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In order to study the effect of liquid nitrogen injection cooling on spontaneous combustion of coal, coal samples from the second and third panel areas of Tingnan Coal Mine were selected for thermal and physical property experiments. First, the coal sample was pretreated by LFA457 laser flash analyzer, and then the thermophysical property parameters of the coal sample were measured in the range of 30-300 ℃, and the change law of the thermophysical property parameters of the coal sample with temperature was obtained after liquid nitrogen injection and cooling, and the factors affecting the thermophysical properties of the coal sample were compared and analyzed. The results show that the thermal diffusivity decreases with the increase of temperature, and the specific heat capacity and thermal conductivity increase with the increase of temperature; in the range of 30-200 ℃, the average change rate of thermal property parameters of coal samples after liquid nitrogen injection treatment is higher than that of raw coal samples, indicating that liquid nitrogen injection treatment will increase the sensitivity of coal samples to temperature; in addition, at the same temperature, the thermal physical property parameters of coal samples after liquid nitrogen injection treatment increased to different degrees compared with the original coal samples, and the average growth rate of thermal diffusion coefficient was the highest, indicating that the thermal diffusion ability of coal samples after liquid nitrogen injection treatment was enhanced during the oxidation and heating process.

Objective: Patients with clear cell renal carcinoma (ccRCC) typically have poor prognosis. Glycosylation modification plays an important role in ccRCC. This study aimed to develop a novel signature for predicting ccRCC prognosis based on glycosylation-related genes (GRGs). Methods: Differentially expressed GRGs (DE_GRGs) were identified using The Cancer Genome Atlas (TCGA) and Gene Expression Omnibus and used for constructing the risk model. The function of key genes was validated. Results: Twenty-two DE_GRGs were intersected between GSE53757 and TCGA. Patients with ccRCC were divided into two clusters based on the expression profile of these DE_GRGs. Significant differences in the infiltration of 10 immune cell types were observed between two subclusters. Subsequently, the prognostic signatures of nine DE_GRGs (CHST9, COLGALT1, FUT3, FUT6, HS3ST2, POMGNT2, ST8SIA4, UGT3A1, and UGT8) were established. Patients in the high-risk group showed a poorer prognosis relative to the low-risk group. According to univariate and multivariate Cox regression analyses, the risk score, stage, and grade could be independent prognostic factors. A nomogram incorporating information on gender, age, risk group, TNM stage, and clinical stage showed accurate prediction in the survival probability. Except for CHST9, HS3ST2, and ST8SIA4, expression patterns of the remaining 6 DE_GRGs in Caki-1 and 786-O cells were confirmed by quantitative real-time PCR. FUT6 overexpression resulted in the inhibition of proliferation, migration, and invasion of ccRCC cells. Conclusion: This study established a nine-DE_GRG-based prognostic signature, which independently predicted ccRCC prognosis. This finding emphasizes that GRGs are stratification factors for the precise prognosis of ccRCC.

BackgroundT cell exhaustion is a state in which T cells become dysfunctional and is associated with a decreased efficacy of immune checkpoint inhibitors. Lung cancer has the highest mortality among all cancers. However, the roles of genetic variants of the T cell exhaustion-related genes in the prognosis of non-small cell lung cancer (NSCLC) patients has not been reported.MethodsWe conducted a two-stage multivariable Cox proportional hazards regression analysis with two previous genome-wide association study (GWAS) datasets to explore associations between genetic variants in the T cell exhaustion-related genes and survival of NSCLC patients. We also performed expression quantitative trait loci analysis for functional validation of the identified variants.ResultsOf all the 52,103 single nucleotide polymorphisms (SNPs) in 672 T cell exhaustion-related genes, 1,721 SNPs were found to be associated with overall survival (OS) of 1185 NSCLC patients of the discovery GWAS dataset from the Prostate, Lung, Colorectal and Ovarian (PLCO) Cancer Screening Trial, and 125 of these 1,721 SNPs remained significant after validation in an additional independent replication GWAS dataset of 984 patients from the Harvard Lung Cancer Susceptibility (HLCS) Study. In multivariable stepwise Cox model analysis, three independent SNPs (i.e., LRRC8C rs10493829 T>C, OAS2 rs2239193 A>G, and CCL25 rs3136651 T>A) remained significantly associated with OS with hazards ratios (HRs) of 0.86 (95% confidence interval (CI) = 0.77-0.96, P = 0.008), 1.48 (95% CI = 1.18-1.85, P < 0.0001) and 0.78 (95% CI = 0.66-0.91, P = 0.002), respectively. Further combined analysis for these three SNPs suggested that an unfavorable genotype score was associated with a poor OS and disease-specific survival. Expression quantitative trait loci analysis suggested that the LRRC8C rs10493829 C allele was associated with elevated LRRC8C mRNA expression levels in normal lymphoblastoid cells, lung tissue, and whole blood.ConclusionOur findings suggested that these functional SNPs in the T cell exhaustion-related genes may be prognostic predictors for survival of NSCLC patients, possibly via a mechanism of modulating corresponding gene expression.

Abstract Chemokines, cytokines, and inflammatory cells mediate the onset and progression of many diseases through the induction of an inflammatory response. LncRNAs have emerged as important regulators of gene expression and signaling pathways. Increasing evidence suggests that lncRNAs are key players in the inflammatory response, making it a potential therapeutic target for various diseases. From the perspective of lncRNAs and inflammatory factors, we summarized the expression level and regulatory mechanisms of lncRNAs in human inflammatory diseases, such as cardiovascular disease, osteoarthritis, sepsis, chronic obstructive pulmonary disease, asthma, acute lung injury, diabetic retinopathy, and Parkinson’s disease. We also summarized the functions of lncRNAs in the macrophages polarization and discussed the potential applications of lncRNAs in human inflammatory diseases. Although our understanding of lncRNAs is still in its infancy, these data will provide a theoretical basis for the clinical application of lncRNAs.

Abstract Background Postoperative acute kidney injury (AKI) is a common and costly complication after non-cardiac surgery. Patients with or without diabetes could develop hyperglycemia before surgery, and preoperative hyperglycemia was closely associated with postoperative poor outcomes, but the association between preoperative fasting blood glucose level and postoperative AKI is still unclear. Methods Data from patients undergoing non-cardiac surgery in Chongqing University Cancer Hospital from January 1, 2017, to May 31, 2023, were collected, preoperative glucose value and perioperative variables were extracted, the primary exposure of interest was preoperative glucose value, and the outcome was postoperative AKI. Results Data from 39,986 patients were included in the final analysis, 741(1.9%) patients developed AKI, 134(5.6%) in the cohort with DM, and 607(1.6%) in the cohort without DM(OR 1.312, 95% CI 1.028–1.675, P = 0.029). A significant non-linear association between preoperative glucose and AKI exists in the cohort without DM after covariable adjustment (P = 0.000), and every 1 mmol/L increment of preoperative glucose level increased OR by 15% (adjusted OR 1.150, 95% CI 1.078–1.227, P = 0.000), the optimal cut-point of preoperative fasting glucose level to predict AKI was 5.39 mmol/L (adjusted OR 1.802, 95%CI 1.513–2.146, P = 0.000). However, in the cohort with DM, the relation between preoperative glucose and postoperative AKI was not significant after adjusting by covariables (P = 0.437). No significance exists between both cohorts in the risk of AKI over the range of preoperative glucose values. Conclusion A preoperative fasting glucose value of 5.39 mmol/L can predict postoperative acute kidney injury after non-cardiac surgery in patients without diagnosed diabetes, but it is not related to AKI in patients with the diagnosis.

Abstract The neural circuits underlying sleep-wakefulness and general anesthesia have not been fully investigated. The GABAergic neurons in the bed nucleus of the stria terminalis (BNST) play a critical role in stress and fear that relied on heightened arousal. Nevertheless, it remains unclear whether BNST GABAergic neurons are involved in the regulation of sleep-wakefulness and anesthesia. Here, using in vivo fiber photometry combined with electroencephalography, electromyography, and video recordings, we found that BNST GABAergic neurons exhibited arousal-state-dependent alterations, with high activities in both wakefulness and rapid-eye movement sleep, but suppressed during anesthesia. Optogenetic activation of these neurons could initiate and maintain wakefulness, and even induce arousal from anesthesia. However, chronic lesion of BNST GABAergic neurons altered spontaneous sleep-wakefulness architecture during the dark phase, but not induction and emergence from anesthesia. Furthermore, we also discovered that the BNST-ventral tegmental area pathway might participate in promoting wakefulness and reanimation from steady-state anesthesia. Collectively, our study explores new elements in neural circuit mechanisms underlying sleep-wakefulness and anesthesia, which may contribute to a more comprehensive understanding of consciousness and the development of innovative anesthetics.

Abstract Background Hypoxia is often involved in tumor microenvironment, and the hypoxia‐induced signaling pathways play a key role in aggressive cancer phenotypes, including angiogenesis, immune evasion, and therapy resistance. However, it is unknown what role genetic variants in the hypoxia‐related genes play in survival of patients with non‐small cell lung cancer (NSCLC). Methods We evaluated the associations between 16,092 single‐nucleotide polymorphisms (SNPs) in 182 hypoxia‐related genes and survival outcomes of NSCLC patients. Data from the Prostate, Lung, Colorectal, and Ovarian (PLCO) Cancer Screening Trial were used as the discovery dataset, and the Harvard Lung Cancer Susceptibility (HLCS) Study served as the replication dataset. We also performed additional linkage disequilibrium analysis and a stepwise multivariable Cox proportional hazards regression analysis in the PLCO dataset. Results An independent SNP, ERRFI1 rs28624 A > C, was identified with an adjusted hazards ratio (HR) of 1.31 (95% CI = 1.14–1.51, p = 0.0001) for overall survival (OS). In further analyses, unfavorable genotypes AC and CC, compared with the AA genotype, were associated a worse OS (HR = 1.20, 95% CI = 1.03–1.39, p = 0.014) and disease‐specific survival (HR = 1.21, 95% CI = 1.04–1.42, p = 0.016). Further expression quantitative trait loci analysis indicated that ERRFI1 rs28624C genotypes were significantly associated with higher ERRFI1 mRNA expression levels in the whole blood. Additional analysis showed that high ERRFI1 mRNA expression levels were associated with a worse OS in patients with lung adenocarcinoma. Conclusion Our findings suggest that genetic variants in the hypoxia‐related gene ERRFI1 may modulate NSCLC survival, potentially through their effect on the gene expression.

B cells are adaptive immune cells in the tumor microenvironment and play an important role in tumor development and metastasis. However, the roles of genetic variants of the immunity B cell-related genes in the survival of patients with non-small cell lung cancer (NSCLC) remain unknown. In the present study, we first evaluated associations between 10,776 single nucleotide polymorphisms (SNPs) in 220 immunity B cell-related genes and survival of NSCLC in a discovery dataset of 1,185 patients from the Prostate, Lung, Colorectal and Ovarian (PLCO) Cancer Screening Trial. We found that 369 SNPs were significantly associated with overall survival (OS) of NSCLC in multivariable Cox proportional hazards regression analysis (P ≤ 0.05, Bayesian false discovery probability ≤ 0.80), of which 18 SNPs were validated in another independent genotyping dataset of 984 patients from the Harvard Lung Cancer Susceptibility (HLCS) Study. We then performed linkage disequilibrium (LD) analysis, followed by stepwise analysis with a multivariable Cox regression model. Finally, two independent SNPs, inositol polyphosphate-5-phosphatase D (INPP5D) rs13385922 C>T and exosome component 3 (EXOSC3) rs3208406 A>G, remained significantly associated withNSCLC OS with a combined hazards ratio (HR) of 1.14 (95% confidence interval = 1.06-1.23, P = 2.41×10-4) and 1.20 (95% confidence interval = 1.14-1.28, P = 3.41×10-9), respectively. Furthermore, NSCLC patients with the combination of unfavorable genotypes for these two SNPs were associated with a poor OS (Ptrend = 0.0002) and disease-specific survival (DSS, Ptrend < 0.0001) in the PLCO dataset. Expression quantitative trait loci (eQTL) analysis suggested that the INPP5D rs6782875 T allele was significantly correlated with elevated INPP5D mRNA expression levels in normal lung tissues and whole blood samples, while the EXOSC3 rs3208406 G allele was significantly correlated with increased EXOSC3 mRNA expression levels in normal lung tissues. Our data indicated that genetic variants in these immunity B cell-related genes may predict NSCLC survival possibly by influencing the gene expression.

Background: To compare the efficacy of Three-scope combined (laparoscopic, rigid choledochoscopy and electronic choledochoscopy, TS) with laparoscopic hepatectomy (LH) for patients with hepatolithiasis (HL). Methods: Between January 2019 and January 2020, 118 consecutive patients with HL treated with TS (TS group, n = 57) or LH (LH group, n = 61) were analyzed in this study. Perioperative and long-term outcomes, including operative time, intraoperative blood loss, blood transfusion, postoperative bowel function recovery time, postoperative hospital stay, complication rate, stone removal rate, and stone recurrence rate, were compared and analyzed between the two groups. Results: Compared with the LH group, the TS group had significantly lower intraoperative blood loss and transfusions, significantly shorter operative time and hospital stay, and fewer complications (P 0.05 for all). Conclusion: TS is a safe and effective treatment for HL and is superior to LH in terms of overall treatment outcome and complications.

Abstract Background The COVID-19 pandemic is a persistent global threat to public health. As for the emerging variants of SARS-CoV-2, it is necessary to develop vaccines that can induce broader immune responses, particularly vaccines with weak cellular immunity. Methods In this study, we generated a double-layered N-S1 protein nanoparticle (N-S1 PNp) that was formed by desolvating N protein into a protein nanoparticle as the core and crosslinking S1 protein onto the core surface against SARS-CoV-2. Results Vaccination with N-S1 PNp elicited robust humoral and vigorous cellular immune responses specific to SARS-CoV-2 in mice. Compared to soluble protein groups, the N-S1 PNp induced a higher level of humoral response, as evidenced by the ability of S1-specific antibodies to block hACE2 receptor binding and neutralize pseudovirus. Critically, N-S1 PNp induced Th1-biased, long-lasting, and cross-neutralizing antibodies, which neutralized the variants of SARS-CoV-2 with minimal loss of activity. N-S1 PNp induced strong responses of CD4+ and CD8+ T cells, mDCs, Tfh cells, and GCs B cells in spleens. Conclusions These results demonstrate that N-S1 PNp vaccination is a practical approach for promoting protection, which has the potential to counteract the waning immune responses against SARS-CoV-2 variants and confer broad efficacy against future new variants. This study provides a new idea for the design of next-generation SARS-CoV-2 vaccines based on the B and T cells response coordination. Graphical Abstract Steps involved in the preparation of double-layered N-S1 protein nanoparticle vaccines and experimental design performed in combating virus infection. After intramuscular immunization of mice, the double-layered N-S1 protein nanovaccine could effectively promote the maturation of antigen-presenting and mature dendritic cells, robust broad-spectrum neutralizing antibody production, cytokines secretion, robust mDC, Tfh cell, and GCs B cell responses induction, T-cell memory formation and durable antibody responses, and unique global transcriptome characteristics, thus achieving a robust cellular immunity and broad antibody responses against SARS-CoV-2 based on the B and T cells response coordination

Abstract Background Continuous cropping challenges constrain the development of agriculture. Three main obstacles limit continuous cropping: autotoxicity of plant allelochemicals, deterioration of physicochemical characteristics of soil, and microflora imbalance. Plant-derived phenolic acids can cause autotoxicity, which is considered the main factor mediating continuous cropping obstacles. Reducing the phenolic acids in continuous cropping soils can decrease the autotoxicity of phenolic acids and ameliorate continuous cropping obstacles. Therefore, it is important to study the microbial resources that degrade allelochemical phenolic acids. Thus, the bacterial strain V4 that can degrade phenolic acids was isolated, identified, and genomically analyzed. Results Strain V4 isolated from strawberry soil using vanillic acid-mineral agar was identified as a Gram-negative short rod bacterium. Subsequent 16S rRNA phylogenetic analysis revealed that V4 clustered with members of the genus Sphingobium. The most closely related species were Sphingobium lactosutens DS20T (99% similarity) and Sphingobium abikonense NBRC 16140T (97.5% similarity). V4 also shared > 95% sequence similarity with other members of Sphingobium, so Sphingobium sp. V4 was named accordingly. Biochemical tests revealed that the biochemical characteristics of Sphingobium sp. V4 were similar to its most similar strains except for some properties. Sphingobium sp. V4 effectively degraded vanillic acid, ferulic acid, p-coumaric acid, p-hydroxybenzoic acid, and syringic acid. V4 grew best at the conditions of 30 °C, pH 6.0–7.0, and 0–0.05% NaCl. 500 mg/L vanillic acid was completely degraded by V4 within 24 h under the optimal conditions. Whole genome analysis showed that Sphingobium sp. V4 contained one chromosome and three plasmids. Two genes involved in vanillic acid degradation were found in the V4 genome: the gene encoding vanillate O-demethylase oxidoreductase VanB on the chromosome and the gene encoding vanillate monooxygenase on a large plasmid. The organization of vanillate catabolic genes differed from the adjacent organization of the genes, encoding vanillate o-demethylase VanA and VanB subunits, in Pseudomonas and Acinetobacter. Conclusions The isolated bacterium Sphingobium sp. V4 degraded multiple phenolic acids. Its properties and genome were further analyzed. The study provides support for further investigation and application of this phenolic acid-degrading microorganism to alleviate continuous cropping obstacles in agriculture.

In this paper, the effect of Ce addition on high temperature oxidation behavior of hot-formed steel was studied by high temperature oxidation experiment. The structure and phase composition of surface oxide layer of specimens with different Ce content were systematically analyzed by SEM, EDS, XPS. The results showed that the addition of Ce promoted the formation of a dense oxide layer during the initial oxidation stage, and effectively weaken the oxidation degree of the steel surface. Meanwhile, the Ce2O3 particles segregation in Si–Cr rich phase reduced the concentration of vacancy defects in oxide layer and enhanced the adhesion between oxide layer and substrate. After Ce addition, the surface oxidation resistance of hot-formed steel is significantly improved.

In order to study the characteristics of low-temperature oxidation of weakly viscous coal under different gas concentration conditions inside the mining area and the change law of kinetic parameters, this paper adopts the coal spontaneous combustion temperature programming experimental system to test and analyze the change law of gaseous products with temperature during the low-temperature oxidation of weakly viscous coal under different gas concentration conditions, and calculate the limit parameters and activation energy during the low-temperature oxidation of weakly viscous coal. The results show that: CO gas can be used as the main predictor gas for spontaneous combustion prevention and control of weakly viscous coal, and C2H4 gas and R2 can be used as auxiliary indicators for predicting the degree of spontaneous combustion of weakly viscous coal; the maximum limit parameters of methane samples with different gas concentration conditions are distributed in the temperature range of 60-85 ℃, which is similar to the critical temperature of spontaneous combustion of coal. With the methane volume fraction increasing from 0 to 4%, the apparent activation energy of weak sticky coal shows a gradual increasing trend, increasing by 35.061, 18.426 and 25.837 kJ/mol, respectively.

An advanced stability analysis of surrounding rock can assure safe construction in tunnels. However, in traditional analysis methods, geometric information on the rock mass discontinuities is obtained by a geological compass and treated as an infinitely expanded plane in a numerical simulation, which is inaccurate in both geometric and numerical models. To solve this problem, this paper studied a control network and an image stitch method to assess the accuracy of a geometric model and proposed a more accurate method to obtain the geometric information of rock mass discontinuities based on digital photogrammetry. Based on discrete fracture network and discrete element method (DFN-DEM), this paper treated the rock mass discontinuities obtained by digital photogrammetry as finite disk planes and simulated the excavation process of the Qianyu tunnel. According to the simulation results, this paper determined the specific location of the collapse disaster on the tunnel face, which is of great significance to tunnel support design. Comparing the deformation of the surrounding rock mass on the tunnel face in the simulation results with the actual situation, this paper verified the feasible accuracy of this method in analysing the stability of the surrounding rock mass on a tunnel face in advance.

BackgroundPatients undergoing gastrointestinal surgery often experience hypotension following general anesthesia induction due to insufficient volume. This study aimed to assess whether pre-rehydration guided by carotid corrected flow time (FTc) could mitigate post-induction hypotension induced by general anesthesia.MethodsPatients undergoing resection of gastrointestinal tumors were assigned to either the conventional treatment group (Group C) or the fluid treatment group based on FTc (Group F). Within Group F, patients were further divided into Group A (carotid FTc

As a traditional Chinese medicinal herb with a long history, Codonopsis pilosula (CP) has attracted much attention from the medical community in recent years. This review summarizes the research progress of CP in the medical field in the past 5 years. By searching and analyzing the literature, and combining with Cytoscape software, we comprehensively examined the role and mechanism of action of CP in individual application, combination drug application, and the role and mechanism of action of codonopsis pilosula’s active ingredients in a variety of diseases. It also analyzes the medicinal use of CP and its application value in medicine. This review found that CP mainly manifests important roles in several diseases, such as cardiovascular system, nervous system, digestive system, immune system, etc., and regulates the development of many diseases mainly through the mechanisms of inflammation regulation, oxidative stress, immunomodulation and apoptosis. Its rich pharmacological activities and diverse medicinal effects endow CP with broad prospects and application values. This review provides valuable reference and guidance for the further development of CP in traditional Chinese medicine.

IntroductionPseudorabies (PR) is a multi-animal comorbid disease caused by pseudorabies virus (PRV), which are naturally found in pigs. At the end of 2011, the emergence of PRV variant strains in many provinces in China had caused huge economic losses to pig farms. Rapid detection diagnosis of pigs infected with the PRV variant helps prevent outbreaks of PR. The immunochromatography test strip with colloidal gold nanoparticles is often used in clinical testing due to its low cost and high throughput.MethodsThis study was designed to produce monoclonal antibodies targeting PRV through immunization of mice using the eukaryotic system to express the gE glycoprotein. Subsequently, paired monoclonal antibodies were screened based on their sensitivity and specificity for use in the preparation of test strips.Results and discussionThe strip prepared in this study was highly specific, only PRV was detected, and there was no cross-reactivity with glycoprotein gB, glycoprotein gC, glycoprotein gD, and glycoprotein gE of herpes simplex virus and varicellazoster virus, porcine epidemic diarrhea virus, Senecavirus A, classical swine fever virus, porcine reproductive and respiratory syndrome virus, and porcine parvovirus. Moreover, it demonstrated high sensitivity with a detection limit of 1.336 × 103 copies/μL (the number of viral genome copies per microliter); the coincidence rate with the RT-PCR detection method was 96.4%. The strip developed by our laboratory provides an effective method for monitoring PRV infection and controlling of PR vaccine quality.

Introduction:Head and neck cancer is one of the most common tumors worldwide. However, drug resistance in its treatment has become a major factor limiting the efficacy. This study aims to comprehensively understand the current status of research in this field.Methods:The study analyzes papers related to therapeutic resistance in head and neck cancer published between 2000 and 2023 in the Web of Science Core Collection To achieve the research objectives, we searched the WoSCC for research and review papers on therapeutic resistance in head and neck cancer from 2000 to 2023, screened the English literature, and analyzed the research hotspots, academic collaborations, and trends in detail using tools such as Citespace, SCImago Graphica, and VOS viewer.Results:This study summarizes 787 head and neck cancer treatment resistance publications from WoSCC. The analysis showed that China and the United States are the major contributors in this field, and Grandis Jennifer R and Yang Jai-Sing are the key scholars. Keyword analysis showed that “cisplatin resistance” is a continuing focus of attention, while “Metastasis” and “Ferroptosis” may be emerging research hotspots. Literature clustering analysis pointed out that “Ferroptosis”, “Immunotherapy” and “ERK signaling” were the recent hotspots that received extensive attention and citations. Finally, we discuss the current status and challenges in drug-resistant therapies for head and neck cancer.Conclusion:This study is the first comprehensive bibliometric analysis of drug resistance in head and neck cancer. Reveals current trends and helps researchers grasp cutting-edge hotspots in the field.

BackgroundThe aim of this study was to evaluate the ability of point-of-care Doppler ultrasound measurements of carotid corrected flow time and its changes induced by volume expansion to predict fluid responsiveness in patients undergoing robot-assisted gynecological surgery.MethodsIn this prospective study, carotid corrected flow time was measured using Doppler images of the common carotid artery before and after volume expansion. The stroke volume index at each time point was recorded using noninvasive cardiac output monitoring with MostCare. Of the 52 patients enrolled, 26 responded.ResultsThe areas under the receiver operating characteristic curves of the carotid corrected flow time and changes in carotid corrected flow time induced by volume expansion were 0.82 and 0.67, respectively. Their optimal cut-off values were 357 and 19.5 ms, respectively.ConclusionCarotid corrected flow time was superior to changes in carotid corrected flow time induced by volume expansion for predicting fluid responsiveness in this population.

Abstract Introduction The global low survival rate among ovarian cancer patients has resulted in significant social and economic burdens. Nevertheless, previous studies have produced mixed results when exploring the link between anesthetic techniques and the prognosis of ovarian cancer. The study aims to compare the effect of epidural anesthesia with general anesthesia on survival time after cytoreductive surgery in patients with ovarian cancer. Methods The PubMed (National Library of Medicine), Cochrane library, Web of science, Embase, CNKI (China National Knowledge Internet), Wanfang Med Online (China database), were systematically searched from inception to May, 2023, using the Medical Subject Headings [MeSH] of “Ovarian Neoplasm” and “Anesthesia, Epidural” and free words to identify systematic reviews or meta-analyses. The research methodology involved analyzing randomized controlled trials (RCTs), as well as prospective or retrospective cohort studies, which compared the long-term prognosis of patients with ovarian cancer under general anesthesia combined with epidural anesthesia (GEA) versus general anesthesia alone (GA). The Newcastle Ottawa Scale (NOS) was used to assess methodological quality and bias. Data extraction and assessment of study quality were conducted by two independent reviewers. A meta-analysis was then performed to calculate hazard ratios (HRs) and corresponding 95% confidence intervals (CIs). Overall survival (OS) was defined as the primary outcome, time to tumor recurrence (TTR) was the secondary outcome. Epidural anesthesia could be used intraoperatively and immediately postoperatively (EIP), or postoperatively only (EP). GEA includes EIP and EP. Results In total, 8 retrospective cohort studies with 2036 participants met the inclusion criteria. The pooled results demonstrated that GEA could extend OS (HR 0.75, 95% CI 0.67–0.84, I2 = 0%, P 0.05. 1-10 mm tumor residuals shorten TTR compared with 0 residuals, HR 1.75, 95% CI1.50–2.04, I2 = 0%, fixed-effect model, P

Abstract In order to study the mining pressure characteristics of the shallow buried coal seam with the same silo working face under the very close mining void zone and the overlying coal rock body, the theoretical analysis is used to determine whether the open-cutting eye bearing layer belongs to the mining under the very close mining void zone or not, based on the numerical simulation of FLAC3D and on-site measurement of the working resistance at the end of the cycle of the working face's hydraulic bracket, It is proposed to divide the mining stress of the working face based on the advancing length of the working face, that is, the high-pressure zone, the transition zone and the low-pressure zone. The results of the study show that: FLAC3D software was used to analyze the stress intensity of the “C” island working face when it was mined back to 50 m, 100 m, 150 m, and 180 m (one time “square”), and the simulation results were imported into the Origin software, which was used to analyze the stress intensity of the working face. The simulation results were imported into Origin software, and the influence range of mining stress was divided into four areas: high-stress area, stress transition area, low-stress area, and "square" stress concentration area. According to the on-site measurement of the working resistance at the end of hydraulic support cycle, the initial pressure step of the working face under the overlying coal rock body is 48.9–55.7 m, with the peak value of 38 MPa, the cycle pressure step is 9.0–23.3 m, with the peak value of 36 MPa, and the dynamic load factor of the working face is 1.14–1.16; relative to the overlying coal rock body, the average decrease of the cycle pressure step is nearly 10% and the average increase of dynamic load factor is 1.14–1.16; compared with that under the overlying coal rock body, the average decrease of the cycle pressure step is nearly 10% and the average increase of dynamic load factor is 1.14–1.16. Compared with the overlying coal rock body, the average decrease of the cycle pressure step under the overlying mining zone is nearly 10%, the average increase of the dynamic load factor is 20%, and there is no obvious regularity and periodicity in the direction of strike, and the working face is divided into three parts along the direction of strike: high-pressure zone, transition zone, and low-pressure zone. Therefore, in the process of mining under the overlying coal rock body, we should strengthen the roadway peripheral rock support and roof and floor management, which is of guiding significance to the mining of similar working faces and mine safety production.

In order to face the challenges of lightweight, safety, and emission reduction in the automotive industry, transformation-induced plasticity aided bainitic ferrite (TBF) steel was fabricated by controlling the size and shape of bainitic ferrite and compared with quenching and partitioning (Q&P) steels. The effects of bainite transformation on the mechanical properties, microvoid formation, and crack propagation were analyzed by dilatometry measurement and microstructure characterization. At lower isothermal bainite transformation (IBT) temperature, the lathy bainitic matrix can prevent crack formation and limit the crack propagation inside its laths, in favor of improving the strength and stretch flangeability simultaneously. In addition, granular bainite, coarse martensite, and austenite (M-A) islands would increase the risk of void formation at higher IBT temperatures. These voids provided the initial sites for crack formation, which was also responsible for the reduction of the hole expansion ratio (HER). In conclusion, the outstanding properties were achieved in the T-375 samples with the HER of 33.5%, the total elongation of 16.9%, the tensile strength of 1191 MPa, and the yield strength of 934 MPa.

Circular RNAs (circRNAs) are a special class of single-stranded RNA molecules with covalently closed loops widely expressed in eukaryotic organisms. CircRNAs have long been considered to play important roles in various physiological and pathological processes as non-coding RNAs. However, circRNAs have recently garnered considerable attention due to their ability to be translated into peptides/proteins via internal ribosome entry site- or N6-methyladenosine-mediated pathways or rolling translation mechanisms. Furthermore, dysregulation of translatable circRNAs and their encoded proteins has been associated with developing and progressing diseases such as cancer. This review aims to summarize the driving mechanisms of circRNA translation and the available strategies in circRNA translation research. The main focus is on the emerging biological functions of translatable circRNAs, their regulatory mechanisms, and potential clinical applications in human diseases to provide new perspectives on disease diagnosis, prognosis, and targeted therapy.

Iodine and fluorine, as halogen elements, are often coexisting in water environments, with nearly 200 million people suffering from fluorosis globally, and, in 11 countries and territories, adolescents have iodine intakes higher than that required for the prevention of iodine deficiency disorders. It has been suggested that excess iodine and/or fluorine can affect thyroid health and intellectual development, especially in children, but their combined effect has been less studied in this population. This study investigated 399 school-age children in Tianjin, China, collected drinking water samples from areas where the school-age children lived, and grouped the respondents according to iodine and fluorine levels. Thyroid health was measured using thyroid hormone levels, thyroid volume, and the presence of thyroid nodules; intelligence quotient (IQ) was assessed using the Raven’s Progressive Matrices (CRT) test; and monoamine neurotransmitter levels were used to explore the potential relationship between thyroid health and intelligence. Multiple linear regression and restricted cubic spline (RCS) analyses showed that iodine and fluorine were positively correlated with thyroid volume and the incidence of thyroid nodules in school-age children, and negatively correlated with IQ; similar results were obtained in the secondary subgroups based on urinary iodine and urinary fluoride levels. Interaction analyses revealed a synergistic effect of iodine and fluorine. A pathway analysis showed that iodine and fluorine were negatively associated with the secretion of free triiodothyronine (FT3) and free tetraiodothyronine (FT4), which in turn were negatively associated with the secretion of thyroid-stimulating hormone (TSH). Iodine and fluorine may affect IQ in school-aged children through the above pathways that affect thyroid hormone secretion; of these, FT3 and TSH were negatively correlated with IQ, whereas FT4 was positively correlated with IQ. The relationship between thyroid hormones and monoamine neurotransmitters may involve the hypothalamic–pituitary–thyroid axis, with FT4 hormone concentrations positively correlating with dopamine (DA), norepinephrine (NE), and 5-hydroxytryptophan (5-HT) concentrations, and FT3 hormone concentrations positively correlating with DA concentrations. Monoamine neurotransmitters may play a mediating role in the effects of iodine and fluoride on intelligence in schoolchildren. However, this study has some limitations, as the data were derived from a cross-sectional study in Tianjin, China, and no attention was paid to the reciprocal effects of iodine and fluorine at different doses on thyroid health and intelligence in schoolchildren in other regions.

The impressive adhesive capacity of marine mussels has inspired various fascinating designs in biomedical fields. Mussel-inspired injectable adhesive hydrogels, as a type of promising mussel-inspired material, have attracted much attention due to their minimally invasive property and desirable functions provided by mussel-inspired components. In recent decades, various mussel-inspired injectable adhesive hydrogels have been designed and widely applied in numerous biomedical fields. The rational incorporation of mussel-inspired catechol groups endows the injectable hydrogels with the potential to exhibit many properties, including tissue adhesiveness and self-healing, antimicrobial, and antioxidant capabilities, broadening the applications of injectable hydrogels in biomedical fields. In this review, we first give a brief introduction to the adhesion mechanism of mussels and the characteristics of injectable hydrogels. Further, the typical design strategies of mussel-inspired injectable adhesive hydrogels are summarized. The methodologies for integrating catechol groups into polymers and the crosslinking methods of mussel-inspired hydrogels are discussed in this section. In addition, we systematically overview recent mussel-inspired injectable adhesive hydrogels for biomedical applications, with a focus on how the unique properties of these hydrogels benefit their applications in these fields. The challenges and perspectives of mussel-inspired injectable hydrogels are discussed in the last section. This review may provide new inspiration for the design of novel bioinspired injectable hydrogels and facilitate their application in various biomedical fields.

Image detection technology is of paramount importance across various fields. This significance is not only seen in general images with everyday scenes but also holds substantial research value in the field of remote sensing. Remote sensing images involve capturing images from aircraft or satellites. These images typically feature diverse scenes, large image formats, and varying imaging heights, thus leading to numerous small-sized targets in the captured images. Accurately identifying these small targets, which may occupy only a few pixels, is a challenging and active research area. Current methods mainly fall into two categories: enhancing small target features by improving resolution and increasing the number of small targets to bolster training datasets. However, these approaches often fail to address the core distinguishing features of small targets in the original images, thus resulting in suboptimal performance in fine-grained classification tasks. To address this situation, we propose a new network structure DDU (Downsample Difference Upsample), which is based on differential and resolution changing methods in the Neck layer of deep learning networks to enhance the recognition features of small targets, thus further improving the feature richness of recognition and effectively solving the problem of low accuracy in small target object recognition. At the same time, in order to take into account the recognition effect of targets of other sizes in the image, a new attention mechanism called PNOC (protecting the number of channels) is proposed, which integrates small target features and universal object features without losing the number of channels, thereby increasing the accuracy of recognition. And experimental verification was conducted on the PASCAL-VOC dataset. At the same time, it was applied to the testing of the fine-grained MAR20 dataset and found that the performance was better than other classic algorithms. At the same time, because the proposed framework belongs to a one-stage detection method, it has good engineering applicability and scalability, and universality in scientific research applications are good. Through comparative experiments, it was found that our algorithm improved the performance of the mAP by 0.7% compared to the original YOLOv8 algorithm.

In this work, we use femtosecond laser direct writing to fabricate two kinds of modified structures with opposite refractive index changes to build new dual-line waveguide configurations in z-cut LiNbO3 (LN) crystals for the first time. These hybrid-structure waveguides, in which type-Ⅰ modifications are induced between two type-Ⅱ tracks have been investigated by an end-face coupling system at 532 nm. The results indicate that TEM00 mode is the only transmission mode for all waveguides. Comparing with the single-modification waveguides, experimental results indicate that the new waveguides in which type-Ⅱ tracks with 12 μm interval exhibit lower transmission losses (about 0.98 dB/cm). The reasons for these interesting guiding performances are analyzed by the confocal micro-Raman results. The beam quality is measured in both directions (x and y) and also in the visible (532 nm) and infrared (1064 nm) regions. This work provides a new perspective for improving the transmission efficiency of waveguides, which is the new hybrid structure in LN crystals. The new-waveguides design method has potential application in the field of photonic chips.

African swine fever (ASF) is a viral disease caused by the African swine fever virus that can be highly transmitted and lethal in domestic pigs. In the absence of a vaccine, effective diagnosis is critical for minimizing the virus’s spread. In recent years, with the decline of African swine fever virus (ASFV) virulence, antibody detection has become an important means of detection. ASFV nucleocapsid protein p34 is a mature hydrolytic product of pp220, which is highly conserved and has a high content in the structural protein of the virus. Prokaryotic cells were chosen to generate highly active and high-yield p34 protein, which was then used as an antigen for producing mouse monoclonal antibodies. The B-cell epitope 202QKELDKLQT210, which was highly conserved and found on the surface of the p34 protein, was first identified by an anti-p34 monoclonal antibody utilizing the peptide scanning technique and visualized in helix. This supported the viability of p34 protein detection even further. In addition, we established an indirect ELISA assay based on p34 to detect ASFV antibodies. The coincidence rate of this method with commercially available kits was shown to be 97.83%. Sensitivity analysis revealed that it could be detected in serum dilution as low as 1:6400, and there was no cross-reaction with other prevalent porcine epidemic diseases classical swine fever virus (CSFV), foot-and-mouth disease virus (FMDV), porcine reproductive and respiratory syndrome virus (PRRSV), and porcine circovirus 2 (PCV2). In summary, the established ELISA method and anti-P34 monoclonal antibody have demonstrated that the p34 protein has a promising application prospect for the detection of African swine fever antibodies.

Abstract Background Heme is an iron/porphyrin complex compound, widely used in the health care, food, and pharmaceutical industries. It is more advantageous and attractive to develop microbial cell factories to produce heme by fermentation, with lower production costs and environmentally more friendly procedures than those of the traditional extraction based on animal blood. In this study, Bacillus subtilis, a typical industrial model microorganism of food safety grade, was used for the first time as the host to synthesize heme. Results The heme biosynthetic pathway was engineered as four modules, the endogenous C5 pathway, the heterologous C4 pathway, the uroporphyrinogen (urogen) III synthesis pathway, and the downstream synthesis pathway. Knockout of hemX encoding the negative effector of the concentration of HemA, overexpression of hemA encoding glutamyl-tRNA reductase, and knockout of rocG encoding the major glutamate dehydrogenase in the C5 pathway, resulted in an increase of 427% in heme production. Introduction of the heterologous C4 pathway showed a negligible effect on heme biosynthesis. Overexpression of hemCDB, which encoded hydroxymethylbilane synthase, urogen III synthase, and porphobilinogen synthase participating in the urogen III synthesis pathway, increased heme production by 39%. Knockouts of uroporphyrinogen methyltransferase gene nasF and both heme monooxygenase genes hmoA and hmoB in the downstream synthesis pathway increased heme production by 52%. The engineered B. subtilis produced 248.26 ± 6.97 mg/L of total heme with 221.83 ± 4.71 mg/L of extracellular heme during the fed-batch fermentation in 10 L fermenter. Conclusions Strengthening endogenous C5 pathway, urogen III synthesis pathway and downstream synthesis pathway promoted the biosynthesis of heme in B. subtilis. The engineered B. subtilis strain has great potential as a microbial cell factory for efficient industrial heme production.

In clinical practice, tissue adhesives have emerged as an alternative tool for wound treatments due to their advantages in ease of use, rapid application, less pain, and minimal tissue damage. Since most tissue adhesives are designed for internal use or wound treatments, the biodegradation of adhesives is important. To endow tissue adhesives with biodegradability, in the past few decades, various biodegradable polymers, either natural polymers (such as chitosan, hyaluronic acid, gelatin, chondroitin sulfate, starch, sodium alginate, glucans, pectin, functional proteins, and peptides) or synthetic polymers (such as poly(lactic acid), polyurethanes, polycaprolactone, and poly(lactic-co-glycolic acid)), have been utilized to develop novel biodegradable tissue adhesives. Incorporated biodegradable polymers are degraded in vivo with time under specific conditions, leading to the destruction of the structure and the further degradation of tissue adhesives. In this review, we first summarize the strategies of utilizing biodegradable polymers to develop tissue adhesives. Furthermore, we provide a symmetric overview of the biodegradable polymers used for tissue adhesives, with a specific focus on the degradability and applications of these tissue adhesives. Additionally, the challenges and perspectives of biodegradable polymer-based tissue adhesives are discussed. We expect that this review can provide new inspirations for the design of novel biodegradable tissue adhesives for biomedical applications.

Rockfalls are an important factor affecting underground engineering safety. However, there has been limited progress in understanding and predicting these disasters in the past few years. Therefore, a large-scale three-dimensional experimental simulation apparatus to study failure mechanisms of rockfalls occurring during underground engineering was developed. This apparatus, measuring 4 m × 4 m × 3.3 m in size, can achieve vertical and horizontal symmetric loading. It not only simulates the structure and stress environment of a rock mass but also simulates the stepwise excavation processes involved in underground engineering. A complete simulation experiment of rockfalls in an underground engineering context was performed using this apparatus. Dynamic evolution characteristics of block displacement, temperature, natural vibration frequency, and acoustic emissions occurring during rockfalls were studied during the simulation. These data indicate there are several indicators that could be used to predict rockfalls in underground engineering contexts, leading to better prevention and control.

Introduction: Network pharmacology has emerged as a forefront and hotspot in anti-cancer. Traditional anti-cancer drugs are limited by the paradigm of “one cancer, one target, one drug,” making it difficult to address the challenges of recurrence and drug resistance. However, the main advantage of network pharmacology lies in its approach from the perspective of molecular network relationships, employing a “one arrow, multiple targets” strategy, which provides a novel pathway for developing anti-cancer drugs. This study employed a bibliometric analysis method to examine network pharmacology’s application and research progress in cancer treatment from January 2008 to May 2023. This research will contribute to revealing its forefront and hotspots, offering new insights and methodologies for future investigations.Methods: We conducted a literature search on network pharmacology research in anti-cancer (NPART) from January 2008 to May 2023, utilizing scientific databases such as Web of Science Core Collection (WoSCC) and PubMed to retrieve relevant research articles and reviews. Additionally, we employed visualization tools such as Citespace, SCImago Graphica, and VOSviewer to perform bibliometric analysis.Results: This study encompassed 3,018 articles, with 2,210 articles from WoSCC and 808 from PubMed. Firstly, an analysis of the annual national publication trends and citation counts indicated that China and the United States are the primary contributing countries in this field. Secondly, the recent keyword analysis revealed emerging research hotspots in “tumor microenvironment,” “anti-cancer drugs,” and “traditional Chinese medicine (TCM). “ Furthermore, the literature clustering analysis demonstrated that “calycosin,” “molecular mechanism,” “molecular docking,” and “anti-cancer agents” were widely recognized research hotspots and forefront areas in 2023, garnering significant attention and citations in this field. Ultimately, we analyzed the application of NPART and the challenges.Conclusion: This study represents the first comprehensive analysis paper based on bibliometric methods, aiming to investigate the forefront hotspots of network pharmacology in anti-cancer research. The findings of this study will facilitate researchers in swiftly comprehending the current research trends and forefront hotspots in the domain of network pharmacology in cancer research.

MicroRNAs (miRNAs) are a class of small non-coding RNAs that post-transcriptionally regulate the expression of approximately 50 % of all protein-coding genes. They have been demonstrated to act as key regulators in various pathophysiological processes and play significant roles in a wide range of human diseases, particularly cancer. Current research highlights the aberrant expression of microRNA-488 (miR-488) in multiple human diseases and its critical involvement in disease initiation and progression. Moreover, the expression level of miR-488 has been linked to clinicopathological features and patient prognosis across different diseases. However, a comprehensive systematic review of miR-488 is lacking. Therefore, our study aims to consolidate the current knowledge surrounding miR-488, with a primary focus on its emerging biological functions, regulatory mechanisms, and potential clinical applications in human diseases. Through this review, we aim to establish a comprehensive understanding of the diverse roles of miR-488 in the development of various diseases.

Spike (S) glycoprotein is the most significant structural protein of SARS-CoV-2 and a key target for neutralizing antibodies. In light of the on-going SARS-CoV-2 pandemic, identification and screening of epitopes of spike glycoproteins will provide vital progress in the development of sensitive and specific diagnostic tools. In the present study, NTD, RBD, and S2 genes were inserted into the pcDNA3.1(+) vector and designed with N-terminal 6× His-tag for fusion expression in HEK293F cells by transient transfection. Six monoclonal antibodies (4G, 9E, 4B, 7D, 8F, and 3D) were prepared using the expressed proteins by cell fusion technique. The characterization of mAbs was performed by indirect -ELISA, western blot, and IFA. We designed 49 overlapping synthesized peptides that cover the extracellular region of S protein in which 6 amino acid residues were offset between adjacent (S1–S49). Peptides S12, S19, and S49 were identified as the immunodominant epitope regions by the mAbs. These regions were further truncated and the peptides S12.2 286TDAVDCALDPLS297, S19.2 464FERDISTEIYQA475, and S49.4 1202ELGKYEQYIKWP1213 were identified as B- cell linear epitopes for the first time. Alanine scans showed that the D467, I468, E471, Q474, and A475 of the epitope S19.2 and K1205, Q1208, and Y1209 of the epitope S49.4 were the core sites involved in the mAbs binding. The multiple sequence alignment analysis showed that these three epitopes were highly conserved among the variants of concern (VOCs) and variants of interest (VOIs). Taken together, the findings provide a potential material for rapid diagnosis methods of COVID-19.

The stress state in a rock mass is complex. Stress redistribution around underground excavation may lead to various failure modes, including compressive-shear, tensile-shear, and tensile failures. The ability to perform laboratory tests with these complex stress states is significant for establishing new strength criteria. The present paper introduces a new rock testing system with “tensile-compressive-shear” loading functions. The device includes bi-directional and double-range hydraulic cylinders, auxiliary loading equipment, and roller rows that can perform direct compressive-shear tests, direct tensile tests, and direct tensile-shear tests. The testing system provides maximum vertical and lateral loading forces of 2000 kN and allows testing cubical rock specimens with dimensions of 0.5 m × 0.5 m × 0.5 m. The performance of the testing machine was evaluated by testing a rock-like material based on cement mortar under compressive-shear, tensile, and tensile-shear stress states. The failure process and deformation characteristics were monitored during loading using acoustic emission (AE) transient recorder, piezoelectric AE sensors, a high-speed camera, and a thermal infrared camera. The failure mechanism was investigated by analyzing AE counts, AE amplitude, strain, and temperature changes on the rock specimen surface. The test results confirmed that the testing system could successfully simulate the abovementioned stress path. The AE counts and amplitude responses were influenced by different failure modes. The temperature response during the compressive-shear test indicated the development of a high-temperature band on the rock specimen surface. In contrast, a negligible temperature change was observed during the tensile and tensile-shear tests. The newly developed multifunctional rock testing system allows laboratory tests under various failure modes. The monitoring results of multiple variables during rock failure tests provide valuable information on failure characteristics.

ABSTRACT Porcine circovirus type 2 (PCV2) is an important swine infectious pathogen that seriously threatens the global swine industry. PCV2 Cap protein is the only structural and the main immunogenic protein constituting the viral capsid. In this study, a gold nanoparticle-based immunochromatographic strip with high sensitivity and specificity was developed which could be used for rapid detection of PCV2 virions or Cap protein in research. The visual detection limit of the strip was 103.18 50% tissue culture infective does (TCID50)/mL for PCV2, and 2.03 μg/mL for PCV2 Cap protein. No cross-reactivity was observed with the PCV1 and PCV3 Cap proteins and other common swine pathogens such as porcine reproductive and respiratory syndrome virus, classical swine fever virus, pseudorabies virus, porcine epidemic diarrhea virus, porcine parvovirus, and swine influenza virus. The repeatability of the strip was good. The stability of the strip was perfect for 12 months in a dry state at room temperature. Visual results could be obtained within 5 min by simply inserting the strip into the diluted sample. The strip is a time-saving, labor-saving, and reliable tool for testing of PCV2 virions or Cap protein in research. The idea of this study might open a new perspective for the application of the strip. IMPORTANCE Porcine circovirus type 2 (PCV2) Cap protein is the only structural and the main immunogenic protein constituting the viral capsid. Although many methods can be used to identify PCV2 or PCV2 Cap protein in vaccine research, they usually require high workload and time. The developed strip can specifically detect PCV2 virions or Cap protein, and visual qualitative results can be obtained within 5 min by simply diluting the sample and inserting the strip into the sample. The final value of the strip is providing a simple and time-saving method for real-time monitoring of PCV2 antigen in vaccine research with reliable results, such as the different stages of PCV2 Cap protein expression and purification, as well as the different stages of PCV2 reproduction and purification.

Summary: Background: Lymphocyte telomere length (LTL)-related genetic variants may modulate LTL and affect recurrence of squamous cell carcinoma of the oropharynx (SCCOP). Methods: A total of 1013 patients with incident SCCOP were recruited and genotyped for 16 genome-wide association study (GWAS)-identified TL-related polymorphisms. Of these patients, 489 had tumour HPV16 status determination. Univariate and multivariate analyses were performed to evaluate associations. Findings: Of the 16 TL-related polymorphisms, four were significantly associated with LTL: rs1920116, rs3027234, rs6772228, and rs11125529, and the patients with putatively favourable genotypes had approximately 1.5–3 times the likelihood of shorter LTL compared with patients with the corresponding risk genotypes. Moreover, patients with one to four favourable genotypes of the four combined polymorphisms had approximately 3–11 times the likelihood of shorter LTL compared with patients with no favourable genotype. The four LTL-related polymorphisms were significantly associated with approximately 40% reduced risk (for favourable genotypes) or doubled risk (for risk genotypes) of recurrence, and similar but more pronounced associations were observed in patients with tumour HPV16-positive SCCOP. Similarly, patients with one to four risk genotypes had significantly approximately 2.5–4 times increased recurrence risk compared with patients with no risk genotype, and similar but more pronounced associations were observed in patients with tumour HPV16-positive SCCOP. Interpretation: Four LTL-related polymorphisms individually or jointly modify LTL and risk of recurrence of SCCOP, particularly HPV-positive SCCOP. These LTL-related polymorphisms could have potential to further stratify patients with HPV-positive SCCOP for individualized treatment and better survival. Funding: Not applicable.

This paper investigates the deterioration of, and the abnormal temperature rise in, the GFRP core rod material of compact V-string composite insulators subjected to prolonged alternating flexural loading under wind-induced stresses. The axial stress on the GFRP (Glass Fiber Reinforced Plastic) core rod, resulting from transverse wind loads, is a focal point of examination. By establishing a stress model and damage model, the paper simulates and computes the evolution of damage in the outer arc material of composite insulator core rods subjected to alternating flexural loads. Additionally, a multi-factor coupled aging platform is set up, integrating humidity, heat, and mechanical stress, to simulate the crazing deterioration process of composite insulators under alternating flexural loads. Experimental results reveal that during 400,000 alternating load cycles, the core rod underwent stages of surface damage, damage increasing, fatigue embrittlement, matrix hydrolysis, and fiber fracture. Simultaneously, the silicone rubber sheath on the outer side of the composite insulator’s bending arc develops cracks over aging time, creating pathways for moisture ingress into the interface and core rod. The dielectric constant and dielectric loss factor of the aging region of the core rod increase to varying degrees compared to the non-aging part. Moreover, the degree of abnormal heating of the samples intensifies with the duration of aging experiments. These findings underscore the significance of understanding the aging and decay-like fracture process of compact line V-string composite insulators. They provide crucial insights for future research aimed at enhancing the material properties of composite insulator core rods.

Abstract Background Perioperative neurocognitive disorders (PNDs) are considered the most common postoperative complication in geriatric patients. However, its pathogenesis is not fully understood. Surgery-triggered neuroinflammation is a major contributor to the development of PNDs. Neuroinflammation can influence N-methyl-D-aspartate receptor (NMDAR) expression or function which is closely associated with cognition. We, therefore, hypothesized that the persistent changes in NMDAR expression or function induced by transient neuroinflammation after surgery were involved in the development of PNDs. Methods Eighteen-month-old male Sprague–Dawley rats were subjected to abdominal surgery with sevoflurane anesthesia to establish the PNDs animal model. Then, we determined the transient neuroinflammation by detecting the protein levels of proinflammatory cytokines and microglia activation using ELISA, western blot, immunohistochemistry, and microglial morphological analysis from postoperative days 1–20. Persistent changes in NMDAR expression were determined by detecting the protein levels of NMDAR subunits from postoperative days 1–59. Subsequently, the dysfunction of synaptic NMDAR was evaluated by detecting the structural plasticity of dendritic spine using Golgi staining. Pull-down assay and western blot were used to detect the protein levels of Rac1-GTP, phosphor-cofilin, and Arp3, which contribute to the regulation of the structural plasticity of dendritic spine. Finally, glycyrrhizin, an anti-inflammatory agent, was administered to further explore the role of synaptic NMDAR dysfunction induced by transient neuroinflammation in the neuropathogenesis of PNDs. Results We showed that transient neuroinflammation induced by surgery caused sustained downregulation of synaptic NR2A and NR2B subunits in the dorsal hippocampus and led to a selective long-term spatial memory deficit. Meanwhile, the detrimental effect of neuroinflammation on the function of synaptic NMDARs was shown by the impaired structural plasticity of dendritic spines and decreased activity of the Rac1 signaling pathways during learning. Furthermore, anti-inflammatory treatment reversed the downregulation and hypofunction of synaptic NR2A and NR2B and subsequently rescued the long-term spatial memory deficit. Conclusions Our results identify sustained synaptic NR2A and NR2B downregulation and hypofunction induced by transient neuroinflammation following surgery as important contributors to the development of PNDs in elderly rats.

Abstract Limited efforts have been made in assessing the effect of genome-wide profiling of RNA splicing-related variation on lung cancer risk. In the present study, we first identified RNA splicing-related genetic variants linked to lung cancer in a genome-wide profiling analysis and then conducted a two-stage (discovery and replication) association study in populations of European ancestry. Discovery and validation were conducted sequentially with a total of 29,266 cases and 56,450 controls from both the Transdisciplinary Research in Cancer of the Lung and the International Lung Cancer Consortium as well as the OncoArray database. For those variants identified as significant in the two datasets, we further performed stratified analyses by smoking status and histological type and investigated their effects on gene expression and potential regulatory mechanisms. We identified three genetic variants significantly associated with lung cancer risk: rs329118 in JADE2 (P = 8.80E−09), rs2285521 in GGA2 (P = 4.43E−08), and rs198459 in MYRF (P = 1.60E−06). The combined effects of all three SNPs were more evident in lung squamous cell carcinomas (P = 1.81E−08, P = 6.21E−08, and P = 7.93E−04, respectively) than in lung adenocarcinomas and in ever smokers (P = 9.80E−05, P = 2.70E−04, and P = 2.90E−05, respectively) than in never smokers. Gene expression quantitative trait analysis suggested a role for the SNPs in regulating transcriptional expression of the corresponding target genes. In conclusion, we report that three RNA splicing-related genetic variants contribute to lung cancer susceptibility in European populations. However, additional validation is needed, and specific splicing mechanisms of the target genes underlying the observed associations also warrants further exploration.

Introduction: Understanding organic amendment and the agglomeration of bauxite residue particles is vital to soil amelioration of bauxite residues. In this study, a pot culture experiment was conducted to illustrate the aggregation of organic amendment on bauxite residues particles and its improvement mechanism. The single organic amendment and its combination with soil inoculum were conducted to explore the aggregation effect of organic matter on bauxite residue particles, and its correlations with microbial rehabilitation.Methods: The dry- and wet-sieving method were used to obtain different sizes of aggregates. The concentrations of soil organic carbon and iron and aluminum (Fe/Al) oxides in the forms extractable by DCB (Fed/Ald) and oxalate (Fe0/Al0) were measured. Microbial rehabilitation after 180 days incubation was determined with the methods of Biolog Ecoplate™ and the high-throughput sequencing.Results and Discussion: The results showed that over 180 days incubation, the alkalinity of bauxite residues was significantly decreased with the organic amendment based on the value of pH, EC and ESP (down to 9.26, 0.61 m/cm and 55.5%, respectively, in HS3). Secondly, organic amendment significantly promoted microbial community establishment and ecological function recovery. Moreover, the MWD value of aggregates also increased to 0.73 mm from the initial 0.32 mm, companied with the increase of the Fe/Al oxidizes. The further Pearson relationship analysis and the characterization of EPMA and SEM indicated that the organic matter and Fe/Al oxides played important roles in cementing fine bauxite residues particles and increasing aggregates stability, while this aggregation process was accelerated by the establishment of microbial ecology in bauxite residues. Therefore, organic amendment was more implication in soil amelioration of bauxite residues other than the directive modifications on alkalinity.

IntroductionSulfadiazine (SDZ) and copper (Cu) are frequently detected in agricultural soils, but little is known on their single or combined impact on ammonia oxidizing microbial community and function across different soils.MethodsIn this study, a microcosm was conducted to distinguish the microbial ecotoxicity of SDZ and Cu across different soils by analyzing soil potential nitrification rate (PNR) and the amoA gene sequences.ResultsThe results showed that the single spiking of SDZ caused a consistent decrease of soil PNR among three tested soils, but no consistent synergistic inhibition of SDZ and Cu was observed across these soils. Moreover, across three tested soils, the distinct responses to the single or joint exposure of SDZ and Cu were found in amoA gene abundance, and diversity as well as the identified genus taxa of ammonia-oxidizing archaea (AOA) and bacteria (AOB). Meanwhile, only the specific genus taxa of AOA or AOB consistently corresponded to the variation of soil PNR across different treated soils. The further principal component analysis (PCA) exhibited that the variable influence of SDZ and Cu on ammonia oxidizing microbial community and function was greatly dependent on soil type.DiscussionTherefore, in addition to ecological functionality and the specific prokaryotic taxa, soil microbial ecotoxicity of SDZ and Cu also was dependent on edaphic factors derived from soil types. This study proposes an integrative assessment of soil properties and multiple microbial targets to soil contamination management.

ObjectiveNeuropathic pain is a common complication after spinal cord injury (SCI). Transcranial direct current stimulation (tDCS) has been confirmed to be effective in relieving neuropathic pain in patients with SCI. The aim of this study is to investigate the effect of tDCS on neuropathic pain induced by SCI and its underlying mechanism.Materials and methodsThe SCI model was induced by a clip-compression injury and tDCS stimulation was performed for two courses (5 days/each). The motor function was evaluated by Basso-Beattie-Bresnahan (BBB) score, and the thermal withdrawal threshold was evaluated by the thermal radiation method. The effects of tDCS on the cerebral cortex, thalamus, midbrain, and medulla were detected by the enzyme-linked immunosorbent assay (ELISA) and immunofluorescence.ResultsThe results showed that SCI reduced the thermal withdrawal threshold and increased the concentration of inflammatory cytokines in the cortex, thalamus, midbrain, and medulla, including the tumor necrosis factor-α (TNF-α), interleukin-1β (IL-1β), and interleukin-6 (IL-6). In addition, the activation of microglia and the proportion of M1 phenotypic polarization increased significantly in the ventral posterolateral (VPL), ventral tegmental (VTA), and periaqueductal gray (PAG) regions after SCI. After tDCS treatment, the thermal withdrawal threshold and motor function of SCI rats were significantly improved compared to the vehicle group. Meanwhile, tDCS effectively reduced the concentration of pro-inflammatory cytokines in the cortex, thalamus, midbrain, and medulla and increased the concentration of anti-inflammatory cytokines interleukin-10 (IL-10) in the thalamus. In addition, tDCS reduced the proportion of the M1 phenotype of microglia in VPL, VTA, and PAG regions and increase the proportion of the M2 phenotype.ConclusionThe results suggest that tDCS can effectively relieve SCI-induced neuropathic pain. Its mechanism may be related to regulating the inflammatory and anti-inflammatory cytokines in corresponding brain regions via promoting the phenotypic transformation of microglia.

BackgroundOmics has emerged as a promising biological science to shed light on the etiology, pathogenesis, and treatment of ulcerative colitis (UC). At present, although research on the omics of UC has drawn global attention, there is still a lack of bibliometric analysis in this field. This study aimed to access the trends and hotspots of omics in UC research.MethodPublications related to omics in UC from 1 January 2000 to 15 October 2022 were retrieved from the Web of Science Core Collection database. VOSviewer, CiteSpace, and the online bibliometric analysis platform “Bibliometrix” were adopted to extract and visualize information.ResultsA total of 385 publications were finally included and the annual number of publications fluctuated. The trend in publications increased rapidly after 2019. The United States showed its dominant position in several publications, total citations, and international collaborations. The top five research organizations for publications on the research of omics in UC were Harvard Medical School, the Icahn School of Medicine at Mount Sinai, Karolinska Institutet, the Brigham and Women's Hospital, and the Massachusetts General Hospital. Ashwin Ananthakrishnan from the Massachusetts General Hospital was the most productive author, and Séverine Vermeire from the Catholic University of Leuven was co-cited most often. Inflammatory bowel disease was the most popular and co-cited journal in this field. The reference with citation bursts and trend topics showed that “ulcerative colitis,” “inflammatory bowel disease,” “microbiome,” “transcriptomics,” “genomics,” “metabolomics,” “proteomics,” “dysbiosis,” “biomarkers,” “loci,” and “therapy” are currently research hotspots.ConclusionOur study presents several important insights into the research trends and developments in the field of omics in UC, which will provide key information for further research.

BackgroundThe cerebellum is involved in the control and coordination of movements but it remains unclear whether stimulation of the cerebellum could improve the recovery of upper limb motor function. Therefore, this study aimed to explore whether cerebellar transcranial direct current stimulation (tDCS) therapy could promote the recovery of upper limb motor function in patients who suffered a stroke.MethodsIn this randomized, double-blind, and sham-controlled prospective study, 77 stroke patients were recruited and randomly assigned to the tDCS group (n = 39) or the control group (n = 38). The patients received anodal (2 mA, 20 min) or sham tDCS therapy for 4 weeks. The primary outcome was the change in the Fugl-Meyer Assessment-Upper Extremity (FMA-UE) score from baseline to the first day after 4 weeks of treatment (T1) and 60 days after 4 weeks of treatment (T2). The secondary outcomes were the FMA-UE response rates assessed at T1 and T2. Adverse events (AEs) related to the tDCS treatment were also recorded.ResultsAt T1, the mean FMA-UE score increased by 10.7 points [standard error of the mean (SEM) = 1.4] in the tDCS group and by 5.8 points (SEM = 1.3) in the control group (difference between the two groups was 4.9 points, P = 0.013). At T2, the mean FMA-UE score increased by 18.9 points (SEM = 2.1) in the tDCS group and by 12.7 points (SEM = 2.1) in the control group (the difference between the two groups was 6.2 points, P = 0.043). At T1, 26 (70.3%) patients in the tDCS group had a clinically meaningful response to the FMA-UE score compared to 12 (34.3%) patients in the control group (the difference between the two groups was 36.0%, P =0.002). At T2, 33 (89.2%) patients in the tDCS group had a clinically meaningful response to the FMA-UE score compared with 19 (54.3%) patients in the control group (the difference between the two groups was 34.9%, P = 0.001). There was no statistically significant difference in the incidence of adverse events between the two groups. In the subgroup analysis of different hemiplegic sides, the rehabilitation effect of patients with right hemiplegia was better than that of patients with left hemiplegia (P < 0.05); in the age subgroup analysis, different age groups of patients did not show a significant difference in the rehabilitation effect (P > 0.05).ConclusionCerebellar tDCS can be used as an effective and safe treatment to promote recovery of upper limb motor function in stroke patients.Trial registrationChiCTR.org.cn, identifier: ChiCTR2200061838.

ObjectiveTo compare the therapeutic effects of wedge resection and liver segment IVb + V resection on patients with T2b gallbladder cancer.MethodsThe clinical and pathological data of 40 patients with gallbladder cancer admitted to the Second Affiliated Hospital of Nanchang University from January 2017 to November 2019 were retrospectively analyzed, and they were divided into two groups according to different surgical methods. The control group underwent liver wedge resection, while the experimental group underwent liver segment IVb + V resection. Preoperative age, bilirubin index, tumor markers, postoperative complications and survival were compared between the two groups. Log-rank test was used for univariate analysis, and Cox proportional hazards regression model was used for multivariate analysis. Kaplan-Meier survival curves were drawn.ResultsUnivariate analysis showed that tumor markers and degree of differentiation were the risk factors for the prognosis of patients with gallbladder carcinoma after radical cholecystectomy (P