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BackgroundBladder cancer (BC) is a disease with significant heterogeneity and poor prognosis. The prognosis and therapeutic response of BC patients are significantly influenced by endothelial cells in the tumor microenvironment. In order to understand BC from the perspective of endothelial cells, we orchestrated molecular subtypes and identified key genes.MethodsSingle-cell and bulk RNA sequencing data were extracted from online databases. R and its relative packages were used to analyze these data. Cluster analysis, prognostic value analysis, function analysis, immune checkpoints, tumor immune environment and immune prediction were conducted.ResultsFive endothelial-related genes (CYTL1, FAM43A, HSPG2, RBP7, and TCF4) divided BC patients in the TCGA, GSE13507, and GSE32894 datasets into two clusters, respectively. In prognostic value analysis, patients in the cluster 2 were substantially associated with worse overall survival than those in the cluster 1 according to the results of TCGA, GSE13507 and GSE32894 datasets. In the results of functional analysis, the endothelial-related clusters was enriched in immune-related, endothelial-related and metabolism-related pathways. Samples in the cluster 1 had a statistically significant increase in CD4+ T cells and NK-cell infiltration. Cluster 1 was positively correlated with the cancer stem score and tumor mutational burden score. The results of immune prediction analysis indicated that 50.6% (119/235) of patients in the cluster 1 responded to immunotherapy, while the response rate in the cluster 2 decreased to 16.7% (26/155).ConclusionIn this study, we categorized and discovered distinctive prognosis-related molecular subtypes and key genes from the perspective of endothelial cells at the genetic level by integrating single-cell and bulk RNA sequencing data, primarily to provide a roadmap for precision medicine.

IntroductionBladder cancer (BLCA) is one of the most lethal diseases. COL10A1 is secreted small-chain collagen in the extracellular matrix associated with various tumors, including gastric, colon, breast, and lung cancer. However, the role of COL10A1 in BLCA remains unclear. This is the first research focusing on the prognostic value of COL10A1 in BLCA. In this research, we aimed to uncover the association between COL10A1 and the prognosis, as well as other clinicopathological parameters in BLCA.MethodsWe obtained gene expression profiles of BLCA and normal tissues from the TCGA, GEO, and ArrayExpress databases. Immunohistochemistry staining was performed to investigate the protein expression and prognostic value of COL10A1 in BLCA patients. GO and KEGG enrichment along with GSEA analyses were performed to reveal the biological functions and potential regulatory mechanisms of COL10A1 based on the gene co-expression network. We used the “maftools” R package to display the mutation profiles between the high and low COL10A1 groups. GIPIA2, TIMER, and CIBERSORT algorithms were utilized to explore the effect of COL10A1 on the tumor immune microenvironment.ResultsWe found that COL10A1 was upregulated in the BLCA samples, and increased COL10A1 expression was related to poor overall survival. Functional annotation of 200 co-expressed genes positively correlated with COL10A1 expression, including GO, KEGG, and GSEA enrichment analyses, indicated that COL10A1 was basically involved in the extracellular matrix, protein modification, molecular binding, ECM-receptor interaction, protein digestion and absorption, focal adhesion, and PI3K-Akt signaling pathway. The most commonly mutated genes of BLCA were different between high and low COL10A1 groups. Tumor immune infiltrating analyses showed that COL10A1 might have an essential role in recruiting infiltrating immune cells and regulating immunity in BLCA, thus affecting prognosis. Finally, external datasets and biospecimens were used, and the results further validated the aberrant expression of COL10A1 in BLCA samples.ConclusionsIn conclusion, our study demonstrates that COL10A1 is an underlying prognostic and predictive biomarker in BLCA.

This paper proposes an information enhancement network based on self-supervised learning (SEL-Net) for runway area detection. During the self-supervised learning phase, the distinctive attributes of PolSAR multi-channel data are fully harnessed to enhance the generated pretrained model’s focus on airport runway areas. During the detection phase, this paper presents an improved U-Net detection network. Edge Feature Extraction Modules (EEM) are integrated into the encoder and skip connection sections, while Semantic Information Transmission Modules (STM) are embedded into the decoder section. Furthermore, improvements have been applied to the network’s upsampling and downsampling architectures. Experimental results demonstrate that the proposed SEL-Net effectively addresses the issues of high false alarms and runway integrity, achieving a superior detection performance.

A method for simultaneous determination of 10 veterinary antibiotics residues in pork by QuEChERS purification combined with ultra performance liquid chromatography tandem quadrupole-time of flight mass spectrometry (UHPLC-Q-TOF/MS) was developed. The sample was extracted and purified by Na2EDTA-Mcllvaine buffer solution-0.1% formic acid acetonitrile-NaCl-anhydrous Na2SO4-C18. The separation was performed on an Infinity Lab Poroshell 120 EC-C18 column and analyzed under the positive ion multi-reaction monitoring mode. The results showed that the correlation coefficients of 10 veterinary drugs were greater than 0.99, and the linear range was 5.0~100.0 μg/kg. The average recoveries were 72.3%~117.3% at the spiked levels of 5, 10, 20 μg/kg. The intra-day relative standard deviations (RSD) was 0.9% to 10.4%, and the within-day RSD was 1.1% to 13.4%. The limit of detection (LOD) was 0.25~1.0 μg/kg, and the limit of quantification (LOQ) was 0.5~5 μg/kg. This method was used to detect 50 fresh raw pork samples purchased in the market. One sample was positive for tetracycline, and none of the other samples were detected. The method was simple and fast to operate, had good precision and limit of quantification, and was suitable for the rapid detection of 10 antibiotic veterinary drugs in pork.

Abstract Transarterial chemoembolization (TACE) combined with apatinib has been used for advanced hepatocellular carcinoma (HCC), and the efficacy is good. The study was conducted to compare the efficacy and safety of drug-eluting bead TACE plus apatinib (D-TACE-A) with conventional TACE plus apatinib (C-TACE-A) in the treatment of HCC with portal vein tumor thrombus (PVTT). A total of 130 continuous patients who received D-TACE-A or C-TACE-A were included in the study from January 2017 to June 2020. Propensity score matching (PSM) was used to reduce potential selection bias. Before PSM, the median overall survival (mOS) (14 months) and median progression-free survival (mPFS) (7 months) in the C-TACE-A group were longer than the mOS (9 months; P = 0.001) and mPFS (4 months; P = 0.001) in the D-TACE-A group. After PSM, the mOS (14 months vs 9 months; P = 0.039) and mPFS (7 months vs 5 months; P = 0.009) in the C-TACE-A group were longer than those in the D-TACE-A group. In the multivariate regression analysis, C-TACE-A reduced the mortality rate and tumor progression rate compared with D-TACE-A. For the subgroup analysis, patients with VP1–2, without extrahepatic metastases, and with multiple TACE sessions who received C-TACE-A had a lower death risk and tumor progression risk than patients who received D-TACE-A. Before PSM, there was no statistically significant difference in any grade or grade III/IV adverse events (all P > 0.05). C-TACE-A could prolong mOS and mPFS in patients with PVTT, especially for patients with VP1–2 stage PVTT, no extrahepatic tumor metastases, and multiple TACE sessions.

Abstract In the face of a burgeoning stream of e‐waste globally, e‐waste recycling becomes increasingly imperative, not only to mitigate the environmental and health risks it poses but also as an urban mining strategy for resource recovery of precious metals, rare Earth elements, and even plastics. As part of the continual efforts to develop greener alternatives to conventional approaches of e‐waste recycling, biologically assisted degradation of e‐waste offers a promising recourse by capitalising on certain microorganisms' innate ability to interact with metals or degrade plastics. By harnessing emerging genetic tools in synthetic biology, the evolution of novel or enhanced capabilities needed to advance bioremediation and resource recovery could be potentially accelerated by improving enzyme catalytic abilities, modifying substrate specificities, and increasing toxicity tolerance. Yet, the management of e‐waste presents formidable challenges due to its massive volume, high component complexity, and associated toxicity. Several limitations will need to be addressed before nascent laboratory‐scale achievements in bioremediation can be translated to viable industrial applications. Nonetheless, vested groups, involving both start‐up and established companies, have taken visionary steps towards deploying microbes for commercial implementation in e‐waste recycling.

Introduction: Bu-Fei-Huo-Xue capsule (BFHX) has been used to treat pulmonary fibrosis (PF) in clinic. However, the mechanism of Bu-Fei-Huo-Xue capsule on pulmonary fibrosis remains unclear. Recent studies have shown that the changes in gut microbiota were closely related to the progression of pulmonary fibrosis. Modulating gut microbiota provides new thoughts in the treatment of pulmonary fibrosis.Methods: In this study,a mouse model of pulmonary fibrosis was induced using bleomycin (BLM) and treated with Bu-Fei-Huo-Xue capsule. We firstly evaluated the therapeutic effects of Bu-Fei-Huo-Xue capsule on pulmonary fibrosis model mice. Besides,the anti-inflammatory and anti- oxidative effects of Bu-Fei-Huo-Xue capsule were evaluated. Furthermore, 16S rRNA sequencing was used to observe the changes in gut microbiota in pulmonary fibrosis model mice after Bu-Fei-Huo-Xue capsule treatment.Results: Our results showed that Bu-Fei-Huo-Xue capsule significantly reduced the collagen deposition in pulmonary fibrosis model mice. Bu-Fei-Huo-Xue capsule treatment also reduced the levels and mRNA expression of pro-inflammatory cytokines and inhibited the oxidative stress in lung. 16S rRNA sequencing showed that Bu-Fei-Huo-Xue capsule affected the diversity of gut microbiota and the relative abundances of gut microbiota such as Lactobacillus, Lachnospiraceae_NK4A136_group, and Romboutsia.Conclusion: Our study demonstrated the therapeutic effects of Bu-Fei-Huo-Xue capsule on pulmonary fibrosis. The mechanisms of Bu-Fei-Huo-Xue capsule on pulmonary fibrosis may be associated with regulating gut microbiota.

Background: To investigate the function of sildenafil on diseases other than urogenital system, an umbrella review was conducted.Methods: Meta-analysis and systematic reviews on this topic were comprehensively evaluated in this umbrella review. Quality of evidence was evaluated through AMSTAR and the Grading of Recommendations, Assessment, Development and Evaluation system to generate a reliable and valid conclusion.Results: 77 out of 1164 meta-analysis were enrolled. 33 significant outcomes and 41 non-significant outcomes were extracted from all eligible articles. We found sildenafil did significant help in reducing arterial systolic pressure, mean pulmonary arterial pressure, pulmonary arterial pressure, systolic pulmonary arterial pressure in patients with pulmonary and cardiovascular diseases. Besides, sildenafil also improved exercise capacity or performance in patients with pulmonary and cardiovascular diseases. Other than these patients, this drug contributed great help in pregnant women with fetal growth restriction and preeclampsia by increasing the weight of newborns and lowering uterine and umbilical pulsatility indices. Additionally, it was reported that utilization of sildenafil has brought increased risk of melanoma.Conclusion: We can conclude from our study that sildenafil played an important role in many fields, especially in vascular protection. This finding provides a strong evidence for further expansion of sildenafil utilization in other diseases.

Due to its wide use in agriculture, a convenient and sensitive detection method for triazophos is urgent need. In this study, a terbium-based metal-organic framework (Tb-MOF) is mildly prepared as a fluorescent probe for triazophos detection. The fluorescence of Tb-MOF can be quenched by triazophos through the inner filter effect (IFE) and static quenching effect (SQE). The fluorescence analysis exhibits high sensitivity and limit of detection of 0.12 ng·mL−1 with a linear range of 3–800 ng·mL−1 to triazophos. The fluorescence analysis displays good selectivity towards triazophos. In addition, this method has been successfully applied to the detection of triazophos in tap water and strawberry with good recovery rates. More importantly, a fluorescent paper-based sensor and a logic gate operation for the detection of triazophos based on the Tb-MOF are designed. This strategy was simple, free of modification and complicated operation, and easy to operate, which has good prospects for future applications of triazophos detection.

To improve the grinding efficiency and service life of rail grinding wheels, a surface porous CBN/Cu-Sn-Zn compact abrasive is prepared. This work discussed the performance of Cu-Sn metal bond used for preparing agglomerated abrasives, the influence of pore structure on CBN agglomerated abrasive and the effect of agglomerated abrasive on the structural strength of grinding wheel. The grinding effect of grinding wheel before and after compound abrasive addition was evaluated by rail grinding experiment. The results show that the best porous CBN agglomerated abrasive sample has a flexural strength of 78.5 MPa, an impact strength of 5.5 kJ/m2, and a surface porosity of 30%～40%. The combined use of abrasive can effectively combine the high hardness of CBN with the good impact toughness of zirconium corundum. The grinding efficiency and grinding quality of rail grinding wheels with 20% volume concentration accumulated abrasives are further improved.

Backgrounds Adenocarcinoma of the bladder (ACB) rarely occurs but is associated with poor outcome. We aim to establish reliable nomograms for estimating cancer-specific survival (CSS) and overall survival (OS) of ACB patients. Methods ACB patients were retrieved from the Surveillance, Epidemiology, and End Results (SEER) database (2004–2015). A total of 1,149 patients were randomly divided into training cohort (n = 692) and validation cohort (n = 457). Multivariate Cox proportional hazards regression models were employed to identify independent prognostic factors. Nomograms predicting OS and CSS were constructed utilizing screened factors. The performance of nomograms was internally and externally validated by calibration curves, the receiver operating characteristic (ROC) curves, concordance index (C-index), and decision curve analysis (DCA). Results OS nomogram incorporated age, race, histologic grade, American Joint Committee of Cancer (AJCC) stage, metastasis, surgery, chemotherapy, and tumor size. The C-indices were 0.754 (95% CI: 0.732–0.775) for training set and 0.743 (95% CI: 0.712–0.767) for validation set. Meanwhile, the calibration plots for 3- and 5-year OS displayed fine concordance between actual and predicted outcomes. In addition, higher areas under the curve (AUCs) were seen in training cohort (3-year: 0.799 vs. 0.630; 5-year: 0.797 vs. 0.648) and validation cohort (3-year: 0.802 vs. 0.662; 5-year: 0.752 vs. 0.660). Finally, DCA curves of the nomograms exhibited larger net benefits than AJCC stage. CSS nomogram showed similar results. Conclusion Our study constructed and validated nomograms with improved discriminative abilities and clinical benefits to predict the survival outcomes of ACB patients. The models might assist clinicians in optimizing therapeutic management on individual levels.

Abstract Background and aim The association between iron-metabolism-related variables and liver fibrosis in chronic hepatitis C and nonalcoholic fatty liver disease is now well known. However, the relationship has not been extensively studied in autoimmune hepatitis (AIH). We aimed to investigate the association between variables associated with iron metabolism and advanced liver fibrosis among untreated patients with AIH. Methods Ninety-seven untreated AIH patients were enrolled in this cross-sectional study. All participants underwent iron metabolism index detection and liver biopsy. Multiple logistic regression analysis was used to explore the association of iron-metabolism-related variables with advanced liver fibrosis. Results Among the 97 AIH patients, 38 (39.2%) had advanced liver fibrosis, and 59 (60.8%) did not. In multivariate logistic regression analysis, immunoglobulin G (odds ratio [OR], 1.123; 95% confidence interval [CI] 1.023–1.232, P = 0.014), platelet count (OR 0.988; 95% CI 0.979–0.997, P = 0.013), prothrombin time (OR 1.758; 95% CI 1.143–2.704, P = 0.010) and ferritin (OR 1.002; 95% CI 1.001–1.004, P = 0.012) were independent risk factors for predicting advanced liver fibrosis in AIH patients. Conclusion Higher serum ferritin was independently associated with advanced liver fibrosis among patients with treatment-naive AIH.

Abstract Distant metastasis remains the major cause for treatment failure in patients with nasopharyngeal carcinoma (NPC). Thus, it is necessary to investigate the underlying regulation mechanisms and potential biomarkers for NPC metastasis. Nogo-B (neurite outgrowth inhibitor B), encoded by reticulon-4, has been shown to be associated with the progression and advanced stage of several cancer types. However, the relationship between Nogo-B and NPC remains unknown. In this study, we found that higher expression of Nogo-B was detected in NPC cells and tissues. Higher expression of Nogo-B was statistically relevant to N stage, M stage, and poor prognosis in NPC patients. Further functional investigations indicated that Nogo-B overexpression could increase the migration, invasion, and metastasis ability of NPC cells in vitro and in vivo. Mechanistically, Nogo-B promoted epithelial-mesenchymal transition (EMT) and enhanced the invasive potency by interacting directly with its receptor NgR3 in NPC. Additionally, overexpression of Nogo-B could upregulate the protein levels of p-RhoA, SRF, and MRTFA. A positive relationship was found between the expression of Nogo-B and the p-RhoA in NPC patients as well as in mouse lung xenografts. Nogo-Bhigh p-RhoAhigh expression was significantly associated with N stage, M stage, and poor prognosis in NPC patients. Notably, CCG-1423, an inhibitor of the RhoA-SRF-MRTFA pathway, could reverse the invasive potency of Nogo-B and NgR3 in NPC cell lines, and decrease the expression of N-Cadherin, indicating that CCG-1423 may be a potential target drug of NPC. Taken together, our findings reveal that Nogo-B enhances the migration and invasion potency of NPC cells via EMT by binding to its receptor NgR3 to regulate the RhoA-SRF-MRTFA pathway. These findings could provide a novel insight into understanding the metastasis mechanism and targeted therapy of advanced NPC.

Abstract Background Ovarian serous cystadenocarcinoma is one of the most serious gynecological malignancies. Circular RNA (circRNA) is a type of noncoding RNA with a covalently closed continuous loop structure. Abnormal circRNA expression might be associated with tumorigenesis because of its complex biological mechanisms by, for example, functioning as a microRNA (miRNA) sponge. However, the circRNA expression profile in ovarian serous cystadenocarcinoma and their associations with other RNAs have not yet been characterized. The main purpose of this study was to reveal the circRNA expression profile in ovarian serous cystadenocarcinoma. Methods We collected six specimens from three patients with ovarian serous cystadenocarcinoma and adjacent normal tissues. After RNA sequencing, we analyzed the expression of circRNAs with relevant mRNAs and miRNAs to characterize potential function. Results 15,092 unique circRNAs were identified in six specimens. Approximately 46% of these circRNAs were not recorded in public databases. We then reported 353 differentially expressed circRNAs with oncogenes and tumor-suppressor genes. Furthermore, a conjoint analysis with relevant mRNAs revealed consistent changes between circRNAs and their homologous mRNAs. Overall, construction of a circRNA–miRNA network suggested that 4 special circRNAs could be used as potential biomarkers. Conclusions Our study revealed the circRNA expression profile in the tissues of patients with ovarian serous cystadenocarcinoma. The differential expression of circRNAs was thought to be associated with ovarian serous cystadenocarcinoma in the enrichment analysis, and co-expression analysis with relevant mRNAs and miRNAs illustrated the latent regulatory network. We also constructed a complex circRNA–miRNA interaction network and then demonstrated the potential function of certain circRNAs to aid future diagnosis and treatment.

Abstract An overreliance on commercial, kit-based RNA extraction in the molecular diagnoses of infectious disease presents a challenge in the event of supply chain disruptions and can potentially hinder testing capacity in times of need. In this study, we adapted a well-established, robust TRIzol-based RNA extraction protocol into a high-throughput format through miniaturization and automation. The workflow was validated by RT-qPCR assay for SARS-CoV-2 detection to illustrate its scalability without interference to downstream diagnostic sensitivity and accuracy. This semi-automated, kit-free approach offers a versatile alternative to prevailing integrated solid-phase RNA extraction proprietary systems, with the added advantage of improved cost-effectiveness for high volume acquisition of quality RNA whether for use in clinical diagnoses or for diverse molecular applications.

Smart security based on object detection is one of the important applications of edge computing in IoT. Anchors in object detection refer to points on the feature map, which can be used to generate anchor boxes and serve as training samples. Current object detection models do not consider the aspect ratio of the ground-truth boxes in anchor assignment and are not well-adapted to objects with very different shapes. Therefore, this paper proposes the Lightweight Anchor Dynamic Assignment algorithm (LADA) for object detection. LADA does not change the structure of the original detection model; first, it selects an equal proportional center region based on the aspect ratio of the ground-truth box, then calculates the combined loss of anchors, and finally divides the positive and negative samples more efficiently by dynamic loss threshold without additional models. The algorithm solves the problems of poor adaptability and difficulty in the selection of the best positive samples based on IoU assignment, and the sample assignment for eccentric objects and objects with different aspect ratios was more reasonable. Compared with existing sample assignment algorithms, the LADA algorithm outperforms the MS COCO dataset by 1.66% over the AP of the baseline FCOS, and 0.76% and 0.24% over the AP of the ATSS algorithm and the PAA algorithm, respectively, with the same model structure, which demonstrates the effectiveness of the LADA algorithm.

Purpose: Many studies identified that the preoperative neutrophil-to-lymphocyte ratio (PNLR) was associated with patient prognosis in non-muscle-invasive bladder cancer (NMIBC). We hypothesized that PNLR could be prognostic in patients with histological variants of NMIBC (VH-NMIBC). Materials and Methods: This retrospective study included patients with VH-NMIBC admitted at our center between January 2009 and May 2019. The best cut-off value of NLR was measured by the receiver operating characteristic curve and Youden index. The Kaplan-Meier method and Cox proportional hazard regression models were employed to evaluate the association between PNLR and disease prognosis, including recurrence-free survival (RFS), progression-free survival (PFS), cancer-specific survival (CSS), and overall survival (OS). Results: A total of 243 patients with VH-NMIBC were enrolled in our study. According to the Kaplan-Meier method results, patients with PNLR ≥2.2 were associated with poor RFS (p

Abstract Background The cause and underlying molecular mechanisms of head and neck squamous cell carcinoma (HNSCC) are unclear. Our study aims to identify the key genes associated with HNSCC and reveal potential biomarkers. Methods In this study, the expression profile dataset GSE83519 of the Gene Expression Omnibus database and the RNA sequencing dataset of HNSCC of The Cancer Genome Atlas were included for analysis. Sixteen differentially expressed genes were screened from these two datasets using R software. Gene Expression Profiling Interactive Analysis 2 (GEPIA2) was then adopted for survival analysis, and finally, three key genes related to the overall survival of HNSCC patients were identified. Furthermore, we verified these three genes using the Oncomine database and from real-time PCR and immunohistochemistry results from HNSCC tissues. Results The expression data of 44 samples from GSE83519 and 545 samples from TCGA-HNSC were collected. Using bioinformatics, the two databases were integrated, and 16 DEGs were screened out. Gene Ontology (GO) enrichment analysis showed that the biological functions of DEGs focused primarily on the apical plasma membrane and regulation of anoikis. Kyoto Encyclopedia of Genes and Genomes (KEGG) signalling pathway analysis showed that these DEGs were mainly involved in drug metabolism-cytochrome P450 and serotonergic synapses. Survival analysis identified three key genes, CEACAM5, CEACAM6 and CLCA4, that were closely related to HNSCC prognosis. The Oncomine database, qRT–PCR and IHC verified that all 3 key genes were downregulated in most HNSCC tissues compared to adjacent normal tissues. Conclusions This study indicates that integrated bioinformatics analyses play an important role in screening for differentially expressed genes and pathways in HNSCC, helping us better understand the biomarkers and molecular mechanism of HNSCC.

Metastasis of head and neck squamous cell carcinoma rarely occurs in hepatic cancer and has a poor prognosis (median survival of 4 months). The efficacy of immunotherapy for these patients remains unknown. Herein, we present a patient with hypopharyngeal carcinoma metastasis to the liver with TERT and TP53 mutations together with a combined positive score of 70. The tumor invaded the abdominal wall, liver, inferior vena cava and retroperitoneal lymph nodes. The patient was treated with pembrolizumab combined with cisplatin and 5-FU for four cycles and has been maintained on pembrolizumab monotherapy until now. The patient achieved a near complete response of hepatic and subcutaneous metastases, and the tumor thrombus disappeared completely. The patient developed grade I rashes on the trunk, which were considered immune-related adverse events; thus, the patient presented a significant tumor response and good tolerance to the therapeutic strategy. On the basis of this observation, pembrolizumab-based therapeutic strategies may be an effective alternative for metastatic hypopharyngeal carcinoma and may prolong overall survival and progression-free survival, which should be confirmed by more patients in the future. Immune-related adverse events also need attention.

This study builds a conceptual model of strategic decision-making ability that leads to entrepreneurial performance (EP) based on the two-system decision-making theory and logical analysis. An empirical approach using structural equation modeling – artificial neural network (SEM-ANN) was performed to describe the linear and nonlinear relationships in the proposed model. The empirical results reveal that strategic decision-making abilities are affected by five factors: attention, memory, thinking, emotion, and sentiment, and whose influence mechanisms and degrees are varied. Results also describe that these abilities have a positive effect on overall EP. Therefore, results suggest that businesses’ strategic decision-making is usually strengthened when entrepreneurs have a clear understanding of these influencing elements, and the interaction between them leads to improved performance.

BackgroundCuproptosis is a novel form of programmed cell death termed as Cu-dependent cytotoxicity. However, the roles of cuproptosis-associated genes (CAGs) in lung adenocarcinoma (LUAD) have not been explored comprehensively.MethodsWe obtained CAGs and utilized consensus molecular clustering by “non-negative matrix factorization (NMF)” to stratify LUAD patients in TCGA (N = 511), GSE13213 (N = 117), and GSE31210 (N = 226) cohorts. The ssGSEA and CIBERSORT algorithms were used to evaluate the relative infiltration levels of immune cell types in tumor microenvironment (TME). The risk score based on CAGs was calculated to predict patients’ survival outcomes.ResultsWe identified three cuproptosis-associated clusters with different clinicopathological characteristics. We found that the cuproptosis-associated cluster with the worst survival rates exhibited a high enrichment of activated CD4/8+ T cells. In addition, we found that the cuproptosis-associated risk score could be used for patients’ prognosis prediction and provide new insights in immunotherapy of LUAD patients. Eventually, we constructed a nomogram-integrated cuproptosis-associated risk score with clinicopathological factors to predict overall survival in LUAD patients, with 1-, 3-, and 5-year area under curves (AUCs) being 0.771, 0.754, and 0.722, respectively, all of which were higher than those of the TNM stage.ConclusionsIn this study, we uncovered the biological function of CAGs in the TME and its correlations with clinicopathological parameters and patients’ prognosis in LUAD. These findings could provide new angles for immunotherapy of LUAD patients.

Background: We sought to determine whether leucine zipper protein 2 (LUZP2) could benefit men with prostate cancer (PCa) undergoing radical radiotherapy (RT) or prostatectomy (RP). Methods: Analysis was done on differentiating expression, clinical prognosis, co-expressed genes, immune infiltration, and epigenetic changes. All of our analyses were done using the R software (version 3.6.3) and the appropriate packages. Results: In terms of PCa, tumor samples expressed LUZP2 more than normal samples did. In the TCGA database and GSE116918, we found that LUZP2 was the only independent risk factor for PCa. The shared enriched pathways for patients undergoing RP or RT were cell-cell adhesion, regulation of filopodium assembly, and extracellular matrix containing collagen. With the exception of TNFRSF14, we discovered that LUZP2 was negatively correlated with 21 immune checkpoints in PCa patients receiving RT. We found a significant inverse relationship between LUZP2 expression and the tumor immune environment, which included B cells, CD4+ T cells, neutrophils, macrophages, dendritic cells, stromal score, immune score, and estimate score, in patients receiving RP or RT. Additionally, tumor purity was positively correlated with LUZP2. We found that the drug bortezomib may be susceptible to the LUZP2. DNA methylation was significantly associated with the mRNA expression of LUZP2 in PCa patients from the TCGA database, and LUZP2 methylation was positively correlated with immune cells. The proliferative activity of various PCa cells, which correlated to different stages of this disease, was also found to be significantly reduced by LUZP2 reduction, according to the results of our experimental work. Conclusions: We proposed a relatively comprehensive understanding of the roles of LUZP2 on PCa from the fresh perspective of senescence.

Extensive research has been conducted on plant protection unmanned aerial vehicle (UAV) chemical application technology in recent years owing to its importance as a means of pest and disease control. UAV spraying in orchards faces the drawback of drift risk and can be hazardous to non-targeted crops, humans, and the environment. A detailed and systematic analysis must be performed to determine the uniformity and drift risk of plant UAV sprays. In this study, a peach orchard is sprayed with a plant-protection UAV at three different flight velocities and we evaluate the combined pesticide deposition performance of the canopy, ground loss, downwind ground drift, and airborne drift. Additionally, the droplet size and coverage rate in the canopy are calculated by using water-sensitive paper. The results demonstrate that there is significant difference in the droplet size at flight velocities of 1–3 m/s. The droplet size in the lower canopy is slightly smaller than those in the middle and upper parts. Increasing the flight velocity helps the pesticide droplets to spread and penetrate the canopy. However, it also causes a non-uniform pesticide deposition, reduced effective coverage ratio and effective density ratio. Among the three pesticides used in the experiment, imidacloprid exhibits the best deposition efficiency. The deposition amount and normalized deposition amount in the canopy were the highest at a flight velocity of 2 m/s, accompanied by a lower ground loss under the canopy. The highest near-field ground drift is observed at a velocity of 1 m/s, and the far-field airborne drift is highest at 3 m/s. Lastly, this study provides a reference for the commercial application of plant-protection UAVs.

Chronic myelocytic leukemia (CML) can occasionally occur after long-term chemotherapy for solid tumors; solid tumors secondary to chemotherapy and biotherapy for CML have also been reported. However, concurrence of these two phenomena in an untreated patient has seldom been reported. Herein, we describe the case of a female patient in her early 60 s who was transferred to the liver surgery department after the discovery of a large liver mass and elevated plasma alpha-fetoprotein levels. She was initially diagnosed with liver cancer. Blood tests indicated an increased platelet count (2464 × 10 9 /L). Chromosomal examination from a bone marrow biopsy indicated the presence of the t(9;22) translocation, and subsequent fluorescence in situ hybridization and PCR were positive for the BCR-ABL rearrangement. A diagnosis of CML was made. The patient received hydroxyurea and imatinib to treat CML and underwent subsequent platelet-lowering therapy and a liver biopsy, which suggested moderately poorly differentiated adenocarcinoma or potentially hepatic metastatic carcinoma. However, the patient refused further pathological examination or screening for the site of the primary tumor. She died 6.5 months after discharge. The exact relationship between the two tumors remains unclear, and more patients need to be evaluated.

Intratumoral copper levels are closely associated with immune escape from diverse cancers. Cuproptosis-related lncRNAs (CRLs), however, have an unclear relationship with hepatocellular carcinoma (HCC). Gene expression data from 51 normal tissues and 373 liver cancer tissues from the Cancer Genome Atlas (TCGA) database were collected and analyzed. To identify CRLs, we employed differentially expressed protein-coding genes (DE-PCGs)/lncRNAs (DE-lncRNAs) analysis, Kaplan–Meier (K-M) analysis, and univariate regression. By univariate and Lasso Cox regression analyses, we screened 10 prognosis-related lncRNAs. Subsequently, five CRLs were identified by multivariable Cox regression analysis to construct the prognosis model. This feature is an independent prognostic indicator to forecast overall survival. According to Gene Set Variation Analysis (GSVA) and Gene Ontology (GO), both immune-related biological processes (BPS) and pathways have CRL participation. In addition, we found that the characteristics of CRLs were associated with the expression of the tumor microenvironment (TME) and crucial immune checkpoints. CRLs could predict the clinical response to immunotherapy based on the studies of tumor immune dysfunction and rejection (TIDE) analysis. Additionally, it was verified that tumor mutational burden survival and prognosis were greatly different between high-risk and low-risk groups. Finally, we screened potential sensitive drugs for HCC. In conclusion, this study provides insight into the TME status in patients with HCC and lays a basis for immunotherapy and the selection of sensitive drugs.

The emergence of the novel human severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) has led to the pandemic of coronavirus disease 2019 (COVID-19), which has markedly affected global health and the economy. Both uncontrolled viral replication and a proinflammatory cytokine storm can cause severe tissue damage in patients with COVID-19. SARS-CoV-2 utilizes angiotensin-converting enzyme 2 (ACE2) as its entry receptor. In this study, we generated ACE2 extracellular domain-Fc and single-chain variable fragment-interleukin 6 (IL-6) single-chain variable fragment against IL-6 receptor (scFv-IL6R)-Fc fusion proteins to differentially neutralize viruses and ameliorate the cytokine storm. The human ACE2 (hACE2)1−740-Fc fusion protein showed a potent inhibitory effect on pseudo-typed SARS-CoV-2 entry and a good safety profile in mice. In addition, scFv-IL6R-Fc strongly blocked IL-6 signal activation. We also established a mesenchymal stromal cell (MSC)-based hACE21−740-Fc and scFv-IL6R-Fc delivery system, which could serve as a potential therapy strategy for urgent clinical needs of patients with COVID-19.

Background: It is not clarified whether the elevation of adiponectin is the results of kidney damage, or the cause of kidney function injury. To explore the causal association of adiponectin on estimated glomerular filtration rate (eGFR) and chronic kidney disease (CKD), this study was performed.Materials and methods: The genetic association of adiponectin were retrieved from one genome-wide association studies with 39,883 participants. The summary-level statistics regarding the eGFR (133,413 participants) and CKD (12,385 CKD cases and 104,780 controls) were retrieved from the CKDGen consortium in the European ancestry. Single-variable Mendelian randomization (MR), bilateral and multivariable MR analyses were used to verify the causal association between adiponectin, eGFR, and CKD.Results: Genetically predicted adiponectin reduces the risk of CKD (OR = 0.71, 95% CI = 0.57–0.89, p = 0.002) and increases the eGFR (β = 0.014, 95% CI = 0.001–0.026, p = 0.034) by the inverse variance weighting (IVW) estimator. These findings remain consistent in the sensitivity analyses. No heterogeneity and pleiotropy were detected in this study (P for MR-Egger 0.617, P for global test > 0.05, and P for Cochran’s Q statistics = 0.617). The bilateral MR identified no causal association of CKD on adiponectin (OR = 1.01, 95% CI = 0.96–1.07, p = 0.658), nor did it support the association of eGFR on adiponectin (OR = 0.86, 95% CI = 0.68–1.09, p = 0.207) by the IVW estimator. All the sensitivity analyses reported similar findings (p > 0.05). Additionally, after adjusting for cigarette consumption, alcohol consumption, body mass index, low density lipoprotein, and total cholesterol, the ORs for CKD are 0.70 (95% CI = 0.55–0.90, p = 0.005), 0.75 (95% CI = 0.58–0.97, p = 0.027), 0.82 (95% CI = 0.68–0.99, p = 0.039), 0.74 (95% CI = 0.59–0.93, p = 0.011), and 0.79 (95% CI = 0.61–0.95, p = 0.018), respectively.Conclusion: Using genetic data, this study provides novel causal evidence that adiponectin can protect the kidney function and further reduce the risk of CKD.

The prognostic value of the lymphocyte-to-monocyte ratio during induction (ILMR) remains unclear in non-muscle-invasive bladder cancer (NMIBC) patients receiving Bacillus Calmette-Guérin (BCG). We aimed to determine and compare the prognostic value of the ILMR, preoperative lymphocyte-to-monocyte ratio (PLMR) and their dynamic changes (PILMR). This study collected the data from NMIBC patients receiving BCG treatment in our institution. The prognostic value of the PLMR, ILMR and PILMR was analyzed by the Kaplan−Meier method and Cox proportional hazard regression models. The concordance index and receiver operating characteristic curve analysis were employed to compare the prognostic value of these three factors. Our study enrolled 197 patients. These patients included 170 male patients, and the mean age was 64.17 years. During the follow-up time, 85 patients experienced recurrence, and 55 patients experienced progression. According to the results of COX multivariable analysis, PLMR (P=0.011) and ILMR (P

Low temperature is among the important factors affecting the distribution, survival, growth, and physiology of aquatic animals. In this study, coordinated transcriptomic responses to 10 °C acute cold stress were investigated in the gills, hearts, livers, and spleens of Japanese flounder (Paralichthys olivaceus), an important aquaculture species in east Asia. Histological examination suggested different levels of injury among P. olivaceus tissues after cold shock, mainly in the gills and livers. Based on transcriptome and weighted gene coexpression network analysis, 10 tissue-specific cold responsive modules (CRMs) were identified, revealing a cascade of cellular responses to cold stress. Specifically, five upregulated CRMs were enriched with induced differentially expressed genes (DEGs), mainly corresponding to the functions of “extracellular matrix”, “cytoskeleton”, and “oxidoreductase activity”, indicating the induced cellular response to cold shock. The “cell cycle/division” and “DNA complex” functions were enriched in the downregulated CRMs for all four tissues, which comprised inhibited DEGs, suggesting that even with tissue-specific responses, cold shock may induce severely disrupted cellular functions in all tissues, reducing aquaculture productivity. Therefore, our results revealed the tissue-specific regulation of the cellular response to low-temperature stress, which warrants further investigation and provides more comprehensive insights for the conservation and cultivation of P. olivaceus in cold water.

In recent years, automatic detection of threats in X-ray baggage has become important in security inspection. However, the training of threat detectors often requires extensive, well-annotated images, which are hard to procure, especially for rare contraband items. In this paper, a few-shot SVM-constraint threat detection model, named FSVM is proposed, which aims at detecting unseen contraband items with only a small number of labeled samples. Rather than simply finetuning the original model, FSVM embeds a derivable SVM layer to back-propagate the supervised decision information into the former layers. A combined loss function utilizing SVM loss is also created as the additional constraint. We have evaluated FSVM on the public security baggage dataset SIXray, performing experiments on 10-shot and 30-shot samples under three class divisions. Experimental results show that compared with four common few-shot detection models, FSVM has the highest performance and is more suitable for complex distributed datasets (e.g., X-ray parcels).

Abstract We aimed to investigate the role of the quantitative parameters of dual-energy computed tomography (DECT) in evaluating patients with hepatocellular carcinoma (HCC) treated by transarterial chemoembolization (TACE). We retrospectively identified 80 HCC patients (mean age, 56 years; 61 men) treated by TACE who received contrast-enhanced DECT and were retreated by TACE within 7 days between November 2018 and December 2019. Taking digital subtraction angiography (DSA) and CT images as reference standard, two readers measured and calculated the values of normalized iodine concentration at arterial phase (NICAP), normalized iodine concentration at portal venous phase (NICPP), iodine concentration difference (ICD), arterial iodine fraction (AIF) and slope of the spectral Hounsfield unit curve (λHu) by placing matched regions of interests (ROIs) within the tumor active area (TAA), adjacent normal hepatic parenchyma (ANHP) and tumor necrotic area (TNA). Differences between the parameters were analyzed by the Kruskal–Wallis H test. Receiver operating characteristic analysis of the parameters performance in differentiating the three tissues types was performed. AIF exhibited a good performance in distinguishing TAA (0.93 ± 0.31) and ANHP (0.18 ± 0.14), the areas under the receiver operating characteristic curve (AUC) was 0.989, while the λHu exhibited an excellent performance in distinguishing TAA (3.32 ± 1.24) and TNA (0.29 ± 0.27), with an AUC of 1.000. In conclusion, quantitative DECT can be effectively used to evaluate the tumor viability in HCC patients treated by TACE.

Abstract Transcatheter embolization is an important treatment method in clinical therapy, and vascular embolization material plays a key role in embolization. The temperature-sensitive p(N-isopropylacrylamide-co-butyl methylacrylate) (PIB) nanogel is a novel embolic agent. To evaluate the feasibility of the nanogel as a blood vessel embolization agent, we aimed to assess the effect of embolization with PIB nanogels in the rabbit renal artery by non-invasive computed tomography (CT) perfusion, macroscopic and histological examination. Ten healthy adult Japanese rabbits were used to implement RAE of PIB nanogels in their right kidneys. CT perfusion scans were performed pre- and post-treatment at various time-points (1, 4, 8, and 12 weeks). Two rabbits were euthanized and histologically examined at each time-point, and the remaining rabbits were euthanized at 12 weeks after embolization. The RAE efficacy of the nanogels was further confirmed by macroscopic and histological examination. The renal volume and renal blood flow (BF) of the right kidney were significantly decreased post-treatment compared with those pre-treatment (volume: pre, 9278 ± 1736 mm3; post 1 week, 5155 ± 979 mm3, P

The objective of this study was to investigate the platelet-to-lymphocyte ratio (PLR) in patients who underwent intravesical treatment for non-muscle invasive bladder cancer (NMIBC). A total of 197 patients who underwent intravesical Bacillus Calmette-Guerin treatment after transurethral resection of bladder (TURB) were included. We divided the patients into different groups according to the treatment stage before and during induction treatment as Group 1 and Group 2, and set the change value of PLR as the Group 3. The cutoff values of PLR were determined through receiver operation characteristics curves analysis. we found a significant difference in recurrence-free survival (RFS) and progression-free survival (PFS) between patients with high serum PLR and those with low serum PLR in Group 1, as well as Group 2. Cox multivariate analysis revealed that tumor number ≥3, high grade, and history of carcinoma in situ (CIS) were significant factors predicting RFS and PFS. The PLR values before and during induction therapy could be used as predictors for the progression and recurrence of NMIBC patients receiving BCG immunotherapy. the PLR values after induction therapy have a stronger predictive power.

Wool keratin is difficult to degrade as comparing to feathers because of its tough secondary structure. In order to develop an approach for high-value utilization of wool fiber waste by keratinolytic microorganisms, which is produced from shearing, weaving, and industrial processing of wool, screening of wool-degrading bacterium with high degradation efficiency were performed in this study. To this end, Lysobacter brunescens YQ20 was identified and characterized. The optimized conditions for wool degradation were pH 9.0 and 37°C with 20% liquid volume of Erlenmeyer flask. After fermentation, 15 essential amino acids were detected when wool fiber waste was fermented. The total amino acids produced from 1% wool per hour were 13.7 mg/L. The concentration was 8.6-fold higher than that produced by the strain Stenotrophomonas maltophilia BBE11-1, which had previously been reported to have the highest wool-degrading capacity. Our study reports the first Lysobacter strain that exhibits efficient wool degradation and yields higher concentrations of amino acids than previously reported strains. Whole-genome sequencing indicated that there were 18 keratinase-like genes in the genome of YQ20, which exhibited a long evolutionary distance from those of Bacillus. Therefore, L. brunescens YQ20 may have applications in the environmentally friendly management of wool waste as fertilizer in agriculture.

SYP-14288 is a fungicide as an uncoupler of oxidative phosphorylation, which is effective in controlling fungal pathogens like Rhizoctonia solani. To determine whether R. solani can develop SYP-14288 resistance and possibly multi-drug resistance (MDR), an SYP-14288-resistant mutant of R. solani X19-7 was generated from wild-type strain X19, and the mechanism of resistance was studied through metabolic and genetic assays. From metabolites of R. solani treated with SYP-14288, three compounds including M1, M2, and M3 were identified according to UPLC-MS/MS analysis, and M1 accumulated faster than M2 and M3 in X19-7. When X19-7 was treated by glutathione-S-transferase (GST) inhibitor diethyl maleate (DEM) and SYP-14288 together, or by DEM plus one of tested fungicides that have different modes of action, a synergistic activity of resistance occurred, implying that GSTs promoted metabolic resistance against SYP-14288 and therefore led to MDR. By comparing RNA sequences between X19-7 and X19, six cytochrome P450s (P450s) and two GST genes were selected as a target, which showed a higher expression in X19-7 than X19 both before and after the exposure to SYP-14288. Furthermore, heterologous expression of P450 and GST genes in yeast was conducted to confirm genes involved in metabolic resistance. In results, the P450 gene AG1IA_05136 and GST gene AG1IA_07383 were related to fungal resistance to multiple fungicides including SYP-14288, fluazinam, chlorothalonil, and difenoconazole. It was the first report that metabolic resistance of R. solani to uncouplers was associated with P450 and GST genes.

Background: The aim of this study was to investigate the performance and predictive value of hypocalcemia in severe COVID-19 patients. Methods: We retrospectively investigated the clinical and laboratory characteristics of severe COVID-19 patients. 107 patients were divided into hypocalcemia group and normal serum calcium group. The clinical and laboratory data were compared between two groups. The discriminative power of hypocalcemia regarding poor outcome were evaluated by receiver operating curves (ROC) analyses. Results: Sixty seven patients (62.6%) had hypocalcemia. In hypocalcemia group, leukocytes, c-reactive protein (CRP), procalcitonin (PCT), Interleukin 6 (IL-6), and D-dimer levels was higher, while lymphocytes and albumin (ALB) levels was lower. No significant difference was identified in gender, age, signs and symptoms, comorbidities and other laboratory indicators. Serum calcium levels were negatively correlated with leukocytes, CRP, PCT, IL-6 and D-dimer, while positively correlated with lymphocytes and ALB. Patients with hypocalcemia more commonly presented poor outcome (47.8% (32/67) vs 25% (10/40), p = 0.02). Median serum calcium levels were significantly lower in the patients with poor outcome (2.01(1.97–2.05) vs 2.10(2.03–2.20), p

Abnormal psychological processing in the central nervous system has been found in Crohn's disease (CD) patients. Resting-state functional magnetic resonance images of 57 inactive and 58 active CD patients, and 92 healthy controls (HC) were obtained. The psychological assessment used a psychological questionnaire that was collected within 1 week before functional MRI examination. We investigated the neural basis of CD patients and the correlation among regional homogeneity (ReHo), clinical features and psychological assessment scores. We found that more severe psychological assessment disorder scores were observed in the active CD group than in the inactive CD group and HC group (P

Based on the existing systematic reviews and meta-analyses, we conducted this umbrella review aiming at evaluating the quality of evidence, validity and biases of the relationship between vitamin C (VC) intake and incidence and outcomes of multiple cancers. We identified 22 cancer outcomes within 3,562 articles. VC consumption was associated with lower incidence of bladder cancer, breast cancer, cervical tumors, endometrial cancer, esophageal cancer, gastric cancer, glioma, lung cancer, pancreatic cancer, prostate cancer, renal cell cancer, and total cancer occurrence. VC intake was also related to decreased risk of breast cancer prognosis (recurrence, cancer-specific mortality, and all-cause mortality).

Abstract Background Protein arginine methylation has emerged a pivotal role in cancer progression. However, the role of protein arginine methyltransferase 3 (PRMT3) in hepatocellular carcinoma (HCC) remains unknown. Methods The expression pattern of PRMT3 in HCC was analysed using quantitative real‐time‐polymerase chain reaction (qRT‐PCR), Western blotting and immunohistochemistry assays. Loss‐ and gain‐of‐function experiments were carried out to determine the oncogenic role of PRMT3 in HCC. Glucose consumption and lactate production assays, seahorse bioscience, mass spectrometry, co‐immunoprecipitation, metabonomic analysis and site‐specific mutation experiments were used to explore the underlying molecular mechanisms. Furthermore, a xenograft mouse model was established to investigate the effects of PRMT3 and its inhibitor, SGC707, treatment on tumour growth in vivo. Results The expression of PRMT3 was significantly upregulated in HCC, with high expression of which correlated with poor prognosis. PRMT3 knockdown led to the decrease in proliferation, glycolysis of HCC cells and tumour growth, whilst its overexpression showed opposite results. The catalytic activity of PRMT3 was important in mediating these biological processes. Mechanistically, our data showed that PRMT3 interacted with and mediated asymmetric dimethylarginine (ADMA) modification of lactate dehydrogenase A (LDHA) at arginine 112 (R112). Compared with LDHA‐wild‐type (LDHA‐WT) cells, LDHA‐R112K‐mutant‐expressing HCC cells exhibited a decrease in lactate dehydrogenase (LDH) activity, HCC cell glycolysis and proliferation. Furthermore, the administration of SGC707, a selective inhibitor of PRMT3, disrupted the PRMT3‐mediated LDHA methylation and abolished PRMT3‐induced HCC glycolysis and tumour growth. Conclusions Our results suggested a novel oncogenic role of PRMT3 in HCC, and it could be a promising therapeutic target for HCC by linking post‐translational modification and cancer metabolism.

Beijing and Tianjin are two of the largest cities in northern China with high population densities and highly developed manufacturing industries. In the past decade, some authors have reported their PAH concentrations in surface soils, identified their sources and quantitatively reported their health risks. However, the contributions of different PAH sources to their toxicity have not been reported thus far. In this study, we reviewed the PAH concentrations, contributions of different sources to the toxicity, and cancer risks in soils from different land use types found within Beijing and Tianjin from data gathered by 41 studies. The total PAH concentration varied in the range of 175.7-1989.0 ng g-1 with a higher median PAH concentration detected in urban soils (789.7 ng g-1), followed by suburban soils (647.3 ng g-1) and rural soils (390.8 ng g-1). Source identification using diagnostic ratios and principal component analysis (PCA) suggested that the PAHs in all three land use types mainly originated from biomass and coal combustion, vehicular emissions, and petrogenic processes with contributions varying from 13% to 62%. Furthermore, results from a positive matrix factorization (PMF) model suggested that vehicular emissions and coal combustion in urban soils, and the vehicular emissions, coal combustion and biomass combustion in suburban and rural soils dominated the total PAH concentrations (>85%). These results were consistent with those of the PCA model. Results of the additional toxicity apportionment performed using the PMF model suggested that vehicular emissions and coal combustion contributed the most to the toxic equivalent quantity for Benzo(a)Pyrene (BaPTEQ) and, by extension, to the carcinogenic potencies. The incremental lifetime cancer risk (ILCR) values suggested a low risk level for adults exposed to PAHs in the different land use types found within Beijing and Tianjin.

BackgroundHigh-volume lymph node metastasis (HVLNM, equal to or more than 5 lymph nodes) is one of the adverse features indicating high recurrence risk in papillary thyroid carcinoma (PTC) and is recommended as one of the indications of completion thyroidectomy for patients undergoing thyroid lobectomy at first. In this study, we aim to develop a preoperative nomogram for the prediction of HVLNMs in the central compartment in PTC (cT1-2N0M0), where preoperative imaging techniques perform poor.MethodsFrom October 2016 to April 2021, 423 patients were included, who were diagnosed as PTC (cT1-2N0M0) and underwent total thyroidectomy and prophylactic central compartment neck dissection in our center. Demographic and clinicopathological features were recorded and analyzed using univariate and multivariate logistic regression analysis. A nomogram was developed based on multivariate logistic regression analysis.ResultsAmong the included patients, 13.4% (57 cases) were found to have HVLNMs in the central compartment. Univariate and multivariate logistic regression analysis showed that age (35 years), BRAF with V600E mutated, nodule diameter, and calcification independently predicted HVLNMs in the central compartment. The nomogram showed good discrimination with an AUC of 0.821 (95% CI, 0.768–0.875).ConclusionThe preoperative nomogram can be used to quantify the probability of HVLNMs in the central compartment and may reduce the reoperation rate after thyroid lobectomy.

Background: The unfolded protein response (UPR) plays a significant role in maintaining protein hemostasis in tumor cells, which are crucial for tumor growth, invasion, and resistance to therapy. This study aimed to develop a UPR-related signature and explore its correlation with immunotherapy and chemotherapy in bladder cancer.Methods: The differentially expressed UPR-related genes were put into Lasso regression to screen out prognostic genes, which constituted the UPR signature, and were incorporated into multivariate Cox regression to generate risk scores. Subsequently, the predictive performance of this signature was estimated by receiver operating characteristic (ROC) curves. The CIBERSORTx, the maftool, and Gene set enrichment analysis (GSEA) were applied to explore infiltrated immune cells, tumor mutational burden (TMB), and enriched signaling pathways in both risk groups, respectively. Moreover, The Cancer Immunome Atlas (TCIA) and Genomics of Drug Sensitivity in Cancer (GDSC) databases were used to predict responses to chemotherapy and immunotherapy.Results: Twelve genes constituted the UPR-related signature. Patients with higher risk scores had worse overall survival (OS) in training and three validation sets. The UPR-related signature was closely correlated with clinicopathologic parameters and could serve as an independent prognostic factor. M0 macrophages showed a significantly infiltrated difference in both risk groups. TMB analysis showed that the risk score in the wild type and mutation type of FGFR3 was significantly different. GSEA indicated that the immune-, extracellular matrix-, replication and repair associated pathways belonged to the high risk group and metabolism-related signal pathways were enriched in the low risk group. Prediction of immunotherapy and chemotherapy revealed that patients in the high risk group might benefit from chemotherapy, but had a worse response to immunotherapy. Finally, we constructed a predictive model with age, stage, and UPR-related risk score, which had a robustly predictive performance and was validated in GEO datasets.Conclusion: We successfully constructed and validated a novel UPR-related signature in bladder cancer, which could robustly predict survival outcomes and closely correlate with the response to immunotherapy and chemotherapy in bladder cancer.

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Objective: To investigate oncological outcomes in patients with bladder cancer who underwent minimally invasive radical cystectomy (MIRC) or open radical cystectomy (ORC). Methods: We identified patients with bladder cancer who underwent radical cystectomy (RC) in 13 centers of the Chinese Bladder Cancer Consortium (CBCC). Perioperative outcomes were compared between MIRC and ORC. The influence of surgical approaches on overall survival (OS) and cancer-specific survival (CSS) in the entire study group and subgroups classified according to pathologic stage or lymph node (LN) status was assessed with the log-rank test. Multivariable Cox proportional hazard models were used to evaluate the association among OS, CSS and risk factors of interest. Results: Of 2 098 patients who underwent RC, 1 243 patients underwent MIRC (1 087 laparoscopic RC and 156 robotic-assisted RC, respectively), while 855 patients underwent ORC. No significant differences were noted in positive surgical margin rate and 90-day postoperative mortality rate. MIRC was associated with less estimated blood loss, more LN yield, higher rate of neobladder diversion, longer operative time, and longer length of hospital stay. There was no significant difference in OS and CSS according to surgical approaches (p=0.653, and 0.816, respectively). Subgroup analysis revealed that OS and CSS were not significantly different regardless of the status of extravesical involvement or LN involvement. Multivariable Cox regression analyses showed that the surgical approach was not a significant predictor of OS and CSS. Conclusions: Our study showed that MIRC was comparable to conventional ORC in terms of OS and CSS.

In this work, a novel two-dimensional coordination polymer was prepared via reaction of 4,4′-dipyridyl (4,4′-bipy) with Zn(NO3)2·6H2O and m-terphenyl pentacarboxylic acid (H5L) within water and DMA mixed solvent, and its chemical formula is [Zn2(HL)(4,4′-bipy)(H2O)](DMA) (1). Due to its good framework stability in water, complex 1 was studied as a catalyst for photocatalytic degradation of methylene blue (MB) in water under the ultraviolet light. Both of the remarkable efficiency and good catalytic stability could be achieved in the complex 1. Furthermore, to evaluate the treatment activity of the compound on the Alzheimer's disease (AD), AD mice model was established and treated with the compound. And then, AD mice brain tissues were weighted and the cognitive function of AD mice was determined. Then, the content of amyloid β peptides (Aβ) in the hippocampus was measured with western blot; the inflammatory cytokines TNF-α along with IL-1β within CSF was detected via ELISA detection kit; oxidative stress level within the cells of nerve was determined via ROS test kit. CCK-8 assay was performed to detect the toxicity of the compound on normal human cells. Keywords: Coordination polymer, Zn(II)-framework, Methylene blue degradation, Alzheimer's disease