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Background: The immune status is closely linked to cancer progression, metastasis, and prognosis. Lipid metabolism, crucial for reshaping immune status, plays a key role in regulating the advancement of lung adenocarcinoma (LUAD) and deserves further investigation. Methods: This study classifies LUAD patients into different immune subtypes based on lipid metabolism-related genes and compares the clinical characteristics among these subtypes. Single-multi COX analysis screens out key genes related to prognosis, and a risk feature and prognostic model are constructed. Cell cloning, scratch, transwell, western blotting and flow cytometry cell cycle analysis to detect the function of key genes. A subcutaneous tumor animal model is used to investigate the in vivo function and molecular mechanisms of key genes. Results: LUAD patients are classified into three immune subtypes, among which C3 subtype has lower immune status and higher frequency of gene mutations, and show lower immunoreactivity in immunotherapy. COX analysis identified a prognostic model for four lipid metabolism factors (IGFBP1, NR0B2, PPARA, and POMC). IGFBP1, a core gene in this model, is highly expressed in the C3 subtype. Functionally, knocking down IGFBP1 significantly inhibits tumor cell cloning, scratch, and migration abilities, and downregulates the expression of cell cycle and EMT-related proteins. Knocking down IGFBP1 significantly inhibits tumor burden (P < 0.05). Mechanistically, knocking down IGFBP1 inhibits the activation of PPARα to regulate tumor cell growth. Conclusions: This study found that lipid metabolism genes are closely related to LUAD, and IGFBP1 may be a key gene in regulating tumor growth and development.

Abstract Objective This study aimed to assess the functions of cell division cycle protein 45 (CDC45) in Non-small cell lung cancer (NSCLC) cancer and its effects on stemness and metastasis. Methods Firstly, differentially expressed genes related to lung cancer metastasis and stemness were screened by differential analysis and lasso regression. Then, in vitro, experiments such as colony formation assay, scratch assay, and transwell assay were conducted to evaluate the impact of CDC45 knockdown on the proliferation and migration abilities of lung cancer cells. Western blotting was used to measure the expression levels of related proteins and investigate the regulation of CDC45 on the cell cycle. Finally, in vivo model with subcutaneous injection of lung cancer cells was performed to verify the effect of CDC45 on tumor growth. Results This study identified CDC45 as a key gene potentially influencing tumor stemness and lymph node metastasis. Knockdown of CDC45 not only suppressed the proliferation and migration abilities of lung cancer cells but also caused cell cycle arrest at the G2/M phase. Further analysis revealed a negative correlation between CDC45 and cell cycle-related proteins, stemness-related markers, and tumor mutations. Mouse experiments confirmed that CDC45 knockdown inhibited tumor growth. Conclusion As a novel regulator of stemness, CDC45 plays a role in regulating lung cancer cell proliferation, migration, and cell cycle. Therefore, CDC45 may serve as a potential target for lung cancer treatment and provide a reference for further mechanistic research and therapeutic development.

Abstract Background Cancer-associated fibroblasts (CAFs) play a crucial role in the tumor microenvironment of lung adenocarcinoma (LUAD) and are often associated with poorer clinical outcomes. This study aimed to screen for CAF-specific genes that could serve as promising therapeutic targets for LUAD. Methods We established a single-cell transcriptional profile of LUAD, focusing on genetic changes in fibroblasts. Next, we identified key genes associated with fibroblasts through weighted gene co-expression network analysis (WGCNA) and univariate Cox analysis. Then, we evaluated the relationship between glutathione peroxidase 8 (GPX8) and clinical features in multiple independent LUAD cohorts. Furthermore, we analyzed immune infiltration to shed light on the relationship between GPX8 immune microenvironment remodeling. For clinical treatment, we used the tumor immune dysfunction and exclusion (TIDE) algorithm to assess the immunotherapy prediction efficiency of GPX8. After that, we screened potential therapeutic drugs for LUAD by the connectivity map (cMAP). Finally, we conducted a cell trajectory analysis of GPX8+ CAFs to show their unique function. Results Fibroblasts were found to be enriched in tumor tissues. Then we identified GPX8 as a key gene associated with CAFs through comprehensive bioinformatics analysis. Further analysis across multiple LUAD cohorts demonstrated the relationship between GPX8 and poor prognosis. Additionally, we found that GPX8 played a role in inducing the formation of an immunosuppressive microenvironment. The TIDE method indicated that patients with low GPX8 expression were more likely to be responsive to immunotherapy. Using the cMAP, we identified beta-CCP as a potential drug-related to GPX8. Finally, cell trajectory analysis provided insights into the dynamic process of GPX8+ CAFs formation. Conclusions This study elucidates the association between GPX8+ CAFs and poor prognosis, as well as the induction of immunosuppressive formation in LUAD. These findings suggest that targeting GPX8+ CAFs could potentially serve as a therapeutic strategy for the treatment of LUAD.

BackgroundTraumatic brain injury (TBI) causes neuronal cell damage and dysfunction. According to previous studies, daphnetin (Dap) has a protective effect in neurological injury. However, the in vivo bioavailability of daphnetin is not high. The purpose of this study was to determine whether administering daphnetin directly into the site of injury via a hydrogel drug carrier could improve its therapeutic impact.MethodsTripolycerol monostearates / daphnetin (TM/Dap) hydrogels were prepared and characterised using water bath heating, scanning electron microscopy (SEM) and small animal in vivo imaging techniques. The TBI model was established using the Feeney free fall impact method. Using the Morris water maze test, the mNSS neurological deficit rating scale, haematoxylin-eosin staining, and liver and kidney function tests, the therapeutic benefit of TM/Dap and its toxic side effects were assessed. The therapeutic effects of TM/Dap were further investigated using wet and dry gravimetric methods, Evans blue staining, protein immunoblotting, immunofluorescence staining techniques and ELISA.ResultsThe efficacy of the TM/Dap hydrogel in gradually releasing daphnetin in the context of traumatic brain damage was shown by both in vitro and in vivo tests. Behavioral experiments showed that the learning and spatial memory abilities of TM/Dap hydrogel treated mice were significantly improved in the water maze experiment. And TM/Dap hydrogel has high biosafety for organisms. The results of the therapeutic mechanism of action showed that TM/Dap hydrogel showed more significant efficacy in reducing the neuroinflammatory response caused by TNF-α, IL-6 and other factors, as well as promoting the recovery of post-traumatic neurological function.ConclusionThe use of hydrogel as a drug carrier for daphnetin showed more significant efficacy in reducing neuroinflammatory response, protecting nerve tissue and promoting post-traumatic neurological recovery compared with traditional drug delivery methods.

BackgroundThe COVID-19 pandemic underscored the critical importance of biosafety in microbiology laboratories worldwide. In response, China has ramped up its efforts to enhance biosafety measures within its Centers for Disease Control and Prevention (CDC) laboratories. This study provides the first comprehensive assessment of biosafety practices across provincial, city, and county levels of CDC microbiology laboratories in China.MethodsWe conducted a nationwide cross-sectional survey from 2021 to 2023, targeting staff from microbiology laboratories within CDCs at all administrative levels in China. Stratified sampling was employed to select respondents, ensuring a representative mix across different CDC hierarchies, job titles, and academic qualifications. The survey encompassed questions on biosafety training, the presence of BSL-2 and BSL-3 laboratories, adherence to general biosafety guidelines, and management practices regarding specimens, reagents, and consumables. Statistical analysis was performed to identify significant differences in biosafety practices among different CDC levels.ResultsA total of 990 valid responses were received, highlighting a nearly universal presence (98.69%) of BSL-2 laboratories and a significant yet varied presence of BSL-3 laboratories across the CDC network. The survey revealed high levels of biosafety training (98.69%) and adherence to biosafety protocols. However, challenges remain in the consistent application of certain safety practices, especially at lower administrative levels. Notable differences in the management of specimens, reagents, and consumables point to areas for improvement in ensuring biosecurity.ConclusionOur findings indicate a robust foundation of biosafety practices within CDC microbiology laboratories in China, reflecting significant advancements in the wake of the Biosecurity Law's implementation. Nevertheless, the variability in adherence to specific protocols underscores the need for ongoing training, resources allocation, and policy refinement to enhance biosafety standards uniformly across all levels. This study's insights are crucial for guiding future improvements in laboratory biosafety, not just in China but potentially in other countries enhancing their public health infrastructures.

ObjectiveBy utilizing machine learning, we can identify genes that are associated with recurrence, invasion, and tumor stemness, thus uncovering new therapeutic targets.MethodsTo begin, we obtained a gene set related to recurrence and invasion from the GEO database, a comprehensive gene expression database. We then employed the Weighted Gene Co-expression Network Analysis (WGCNA) to identify core gene modules and perform functional enrichment analysis on them. Next, we utilized the random forest and random survival forest algorithms to calculate the genes within the key modules, resulting in the identification of three crucial genes. Subsequently, one of these key genes was selected for prognosis analysis and potential drug screening using the Kaplan-Meier tool. Finally, in order to examine the role of CDC20 in lung adenocarcinoma (LUAD), we conducted a variety of in vitro and in vivo experiments, including wound healing assay, colony formation assays, Transwell migration assays, flow cytometric cell cycle analysis, western blotting, and a mouse tumor model experiment.ResultsFirst, we collected a total of 279 samples from two datasets, GSE166722 and GSE31210, to identify 91 differentially expressed genes associated with recurrence, invasion, and stemness in lung adenocarcinoma. Functional enrichment analysis revealed that these key gene clusters were primarily involved in microtubule binding, spindle, chromosomal region, organelle fission, and nuclear division. Next, using machine learning, we identified and validated three hub genes (CDC45, CDC20, TPX2), with CDC20 showing the highest correlation with tumor stemness and limited previous research. Furthermore, we found a close association between CDC20 and clinical pathological features, poor overall survival (OS), progression-free interval (PFI), progression-free survival (PFS), and adverse prognosis in lung adenocarcinoma patients. Lastly, our functional research demonstrated that knocking down CDC20 could inhibit cancer cell migration, invasion, proliferation, cell cycle progression, and tumor growth possibly through the MAPK signaling pathway.ConclusionCDC20 has emerged as a novel biomarker for monitoring treatment response, recurrence, and disease progression in patients with lung adenocarcinoma. Due to its significance, further research studying CDC20 as a potential therapeutic target is warranted. Investigating the role of CDC20 could lead to valuable insights for developing new treatments and improving patient outcomes.

Abstract Objection Investigating the key genes and mechanisms that influence stemness in lung adenocarcinoma. Methods First, consistent clustering analysis was performed on lung adenocarcinoma patients using stemness scoring to classify them. Subsequently, WGCNA was utilized to identify key modules and hub genes. Then, machine learning methods were employed to screen and identify the key genes within these modules. Lastly, functional analysis of the key genes was conducted through cell scratch assays, colony formation assays, transwell migration assays, flow cytometry cell cycle analysis, and xenograft tumor models. Results First, two groups of patients with different stemness scores were obtained, where the high stemness score group exhibited poor prognosis and immunotherapy efficacy. Next, LASSO regression analysis and random forest regression were employed to identify genes (PBK, RACGAP1) associated with high stemness scores. RACGAP1 was significantly upregulated in the high stemness score group of lung adenocarcinoma and closely correlated with clinical pathological features, poor overall survival (OS), recurrence-free survival (RFS), and unfavorable prognosis in lung adenocarcinoma patients. Knockdown of RACGAP1 suppressed the migration, proliferation, and tumor growth of cancer cells. Conclusion RACGAP1 not only indicates poor prognosis and limited immunotherapy benefits but also serves as a potential targeted biomarker influencing tumor stemness.

Abstract The invasive capacity of lung adenocarcinoma (LUAD) is an important factor influencing patients’ metastatic status and survival outcomes. However, there is still a lack of suitable biomarkers to evaluate tumor invasiveness. LUAD molecular subtypes were identified by unsupervised consistent clustering of LUAD. The differences in prognosis, tumor microenvironment (TME), and mutation were assessed among different subtypes. After that, the invasion-related gene score (IRGS) was constructed by genetic differential analysis, WGCNA analysis, and LASSO analysis, then we evaluated the relationship between IRGS and invasive characteristics, TME, and prognosis. The predictive ability of the IRGS was verified by in vitro experiments. Next, the “oncoPredict” R package and CMap were used to assess the potential value of IRGS in drug therapy. The results showed that LUAD was clustered into two molecular subtypes. And the C1 subtype exhibited a worse prognosis, higher stemness enrichment activity, less immune infiltration, and higher mutation frequency. Subsequently, IRGS developed based on molecular subtypes demonstrated a strong association with malignant characteristics such as invasive features, higher stemness scores, less immune infiltration, and worse survival. In vitro experiments showed that the higher IRGS LUAD cell had a stronger invasive capacity than the lower IRGS LUAD cell. Predictive analysis based on the “oncoPredict” R package showed that the high IRGS group was more sensitive to docetaxel, erlotinib, paclitaxel, and gefitinib. Among them, in vitro experiments verified the greater killing effect of paclitaxel on high IRGS cell lines. In addition, CMap showed that purvalanol-a, angiogenesis-inhibitor, and masitinib have potential therapeutic effects in the high IRGS group. In summary we identified and analyzed the molecular subtypes associated with the invasiveness of LUAD and developed IRGS that can efficiently predict the prognosis and invasive ability of the tumor. IRGS may be able to facilitate the precision treatment of LUAD to some extent.

Abstract Background The occurrence of epithelial-mesenchymal transition (EMT) and immune evasion is considered to contribute to poor prognosis in lung adenocarcinoma (LUAD). Therefore, this study aims to explore the key oncogenes that promote EMT and immune evasion and reveal the expression patterns, prognostic value, and potential biological functions. Methods Firstly, we identified gene modules associated with EMT and Tumor Immune Dysfunction and Exclusion (TIDE) through weighted gene co-expression network analysis (WGCNA). Next, we utilized differential analysis and machine learning to identify the key genes and validate them. Moreover, we analyzed the correlation between key genes and tumor microenvironment remodeling, drug sensitivity, as well as mutation frequency. Furthermore, we explored and validated their malignant biological characteristics through in vitro experiments and clinical samples. Finally, potential drugs for LUAD were screened based on CMap and validated through experiments. Results Firstly, WGCNA analysis revealed that red and green modules were highly correlated with EMT and TIDE. Among them, upregulated expression of SPOCK1 was observed in lung adenocarcinoma tissues and was associated with poor prognosis. Additionally, patients in the high SPOCK1 group showed more activation of malignant oncogenic pathways, higher infiltration of immunosuppressive components, and a higher frequency of mutations. The knockdown of SPOCK1 suppressed invasion and metastasis capabilities of lung adenocarcinoma cells, and the high expression of SPOCK1 was associated with low infiltration of CD8+ T cells. Therapeutic aspects, SPOCK1 can be a candidate indicator for drug sensitivity and CMap showed that VER-155008 was the drug candidate with the largest perturbation effect on the SPOCK1 expression profile. In vitro and in vivo experiments validated the cancer-inhibitory effect of VER-155008 in LUAD. Conclusion This study revealed through comprehensive bioinformatics analysis and experimental analysis that SPOCK1 can promote EMT and immune escape in LUAD, and it may serve as a promising candidate prognostic biomarker and therapeutic target for LUAD.

Idiopathic pulmonary fibrosis (IPF) is a life-threatening disease characterized by severe pulmonary fibrosis, for which there is an urgent need for effective therapeutic agents. Mefloquine (Mef) is a quinoline compound primarily used for the treatment of malaria. However, high doses (>25 mg/kg) may lead to side effects such as cardiotoxicity and psychiatric disorders. Here, we found that low-dose Mef (5 mg/kg) can safely and effectively treat IPF mice. Functionally, Mef can improve the pulmonary function of IPF mice (PIF, PEF, EF50, VT, MV, PENH), alleviating pulmonary inflammation and fibrosis by inhibiting macrophage activity. Mechanically, Mef probably regulates the Jak2/Stat3 signaling pathway by binding to the 492HIS site of Potassium voltage-gated channel subfamily H member 2 (KCNH2) protein in macrophages, inhibiting the secretion of macrophage inflammatory and fibrotic factors. In summary, Mef may inhibit macrophage activity by binding to KCNH2 protein, thereby slowing down the progress of IPF.

Abstract In lung adenocarcinoma (LUAD), immune heterogeneity of hot and cold tumors has been recognized as one of the major factors affecting immunotherapy and other common treatments. However, there is still a lack of biomarkers that can effectively identify the immunophenotype of cold and hot tumors. First, the immune signatures were obtained based on literature mining, including macrophage/monocyte, IFN-γ response, TGF-β response, IL12 response, lymphocyte activation, and ECM/Dve/immune response. Subsequently, LUAD patients were further clustered into different immune phenotypes based on these immune signatures. Next, the key genes related to the immune phenotypes were screened by WGCNA analysis, univariate analysis, and lasso-cox analysis, and the risk signature was established via the key genes. In additional, we compared the clinicopathological characteristics, drug sensitivity, the abundance of immune infiltration, and the efficacy of immunotherapy and commonly used therapies between patients in the high- and low-risk groups in LUAD. LUAD patients were divided into immune hot phenotype and immune cold phenotype groups. The clinical presentation showed that patients with the immune hot phenotype had higher immunoactivity (including higher MHC, CYT, immune, stromal, ESTIMATE scores, higher abundance of immune cell infiltration, higher abundance of TIL, and enrichment of immune-enriched subtypes) and better survival outcomes than those with the immune cold phenotype. Subsequently, WGCNA analysis, univariate analysis, and lasso-cox analysis identified the genes highly associated with the immune phenotype: BTK and DPEP2. The risk signature, consisting of BTK and DPEP2, is highly correlated with the immune phenotype. High-risk scores were enriched in patients with immune cold phenotype and low-risk scores were enriched in patients with immune hot phenotype. Compared to the high-risk group, the low-risk group had better clinical performance, higher drug sensitivity, and a higher degree of immunoactivity, as well as better efficacy in receiving immunotherapy and common adjuvant therapy. This study developed an immune indicator consisting of BTK and DPEP2 based on the heterogeneity of hot and cold Immunophenotypes of the tumor microenvironment. This indicator has good efficacy in predicting prognosis and assessing the efficacy of immunotherapy, chemotherapy, and radiotherapy. It has the potential to facilitate personalized and precise treatment of LUAD in the future.

It is widely acknowledged that the operating parameters of fuel cell stack have significant influences on the output performances. However, there is still a lack of relevant research on the parameter sensitivity test for high-power vehicular stacks. In the study, the orthogonal test method is adopted for a 65 kW fuel cell stack. Effects of operating temperature, relative humidity, stoichiometric ratio, and inlet pressure are quantitatively investigated. It is found that the stack voltage increases significantly when the operating temperature rises from 60 °C to 70 °C while no remarkable performance differences are observed when the temperature further rises from 75 °C to 80 °C. With the increase of reactant relative humidity, the change of voltage change ratio is more obvious in the low current density regions. It is also inferred that the stack performance enhancement caused by better hydration level will be less effective once the inlet relative humidity reaches a certain degree. Increasing the inlet reactant pressure promotes the mass transfer capacity. Besides, the performance is improved more significantly in the high current density regions, which may be attributed to the improvement of concentration polarization. When the stoichiometric ratio increases, the stack output voltage does not increase significantly at lower current regions, but there exists significant performance optimization at higher current regions. The paper contributes to the deeper understanding of transport phenomena as well as better performance enhancement suggestions for vehicular fuel cell stacks.

Silicosis is a complex occupational disease without recognized effective treatment. Celastrol, a natural product, has shown antioxidant, anti-inflammatory, and anti-fibrotic activities, but the narrow therapeutic window and high toxicity severely limit its clinical application. Through structural optimization, we have identified a highly efficient and low-toxicity celastrol derivative, CEL-07. In this study, we systematically investigated the therapeutic potential and underlying mechanisms of CEL-07 in silicosis fibrosis. By constructing a silicosis mouse model and analyzing with HE, Masson, Sirius Red, and immunohistochemical staining, CEL-07 significantly prevented the progress of inflammation and fibrosis, and it effectively improved the lung respiratory function of silicosis mice. Additionally, CEL-07 markedly suppressed the expression of inflammatory factors (IL-6, IL-1α, TNF-α, and TNF-β) and fibrotic factors (α-SMA, collagen I, and collagen III), and promoted apoptosis of fibroblasts by increasing ROS accumulation. Moreover, bioinformatics analysis combined with experimental validation revealed that CEL-07 inhibited the pathways associated with inflammation (PI3K-AKT and JAK2-STAT3) and the expression of apoptosis-related proteins. Overall, these results suggest that CEL-07 may serve as a potential candidate for the treatment of silicosis.

Objective To analyze the comprehensive factors causing adverse reactions to apheresis platelet donation(ARAPD), so as to provide references for effective prevention of ARAPD. Methods The 272 cases of ARAPD from 2012 to 2019 in Lanzhou were statistically analyzed, and factors that induced ARAPD were studied. Statistical analysis were performed according to the gender, nationality, occupation, age, weight, donation units, and number of donations. Results As to the factors inducing ARAPD, anticoagulant reactions accounted for the first(32.4%, 88/272). Women and students were prone to develop ARAPD. Among all age groups, 18~25 years old were most likely to develop ARAPD(53.68%, 10 572/35 265). The incidence of ARAPD were significantly different by ages and weights(P

BackgroundThe prevalence of diabetes mellitus-induced erectile dysfunction (DMED) has recently increased, which has prompted numerous DMED studies. Here, we conduct a bibliometric analysis of relevant literature in the field of DMED and to discuss the research hotspots and future development directions.MethodsThe Web of Science Core Collection database was searched for literature on DMED, and literature characterization including the number of articles, journals, countries/regions, institutions, authors, keywords, and other information was performed using VOS viewer and CiteSpace software. In addition, Pajek software was used for visual map adjustment, and GraphPad Prism was used to generate line graphs.ResultsA total of 804 articles concerning DMED were included in this study. The Journal of Sexual Medicine issued the most documents(92 articles). The United States and China were in the leading position in the field of DMED research, and cross-institutional collaboration on DMED research worldwide needs to be further strengthened. Ryu JK were the authors with the highest number of documents issued (22 articles) while Bivalacqua TJ was the author with the most co-citated(249 co-citated). The keywords analysis shows that the main research hotspots in the field of DMED were mechanism discussions and disease treatment and management.ConclusionsGlobal research on DMED is expected to increase further. The investigation of the mechanism of DMED and the exploration of new therapeutic means and targets are the focus of future research.

Objective To study the current situation of apheresis platelets collection in various regions of Gansu province by comparing and analyzing relevant data from blood stations in 14 prefecture-level cities of Gansu province. Methods The units of collected platelets and rate of double-dose collection in 13 regional blood stations and 1 provincial blood center from 2016 to 2020, as well as the clinical supply and demand was statistically analyzed. Results From 2016 to 2020, the total units of platelets collected by 13 blood stations and 1 blood center in Gansu increased from 11 255 U to 15 270 U, with the increase rate at 35.7% in 5 years, and mainly were collected by the provincial blood center (74.57%, 50 253/ 67 392). Although the rate of double-dose collection in the province showed a steady upward trend, only 3 blood stations realized annual double-dose collection more than 20%. There was still a gap of about 10% between supply and clinical needs. Conclusion Although the number of platelet collections and units in each blood station in Gansu is on the rise in general, the units collected varies in each blood station. Therefore, further measures need to be taken from the aspects of publicity, recruitment, optimizing the collection process, improving the rate of double-dose collection, retention of regular blood donors and regional coordination to increase the collection units, narrow down the regional gap and ensure the balance between supply and demand.

Object Focus on immune-related gene pairs (IRGPs) and develop a prognostic model to predict the prognosis of patients with lung adenocarcinoma (LUAD). Methods First, the LUAD patient dataset was downloaded from The Cancer Genome Atlas database, and paired analysis of immune-related genes was subsequently conducted. Then, LASSO regression was used to screen prognostic IRGPs for building a risk prediction model. Meanwhile, the Gene Expression Omnibus database was used for external validation of the model. Next, the clinical predictive power of IRGPs features was assessed by uni-multivariate Cox regression analysis, the infiltration of key immune cells in high and low IRGPs risk groups was analyzed with CIBERSORT, quanTIseq, and Timer, and the key pathways enriched for IRGPs were assessed using the Kyoto Encyclopedia of Genes and Genomes. Finally, the expression and related functions of key immune cells and genes were verified by immunofluorescence and cell experiments of tissue samples. Results It was revealed that the risk score of 19 IRGPs could be used as accurate indicators to evaluate the prognosis of LUAD patients, and the risk score was mainly related to T cell infiltration based on CIBERSORT analysis. Two genes of IRGPs, IL6, and CCL2, were found to be closely associated with the expression of PD-1/PD-L1 and the function of T-cells. Depending on the results of tissue immunofluorescence, IL6, CCL2, and T cells were highly expressed in the LUAD tissues of patients. Furthermore, IL6 and CCL2 were positively correlated with the expression of T cells. Besides, qRT-PCR assay in four different LUAD cells proved that IL6 and CCL2 were positively correlated with the expression of PD-L1 (P < .001). Conclusions Based on 19 IRGPs, an effective prognosis model was established to predict the prognosis of LUAD patients. In addition, IL6 and CCL2 are closely related to the function of T-cells.

Background To determine the populations who suitable for surgical treatment in elderly patients (age ≥ 75 y) with IA stage. Methods The clinical data of NSCLC patients diagnosed from 2010 to 2015 were collected from the SEER database and divided into surgery group (SG) and no-surgery groups (NSG). The confounders were balanced and differences in survival were compared between groups using PSM (Propensity score matching, PSM). Cox regression analysis was used to screen the independent factors that affect the Cancer-specific survival (CSS). The surgery group was defined as the patients who surgery-benefit and surgery-no benefit according to the median CSS of the no-surgery group, and then randomly divided into training and validation groups. A surgical benefit prediction model was constructed in the training and validation group. Finally, the model is evaluated using a variety of methods. Results A total of 7297 patients were included. Before PSM (SG: n = 3630; NSG: n = 3665) and after PSM (SG: n = 1725, NSG: n = 1725) confirmed that the CSS of the surgery group was longer than the no-surgery group (before PSM: 82 vs. 31 months, P < .0001; after PSM: 55 vs. 39 months, P < .0001). Independent prognostic factors included age, gender, race, marrital, tumor grade, histology, and surgery. In the surgery cohort after PSM, 1005 patients (58.27%) who survived for more than 39 months were defined as surgery beneficiaries, and the 720 patients (41.73%) were defined surgery-no beneficiaries. The surgery group was divided into training group 1207 (70%) and validation group 518 (30%). Independent prognostic factors were used to construct a prediction model. In training group (AUC = .678) and validation group (AUC = .622). Calibration curve and decision curve prove that the model has better performance. Conclusions This predictive model can well identify elderly patients with stage IA NSCLC who would benefit from surgery, thus providing a basis for clinical treatment decisions.

Abstract The use of two-dimensional materials in bulk functional applications requires the ability to fabricate defect-free 2D sheets with large aspect ratios. Despite huge research efforts, current bulk exfoliation methods require a compromise between the quality of the final flakes and their lateral size, restricting the effectiveness of the product. In this work, we describe an intercalation-assisted exfoliation route, which allows the production of high-quality graphene, hexagonal boron nitride, and molybdenum disulfide 2D sheets with average aspect ratios 30 times larger than that obtained via conventional liquid-phase exfoliation. The combination of chlorosulfuric acid intercalation with in situ pyrene sulfonate functionalisation produces a suspension of thin large-area flakes, which are stable in various polar solvents. The described method is simple and requires no special laboratory conditions. We demonstrate that these suspensions can be used for fabrication of laminates and coatings with electrical properties suitable for a number of real-life applications.

Abstract Background Acute respiratory tract infections (ARTIs) causes high amounts of morbidity and mortality worldwide every year. Human metapneumovirus (HMPV) is a major pathogen of ARTIs in children. In this study, we aimed to investigate the epidemiology and genotypic diversity of HMPV in children hospitalized with ARTIs in Beijing, China. Methods Hospitalized children aged

Objective To develop and validate a generalized prediction model that can classify epidermal growth factor receptor (EGFR) mutation status in non–small cell lung cancer patients. Methods A total of 346 patients (296 in the training cohort and 50 in the validation cohort) from four centers were included in this retrospective study. First, 1085 features were extracted using IBEX from the computed tomography images. The features were screened using the intraclass correlation coefficient, hypothesis tests and least absolute shrinkage and selection operator. Logistic regression (LR), decision tree (DT), random forest (RF), and support vector machine (SVM) were used to build a radiomics model for classification. The models were evaluated using the following metrics: area under the curve (AUC), calibration curve (CAL), decision curve analysis (DCA), concordance index (C-index), and Brier score. Results Sixteen features were selected, and models were built using LR, DT, RF, and SVM. In the training cohort, the AUCs was .723, .842, .995, and .883; In the validation cohort, the AUCs were .658, 0567, .88, and .765. RF model with the best AUC, its CAL, C-index (training cohort=.998; validation cohort=.883), and Brier score (training cohort=.007; validation cohort=0.137) showed a satisfactory predictive accuracy; DCA indicated that the RF model has better clinical application value. Conclusion Machine learning models based on computed tomography images can be used to evaluate EGFR status in patients with non–small cell lung cancer, and the RF model outperformed LR, DT, and SVM.

Introduction: Linaclotide, a guanylate cyclase C agonist that improves the symptoms of irritable bowel syndrome with predominant constipation (IBS-C), has been recently approved for IBS-C treatment. This study aimed to report real-world data on linaclotide treatment in China. Methods: This was a prospective multicentre study of the effectiveness of linaclotide treatment in patients with IBS-C from 10 primary medical institutions. Changes in defecation, abdominal symptoms, the IBS symptom severity scale (IBS-SSS), IBS quality of life questionnaire (IBS-QOL), Zung Self-Rating Anxiety Scale and Self-Rating Depression Scale in patients were evaluated to determine the drug’s clinical efficacy and safety. Results: We enrolled 97 patients (mean age: 52.39 ± 13.99 years), 55 of whom were women (56.7%). In terms of efficacy, the number of the patients’ defecation per week and Bristol stool form scale scores significantly increased at week 4 and week 12 compared with the values at the baseline. The baseline average IBS-SSS score was 211.01 ± 81.23. Of the patients, 24 had severe IBS-C, and their IBS-SSS scores at week 4 (51.81 ± 54.42) and week 12 (9.3 ± 30.39) significantly decreased and showed a pronounced improvement. The IBS-QOL total scores at week 4 and week 12 gradually decreased compared with that at the baseline and the QOL significantly improved. Treatment satisfaction rate was 79.3% in week 4 and 100% in week 12, showing a gradually increased satisfaction and significant differences. However, 11 cases (11.3%) had diarrhoea. Conclusion: Linaclotide has proved to be a safe and effective drug to improve IBS-C symptoms and severity.

Objective To investigate the relationship between the neutrophil-to-lymphocyte ratio (NLR) of patients with non-small cell lung cancer (NSCLC) and their risk of developing brain metastases after adjusting for confounding factors. Methods A retrospective observational study of the general data of patients with NSCLC diagnosed from January 2016 to December 2020. Multivariate logistic regression was used to calculate the dominance ratio (OR) with 95% confidence interval (CI) for NLR and NSCLC brain metastases with subgroup analysis. Generalized summation models and smoothed curve fitting were used to identify whether there was a nonlinear relationship between them. Results In all 3 models, NLR levels were positively correlated with NSCLC brain metastasis (model 1: OR: 1.12, 95% CI: 1.01-1.23, P = .025; model 2: OR: 1.16, 95% CI: 1.04-1.29, P = .007; model 3: OR: 1.20, 95% CI: 1.05-1.37, P = .006). Stratified analysis showed that this positive correlation was present in patients with adenocarcinoma (LUAD) and female patients (LUAD: OR: 1.30, 95% CI: 1.10-1.54, P = .002; female: OR: 1.52, 95% CI: 1.05-2.20, P = .026), while there was no significant correlation in patients with squamous carcinoma (LUSC) and male patients (LUSC: OR:0.76,95% CI:0.38- 1.53, P = .443; male: OR:1.13, 95% CI:0.95-1.33, P = .159). Conclusion This study showed that elevated levels of NLR were independently associated with an increased risk of developing brain metastases in patients with NSCLC, and that this correlation varied by TYPE and SEX, with a significant correlation in female patients and patients with LUAD.

The identification of reliable indicators in the tumor microenvironment (TME) is critical for tumor prognosis. Tumor associated macrophages (TAMs) are the major component of non-tumor stromal cells in TME and have increasingly been recognized as a predictive biomarker for lung adenocarcinoma (LUAD) prognosis. Here, we report the development of a prognosis model for LUAD using three immune-related genes (IRGs) detected in The Cancer Genome Atlas (TCGA) which potentially regulate TAMs in TME. In 497 LUAD patients, higher immune scores conferred better overall survival (OS). We identified 93 hub IRGs out of 234 for further prognostic significance. Among them, three IRGs (BTK, Cd1c, and S100P) were proved to be closely correlated to the prognosis of patients with LUAD. Moreover, the immune risk score (IRS) based on the gene expression level of the three IRGs was an independent prognostic factor for OS. Higher IRS predicted lower OS, higher mortality and worse tumor stage. With a good predictive ability [area under the ROC curve (AUC) in TCGA = 0.701, AUC in GEO = 0.722], the IRS contributed to a good risk stratification ability of the nomogram. Immunologically, the three IRGs were related to M1 macrophages and NK cell subsets in TME. Interestingly, by characterizing these immune components in situ we found that S100P is a driver for tumor cells to induce TAM migration and M2 polarization in the immunosuppressive tumor niche. We identified the key genes driving TAM migration and transformation and elucidated the immune landscape of LUAD. The data suggest that IRGs from TME have the potential to become indicators for estimating cancer prognosis and guiding individualized treatment.

Point cloud registration aims to find a rigid spatial transformation to align two given point clouds; it is widely deployed in many areas of computer vision, such as target detection, 3D localization, and so on. In order to achieve the desired results, registration error, robustness, and efficiency should be comprehensively considered. We propose a deep learning-based point cloud registration method, called DOPNet. DOPNet extracts global features of point clouds with a dynamic graph convolutional neural network (DGCNN) and cascading offset-attention modules, and the transformation is predicted by a multilayer perceptron (MLP). To enhance the information interaction between the two branches, the feature interaction module is inserted into the feature extraction pipeline to implement early data association. We compared DOPNet with the traditional method of using the iterative closest point (ICP) algorithm along with four learning-based registration methods on the Modelnet40 data set. In the experiments, the source and target point clouds were generated by sampling the original point cloud twice independently; we also conducted additional experiments with asymmetric objects. Further evaluation experiments were conducted with point cloud models from Stanford University. The results demonstrated that our DOPNet method outperforms these comparative methods in general, achieving more accurate and efficient point cloud registration.

The formation and expansion of the plastic zone is always accompanied by the deformation and failure of the roadway-surrounding rock. Based on elastoplastic theory, this paper considers the gas pressure parameters and uses the Mohr–Coulomb strength criterion to derive the implicit equation of the plastic zone boundary in the rock surrounding gas-coal roadways. The distribution characteristics of the plastic zone of gas-coal roadway-surrounding rock are studied, and the sensitivity to the gas pressure, cohesion, internal friction angle, and support strength of the roadway free face on the plastic zone of the surrounding rock is analyzed. The research results show that the plastic zone of the surrounding rock has four distribution patterns: circular, elliptical, rounded rectangle, and butterfly. Additionally, the lateral pressure coefficient, gas pressure, cohesion, and internal friction angle are found to jointly determine the distribution and range of the plastic zone. However, the support strength of the roadway free face does not change the distribution of the plastic zone but only affects its range. The circular and elliptical plastic zones are less sensitive to gas pressure, cohesion, and internal friction angle, whereas butterfly-shaped plastic zones are highly sensitive to these factors. The main manifestation of this sensitivity is that the four butterfly leaves degenerate rapidly with any decrease in the gas pressure or increase in the cohesion and internal friction angle. Larger butterfly leaves are prone to faster degeneration. The research results presented in this paper have important theoretical guiding significance and engineering application value for the design of high-gas-coal roadway support and gas drilling.

The deformation and failure of the uphill roadway on the 3rd horizontal track in the No. 6 Mine of Pingdingshan Coal Group was taken as the engineering background. The similar simulation material of the roadway surrounding rock with quartz sand as the aggregate, cement as the cementing agent, and gypsum powder as the regulator was selected. Through mechanical tests on 25 sets of specimens with different proportions, the best proportion of similar simulated materials for simulating the deformation and failure of the surrounding rock of the roadway was obtained. Later, a large-scale deep mine roadway simulation test system independently developed by the company was used to carry out the roadway deformation and failure test. First, load the test body to the set initial stress state, and then carry out the full-face excavation and unloading of the roadway; finally, load it in the vertical direction until the roadway wall is damaged. It can realize the actual effect of simulation of roadway deformation and failure under the path of “high stress + internal unloading + stress adjustment.” The results showed that after the deep roadway is excavated with preload and high stress, the surrounding rock deformation, failure, and instability of the roadway mainly experience 3 periods: the first period is the period of uniform deformation of the roadway surrounding rock, the second period is the development period of the roadway surrounding rock slab structure, and the third period is the period of instability of the roadway surrounding rock slab structure. Combined with the time period of deformation and failure of the surrounding rock of the roadway, the damage scope of the surrounding rock and the actual situation of the site engineering. A step-by-step combined roadway repair and support plan of “bolt mesh + shotcrete + full-face hollow grouting anchor cable” with hollow grouting anchor cable as the core was determined. The stability of the repaired roadway has been significantly improved, ensuring the long-term use of the roadway.

Abstract Background This study aims to investigate the effect of miR-21-5p on process of colon adenocarcinoma (COAD) cells and its connection with neural cell adhesion molecule L1 (CHL1). Methods Different expressions of mRNAs and miRNAs were calculated with microarray analysis. QRT-PCR and western blot were performed to quantify miR-21-5p and CHL1 expression. Flow Cytometry, MTT assay, colony formation assay, transwell assay and ELISA were performed to evaluate propagation and invasiveness of COAD cells. Dual luciferase reporter assay was employed to scrutinize the relationship between miR-21-5P and CHL1. We performed in vivo experiment to detect the impact of miR-21-5p and CHL1 on COAD tumor growth. Results Expression level of miR-21-5p increased in both COAD tissues and cells. MTT and Cell cycle assay showed that overexpression of miR-21-5p accelerated proliferation of COAD cells. Transwell assay indicated that miR-21-5p promoted cell invasion. The result of dual luciferase reporter assay indicated that miR-21-5p targeted CHL1 directly and inhibited its expression. The result of in vivo experiments showed that down-regulation of miR-21-5p decreased the volume and weight of tumor, while knockdown of CHLI stimulated tumor growth. Conclusions The overexpression of miR-21-5p can promote propagation and invasiveness of COAD cells through inhibiting the expression of CHL1.

This paper deals with the numerical analysis of nonlinear Black-Scholes equation with transaction costs. An unconditionally stable and monotone splitting method, ensuring positive numerical solution and avoiding unstable oscillations, is proposed. This numerical method is based on the LOD-Backward Euler method which allows us to solve the discrete equation explicitly. The numerical results for vanilla call option and for European butterfly spread are provided. It turns out that the proposed scheme is efficient and reliable.

Ideological and Political courses are compulsory lessons for Chinese students throughout their schooling, which also are taken for granted as Citizenship Education courses by the authority. What's the real state of the lesson? Here we show you one example of the lesson. The lesson was recorded in September 2013, in a special classroom with two cameras, one of which is focused on the teacher and the other on the students.