellular apoptosis. However, the correlation between disulfidptosis and immune responses in relation to glioblastoma survival rates and immunotherapy sensitivity remains understudied. Therefore, we utilized The Cancer Genome Atlas and The Chinese Glioma Genome Atlas to identify disulfidptosis-related immune checkpoint genes and established an overall survival (OS) prediction model comprising six genes: CD276, TNFRSF 14, TNFSF14, TNFSF4, CD40, and TNFRSF18, which could also be used for predicting immunotherapy sensitivity. We identified a cohort of glioblastoma patients classified as high-risk, which exhibited an upregulation of angiogenesis, extracellular matrix remodeling, and epithelial-mesenchymal transition as well as an immunosuppressive tumor microenvironment (TME) enriched with tumor associated macrophages, tumor associated neutrophils, CD8 + T-cell exhaustion. Immunohistochemical staining of CD276 in 144 cases further validated its negative correlation with OS in glioma. Disulfidptosis has the potential to induce chronic inflammation and an immunosuppressive TME in glioblastoma.

Abstract At the seedling and adult plant phases, pot experiments were carried out to enhance the physiological-biochemical characteristics of cucumber, guarantee its high yield, and ensure its cultivation of quality. Trichoderma harzianum conidia agents at 104, 105, 106, and 107 cfu g−1 were applied in accordance with the application of Fusarium oxysporum powder at concentrations of 104 cfu/g on the protective enzyme activity, physiological and biochemical indices, seedling quality, resilience to Fusarium wilt, quality, and yield traits. Fusarium oxysporum powder at 104 cfu g−1 was used to treat CK1, while Fusarium oxysporum powder and T. harzianum conidia agents were not used to treat CK2. The results show that different T. harzianum agents improved the activities of superoxide dismutase (SOD), ascorbate peroxidase (APX), catalase (CAT), and peroxidase (POD) in cucumber seedlings, improved chlorophyll content, root activity, root-shoot ratio, and seedling strength index, and decreased malondialdehyde (MAD) content (P

Abstract Taking major emergencies as the research background, the transmission mechanism for panic spread and the decision behaviour of the opinion field are explored in this paper. By using evolutionary game theory to explore the game relationship between the official opinion field and the public opinion field and by considering the existence of strategy dependency in the same game group, the dependence coefficient is introduced to improve replicator dynamics. The dynamic delayed SEIR evolutionary game model is built by combining the epidemic model with the delay effect within the group, and the stability of the proposed model is analysed. The research results show that the strategy dependency among the same game group has positive and negative effects on the evolution process. The evolution of the dynamic delayed panic SEIR evolutionary game spread model under the effect of a positive effect is simulated. The results suggest that the official opinion field and the public opinion field should actively deal with emergencies, formulate effective control strategies to make the panic within the group disappear, and provide theoretical guidance for the relevant government to formulate plans.

Abstract The evaluation of soil quality can provide new insights into the sustainable management of forests. This study investigated the effects of three types of forest management intensities (non-management (CK), extensive management (EM), and intensive management (IM)), and five management durations (0, 3, 8, 15, and 20 years) on the soil quality of a Carya dabieshanensis forest. Further, minimum data sets (MDS) and optimized minimum data sets (OMDS) were established to evaluate the soil quality index (SQI). A total of 20 soil indicators representing its physical, chemical, and biological properties were measured for the 0–30 cm layer. Using one-way ANOVA and principal component analysis (PCA), the total data set (TDS), the minimum data set (MDS), and optimized minimum data set (OMDS) were established. The MDS and OMDS contained three (alkali hydrolyzed nitrogen (AN), soil microbial biomass nitrogen (SMBN), and pH) and four (total phosphorus (TP), soil organic carbon (SOC), AN, and bulk density (BD)) soil indicators, respectively. The SQI derived from the OMDS and TDS exhibited a stronger correlation (r = 0.94, p

Abstract This paper takes the P-RAN, a proximity wireless access network system for 5G and 6G, as an example, and uses the theory related to value evaluation to discuss how to realize the decentralization of underlying infrastructure from the perspective of different interactive players in the system. The analysis of P-RAN helps to promote mobile network operators to recognize network interaction and solve the problems of weak coverage, reduce the cost of network construction, and provides a new research idea for exploring more network evaluation indicators in the future.

Abstract Bunch compactness is an important trait that affects the sanitary status and quality of wine grapes. Many studies have demonstrated that canopy managements, such as leaf removal, shoot trimming, and postponed first shoot topping, can effectively reduce compactness. However, few studies have determined the effects of canopy management measures on bunch compactness. Shoot wrapping has been previously shown to elongate the rachis length and reduce bunch compactness. Here, we tested whether the presence of laterals affects cluster growth in Vitis vinifera L. ‘Riesling’ through a field experiment with four treatments over two consecutive seasons: shoot wrapping with laterals, shoot wrapping without laterals, hedging with laterals, and hedging without laterals. Laterals were removed weekly. Lateral removal had little effect on cluster compactness; the effect was shown temporarily and not consistent the growing seasons. The effect of laterals on cluster compactness and rachis length slightly varied with years. The short-term and variable effect of laterals may be explained by the fact that they experienced little competition with clusters.

Abstract Cryptosporidium spp. and Giardia duodenalis are commonly detected intestinal protozoa species in humans and animals, contributing to global gastroenteritis spread. The present study examined the prevalence and zoonotic potential of Cryptosporidium spp. and G. duodenalis in Himalayan marmots and Alashan ground squirrels in China's Qinghai-Tibetan Plateau area (QTPA) for the first time. Four hundred ninety-eight intestinal content samples were collected from five counties of QTPA of Gansu province, China. All samples were examined for Cryptosporidium spp. and G. duodenalis by PCR amplification. The resultant data were statistically analyzed by chi-square, Fisher's test and Bonferroni correction using SPSS software 25. 0. Cryptosporidium positive samples were further subtyped through analysis of the 60-kDa glycoprotein (gp60) gene sequence. A total of 11 and 8 samples were positive for Cryptosporidium spp. and G. duodenalis, respectively. Prevalence of Cryptosporidium spp. and G. duodenalis were 2.5% (10/399) and 1.5% (6/399) in Himalayan marmots, 1.0% (1/99) and 2.0% (2/99) in Alashan ground squirrels, respectively. Sequence analysis confirmed the presence of C. rubeyi (n = 2), ground squirrel genotype II (n = 7), chipmunk genotype V (n = 1) and horse genotype (n = 1). The horse genotype was further subtyped as novel subtype VIbA10. G. duodenalis zoonotic assemblages A (n = 1), B (n = 6), E (n = 1) were identified in the present study. This is the first study to identify Cryptosporidium spp. and G. duodenalis in Himalayan marmots and Alashan ground squirrels, suggesting the potential zoonotic transmission of the two pathogens in QTPA.

Abstract To observe the safety and efficacy of CT-guided 3D template-assisted radioactive 125I seed implantation in the treatment of unresectable advanced soft tissue sarcoma (STS). Sixty-two patients who underwent continuous 3D template-assisted radioactive 125I seed implantation for the treatment of unresectable advanced STS from August 2017 to August 2018 were selected from four tumor treatment centers for retrospective analysis. The postoperative adverse reactions and tumor response were recorded, and the postoperative complications were observed and treated at the same time. The overall survival (OS) rate was determined. All patients successfully completed 125I seed implantation. In practice, the median number of puncture needles used during the operation was 20, and the median number of 125I particles was 88. There were no statistical differences in the relative dosimetry parameters before and after the operation (P > 0.05). Tumor evaluation was performed 6 months after the operation. The effective rate was 61.3%, and the local control rate was 93.5%. As of March 2020, the 1-year survival rate was 85.2%, and the 2-year survival rate was 49.0%. The OS was 23 months. CT-guided 3D template-assisted 125I seed implantation for the treatment of unresectable STS has a high local control rate, thereby further prolonging the OS of patients with unresectable STS.

Abstract Blastocystis hominis and Cystoisospora belli are considered to be common opportunistic intestinal protozoa in HIV/AIDS patients. In order to investigate the prevalence and genetic characteristics of B. hominis and C. belli in HIV/AIDS patients, a total of 285 faecal samples were individually collected from HIV/AIDS patients in Guangxi, China. B. hominis and C. belli were investigated by amplifying the barcode region of the SSU rRNA gene and the internal transcribed spacer 1 (ITS-1) region of the rRNA gene, respectively. Chi-square test or Fisher’s exact test were conducted to assess the risk factors related to B. hominis and C. belli infection. The prevalence of B. hominis and C. belli was 6.0% (17/285) and 1.1% (3/285) respectively. Four genotypes of B. hominis were detected, with ST3 (n = 8) and ST1 (n = 6) being predominant, followed by ST6 (n = 2) and ST7 (n = 1). Females had a statistically higher prevalence of B. hominis (11.6%) than males (4.2%). The statistical analysis also showed that the prevalence of B. hominis was significantly associated with age group and educational level. Our study provides convincing evidence for the genetic diversity of B. hominis, which indicates its potential zoonotic transmission and is the first report on the molecular characteristics of C. belli in HIV/AIDS patients in China.

Abstract Available evidence linking serum uric acid (SUA) and bone mineral density (BMD) remains controversial, and data on this association are limited among adult men in the general population. Thus, the aim of this study was to evaluate the association of SUA with lumbar spine BMD in US adult males. A cross-sectional study was conducted based on the National Health and Nutrition Examination Survey (NHANES, 1999–2006) database. Multivariate linear regression analyses were employed to assess the association of SUA with lumbar spine BMD, considering complex survey design and sampling weights. Through rigorous eligibility criteria, a total of 6704 individuals were yielded for final data analysis (average age, 40.5 years; 70.6% white). After fully adjusting potential confounders, no associations were detected between SUA and lumbar spine BMD [β (95% confidence interval, CI), − 0.003 (− 0.007, 0.002)]. Additionally, similar results were observed in all stratification analyses, and no interactions were found based on all priori specifications. In brief, our findings did not provide an inspiring clue for the hypothesis that SUA may be beneficial to lumbar spine BMD. Future more prospective studies are needed to further explore the causal relationship of SUA with lumbar spine BMD.

Abstract Osteoarthritis (OA), a most common and highly prevalent joint disease, is closely associated with dysregulated expression and modification of RXRα. However, the role of RXRα in the pathophysiology of OA remains unknown. The present study aimed to investigate whether RXRα modulator, such as K-80003 can treat OA. Experimental OA was induced by intra-articular injection of monosodium iodoacetate (MIA) in the knee joint of rats. Articular cartilage degeneration was assessed using Safranin-O and fast green staining. Synovial inflammation was measured using hematoxylin and eosin (H&E) staining and enzyme-linked immunosorbent assay (ELISA). Expressions of MMP-13, ADAMTS-4 and ERα in joints were analyzed by immunofluorescence staining. Western blot, RT-PCR and co-Immunoprecipitation (co-IP) were used to assess the effects of K-80003 on RXRα-ERα interaction. Retinoid X receptor α (RXRα) modulator K‐80003 prevented the degeneration of articular cartilage, reduced synovial inflammation, and alleviated osteoarthritic pain in rats. Furthermore, K-80003 markedly inhibited IL-1β‐induced p65 nuclear translocation and IκBα degradation, and down-regulate the expression of HIF-2α, proteinases (MMP9, MMP13, ADAMTS-4) and pro-inflammatory factors (IL-6 and TNFα) in primary chondrocytes. Additionally, knockdown of ERα with siRNA blocked these effects of K-80003 in chondrocytes. In conclusion, RXRα modulators K-80003 suppresses inflammatory and catabolic responses in OA, suggesting that targeting RXRα‐ERα interaction by RXRα modulators might be a novel therapeutic approach for OA treatment.

Abstract Interferon-gamma (IFN-γ) is a cytokine involved in the pathogenesis of Takayasu’s arteritis (TAK). However, the source of IFN-γ in TAK patients is not fully clear. We aimed to investigate the source of IFN-γ in TAK. 60 TAK patients and 35 health controls were enrolled. The lymphocyte subsets of peripheral blood were detected by flow cytometry, cytokines were detected by Bio-plex. The correlation among lymphocyte subsets, cytokines and disease activity indexes was analyzed by person correlation. The level of serum IFN-γ in TAK patients was significantly increased (P

Abstract To understand the characteristic of changes of serum metabolites between healthy people and patients with hepatitis B virus (HBV) infection at different stages of disease, and to provide reference metabolomics information for clinical diagnosis of liver disease patients. 255 patients with different stages of HBV infection were selected. 3 mL blood was collected from each patient in the morning to detect differences in serum lysophosphatidylcholine, acetyl-l-carnitine, oleic acid amide, and glycocholic acid concentrations by UFLC-IT-TOF/MS. The diagnostic values of four metabolic substances were evaluated by receiver operating characteristic (ROC) curve. The results showed that the optimal cut-off value of oleic acid amide concentration of the liver cirrhosis and HCC groups was 23.6 mg/L, with a diagnostic sensitivity of 88.9% and specificity of 70.6%. The diagnostic efficacies of the three substances were similar in the hepatitis and HCC groups, with an optimal cut-off value of 2.04 mg/L, and a diagnostic sensitivity and specificity of 100% and 47.2%, respectively. The optimal cut-off value of lecithin of the HBV-carrier and HCC groups was 132.85 mg/L, with a diagnostic sensitivity and specificity of 88.9% and 66.7%, respectively. The optimal cut-off value of oleic acid amide of the healthy and HCC groups was 129.03 mg/L, with a diagnostic sensitivity and specificity of 88.4% and 83.3%, respectively. Lysophosphatidylcholine, acetyl-l-carnitine, and oleic acid amide were potential metabolic markers of HCC. Among them, lysophosphatidylcholine was low in the blood of HCC patients, and its diagnostic efficacy was better than that of acetyl-l-carnitine and oleic acid amide, providing reference metabolomics information in clinical diagnosis and future research.

Abstract Accumulating studies appear to suggest that the risk factors for venous thromboembolism (VTE) among young-middle-aged inpatients are different from those among elderly people. Therefore, the current prediction models for VTE are not applicable to young-middle-aged inpatients. The aim of this study was to develop and externally validate a new prediction model for young-middle-aged people using machine learning methods. The clinical data sets linked with 167 inpatients with deep venous thrombosis (DVT) and/or pulmonary embolism (PE) and 406 patients without DVT or PE were compared and analysed with machine learning techniques. Five algorithms, including logistic regression, decision tree, feed-forward neural network, support vector machine, and random forest, were used for training and preparing the models. The support vector machine model had the best performance, with AUC values of 0.806–0.944 for 95% CI, 59% sensitivity and 99% specificity, and an accuracy of 87%. Although different top predictors of adverse outcomes appeared in the different models, life-threatening illness, fibrinogen, RBCs, and PT appeared to be more consistently featured by the different models as top predictors of adverse outcomes. Clinical data sets of young and middle-aged inpatients can be used to accurately predict the risk of VTE with a support vector machine model.

Abstract The LOX genes have been identified and characterized in many plant species, but studies on the banana LOX genes are very limited. In this study, we respectively identified 18 MaLOX, 11 MbLOX, and 12 MiLOX genes from the Musa acuminata, M. balbisiana and M. itinerans genome data, investigated their gene structures and characterized the physicochemical properties of their encoded proteins. Banana LOXs showed a preference for using and ending with G/C and their encoded proteins can be classified into 9-LOX, Type I 13-LOX and Type II 13-LOX subfamilies. The expansion of the MaLOXs might result from the combined actions of genome-wide, tandem, and segmental duplications. However, tandem and segmental duplications contribute to the expansion of MbLOXs. Transcriptome data based gene expression analysis showed that MaLOX1, 4, and 7 were highly expressed in fruit and their expression levels were significantly regulated by ethylene. And 11, 12 and 7 MaLOXs were found to be low temperature-, high temperature-, and Fusarium oxysporum f. sp. Cubense tropical race 4 (FocTR4)-responsive, respectively. MaLOX8, 9 and 13 are responsive to all the three stresses, MaLOX4 and MaLOX12 are high temperature- and FocTR4-responsive; MaLOX6 and MaLOX17 are significantly induced by low temperature and FocTR4; and the expression of MaLOX7 and MaLOX16 are only affected by high temperature. Quantitative real-time PCR (qRT-PCR) analysis revealed that the expression levels of several MaLOXs are regulated by MeJA and FocTR4, indicating that they can increase the resistance of banana by regulating the JA pathway. Additionally, the weighted gene co-expression network analysis (WGCNA) of MaLOXs revealed 3 models respectively for 5 (MaLOX7-11), 3 (MaLOX6, 13, and 17), and 1 (MaLOX12) MaLOX genes. Our findings can provide valuable information for the characterization, evolution, diversity and functionality of MaLOX, MbLOX and MiLOX genes and are helpful for understanding the roles of LOXs in banana growth and development and adaptations to different stresses.

Abstract MicroRNAs are non-coding RNAs that act to downregulate the expression of target genes by translational repression and degradation of messenger RNA molecules. Individual microRNAs have the ability to specifically target a wide array of gene transcripts, therefore allowing each microRNA to play key roles in multiple biological pathways. miR-324 is a microRNA predicted to target thousands of RNA transcripts and is expressed far more highly in the brain than in any other tissue, suggesting that it may play a role in one or multiple neurological pathways. Here we present data from the first global miR-324-null mice, in which increased excitability and interictal discharges were identified in vitro in the hippocampus. RNA sequencing was used to identify differentially expressed genes in miR-324-null mice which may contribute to this increased hippocampal excitability, and 3′UTR luciferase assays and western blotting revealed that two of these, Suox and Cd300lf, are novel direct targets of miR-324. Characterisation of microRNAs that produce an effect on neurological activity, such as miR-324, and identification of the pathways they regulate will allow a better understanding of the processes involved in normal neurological function and in turn may present novel pharmaceutical targets in treating neurological disease.

Abstract Cryptococcal meningitis (CM) is the most fatal adult meningitis in patients with human immunodeficiency virus (HIV). There is no conclusive evidence for the superiority of 1-week amphotericin B deoxycholate (AmphB) + flucytosine (5-FC) regimen over other antifungals in the management of HIV patients with CM (HIV–CM patients). We aimed to evaluate the differences in efficacy and tolerability of different antifungal agents in HIV–CM patients by conducting a current network meta-analysis NMA. Overall, 19 randomized controlled trials were included with 2642 participants. A regimen indicated a possibly lower early mortality rate, namely, AmphB + 5-FC + Azole (OR = 1.1E−12, 95% CIs = 1.3E−41 to 0.06) comparing to AmphB + 5-FC. The current NMA provides evidence that AmphB + 5-FC + Azole are superior to all the investigated treatments for induction regimen in HIV–CM patients.

Abstract To evaluate the surgical effect on survival in patients with incidental low-grade glioma (LGG) through comparison between asymptomatic and symptomatic patients. The medical records of surgically treated adult cerebral incidental LGG (iLGG) patients in our department between January 2008 and December 2015 were retrospectively reviewed. The survival of patients was calculated starting from the initial imaging diagnosis. Factors related to progression-free survival (PFS), overall survival (OS) and malignant progression-free survival (MPFS) were statistically analyzed. Seventy-five iLGG patients underwent surgery: 49 in the asymptomatic group, who underwent surgery in the asymptomatic period, and 26 in the symptomatic group, who underwent surgery after the tumor had grown and the patients had developed tumor-related symptoms. Significantly more tumors were initially located adjacent to the functional area in the symptomatic group than in the asymptomatic group (P

Abstract Cadmium (Cd) presents severe risks to human health and environments. The present study proposed a green option to reduce bioavailable Cd. Rice pot experiments were conducted under continuous flooding with three treatments (T1: intercropping azolla with rice; T2: incorporating azolla into soil before rice transplantation; CK: no azolla). The results showed that azolla incorporation reduced soluble Cd by 37% compared with the CK treatment, which may be explained by the decreased soil redox potential (Eh) (r = 0.867, P

Abstract Foot electrical stimulation (FES) has been considered as a classic stressor that can disturb homeostasis. Acute anemia was observed in the model induced by FES. The aim of this study was to explore the role of inflammatory cytokines underlying the acute anemia and gastrointestinal (GI) mucosal injury in the FES. Twenty-four male Kunming mice (20 ± 2 g) were randomly divided into control group and experimental group. The mice were placed in a footshock chamber that can generate 0.5 mA electrical impulse periodically for 0.5 h. After the process, red blood cell count, hemoglobin concentration and hematocrit, the levels of corticotropin releasing hormone (CRH) in serum and hypothalamus, and adrenocorticotropic hormone (ACTH) in serum and pituitary were detected separately. In addition, we investigated the expressions of inflammatory cytokines (IL-1, IL-6, TNF-α, iNOS, and IL-10) in the hypothalamus and duodenum by Polymerase Chain Reaction (PCR). Results showed that this FES model induced anemia, increased CRH and ACTH activity in the serum after the FES. Moreover, the expressions of IL-1β, IL-6, TNF-α, and iNOS were significantly increased following the process, while IL-10 was not activated. These findings suggest that anemia, the inflammatory cytokines in the hypothalamus and duodenum of the mice in the model induced by FES is closely related to GI mucosal injury/bleeding. Taken together, these results underscore the importance of anemia, GI mucosal injury/bleeding and stress, future studies would be needed to translate these findings into the benefit of affected patients.

Abstract To investigate the prognostic value of occult lymph node metastases (OLNMs) in patients with pathologically lymph node negative (pN0) esophageal squamous cell carcinoma (ESCC). OLNMs were detected in 516 pN0 ESCC patients by immunohistochemical staining. The correlation between the clinicopathological features and OLNM, and the prognostic value of OLNM was explored. Eighty-eight patients (17.1%) had OLNMs, including 37 patients with isolated tumor cells (ITCs), 49 patients with micrometastases, and 2 patients with macrometastases (> 2 mm). The OLNM-positive group had poorer differentiation and a more advanced pT category. The 5-year overall survival and disease-free survival for patients with OLNMs were significantly worse than those of IHC-negative patients (P 0.05). The multivariate analysis showed that OLNM was an independent prognostic factor. In subgroup analyses, the IHC-negative patients had significant survival advantages compared with the ITC group and the micrometastasis group, whereas the survival for the ITC group was similar to that of the micrometastasis group. IHC staining in pN0 ESCC patients might help to identify patients at high risk of death after resection, and ITCs in the lymph nodes appear to have a prognostic value equal to that of micrometastases.

Abstract The mechanism of how chronic hepatitis C virus (HCV) infection leads to such a high rate of hepatocellular carcinoma (HCC) is unknown. We found that the PERK axis of endoplasmic reticulum (ER) stress elicited prominent nuclear translocation of Nrf2 in 100% of HCV infected hepatocytes. The sustained nuclear translocation of Nrf2 in chronically infected culture induces Mdm2-mediated retinoblastoma protein (Rb) degradation. Silencing PERK and Nrf2 restored Mdm2-mediated Rb degradation, suggesting that sustained activation of PERK/Nrf2 axis creates oncogenic stress in chronically infected HCV culture model. The activation of Nrf2 and its nuclear translocation were prevented by ER-stress and PERK inhibitors, suggesting that PERK axis is involved in the sustained activation of Nrf2 signaling during chronic HCV infection. Furthermore, we show that HCV clearance induced by interferon-α based antiviral normalized the ER-stress response and prevented nuclear translocation of Nrf2, whereas HCV clearance by DAAs combination does neither. In conclusion, we report here a novel mechanism for how sustained activation of PERK axis of ER-stress during chronic HCV infection activates oncogenic Nrf2 signaling that promotes hepatocyte survival and oncogenesis by inducing Mdm2-mediated Rb degradation.

Abstract TAp63, a member of the p53 family, has been shown to regulate energy metabolism. Here, we report coiled coil domain-containing 3 (CCDC3) as a new TAp63 target. TAp63, but not ΔNp63, p53 or p73, upregulates CCDC3 expression by directly binding to its enhancer region. The CCDC3 expression is markedly reduced in TAp63-null mouse embryonic fibroblasts and brown adipose tissues and by tumor necrosis factor alpha that reduces p63 transcriptional activity, but induced by metformin, an anti-diabetic drug that activates p63. Also, the expression of CCDC3 is positively correlated with TAp63 levels, but conversely with ΔNp63 levels, during adipocyte differentiation. Interestingly, CCDC3, as a secreted protein, targets liver cancer cells and increases long chain polyunsaturated fatty acids, but decreases ceramide in the cells. CCDC3 alleviates glucose intolerance, insulin resistance and steatosis formation in transgenic CCDC3 mice on high-fat diet (HFD) by reducing the expression of hepatic PPARγ and its target gene CIDEA as well as other genes involved in de novo lipogenesis. Similar results are reproduced by hepatic expression of ectopic CCDC3 in mice on HFD. Altogether, these results demonstrate that CCDC3 modulates liver lipid metabolism by inhibiting liver de novo lipogenesis as a downstream player of the p63 network.

Abstract Low density lipoprotein receptor-related protein 1 (LRP1) C766T polymorphism (rs1799986) has been extensively investigated for Alzheimer’s disease (AD) susceptibility. However, results in different studies have been contradictory. Therefore, we conducted a meta-analysis containing 6455 AD cases and 6304 controls from 26 independent case–control studies to determine whether there was an association between the LRP1 C766T polymorphism and AD susceptibility. The combined analysis showed that there was no significant association between LRP1 C766T polymorphism and AD susceptibility (TT + CT versus CC: OR = 0.920, 95% CI = 0.817–1.037, P = 0.172). In subgroup analysis, significant decreased AD susceptibility was found among Asian population in allele model (T versus C: OR = 0.786, 95% CI = 0.635–0.974, P = 0.028) and dominant model (TT + CT versus CC: OR = 0.800, 95% CI = 0.647–0.990, P = 0.040). Moreover, T allele of LRP1 C766T was statistically associated with late onset of AD (LOAD) (T versus C: OR = 0.858, 95% CI = 0.748–0.985, P = 0.029; TT + CT versus CC: OR = 0.871, 95% CI = 0.763–0.994, P = 0.040). In conclusion, our meta-analysis suggested that LRP1 C766T polymorphism was associated with lower risk of AD in Asian, and could reduce LOAD risk especially. Considering some limitations of our meta-analysis, further large-scale studies should be done to reach a more comprehensive understanding.

Abstract In recent years shape-memory polymers have been under intense investigation due to their unique mechanical, thermal, and electrical properties that could potentially make them extremely valuable in numerous engineering applications. In this manuscript, we report a polymer-template-assisted assembly manufacturing strategy used to fabricate graphite/silver nanowires/epoxy resin (PGSE) composite. In the proposed method, the porous polymer foams work as the skeleton by forming three-dimensional graphite structure, whereas the silver nanowires act as the continuous conductive network. Preliminary testing on hybrid foams after vacuum infusion showed high electrical conductivity and excellent thermal stability. Furthermore, the composites were found to recover their original shape within 60 seconds from the application of a 0.8 V mm−1 electric field. Notably, the reported shape-memory polymer composites are manufactured with readily-available raw materials, they are fast to manufacture, and are shape-controlled.

Abstract The lymph node ratio(LNR) has been described as a novel predictor of the survival of patients with oral and oropharyngeal squamous cell carcinoma(O/OPSCC). The purpose of this study was to evaluate whether LNR is better at predicting survival and the need for adjuvant treatment than traditional tumour-nodal-metastasis(TNM) staging. Eight hundred nine patients with O/OPSCC and positive lymph node disease were retrospectively enrolled in this study. LNR equal to 0.075 is the best cut-off value for stratifying 5-year disease-free survival(DFS). High LNR is closely associated with more advanced T stage, higher N stage, more severe pathological grade, the presence of diffuse infiltration and extracapsular spread(ECS). LNR is better for evaluating prognosis than the pathological N stage. Patients with high LNR coupled with high number of positive lymph nodes who received adjuvant concurrent chemo-radiotherapy(CCRT) had a better 5-year DFS than patients who received surgery alone. Multivariate analyses revealed that T stage, ECS and LNR are independent prognostic factors of 5-year DFS and disease-specific survival(DSS). Therefore, high LNR is closely correlated with adverse parameters that markedly hinder prognosis. LNR is superior to traditional TNM staging for the evaluation of prognosis,and the combination of the LNR with the number of positive lymph nodes can predict the benefits of adjuvant CCRT.

Abstract 2-hydroxy-1,4 naphthoquinone (lawsone) is widely used and induces environmental pollutions during its production and application. In the present study, a lawsone-degrading bacterium strain, LH-3 was successfully isolated from the activated sludge. Based on the 16S rRNA gene analysis, the strain LH-3 phylogenetically belonged to the Pseudomonas taiwanensis. It could degrade 200 mg L−1 lawsone completely in 9 h with an inoculum quantity of 1% (v/v). The effects of environmental conditions on the degradation process and the degradation pathway were systematically investigated. LH-3 could maintain its high degradation efficiency under high salt condition. The identified intermediates of salicylic acid, 2-hydroxy-4-oxo-chroman-2-carboxylic acid, and catechol elucidated the potential degradation pathway. Furthermore, the immobilized LH-3 strain cells prepared with alginate gel and biochar performed excellent stability in nine successive degradation runs. It could sucessfully survive in laboratory scale sequencing batch reactor and become to be the dominant species. This study clearly revealed that LH-3 could serve as an attractive candidate for the microbial remediation of lawsone-containing wastewater.

Abstract T-type calcium channels are intimately involved in the local anesthetics neurotoxicity. Does CaMKIIγ regulate T-type calcium currents in local anesthetics neurotoxicity? This study generated pAd-CaMKIIγ and pAd-shRNA adenovirus vectors to up- and down-regulate CaMKIIγ mRNA expression in dorsal root ganglion neurons (DRG). Normal DRG (Normal group), empty vector DRG (Empty vector group), pAd-CaMKIIγ DRG (pAd-CaMKIIγ group) and pAd-shRNA DRG (pAd-shRNA group) were treated or untreated with 3 mM ropivacaine hydrochloride for 4 h. Cell viability, apoptosis rate, CaMKIIγ, pCaMKIIγ, Cav3.2, and Cav3.3 expression were detected. Ultrastructural changes in DRG were observed under a transmission electron microscope. The results demonstrated that the cell viability of DRG treated with ropivacaine hydrochloride decreased markedly, the apoptosis rate, CaMKIIγ, pCaMKIIγ, Cav3.2, Cav3.3 expression increased significantly. CaMKIIγ up-regulation aggravated ropivacaine hydrochloride-induced cell damage and increased Cav3.2 and Cav3.3 expression. In conclusion, CaMKIIγ regulated Cav3.2 and Cav3.3 expression in DRG, which was involved with ropivacaine hydrochloride-induced cell injury.

Abstract The fast detection of terahertz radiation is of great importance for various applications such as fast imaging, high speed communications, and spectroscopy. Most commercial products capable of sensitively responding the terahertz radiation are thermal detectors, i.e., pyroelectric sensors and bolometers. This class of terahertz detectors is normally characterized by low modulation frequency (dozens or hundreds of Hz). Here we demonstrate the first fast semiconductor-based terahertz quantum well photodetectors by carefully designing the device structure and microwave transmission line for high frequency signal extraction. Modulation response bandwidth of gigahertz level is obtained. As an example, the 6.2-GHz modulated terahertz light emitted from a Fabry-Pérot terahertz quantum cascade laser is successfully detected using the fast terahertz quantum well photodetector. In addition to the fast terahertz detection, the technique presented in this work can also be used for optically characterizing the frequency stability of terahertz quantum cascade lasers, heterodyne detections and photomixing applications.

Abstract Cervical oesophageal cancer (CEC) is a relatively uncommon malignancy. The biological behaviour and treatment have not been well studied. This retrospective study reviewed the clinicopathological features of 28 patients with CEC who underwent surgical resection to investigate the biological behaviour, treatment and prognosis of CEC. The long-term outcomes of these patients were compared with those of the CEC patients who received definitive chemoradiotherapy and those of thoracic or abdominal oesophageal cancer patients who underwent surgery. The study group contained 21 men and 7 women, ranging in age from 41 to 67 years (median: 56.5 years). The median survival time and the 1-, 3-, and 5-year overall survival rates were 25.0 months, 83.8%, 48.8%, and 41.9%, respectively. Only salvage surgery was found to affect the overall survival (P = 0.007). The long-term outcomes for CEC patients who underwent surgery were significantly better than those who received definitive chemoradiotherapy (P = 0.045) but were similar to those of thoracic or abdominal oesophageal cancer patients. In summary, CEC is an uncommon and aggressive malignancy. The malignant potential of CEC is similar to that of thoracic or abdominal oesophageal cancer. Surgical resection is an important therapeutic strategy and may be associated with better survival rates than definitive chemoradiotherapy.

Abstract The aim of this study was to find an accurate method for the detection of extracapsular extension (ECE) in papillary thyroid carcinoma (PTC). A total of 102 patients with 109 PTC nodules were retrospectively enrolled. Contrast-enhanced ultrasound (CEUS) characteristics were evaluated. The diagnostic efficacy of quantitative CEUS and tumor size was analyzed. The qualitative CEUS features did not differ significantly between the ECE and non-ECE groups (P > 0.05). All of the quantitative CEUS parameters with the exception of peak intensity and tumor size were found to differ significantly between the ECE and non-ECE groups (P

Abstract Microorganism immobilization has attracted great attention as a traditional method to overcome aqueous organic wastes containing N, N-dimethylformamide (DMF). In this approach, graphene oxide was modified with functional polymer firstly to obtain micro-composites material (PGO), and then the prepared composites were deposited on the surface of copper mesh (CM) to block the meshes and CM@PGO was achieved. Moreover, cage-shaped model was designed based on CM@PGO and P. denitrificans was packed inside the cage for batch experiments. This strategy could enrich the local concentration of DMF due to the formation of hydrogen bonds with the oxygen-containing groups from PGO and the character of bacteria in captivity could also contribute to the process of degradation. Results showed that the approach could remove DMF more efficiently about 15% compared with free microorganism and presented excellent cycling performance. Meantime, physical adsorption and chemical adsorption were both contributed to the process of PGO adsorption, and the adsorption isotherm fits Langmuir model well, furthermore, the theoretical maximum of adsorption ability calculated through Langmuir model is 95 mg/g. In other words, this cage-shaped CM@PGO provided a facile platform for treating various wastewaters by altering the species of packed microorganisms, which exhibited considerable prospects for wastewater treatment.

Abstract A chitosan-based microsphere delivery system has been fabricated for controlled release of alendronate (AL). The present study aimed to incorporate the chitosan/hydroxyapatite microspheres-loaded with AL (CH/nHA-AL) into poly(L-lactic acid)/nanohydroxyapatite (PLLA/nHA) matrix to prepare a novel microspheres-scaffold hybrid system (CM-ALs) for drug delivery and bone tissue engineering application. The characteristics of CM-ALs scaffolds containing 10% and 20% CH/nHA-AL were evaluated in vitro, including surface morphology and porosity, mechanical properties, drug release, degradation, and osteogenic differentiation. The in vivo bone repair for large segmental radius defects (1.5 cm) in a rabbit model was evaluated by radiography and histology. In vitro study showed more sustained drug release of CM-AL-containing scaffolds than these of CM/nHA-AL and PLLA/nHA/AL scaffolds, and the mechanical and degradation properties of CM-ALs (10%) scaffolds were comparable to that of PLLA/nHA control. The osteogenic differentiation of adipose-derived stem cells (ASCs) was significantly enhanced as indicated by increased alkaline phosphates (ALP) activity and calcium deposition. In vivo study further showed better performance of CM-ALs (10%) scaffolds with complete repair of large-sized bone defects within 8 weeks. A microspheres-scaffold-based release system containing AL-encapsulated chitosan microspheres was successfully fabricated in this study. Our results suggested the promising application of CM-ALs (10%) scaffolds for drug delivery and bone tissue engineering.

Hypertrophic cardiomyopathy (HCM) may lead to cardiac dysfunction and sudden death. This study was designed to develop a HCM signature applying bioinformatics and machine learning methods. Data of HCM and normal tissues were obtained from public databases to screen differentially expressed genes (DEGs) using the R software limma package. The Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) were performed for enrichment analysis of HCM-associated DEGs. Hub genes for HCM were determined using weighted gene co-expression network analysis (WGCNA) together with two machine learning algorithms (SVM-RFE and LASSO). Finally, we introduced a zebrafish model to simulate changes in the hub genes in the HCM and to observe their effects on cardiac disease development. The mRNA expression data from a total of 106 HCM tissues and 39 normal samples were collected and we screened 157 DEGs. Enrichment analysis showed that immune pathways played an important role in the pathogenesis of HCM. Three hub genes (FCN3, MYH6 and RASD1) were identified using WGCNA, SVM-RFE, and LASSO analysis. In a zebrafish model, knockdown of MYH6 and RASD1 resulted in cardiac malformations with reduced ventricular capacity and heart rate, which validated the clinical significance of these genes in the diagnosis of HCM. Based on machine learning algorithms, our study created a signature with potential impact on cardiac function and cardiac quality index for HCM. The current findings had important implications for the early diagnosis and treatment of HCM., (© 2024. The Author(s).)

Mitotic catastrophe (MC) is a novel form of cell death that plays an important role in the treatment and drug resistance of colon adenocarcinoma (COAD). However, MC related genes in COAD treatment and prognosis evaluation are rarely studied. In this study, the transcriptome data, somatic mutation and copy number variation data were obtained from The Cancer Genome Atlas (TCGA) database. The mitotic catastrophe related genes (MCRGs) were obtained from GENCARDS website. Differential gene analysis was conducted with LIMMA package. Univariate Cox regression analysis was used to identify prognostic related genes. Mutation analysis was performed and displayed by maftools package. RCircos package was used for localizing the position of genes on chromosomes. "Glmnet" R package was applied for constructing a risk model via the LASSO regression method. Consensus clustering analyses was implemented for clustering different subtypes. Functional enrichment analysis through Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) methods, immune infiltration analysis via single sample gene set enrichment analysis (ssGSEA), tumor mutation burden and drug sensitivity analysis by pRRophetic R package were also carried out for risk model or molecular subtype's assessment. Additionally, the connections between the expression of hub genes and overall survival (OS) were obtained from online Human Protein Atlas (HPA) website. Real-Time Quantitative Polymerase Chain Reaction (RT‑qPCR) further validated the expression of hub genes. A total of 207 differentially expressed MCRGs were selected in the TCGA cohort, 23 of which were significantly associated with OS in COAD patients. Subsequently, we constructed risk score prognostic models with 5 hub MCRGs, including SYCE2, SERPINE1, TRIP6, LIMK1, and EEPD1. The high-risk patients suffered from poorer prognosis. Furthermore, we developed a nomogram that gathered age, sex, staging, and risk score to accurately forecast the clinical survival outcomes in 1, 3, and 5 years. The results of functional enrichment suggested a significant correlation between MCRGs characteristics and cancer progression, with important implications for the immune microenvironment. Moreover, patients who displayed high TMB and high risk score showed worse prognosis, and risk characteristics were associated with different chemotherapeutic agents. Finally, RT‑qPCR verified the increased expression of the five MCRGs in clinical samples. The five MCRGs in the prognostic signature were associated with prognosis, and could be treated as reliable prognostic biomarkers and therapeutic targets for COAD patients with distinct clinicopathological characteristics, thereby providing a foundation for the precise application of pertinent drugs in COAD patients., (© 2024. The Author(s).)

To investigate if a magnetic resonance imaging (MRI)-based model reduced postoperative biochemical failure (BF) incidence in patients with prostate cancer (PCa). From June 2018 to January 2020, we retrospectively analyzed 967 patients who underwent prostate bi-parametric MRI and radical prostatectomy (RP). After inclusion criteria were applied, 446 patients were randomized into research (n = 335) and validation cohorts (n = 111) at a 3:1 ratio. In addition to clinical variables, MRI models also included MRI parameters. The area under the curve (AUC) of receiver operating characteristic and decision curves were analyzed. The risk of postoperative BF, defined as persistently high or re-elevated prostate serum antigen (PSA) levels in patients with PCa with no clinical recurrence. In the research (age 69 [63-74] years) and validation cohorts (age 69 [64-74] years), the postoperative BF incidence was 22.39% and 27.02%, respectively. In the research cohort, the AUC of baseline and MRI models was 0.780 and 0.857, respectively, with a significant difference (P < 0.05). Validation cohort results were consistent (0.753 vs. 0.865, P < 0.05). At a 20% risk threshold, the false positive rate in the MRI model was lower when compared with the baseline model (31% [95% confidence interval (CI): 9-39%] vs. 44% [95% CI: 15-64%]), with the true positive rate only decreasing by a little (83% [95% CI: 63-94%] vs. 87% [95% CI: 75-100%]). 32 of 100 RPs can been performed, with no raise in quantity of patients with missed BF. We developed and verified a MRI-based model to predict BF incidence in patients after RP using preoperative clinical and MRI-related variables. This model could be used in clinical settings., (© 2023. The Author(s).)