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Abstract Background Neoadjuvant immune checkpoint blockade (ICB) combined with chemoradiotherapy offers high pathologic complete response (pCR) rate for patients with locally advanced esophageal squamous cell carcinomas (ESCC). But the dynamic tumor immune microenvironment modulated by such neoadjuvant therapy remains unclear. Patients and methods A total of 41 patients with locally advanced ESCC were recruited. All patients received neoadjuvant toripalimab combined with concurrent chemoradiotherapy. Matched pre- and post-treatment tissues were obtained for fluorescent multiplex immunohistochemistry (mIHC) and IHC analyses. The densities and spatial distributions of immune cells were determined by HALO modules. The differences of immune cell patterns before and after neoadjuvant treatment were investigated. Results In the pre-treatment tissues, more stromal CD3 + FoxP3 + Tregs and CD86+/CD163 + macrophages were observed in patients with residual tumor existed in the resected lymph nodes (pN1), compared with patients with pCR. The majority of macrophages were distributed in close proximity to tumor nest in pN1 patients. In the post-treatment tissues, pCR patients had less CD86 + cell infiltration, whereas higher CD86 + cell density was significantly associated with higher tumor regression grades (TRG) in non-pCR patients. When comparing the paired pre- and post-treatment samples, heterogeneous therapy-associated immune cell patterns were found. Upon to the treatment, CD3 + T lymphocytes were slightly increased in pCR patients, but markedly decreased in non-pCR patients. In contrast, a noticeable increase and a less obvious decrease of CD86 + cell infiltration were respectively depicted in non-pCR and pCR patients. Furthermore, opposite trends of the treatment-induced alterations of CD8 + and CD15 + cell infiltrations were observed between pN0 and pN1 patients. Conclusions Collectively, our data demonstrate a comprehensive picture of tumor immune landscape before and after neoadjuvant ICB combined with chemoradiotherapy in ESCC. The infiltration of CD86 + macrophage may serve as an unfavorable indicator for neoadjuvant toripalimab combined with chemoradiotherapy.

The contamination of soil with the heavy metal cadmium (Cd) is increasingly prominent and severely threatens food security in China. Owing to its low cost, suitable efficacy, and ability to address the shortcomings of plant remediation by enhancing the ability of plants to take up Cd, plant–microbe combination remediation technology has become a research hotspot in heavy metal pollution remediation. A pot experiment was performed to examine the effects of inoculation with the plant-growth-promoting bacterium Brevibacillus sp. SR-9 on the biomass, Cd accumulation, and soil nutrients of hybrid Pennisetum. The purpose of this study was to determine how Brevibacillus sp. SR-9 alleviates stress caused by heavy metal contamination. High-throughput sequencing and metabolomics were used to determine the effects of inoculation on the soil bacterial community composition and microbial metabolic functions associated with hybrid Pennisetum. The results suggest that mutation of Brevibacillus sp. SR-9 effectively alleviates Cd pollution stress, leading to increased biomass and accumulation of Cd in hybrid Pennisetum. The aboveground biomass and the root weight increased by 12.08% and 27.03%, respectively. Additionally, the accumulation of Cd in the aboveground sections and roots increased by 21.16% and 15.50%, respectively. Measurements of the physicochemical properties of the soil revealed that the strain Brevibacillus sp. SR-9 slightly increased the levels of available phosphorus, total nitrogen, total phosphorus, and available potassium. High-throughput DNA sequencing revealed that Brevibacillus sp. SR-9 implantation modified the composition of the soil bacterial community by increasing the average number of Actinobacteria and Bacillus. The total nitrogen content of the soil was positively correlated with the Actinobacteria abundance, total phosphorus level, and available phosphorus level. Metabolomic analysis revealed that inoculation affected the abundance of soil metabolites, and 59 differentially abundant metabolites were identified (p < 0.05). Among these, 14 metabolites presented increased abundance, whereas 45 metabolites presented decreased abundance. Fourteen metabolic pathways were enriched in these metabolites: the folate resistance pathway, the ABC transporter pathway, D-glutamine and D-glutamic acid metabolism, purine metabolism, and pyrimidine metabolism. The abundance of the metabolites was positively correlated with the levels of available phosphorus, total potassium, total phosphorus, and total nitrogen. According to correlation analyses, the development of hybrid Pennisetum and the accumulation of Cd are strongly associated with differentially abundant metabolites, which also impact the abundance of certain bacterial populations. This work revealed that by altering the makeup of microbial communities and their metabolic processes, bacteria that promote plant development can mitigate the stress caused by Cd. These findings reveal the microbiological mechanisms through which these bacteria increase the ability of hybrid Pennisetum to take up the Cd present in contaminated soils.

The interaction between microplastics (MPs) and cadmium (Cd) poses a threat to agricultural soil environments, and their effects on plant growth and rhizosphere microbial community functions are not yet clear. In this study, energy sorghum was used as a test plant to investigate the effects of two types of MPs, polystyrene (PS) and polyethylene (PE), at different particle sizes (13 μm, 550 μm) and concentrations (0.1%, 1% w/w), and Cd, as well as their interactions, on the growth of sorghum in a soil-cultivation pot experiment. The results showed that the combined effects of MP and Cd pollution on the dry weight and Cd accumulation rate in sorghum varied depending on the type, concentration, and particle size of the MPs, with an overall trend of increasing stress from combined pollution with increasing Cd content and accumulation. High-throughput sequencing analysis revealed that combined MP and Cd pollution increased bacterial diversity, and the most significant increase was observed in the abundance-based coverage estimator (ACE), Shannon, and Sobs indices in the 13 μm 1% PS+Cd treatment group. Metagenomic analysis based on the Kyoto Encyclopedia of Genes and Genomes (KEGG) metabolic pathways revealed that 19 groups of metabolic pathways, including microbial metabolism and methane metabolism, differed significantly under combined MP and Cd pollution. Hierarchical clustering results indicated that Cd treatment and combined MP and Cd treatment affected the abundances of sorghum rhizosphere soil nitrogen (N) and phosphorus (P) cycling genes and that the type of MP present was an important factor affecting N and P cycling genes. The results of this study provide a basis for exploring the toxic effects of combined MP and Cd pollution and for conducting soil environmental risk assessments.

Introduction: Acquired resistance to BRAF inhibitor vemurafenib is frequently observed in metastatic colorectal cancer (CRC), and it is a thorny issue that results in treatment failure. As adaptive responses for vemurafenib treatment, a series of cellular bypasses are response for the adaptive feedback reactivation of ERK signaling, which warrant further investigation. Objectives: We identified ARF1 (ADP-ribosylation factor 1) as a novel regulator of both vemurafenib resistance and cancer metastasis, its molecular mechanism and potential inhibitor were investigated in this study. Methods: DIA-based quantitative proteomics and RNA-seq were performed to systematic analyze the profiling of vemurafenib-resistant RKO cells (RKO-VR) and highly invasive RKO cells (RKO-I8), respectively. Co‑immunoprecipitation assay was performed to detect the interaction of ARF1 and IQGAP1 (IQ-domain GTPase activating protein 1). An ELISA-based drug screen system on FDA-approved drug library was established to screen the compounds against the interaction of ARF1-IQGAP1.The biological functions of ARF1 and LY2835219 were determined by transwell, western blotting, Annexin V-FITC/PI staining and in vivo experimental metastasis assays. Results: We found that ARF1 strongly interacted with IQGAP1 to activate ERK signaling in VR and I8 CRC cells. Deletion of IQGAP1 or inactivation of ARF1 (ARF-T48S) restored the invasive ability induced by ARF1. As ARF1-IQGAP1 interaction is essential for ERK activation, we screened LY2835219 as novel inhibitor of ARF1-IQGAP1 interaction, which inactivated ERK signaling and suppressed CRC metastasis and vemurafenib-resistance in vitro and in vivo with no observed side effect. Furthermore, LY2835219 in combined treatment with vemurafenib exerted significantly inhibitory effect on ARF1-mediated cancer metastasis than used independently. Conclusion: This study uncovers that ARF1-IQGAP1 interaction-mediated ERK signaling reactivation is critical for vemurafenib resistance and cancer metastasis, and that LY2835219 is a promising therapeutic agent for CRC both as a single agent and in combination with vemurafenib.

Periodontal defects present a significant challenge in dentistry, necessitating innovative solutions for comprehensive regeneration. Traditional restoration methods have inherent limitations in achieving complete and functional periodontal tissue reconstruction. Tissue engineering, a multidisciplinary approach integrating cells, biomaterials, and bioactive factors, holds tremendous promise in addressing this challenge. Central to tissue engineering strategies are scaffolds, pivotal in supporting cell behavior and orchestrating tissue regeneration. Natural and synthetic materials have been extensively explored, each offering unique advantages in terms of biocompatibility and tunable properties. The integration of growth factors and stem cells further amplifies the regenerative potential, contributing to enhanced tissue healing and functional restoration. Despite significant progress, challenges persist. Achieving the seamless integration of regenerated tissues, establishing proper vascularization, and developing biomimetic scaffolds that faithfully replicate the natural periodontal environment are ongoing research endeavors. Collaborative efforts across diverse scientific disciplines are essential to overcoming these hurdles. This comprehensive review underscores the critical need for continued research and development in tissue engineering strategies for periodontal regeneration. By addressing current challenges and fostering interdisciplinary collaborations, we can unlock the full regenerative potential, paving the way for transformative advancements in periodontal care. This research not only enhances our understanding of periodontal tissues but also offers innovative approaches that can revolutionize dental therapies, improving patient outcomes and reshaping the future of periodontal treatments.

The green and efficient remediation of soil cadmium (Cd) is an urgent task, and plant-microbial joint remediation has become a research hotspot due to its advantages. High-throughput sequencing and metabolomics have technical advantages in analyzing the microbiological mechanism of plant growth-promoting bacteria in improving phytoremediation of soil heavy metal pollution. In this experiment, a pot trial was conducted to investigate the effects of inoculating the plant growth-promoting bacterium Enterobacter sp. VY on the growth and Cd remediation efficiency of the energy plant Hybrid pennisetum. The test strain VY-1 was analyzed using high-throughput sequencing and metabolomics to assess its effects on microbial community composition and metabolic function. The results demonstrated that Enterobacter sp. VY-1 effectively mitigated Cd stress on Hybrid pennisetum, resulting in increased plant biomass, Cd accumulation, and translocation factor, thereby enhancing phytoremediation efficiency. Analysis of soil physical-chemical properties revealed that strain VY-1 could increase soil total nitrogen, total phosphorus, available phosphorus, and available potassium content. Principal coordinate analysis (PCoA) indicated that strain VY-1 significantly influenced bacterial community composition, with Proteobacteria, Firmicutes, Chloroflexi, among others, being the main differential taxa. Redundancy analysis (RDA) revealed that available phosphorus, available potassium, and pH were the primary factors affecting bacterial communities. Partial Least Squares Discriminant Analysis (PLS-DA) demonstrated that strain VY-1 modulated the metabolite profile of Hybrid pennisetum rhizosphere soil, with 27 differential metabolites showing significant differences, including 19 up-regulated and eight down-regulated expressions. These differentially expressed metabolites were primarily involved in metabolism and environmental information processing, encompassing pathways such as glutamine and glutamate metabolism, α-linolenic acid metabolism, pyrimidine metabolism, and purine metabolism. This study utilized 16S rRNA high-throughput sequencing and metabolomics technology to investigate the impact of the plant growth-promoting bacterium Enterobacter sp. VY-1 on the growth and Cd enrichment of Hybrid pennisetum, providing insights into the regulatory role of plant growth-promoting bacteria in microbial community structure and metabolic function, thereby improving the microbiological mechanisms of phytoremediation.

Seneca Valley virus (SVV), a member of the Picornaviridae family, may cause serious water blister diseases in pregnant sows and acute death in newborn piglets, which have resulted in economic losses in pig production. The 3C protease is a vital enzyme for SVV maturation and is capable of regulating protein cleavage and RNA replication of the virus. Additionally, this protease can impede the host’s innate immune response by targeting the interferon pathway’s principal factor and enhance virus replication by modulating the host’s RNA metabolism while simultaneously triggering programmed cell death. This article reviews recent studies on SVV 3C functions, which include viral replication promotion, cell apoptosis modulation and host immune response evasion, and provides a theoretical basis for research on preventing and controlling SVV infection.

Microplastics (MPs) can act as carriers for environmental pollutants; therefore, MPs combined with heavy metal pollution are attracting increasing attention from researchers. In this study, the potential of the plant growth-promoting bacterium Bacillus sp. SL-413 to mitigate the stress caused by exposure to both MPs and cadmium (Cd) in sorghum plants was investigated. The effects of inoculation on sorghum biomass were investigated using hydroponic experiments, and evaluation of Cd accumulation and enzyme activity changes and transcriptomics approaches were used to analyze its effect on sorghum gene expression. The results showed that combined polyethylene (PE) and Cd pollution reduced the length and the fresh and dry weights of sorghum plants and thus exerted a synergistic toxic effect. However, inoculation with the strains alleviated the stress caused by the combined pollution and significantly increased the biomass. Inoculation increased the dry weights of the aboveground and belowground parts by 11.5–44.6% and 14.9–38.4%, respectively. Plant physiological measurements indicated that inoculation reduced the reactive oxygen species (ROS) content of sorghum by 10.5–27.2% and thereby alleviated oxidative stress. Transcriptome sequencing showed that exposure to combined Cd+MP contamination induced downregulation of gene expression, particularly that of genes related to amino sugar and nucleotide sugar metabolism, starch and sucrose metabolism, and plant hormone signal transduction, in sorghum. However, inoculation with Bacillus sp. SL-413 resulted in an increase in the proportion of upregulated genes involved in signal transduction, antioxidant defense, cell wall biology, and other metabolic pathways, which included the phenylpropanoid biosynthesis, photosynthesis, flavonoid biosynthesis, and MAPK signaling pathways. The upregulation of these genes promoted the tolerance of sorghum under combined Cd+MP pollution stress and alleviated the stress induced by these conditions. This study provides the first demonstration that plant growth-promoting bacteria can alleviate the stress caused by combined pollution with MPs and Cd by regulating plant gene expression. These findings provide a reference for the combined plant-microbial remediation of MPs and Cd.

Clear cell renal cell carcinoma (ccRCC) is of poor clinical outcomes, and currently lacks reliable prognostic biomarkers. By analyzing the datasets of the Cancer Genome Atlas (TCGA) and the Clinical Proteomic Tumor Analysis Consortium (CPTAC), we established a five-protein prognostic signature containing GBP2, HLA-DRA, ISG15, ISG20 and ITGAX. Our data indicate that this signature was closely correlated with advanced stage, higher pathological grade, and unfavorable survivals in patients with ccRCC. We further functionally characterized GBP2. Overexpression of GBP2 enhanced the phosphorylation of STAT2 and STAT3 to trigger JAK-STAT signaling and promote cell migration and invasion in ccRCC. Treatment of Ruxolitinib, a specific inhibitor of JAK/STAT, attenuated the GBP2-mediated phenotypes. Patients with high GBP2 expression were accompanied with more infiltration of immune cells positively stained with CD3, CD8, CD68, and immune checkpoint markers PD-1 and CTLA4, which was validated by Opal multiplex immunohistochemistry in ccRCC tissues. More CD8 + T cells and CD68 + macrophages were observed in patients expressing high GBP2. Taken together, a five-protein prognostic signature was constructed in our study. GBP2 has an oncogenic role via modulating JAK-STAT signaling and tumor immune infiltration, and thus may serve as a potential therapeutic target in ccRCC.

Swine acute diarrhoea syndrome coronavirus (SADS-CoV), which is a recently discovered enteric coronavirus, is the major aetiological agent that causes severe clinical diarrhoea and intestinal pathological damage in pigs, and it has caused significant economic losses to the swine industry. Nonstructural protein 5, also called 3C-like protease, cleaves viral polypeptides and host immune-related molecules to facilitate viral replication and immune evasion. Here, we demonstrated that SADS-CoV nsp5 significantly inhibits the Sendai virus (SEV)-induced production of IFN-β and inflammatory cytokines. SADS-CoV nsp5 targets and cleaves mRNA-decapping enzyme 1a (DCP1A) via its protease activity to inhibit the IRF3 and NF-κB signaling pathways in order to decrease IFN-β and inflammatory cytokine production. We found that the histidine 41 and cystine 144 residues of SADS-CoV nsp5 are critical for its cleavage activity. Additionally, a form of DCP1A with a mutation in the glutamine 343 residue is resistant to nsp5-mediated cleavage and has a stronger ability to inhibit SADS-CoV infection than wild-type DCP1A. In conclusion, our findings reveal that SADS-CoV nsp5 is an important interferon antagonist and enhance the understanding of immune evasion by alpha coronaviruses.

Sucrose non-fermenting 1-related protein kinase 2 (SnRK2) is a plant-specific serine/threonine kinase involved in response to adverse environmental stimuli. Previous studies showed that TaSnRK2.4 was involved in response to abiotic stresses and conferred enhanced tolerance to multiple stresses in Arabidopsis. Further experiments were performed to decipher the underlying mechanisms and discover new functions. The genomic sequences of TaSnRK2.4s locating on chromosome 3A, 3B and 3D were obtained. Sequencing identified one and 13 variations of TaSnRK2.4–3A and TaSnRK2.4-3B, respectively, but no variation was detected in TaSnRK2.4-3D. The markers 2.4AM1, 2.4BM1 and 2.4BM2 were developed based on three variations. Association analysis showed that both TaSnRK2.4-3A and TaSnRK2.4-3B were significantly associated with thousand-kernel weight (TKW), and that SNP3A-T and SNP3B-C were favorable alleles for higher TKW. Yeast two-hybrid and split luciferase assays showed that TaSnRK2.4 physically interacted with abiotic stress responsive protein TaLTP3, suggesting that TaSnRK2.4 enhanced abiotic stress tolerance by activating TaLTP3. Our studies suggested that TaSnRK2.4 have potential in improving TKW and response to abiotic stress.

As the water source for the Middle Route Project of the South-to-North Water Diversion Project (MR-SNWD) of China, the Danjiangkou Reservoir (DJR) is in the process of ecosystem reassembly, but the composition, function, and assembly mechanisms of bacterioplankton communities are not yet clear. In this study, the composition, distribution characteristics and influencing factors of bacterioplankton communities were analyzed by high-throughput sequencing (HTS); PICRUSt2 was used to predict community function; a molecular ecological network was used to analyze bacterioplankton interactions; and the assembly process of bacterioplankton communities was estimated with a neutral model. The results indicated that the communities, function and interaction of bacterioplankton in the DJR had significant annual and seasonal variations and that the seasonal differences were greater than that the annual differences. Excessive nitrogen (N) and phosphorus (P) nutrients in the DJR are the most important factors affecting water quality in the reservoir, N and P nutrients are the main factors affecting bacterial communities. Season is the most important factor affecting bacterioplankton N and P cycle functions. Ecological network analysis indicated that the average clustering coefficient and average connectivity of the spring samples were lower than those of the autumn samples, while the number of modules for the spring samples was higher than that for the autumn samples. The neutral model explained 66.3%, 63.0%, 63.0%, and 70.9% of the bacterioplankton community variations in samples in the spring of 2018, the autumn of 2018, the spring of 2019, and the autumn of 2019, respectively. Stochastic processes dominate bacterioplankton community assembly in the DJR. This study revealed the composition, function, interaction, and assembly of bacterioplankton communities in the DJR, providing a reference for the protection of water quality and the ecological functions of DJR bacterioplankton.

Medicago ruthenica is an important perennial forage with multiple characteristics of resistance. In this study, we sequenced and characterized the complete chloroplast genome of M. ruthenica ‘Taihang’, which is 124, 254 bp in length. A total of 108 genes were identified, including 74 protein-coding, 30 tRNA, and four rRNA genes. Phylogenetic analysis based on 27 chloroplast genomes showed that M. ruthenica ‘Taihang’ has a close relationship with M. ruthenica from Qinghai Province, China. The data are useful in better understanding the genetic diversity and stress resistance of Medicago and contribute to the phylogenetic study of Trifolieae.

Glucose sensors based blood glucose detection are of great significance for the diagnosis and treatment of diabetes because diabetes has aroused wide concern in the world. In this study, bovine serum albumin (BSA) was used to cross-link glucose oxidase (GOD) on a glassy carbon electrode (GCE) modified by a composite of hydroxy fullerene (HFs) and multi-walled carbon nanotubes (MWCNTs) and protected with a glutaraldehyde (GLA)/Nafion (NF) composite membrane to prepare a novel glucose biosensor. The modified materials were analyzed by UV-visible spectroscopy (UV-vis), transmission electron microscopy (TEM), and cyclic voltammetry (CV). The prepared MWCNTs-HFs composite has excellent conductivity, the addition of BSA regulates MWCNTs-HFs hydrophobicity and biocompatibility, and better immobilizes GOD on MWCNTs-HFs. MWCNTs-BSA-HFs plays a synergistic role in the electrochemical response to glucose. The biosensor shows high sensitivity (167 μA·mM−1·cm−2), wide calibration range (0.01–3.5 mM), and low detection limit (17 μM). The apparent Michaelis–Menten constant Kmapp is 119 μM. Additionally, the proposed biosensor has good selectivity and excellent storage stability (120 days). The practicability of the biosensor was evaluated in real plasma samples, and the recovery rate was satisfactory.

Rutin is a natural antioxidant flavonoid compound with anti-inflammatory, antioxidant, and antiviral effects that is used to prepare drugs with wide application in clinical treatment. Therefore, the quantitative detection of rutin has important practical significance. In this work, a novel electrochemical sensor based on glassy carbon electrodes (GCEs) modified with sodium carboxymethylcellulose (CMC), multi-walled carbon nanotubes (MWCNTs), and 1-butyl-3-methylimid (ionic liquid, IL) was developed for the super-sensitive detection of the flavonoid rutin. The properties of these modified materials were analyzed by transmission electron microscope (TEM), cyclic voltammograms (CVs), and electrochemical-impedance spectroscopy (EIS). CMC was used to disperse MWCNTs to further enhance their hydrophilicity and biocompatibility. The modified MWCNTs improved the sensitivity of rutin detection. The square-wave voltammetry (SWV) technique showed that the linear range of rutin concentration determination was 0.01 μM to 1 µM and 1 µM to 10 µM. The minimum concentration detection of rutin was 0.83 nM and 6.6 nM, respectively. The proposed sensor presented good selectivity for rutin and successfully analyzed rutin content in the pharmaceutical rutin tablets. These results are consistent with those measured by ultra-high-performance liquid chromatography (UHPLC). Therefore, this sensor has latent application value in the analysis of rutin in food and drug tablets and nutraceutical samples.

Bothriochloa ischaemum (Linn.) 1936 is a high-quality perennial forage in Loess Plateau of China. In this study, we sequenced and characterized the complete chloroplast genome of B. ischaemum, which was a circular DNA of 138,316 bp in length, including a large single copy (LSC) region of 80,226 bp, a small single copy (SSC) region of 12,526 bp, and the circular DNA was separated by a pair of identical inverted repeat regions (IRs) of 22,782 bp each. A total of 134 genes were identified, including 87 protein-coding genes, 39 tRNA genes, and eight rRNA genes. Phylogenetic tree showed that B. ischaemum was closer to B. decipiens and B. alta, genus Bothriochloa was closely related to genus Pseudanthistiria. Our findings will be helpful for better understanding of genetic diversity of Bothriochloa plants.

This paper presents a broadband band-pass filter with cross-coupled line structure. The cross-coupled line structure is composed of the parallel coupled lines and an open stub. It can be analyzed by the odd- and even-mode method due to its symmetric structure. There are three transmission poles in the passband and two transmission zeros out of passband. Then, the influence of the impedance parameters on the transmission zeros and transmission poles are analyzed. Then, the physical parameters of the proposed band-pass filter are given. And using HFSS for simulation and optimization, the final insertion loss and return loss of filter are obtained. The simulation and measurement results are in good agreement, which validates the design idea.

Background. Heart failure (HF) is the terminal stage of all cardiovascular events. Although implantable cardioverter defibrillator (ICD) therapies have reduced mortality among the high-risk HF population, it is necessary to determine whether certain factors can predict mortality even after cardiac device implantation. Growth stimulation expressed gene 2 (ST2) is an emerging biomarker for HF patient stratification in different clinical settings. Aims. This study aimed to investigate the relationship between baseline soluble ST2 (sST2) levels in serum and the clinical outcomes of high-risk HF patients with device implantation. Methods. Between January 2017 and August 2018, we prospectively recruited consecutive patients implanted with an ICD for heart failure, with LVEF ≤35% as recommended, and analyzed the basic characteristics, baseline serum sST2, and NT-proBNP levels, with at least 1-year follow-up. All-cause mortality was the primary endpoint. Results. During a 643-day follow-up, all-cause mortality occurred in 16 of 150 patients (10.67%). Incidence of all-cause mortality increased significantly in patients with sST2 levels above 34.98846 ng/ml (16.00% vs. 5.33%, P=0.034). After adjusting the model (age, gender, device implantation, prevention of sudden death, LVEDD, LVEF, WBC and CLBBB, hsTNT, etiology, and eGFR) and the model combined with NT-proBNP, the risk of all-cause death was increased by 2.5% and 1.9%, respectively, per ng/ml of sST2. The best sST2 cutoff for predicting all-cause death was 43.42671 ng/ml (area under the curve: 0.72, sensitive: 0.69, and specificity: 0.69). Compared to patients with sST2 levels below 43.42671 ng/ml, the risk of all-cause mortality was higher in those with values above the threshold (5.1% vs. 21.2%, P=0.002). ST2 level ≥43.42671 ng/ml was an independent predictor of all-cause mortality (HR: 3.30 [95% CI 1.02–10.67]). Age (HR: 1.06 [95% CI: 1.01–1.12]) and increased NT-proBNP per 100 (HR: 1.02 [95% CI: 1.01–1.03]) were also associated with all-cause mortality in ICD patients. Conclusions. sST2 level was associated with risk of all-cause mortality, and a threshold of 43.43 ng/ml showed good distinguishing performance to predict all-cause mortality in patients with severe heart failure, recommended for ICD implantation. Patients with sST2 levels more than 43.42671 ng/ml even after ICD implantation should therefore be monitored carefully.

Objective To investigate the efficacy and safety of temperature-controlled radiofrequency thermocoagulation for the treatment of upper extremity cancer pain, and to evaluate its impact on upper extremity motor function. Methods A total of 56 patients with upper extremity cancer pain who were mainly involved in brachial plexus were treated with radiofrequency thermocoagulation (N = 36) and nerve block (N = 20). Before and 1 d, 3 d and 7 d after treatment, Visual Analogue Scale (VAS) was used to assess the degree of pain, upper extremity strength and complications were recorded. Results Compared with nerve block group, patients in radiofrequency thermocoagulation group had lower VAS scores (F = 64.406, P = 0.000) and higher muscle strength (F = 64.405, P = 0.000). Compared with before treatment, patients in radiofrequency thermocoagulation group had lower VAS scores at 1, 3 and 7 d after surgery (t = 25.931, P = 0.000; t = 19.600, P = 0.000; t = 24.817, P = 0.000). There was no significant difference in muscle strength at each time point (P > 0.05, for all). The VAS scores of patients in nerve block group decreased at 1 and 3 d after surgery (t = 19.298, P = 0.000; t = 14.918, P = 0.000), while returned to preoperative level at 7 d after surgery (P > 0.05); muscle strength decreased 1 d after surgery (t = 13.069, P = 0.000), and returned to preoperative level 3 and 7 d after surgery (P > 0.05, for all). No one suffered from complications such as infection or pneumothorax in 2 groups. Conclusions Radiofrequency thermocoagulation is safe and effective in the treatment of upper extremity cancer pain, and has little effect on upper extremity motor function. DOI: 10.3969/j.issn.1672-6731.2018.10.007

Objective: To test the feasibility of establishing a senior volunteer cohort and describe vascular risks, cognitive function, and brain aging indices in a pilot study. Materials and Methods: We enrolled 40 senior volunteers from the Tzu Chi Foundation and other organizations in Hualien in 2014–2015. We conducted in-person interviews to collect information on demographic features, physical fitness, dietary habits, comorbidities, and narratives of aging. Vascular risks including blood pressure, body mass index (BMI), serum glucose level, and lipid profile were examined. Each participant underwent a comprehensive battery of neuropsychological tests and structural brain magnetic resonance imaging (MRI). Descriptive statistics and tabulation were applied to characterize this pilot cohort. Results: There were more volunteers from the Tzu Chi Foundation (n = 25) than other organizations. The mean age was 66.7 years (standard deviation = 5.1) and there was a female predominance (M:F = 13:27). The mean number of comorbid chronic diseases was 2.1 and the mean BMI was 24.5. Most participants (77.5%) engaged in outdoor walking activities every week. Nutrient intake in vegetarians (n = 18) did not differ from nonvegetarians except for lower Vitamin B12 levels (mean = 0.9 μg). All participants but one scored 26 or above in the Mini–Mental State Examination (mean = 28.4). Among the other cognitive tests, only one task related to inhibition and switching abilities was at the low average level. The mean values of vascular risk markers were within the normal ranges. The most common genotype of apolipoprotein E was μ3/μ3 (n = 32). The quality of MRI was sufficient for volumetric analysis. Conclusion: It is feasible to establish a volunteer-based cohort to study brain aging in Taiwan. The senior volunteers were physically active and cognitively healthy. Vascular risks were well distributed among these participants. Future longitudinal study will allow us to observe changes in these markers over time and provide dynamic evidence about vascular health and cognitive aging.

A previous study by our group found that inhibition of nischarin promotes neurite outgrowth and neuronal regeneration in Neuro-2a cells and primary cortical neurons. In recent years, more and more studies have shown that nanomaterials have good prospects in treatment of spinal cord injury. We proposed that small interfering RNA targeting nischarin (Nis-siRNA) delivered by polyethyleneimine-alginate (PEI-ALG) nanoparticles promoted motor function recovery in rats with spinal cord injury. Direct microinjection of 5 μL PEI-ALG/Nis-siRNA into the spinal cord lesion area of spinal cord injury rats was performed. From day 7 after surgery, Basso, Beattie and Bresnahan score was significantly higher in rats from the PEI-ALG/Nis-siRNA group compared with the spinal cord injury group and PEI-ALG/Control-siRNA group. On day 21 after injection, hematoxylin-eosin staining showed that the necrotic area was reduced in the PEI-ALG/Nis-siRNA group. Immunohistochemistry and western blot assay results confirmed successful inhibition of nischarin expression and increased protein expression of growth-associated protein-43 in the PEI-ALG/Nis-siRNA group. These findings suggest that a complex of PEI-ALG nanoparticles and Nis-siRNA effectively suppresses nischarin expression, induces expression of growth-associated protein-43, and accelerates motor function recovery after spinal cord injury.

Objective: Obstructive sleep apnea (OSA) is associated with bad cardiovascular outcomes and a high prevalence of anxiety and depression. This study investigated the effects of continuous positive airway pressure (CPAP) on the severity of anxiety and depression in OSA patients with or without coronary artery disease (CAD) and on the rate of cardio- and cerebro-vascular events in those with OSA and CAD. Materials and Methods: This prospective study included patients with moderate-to-severe OSA, with or without a recent diagnosis of CAD; all were started on CPAP therapy. Patients completed the Chinese versions of the Beck Anxiety Inventory (BAI) and Beck Depression Inventory-II (BDI-II) at baseline and after 6-month follow-up. The occurrence of major adverse cardiac and cerebrovascular events (MACCE) was assessed every 3 months up to 1 year. Results: BAI scores decreased from 8.5 ± 8.4 at baseline to 5.4 ± 6.9 at 6 months in CPAP-compliant OSA patients without CAD (P < 0.05). BAI scores also decreased from 20.7 ± 14.9 to 16.1 ± 14.5 in CPAP-compliant OSA patients with CAD. BDI-II scores decreased in CPAP-compliant OSA patients without CAD (from 11.1 ± 10.7 at baseline to 6.6 ± 9.5 at 6 months) and in CPAP-compliant OSA patients with CAD (from 20.4 ± 14.3 to 15.9 ± 7.3). In addition, there was a large effect size (ES) of BAI and BDI in 6-month CPAP treatment of OSA patients with CAD and a large ES in those with OSA under CPAP treatment. In OSA patients with CAD, the occurrence of MACCE was significantly lower in CPAP-compliant patients than that in CPAP noncompliant patients (11% in CPAP compliant and 50% in noncompliant; P < 0.05). Conclusions: CPAP improved anxiety and depression in OSA patients regardless of CAD. In OSA patients with CAD, CPAP-compliant patients had a lower 1-year rate of MACCE than CPAP-noncompliant patients.

Previous analyses of plant growth-promoting bacteria (PGPB) combined with the remediation of heavy metal pollution in soil have largely been performed under potting or greenhouse conditions, and in situ remediation experiments under field conditions have rarely been reported. In this study, the effects of the metal-resistant PGPB Microbacterium oxydans JYC17, Pseudomonas thivervalensis Y1-3-9, and Burkholderia cepacia J62 on soil Cu pollution under rape remediation were studied in the farmland surrounding the Nanjing Jiuhuashan copper mining region in China. Following inoculation treatment for 50 days, the biomasses of the rape inoculated with strains JYC17, Y1-3-9, and J62 increased, and the total amounts of Cu uptake increased by 113.38, 66.26, and 67.91%, respectively, the translocation factor (TF) of rape inoculated with J62 was 0.85, a significant increase of 70.68%, thus improving the Cu remediation efficiency of the rape. Y1-3-9 and J62 affected the bioavailability of Cu in the soil, and the water-soluble Cu contents were increased by 10.13 and 41.77%, respectively, compared with the control. The antioxidant activities in the rape leaves showed that the tested bacteria increased the contents of antioxidant non-enzymatic substances, including ascorbic acid (ASA) and glutathione (GSH), which were increased by 40.24–91.22% and 9.89–17.67%, respectively, thereby reducing the oxidative stress caused by heavy metals and the contents of thiobarbituric acid-reactive substances (TBARS) and peroxidase (POD). PCR-denaturing gradient gel electrophoresis (PCR-DGGE) was used to analyze the effects of the tested bacteria on the cultivation-dependent and cultivation-independent bacterial communities in the root endosphere and rhizosphere soil of the rape. The sequencing results of the DGGE bands indicated that the tested bacteria colonized the endosphere and rhizosphere, and they became an important component of the cultivation-dependent bacteria. The canonical correspondence analysis (CCA) of the DGGE profile and similarity cluster analysis showed that the tested bacteria affected the cultivation-dependent and cultivation-independent bacterial communities in the root endosphere and rhizosphere. In this experiment, the effects and mechanisms of the combined plant-microbe remediation under field conditions were preliminarily studied, and the results are expected to provide a theoretical basis for future combined remediation experiments.

Electromagnetic stirring is one of the widely applied techniques to modify the quality of casting billets. Different from conventional rotate stirring, the helical stirring is more professional in assisting multi-dimensional flow of molten metal and eliminating solidification defects. In this study, the single-winding helical stirring (SWHS) was introduced, offering advantages such as smaller volume and lower electromagnetic shielding compared to traditional helical stirring methods. Following a comprehensive numerical simulation, the stirring parameters of SWHS were adjusted to yoke inclination angle of 43° and frequency of 12 Hz. The higher electromagnetic force and flow velocity in drawing direction, as well as the lower temperature gradient induced by the SWHS, are positive factors for homogeneous solidification of billet. The experimental results on Al-8%Si alloy and 0.4%C-1.1%Mn steel demonstrate that compared to rotate stirring, the SWHS process can induce better billet quality and is more effective in accelerating the equiaxed expansion and reducing element segregation. The SWHS process can enhance the equiaxed ratio of the billet by 58.3% and reduce segregation degree of carbon element by 10.97%. Consequently, SWHS holds great promise as a potential approach for improving the quality of continuous casting billets. [ABSTRACT FROM AUTHOR]

BACKGROUND: Phthalates have been reported to impair fertility in various studies. However, evidence exploring the associations between phthalate metabolites in follicular fluid (FF) and reproductive outcomes is lacking. OBJECTIVES: To investigate the associations between phthalate metabolite concentrations in FF and in vitro fertilization/intracytoplasmic sperm injection (IVF/ICSI) outcomes among women recruited from a fertility clinic. METHODS: We included 641 women undergoing IVF/ICSI treatment from December 2018 to January 2020. The levels of eight phthalate metabolites, including monoethyl phthalate (MEP), mono-isobutyl phthalate (MiBP), mono-푛-butyl phthalate (MBP), monobenzyl phthalate (MBzP), mono(2- ethylhexyl) phthalate (MEHP), mono(2-ethyl-5-hydroxyhexyl) phthalate (MEHHP), mono(2-ethyl-5-oxohexyl) phthalate (MEOHP), and mono(2- ethyl-5-carboxypentyl) phthalate (MECPP), were quantified in FF collected on the oocyte retrieval day. Associations between quartiles of individual phthalate metabolite concentrations and nine IVF/ICSI outcomes, including oocyte yield, mature oocyte number, two distinct pronuclei (2PN) zygote number, fertilization rate, blastocyst formation rate, implantation, clinical pregnancy, miscarriage, and live birth, were estimated with generalized linear models. The effects of phthalate mixtures on IVF/ICSI outcomes were assessed using Bayesian kernel machine regression (BKMR) models. RESULTS: After adjusting for relevant confounders, elevated quartiles of MBzP, MEHHP, and MEHP in FF were inversely associated with the numbers of retrieved oocytes, mature oocytes, and 2PN zygotes (all 푝 for trends <0.10). In comparison with the lowest quartile, the highest quartile of molar sum of di(2-ethylhexyl) phthalate metabolites (RDEHP) was associated with a reduction of 9.1% [95% confidence interval (CI): –17:1%, –0:37%] and 10.3% (95% CI: –18:8%, –0:94%) in yielded oocyte and mature oocyte numbers, respectively. Furthermore, the BKMR models revealed inverse associations between phthalate mixtures and the numbers of retrieved oocytes and mature oocytes. We generally found null results for implantation, clinical pregnancy, miscarriage, and live birth. DISCUSSION: Certain phthalate metabolites in FF are inversely associated with the numbers of retrieved oocytes, mature oocytes, and 2PN zygotes among women undergoing IVF/ICSI treatment. [ABSTRACT FROM AUTHOR]

Seneca Valley virus (SVV), a member of the Picornaviridae family, may cause serious water blister diseases in pregnant sows and acute death in newborn piglets, which have resulted in economic losses in pig production. The 3C protease is a vital enzyme for SVV maturation and is capable of regulating protein cleavage and RNA replication of the virus. Additionally, this protease can impede the host's innate immune response by targeting the interferon pathway's principal factor and enhance virus replication by modulating the host's RNA metabolism while simultaneously triggering programmed cell death. This article reviews recent studies on SVV 3C functions, which include viral replication promotion, cell apoptosis modulation and host immune response evasion, and provides a theoretical basis for research on preventing and controlling SVV infection. [ABSTRACT FROM AUTHOR]

Abstract The NK-92MI cell line has displayed significant promise in clinical trials for cancer treatment. However, challenges persist in obtaining sufficient cell quantities and achieving optimal cytotoxicity. The proliferation of natural killer (NK) cells involves the formation of cell aggregates, but excessively large aggregates can impede nutrient and waste transport, leading to reduced cell survival rates. In this study, a custom bioreactor was designed to mimic pseudostatic culture conditions by integrating brief mechanical rotation during a 6-h static culture period. This method aimed to achieve an optimal aggregate size while improving cell viability. The findings revealed a 144-fold expansion of 3D NK-92MI cell aggregates, reaching an ideal size of 80–150 µm, significantly increasing both cell proliferation and survival rates. After 14 days of culture, the NK-92MI cells maintained their phenotype during the subsequent phase of cell activation. Moreover, these cells presented elevated levels of IFN-γ expression after IL-18 activation, resulting in enhanced NK cell-mediated cytotoxicity against K562 cells. This innovative strategy, which uses a closed suspension-based culture system, presents a promising approach for improving cell expansion and activation techniques in immunocellular therapy.

Sarcodon mushrooms are esteemed as a rare and highly valuable resource for both culinary and medicinal purposes. Ancient medical classics have documented their beneficial effects on conditions such as indigestion, loss of appetite, and neurological disorders. Modern phytochemical research into their secondary metabolites has led to the discovery of numerous bioactive compounds with significant biological activities. Despite notable achievements in the study of the chemical composition and bioactivity of Sarcodon mushrooms, a comprehensive understanding of these findings has been lacking. This review provides an exhaustive summary of the advancements in the phytochemistry of Sarcodon mushrooms, as well as the biological and pharmacological activities of the isolated compounds and crude extracts derived from Sarcodon over the past nine decades. A total of 100 secondary metabolites isolated from these mushrooms have been classified into five major categories based on their chemical structures, which exhibit bioactivities such as anti-tumour, neurotrophic, and neuroprotective, antioxidant, anti-inflammatory, antimicrobial, and hypoglycaemic properties. The aim of this study is to establish a scientific foundation for future research in drug discovery, biotechnological development, and the exploration of functional foods involving Sarcodon mushrooms.

The surge in urbanization has correspondingly given rise to exacerbated carbon footprint and burgeoning heavy metal (HM) contamination, constituting a critical impediment to the realization of environmentally sustainable urban development pathways. Therefore, it is highly essential to investigate the impacts of urbanization process on soil carbon, heavy metals (HMs), as well as their interrelationships. Employing remote sensing and land use data within a 45 km radius in Chongqing, this study selected 31 sites to assess the variation in urban green spaces (UGSs) carbon sequestration capabilities and associated HM pollution risks across differing urbanization levels. Results showed that urbanization dynamics and land use history play a more decisive role than current anthropogenic management in shaping the distribution of soil carbon and HMs within urban environments. The average soil organic carbon (SOC) distribution of UGSs is 8.47 mg ha−1 (1.50–24.20 mg ha−1), concurrent with moderate HM pollution showing Ni: 32.03–33.50 mg kg−1, Pb: 27.93–29.65 mg kg−1, Cu: 26.97–41.20 mg kg−1, while Cd exhibits the most severe pollution range of 0.23–0.30 mg kg−1. The rate of urbanization significantly influences SOC stocks, exhibiting an increase when the urbanization rate is below 70.79 % and a decrease upon surpassing this threshold. The concentration of HMs is predominantly determined by the historical usage of the land, with a marked escalation correlating with the duration of land utilization history. These relationships were quantitatively modeled through the application of fitted linear functions. The structural equation model demonstrated that UGSs operating without anthropogenic disturbance tend towards degradation, indicating that temporary homeostasis might be sustained via the addition of N and P nutrients and pH modulation. In conclusion, we formulate an Urban Green Spaces Development Hypothesis that aims to shed light on the multifaceted challenges encountered by cities amidst varying degrees of urbanization and, concurrently, to probe potential ameliorative strategies.

Abstract Background Gastric cancer (GC) ranks fifth in global cancer incidence and third in mortality rate among all cancer types. Circular RNAs (circRNAs) have been extensively demonstrated to regulate multiple malignant biological behaviors in GC. Emerging evidence suggests that several circRNAs derived from FNDC3B play pivotal roles in cancer. However, the role of circFNDC3B in GC remains elusive. Methods We initially screened circFNDC3B with translation potential via bioinformatics algorithm prediction. Subsequently, Sanger sequencing, qRT-PCR, RNase R, RNA-FISH and nuclear-cytoplasmic fractionation assays were explored to assess the identification and localization of circ0003692, a circRNA derived from FNDC3B. qRT-PCR and ISH were performed to quantify expression of circ0003692 in human GC tissues and adjacent normal tissues. The protein-encoding ability of circ0003692 was investigated through dual-luciferase reporter assay and LC/MS. The biological behavior of circ0003692 in GC was confirmed via in vivo and in vitro experiments. Additionally, Co-IP and rescue experiments were performed to elucidate the interaction between the encoded protein and c-Myc. Results We found that circ0003692 was significantly downregulated in GC tissues. Circ0003692 had the potential to encode a novel protein FNDC3B-267aa, which was downregulated in GC cells. We verified that FNDC3B-267aa, rather than circ0003692, inhibited GC migration in vitro and in vivo. Mechanistically, FNDC3B-267aa directly interacted with c-Myc and promoted proteasomal degradation of c-Myc, resulting in the downregulation of c-Myc-Snail/Slug axis. Conclusions Our study revealed that the novel protein FNDC3B-267aa encoded by circ0003692 suppressed GC metastasis through binding to c-Myc and enhancing proteasome-mediated degradation of c-Myc. The study offers the potential applications of circ0003692 or FNDC3B-267aa as therapeutic targets for GC. Graphical abstract The mechanism of circ0003692 in suppressing metastasis of GC. FNDC3B-267aa encoded by circ0003692 interacted with c-Myc and promoted the proteasomal degradation of c-Myc, thereby down-regulated c-Myc-Snail/Slug axis and EMT pathway.

Abstract Activation of the NF-κB pathway is strictly regulated to prevent excessive inflammatory and immune responses. In a well-known negative feedback model, IκBα-dependent NF-κB termination is a delayed response pattern in the later stage of activation, and the mechanisms mediating the rapid termination of active NF-κB remain unclear. Here, we showed IκBα-independent rapid termination of nuclear NF-κB mediated by CLK2, which negatively regulated active NF-κB by phosphorylating the RelA/p65 subunit of NF-κB at Ser180 in the nucleus to limit its transcriptional activation through degradation and nuclear export. Depletion of CLK2 increased the production of inflammatory cytokines, reduced viral replication and increased the survival of the mice. Mechanistically, CLK2 phosphorylated RelA/p65 at Ser180 in the nucleus, leading to ubiquitin‒proteasome-mediated degradation and cytoplasmic redistribution. Importantly, a CLK2 inhibitor promoted cytokine production, reduced viral replication, and accelerated murine psoriasis. This study revealed an IκBα-independent mechanism of early-stage termination of NF-κB in which phosphorylated Ser180 RelA/p65 turned off posttranslational modifications associated with transcriptional activation, ultimately resulting in the degradation and nuclear export of RelA/p65 to inhibit excessive inflammatory activation. Our findings showed that the phosphorylation of RelA/p65 at Ser180 in the nucleus inhibits early-stage NF-κB activation, thereby mediating the negative regulation of NF-κB.

Achieving high cell transfection efficiency is essential for various cell types in numerous disease applications. However, the efficient introduction of genes into natural killer (NK) cells remains a challenge. In this study, we proposed a design strategy for delivering exogenous genes into the NK cell line, NK-92, using a modified non-viral gene transfection method. Calcium phosphate/DNA nanoparticles (pDNA-CaP NPs) were prepared using co-precipitation methods and combined with low-voltage pulse electroporation to facilitate NK-92 transfection. The results demonstrated that the developed pDNA-CaP NPs exhibited a uniform diameter of approximately 393.9 nm, a DNA entrapment efficiency of 65.8%, and a loading capacity of 15.9%. Furthermore, at three days post-transfection, both the transfection efficiency and cell viability of NK-92 were significantly improved compared to standalone plasmid DNA (pDNA) electroporation or solely relying on the endocytosis pathway of pDNA-CaP NPs. This study provides valuable insights into a novel approach that combines calcium phosphate nanoparticles with low-voltage electroporation for gene delivery into NK-92 cells, offering potential advancements in cell therapy.

As a medicinal and edible homologous Chinese herb, Polygonatum sibiricum has been used as a primary ingredient in various functional and medicinal products. Damage to the intestinal mucosal barrier can lead to or worsen conditions such as type 2 diabetes and Alzheimer’s disease. Traditional Chinese medicine and its bioactive components can help prevent and manage these conditions by restoring the integrity of the intestinal mucosal barrier. This review delves into the mode of action of P. sibiricum polysaccharide in disease prevention and management through the restoration of the intestinal barrier. Polysaccharide from P. sibiricum effectively treats conditions by repairing the intestinal mucosal barrier, offering insights for treating complex diseases and supporting the application of P. sibiricum in clinical settings.

Abstract Knowledge regarding the ligament footprints in the canine stifle is essential for biomechanical modeling of the joint and patient-specific surgical planning for anatomical ligament reconstruction. The present study aimed to establish and evaluate deformable shape templates (DSTs) of the femur and tibia with footprints of the cruciate and collateral ligaments embedded for the noninvasive estimation of ligament footprint positions. To this end, a data set of computed tomography (CT)-derived surface models of the femur and tibia were established and used to build statistical shape models (SSMs). The contours of the stifle ligaments were obtained from CT scans of 27 hindlimb specimens with radio-opaque markings on the ligament footprints. The DST, constructed by embedding averaged footprint contours into the SSM, was used to estimate subject-specific ligament footprints in a leave-one-out cross-validation framework. The DST predictions were compared with those derived from radio-opaque-marked footprints. The results showed that the averaged Euclidean distances between the estimated and reference footprint centroids were less than 1.2 mm for the cruciate ligaments and 2.0 mm for the collateral ligaments. The DST appeared to provide a feasible alternative approach for noninvasively estimating the footprints of the stifle ligaments in vivo.

Abstract Introduction Observational studies have found that most patients with arthritis have depression. We aimed to determine the causal relationship between various types of arthritis and depression. Methods We conducted a two‐sample bidirectional Mendelian randomized (MR) analysis to determine whether there was a significant causal relationship between depression and multiple types of arthritis. The data of our study were derived from the publicly released genome‐wide association studies (GWASs) and the largest GWAS meta‐analysis. MR analysis mainly used inverse‐variance weighted method; supplementary methods included weighted median, weighted mode, and MR‐Egger using MR pleiotropy residual sum and outlier to detect and correct for the presence of pleiotropy. Results After adjusting for heterogeneity and horizontal pleiotropy, we found that depression was associated with an increased risk of osteoarthritis (OA) (OR = 1.02, 95%CI: 1.01–1.02, p = 2.96 × E − 5). In the reverse analysis, OA was also found to increase the risk of depression (OR = 1.10, 95%CI: 1.04–1.15, p = .0002). Depression only increased the risk of knee OA (KOA) (OR = 1.25, 95%CI: 1.10–1.42, p = 6.46 × E − 4). Depression could potentially increase the risk of spondyloarthritis (OR = 1.52, 95%CI: 1.19–1.94, p ≤ 8.94 × E − 4). Conclusion There is a bidirectional causal relationship of depression with OA. However, depression only augments the risk of developing KOA. Depression may increase the risk of spondyloarthritis and gout.

PurposeWe investigated the value of magnetic resonance imaging (MRI) histogram features, a non-invasive method, in assessing the changes in chemoresistance of colorectal cancer xenografts in rats.MethodsA total of 50 tumor-bearing mice with colorectal cancer were randomly divided into two groups: control group and 5-fluorouracil (5-FU) group. The MRI histogram characteristics and the expression levels of p53 protein and MRP1 were obtained at 24 h, 48 h, 72 h, 120 h, and 168 h after treatment.ResultsSixty highly repeatable MRI histogram features were obtained. There were 16 MRI histogram parameters and MRP1 resistance protein differences between groups. At 24 h after treatment, the MRI histogram texture parameters of T2-weighted imaging (T2WI) images (10%, 90%, median, energy, and RootMeanSquared) and D images (10% and Range) were positively correlated with MRP1 (r = 0.925, p = 0.005). At 48 h after treatment, histogram texture parameters of apparent diffusion coefficient (ADC) images (Energy) were positively correlated with the presence of MRP1 resistance protein (r = 0.900, p = 0.037). There was no statistically significant difference between MRI histogram features and p53 protein expression level.ConclusionsMRI histogram texture parameters based on T2WI, D, and ADC maps can help to predict the change of 5-FU resistance in colorectal cancer in the early stage and provide important reference significance for clinical treatment.

Abstract To study the role of Body Mass Index (BMI) and serum lipid profile molecules, as well as their derivative indexes in primary pterygium patients. The patient group consisted of 110 patients with primary pterygium diagnosed in our center between January 2019 and December 2020, while the control group consisted of 144 healthy persons of similar age and sex diagnosed during the same time period. The BMI, serum lipid profile molecules and their derivative indexes of both groups were analyzed retrospectively. In the patient group, 62 patients were overweight or obesity and 104 patients with dyslipidemia. Among them, body mass index (BMI), serum triglycerides (TG), total cholesterol (TC), low‐density lipoprotein cholesterol (LDL‐C) and apolipoprotein B (Apo‐B) levels were significantly higher than those in the control group (p 0.05). Logistic analysis indicated that obesity, TC and HDL‐C/LDL‐C ratio are independent risk factors influencing the onset of pterygium (p

A method for the simultaneous quantification of 13 bioactive compounds (psoralen, isopsoralen, isobavachin, bakuchalcone, neobabaisoflavone, bavachin, corylin, psoralidin, isobavachalcone, bavachinin, corylifol A, bavachalcone, and bakuchiol) by ultra‐high‐performance liquid chromatography coupled with triple quadrupole mass spectrometry has been developed and validated in rat plasma. Osthol was used as an internal standard and plasma samples were pretreated with one‐step liquid–liquid extraction. These analytes were separated using a gradient mobile phase system of water and acetonitrile at a flow rate of 0.2 mL/min on a reverse‐phase C18 column and analyzed in the selected multiple reactions monitoring mode. All calibration curves were linear (r > 0.9952) over the tested ranges. The intra‐ and interday accuracy and precisions of these analytes at three different concentration levels were within the acceptable limits of <15% at all concentrations. The mean recoveries of these analytes at three concentrations were more than 60.2% and the matrix effects were in the range of 85–115%. Stability studies proved that the analytes were stable under the tested conditions. The developed method was applied to evaluating the pharmacokinetic study of 13 bioactive compounds after oral administration of Psoraleae Fructus in rat of different genders. Some active compounds in Psoraleae Fructus had sex‐related pharmacokinetics. [ABSTRACT FROM AUTHOR]

A coupled line cross-shaped resonator (CLCSR) is proposed, which consists of four parallel coupled lines. By using even- and odd-mode approach, this resonator is characterized and designed to build up a wide band-pass filter. There are three transmission poles in the pass-band and two transmission zeros out of the pass-band. The positions of the transmission zeros are fixed. The transmission poles are determined and adjusted by the parameters: 1z, 2 z, 1k, and 2 k. Then two coupled line cross-shaped resonators are cascaded to realize a wide band-pass filter. The sharper selectivity and better performance can be obtained by cascading two CLCSRs. Good S-parameters are achieved as demonstrated in both simulated and measured results. [ABSTRACT FROM AUTHOR]

Background: The main bioactive components of Fructus psoraleae, such as psoralen and isopsoralen, are known to be hepatotoxic. However, its underlying mechanism is to be elucidated. Methods: To address this, SD rats were randomly divided into control group, 60 mg/kg psoralen group and 60 mg/kg isopsoralen group. Blood was collected to detect serum biochemical indices. RNA was extracted from liver samples, and then, cDNA gene expression profiles were analysed. Results: Psoralen administration significantly up‐regulated serum AST (aspartate aminotransferase) while addition of isopsoralen increased serum ALT (alanine aminotransferase), AST, TBA (total bile acid) and TG (total triglyceride) levels. A total of 172 differentially expressed genes (DEGs) were acquired between psoralen group and control group while 884 DEGs were screened between isopsoralen group and control group. Chemical Carcinogenesis and Metabolism of Xenobiotics by Cytochrome P450 were the two most significantly enriched pathways as revealed by DEGs. Liver was the most impacted organ, and endoplasmic reticulum was the most impacted organelle in subcellular level. Finally, some kinds of cancers and cytochrome p450 oxidoreductase deficiency were predicted. Taken together, psoralen and isopsoralen might cause hepatotoxicity mainly through cytochrome P450 metabolism of xenobiotics. Furthermore, Cyp1a1, Cyp1a2, Gstm1 and Akr7a3 worked as key genes in hepatotoxicity. Moreover, endoplasmic reticulum was the main target subcellular structure in hepatotoxicity induced by psoralen and isopsoralen. [ABSTRACT FROM AUTHOR]

Abstract The intestinal hormone and neuromodulator cholecystokinin (CCK) receptors CCK1R and CCK2R act as a signaling hub in brain–gut axis, mediating digestion, emotion, and memory regulation. CCK receptors exhibit distinct preferences for ligands in different posttranslational modification (PTM) states. CCK1R couples to Gs and Gq, whereas CCK2R primarily couples to Gq. Here we report the cryo-electron microscopy (cryo-EM) structures of CCK1R–Gs signaling complexes liganded either by sulfated cholecystokinin octapeptide (CCK-8) or a CCK1R-selective small-molecule SR146131, and CCK2R–Gq complexes stabilized by either sulfated CCK-8 or a CCK2R-selective ligand gastrin-17. Our structures reveal a location-conserved yet charge-distinct pocket discriminating the effects of ligand PTM states on receptor subtype preference, the unique pocket topology underlying selectivity of SR146131 and gastrin-17, the conformational changes in receptor activation, and key residues contributing to G protein subtype specificity, providing multiple structural templates for drug design targeting the brain–gut axis.

Abstract Background Chlamydia trachomatis (CT) and Neisseria gonorrhoeae (NG) infections are prevalent among men who have sex with men (MSM) in China. However, compared to syphilis and HIV, the testing rate for chlamydia and gonorrhea remains low. The purpose of this pilot study was to evaluate the feasibility for conducting rapid nucleic acid test for chlamydia and gonorrhea in MSM community-based organizations (CBO). Method We recruited our participants through an MSM CBO where free HV and syphilis testing were routinely provided. We collected data including social-demographic background, sexual history, chlamydia and gonorrhea testing history, and reasons for accepting this on-site rapid testing. Urine and/or anorectal swab samples were collected and tested for chlamydia and gonorrhea on-site and the testing results were delivered in about 1.5 h. Positive cases received on-site free treatment. Results From August 2020 to October 2020, 634 MSM visited the CBO for syphilis and HIV testing and 158 (158/634, 24.9%) accepted the on-site chlamydia and gonorrhea rapid test, 135 were finally enrolled. The positive rate fo chlamydia was 16.3% (22/135) and 3.0% (4/135) for gonorrhea, respectively. Only 19.3% participants had previously undergone chlamydia and gonorrhea testing and 68.9% (93/135) participants reported that they had heard of gonorrhea, 47.4% (64/135) had heard of chlamydia. The main reason for testing was “free for charge” (66.2%), followed by “convenient, ‘shorter waiting time” (45.2%) and “had high-risk sexual behavior recently” (16.3%). Conclusions This pilot study showed that the chlamydia and gonorrhea infection rate remains high among MSM, while the testing rate was low. On-site rapid testing is feasible and potentially preferred by MSM.

BackgroundColorectal cancer (CRC) is among the most common malignant cancers worldwide, and its development is influenced by inflammation, nutrition, and the immune status. Therefore, we combined C-reactive protein (CRP), albumin, and lymphocyte, which could reflect above status, to be the CRP-albumin-lymphocyte (CALLY) index, and evaluated its association with overall survival (OS) in patients with CRC.MethodsThe clinicopathological and laboratory characteristics of 1260 patients with CRC were collected from the Investigation on Nutrition Status and Clinical Outcome of Common Cancers (INSCOC) study. Cox regression analysis was performed to assess the association between the CALLY index and OS. A nomogram including sex, age, the CALLY index and TNM stage was constructed. The Concordance Index (C-index) was utilized to evaluate the prognostic value of the CALLY index and classical CRC prognostic factors, such as modified Glasgow prognostic score (mGPS), neutrocyte to lymphocyte ratio (NLR), systemic immune inflammation index (SII), and platelet to lymphocyte ratio (PLR), as well as to assess the prognostic value of the nomogram and TNM stage.ResultsMultivariate Cox regression analyses demonstrated that the CALLY index was independently associated with OS in patients with CRC [Hazard ratio (HR) = 0.91, 95% confidence interval (CI) = 0.87-0.95, P

PurposePrevious studies have shown that both hand grip strength (HGS) and the modified Glasgow Prognostic Score (mGPS) are associated with poor clinical outcomes in patients with liver cancer. In spite of this, no relevant studies have been conducted to determine whether the combination of HGS and mGPS can predict the prognosis of patients with liver cancer. Accordingly, this study sought to explore this possibility.MethodsThis was a multicenter study of patients with liver cancer. Based on the optimal HGS cutoff value for each sex, we determined the HGS cutoff values. The patients were divided into high and low HGS groups based on their HGS scores. An mGPS of 0 was defined as low mGPS, whereas scores higher than 0 were defined as high mGPS. The patients were combined into HGS-mGPS groups for the prediction of survival. Survival analysis was performed using Kaplan–Meier curves. A Cox regression model was designed and adjusted for confounders. To evaluate the nomogram model, receiver operating characteristic curves and calibration curves were used.ResultsA total of 504 patients were enrolled in this study. Of these, 386 (76.6%) were men (mean [SD] age, 56.63 [12.06] years). Multivariate analysis revealed that patients with low HGS and high mGPS had a higher risk of death than those with neither low HGS nor high mGPS (hazard ratio [HR],1.50; 95% confidence interval [CI],1.14–1.98; p = 0.001 and HR, 1.55; 95% CI, 1.14–2.12, p = 0.001 respectively). Patients with both low HGS and high mGPS had 2.35-fold increased risk of death (HR, 2.35; 95% CI, 1.52–3.63; p

PurposeUniversity freshmen are particularly vulnerable as they are undergoing the transition from high school to university with a range of changes. Sleep problems among this group in the Qinghai–Tibet Plateau of China were barely studied. This study aimed to explore sleep disturbance, and its association with quality of life (QoL) and demographic and clinical characteristics among university freshmen in Qinghai–Tibet Plateau, China.MethodsA multistage stratified cluster random sampling method was performed to recruit student participants with a structured questionnaire to collect sociodemographic and clinical characteristics, and lifestyle behaviors. Sleep disturbance including three aspects of sleep disturbance (i.e., difficulty initiating sleep (DIS), difficulty maintaining sleep (DMS), and early morning awakening (EMA)) was assessed using standardized measurement. Multiple logistic regression models were applied to analyze the data.ResultsAmong included 2,769 freshmen, the prevalence of sleep disturbance was 14.8% (95% CI: 14.2–15.5%), and corresponding prevalence of DIS, DMS, and EMA was 8.2% (95% CI: 7.7–8.7%), 8.3% (95% CI: 7.8–8.8%), and 4.2% (95% CI: 3.8–4.6%), respectively. Freshmen with sleeping disturbance had significantly lower QoL in physical [F(1, 2769) = 60.23, p < 0.001], psychological [F(1, 2769) = 46.18, p < 0.001], social [F(1, 2769) = 23.04, p < 0.001], and environment [F(1, 2769) = 6.07, p = 0.01] domains. Multiple logistic regression analyses revealed that having breakfast five times a week or less (less than three times, OR = 1.79, 95% CI: 1.34–2.40; 3–5 times, OR = 1.40, 95% CI: 1.09–1.79), self-perceived severe Internet dependence (OR = 1.71, 95% CI: 1.11–2.65), self-perceived poor health status (OR = 3.44, 95% CI: 2.06–5.74), high academic stress (OR = 1.42, 95% CI: 1.13–1.78), poor relationship with classmates (OR = 3.44, 95% CI: 1.53–7.71), and severe ADHD symptoms (OR = 1.08, 95% CI: 1.05–1.12) were positively associated with sleeping disturbance.ConclusionSleep disturbance was common among freshmen and is associated with poorer QoL. Prevention and intervention strategies should be developed and implemented, especially among the vulnerable university freshman groups.