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Purpose: In the military, neck pain is second to low back pain among musculoskeletal disorders. However, the prevalence and related factors of neck pain in military personnel have not been systematically investigated, which may lead to the lack of neck pain prevention and the generation of additional medical expenses, posing challenges to medical care. This review aimed to obtain the prevalence and related factors for neck pain in military personnel in an attempt to provide directions for prevention and intervention. Methods: We searched PubMed, Embase, and Cochrane databases in December 2021. Two researchers independently screened studies according to eligibility criteria and assessed study quality. Results: We screened titles and abstracts of 503 articles, and 17 articles met the inclusion criteria. Sixteen articles received moderate to high-quality evaluations. Neck pain is common in the military, with 1-year prevalence as high as 83% and lifetime prevalence as high as 78%. Old age (OR = 5.0), poor neck mobility (OR = 3.61), shoulder pain (OR = 4.9), low back pain (OR = 2.3), high-G pilots (OR = 1.6), longer flight time (OR = 2.53), type of aircraft (OR = 3.93), and use of helmets and night vision systems (OR = 1.9) may be associated with the prevalence of neck pain. Conclusion: Neck pain is highly prevalent in military personnel and exhibits a substantial lifetime prevalence rate. The high prevalence rate of neck pain in the military is related to many individual-related factors and work-related factors. The in-depth assessment and prevention of specific factors is an important direction of future research.

Abstract Introduction Identifying new biomarkers for predicting immune checkpoint inhibitors (ICIs) response in non-small cell lung cancer (NSCLC) is crucial. We aimed to assess the variant allele frequency (VAF)-related profile as a novel biomarker for NSCLC personalized therapy. Methods We utilized genomic data of 915 NSCLC patients via cBioPortal and a local cohort of 23 patients for model construction and mutational analysis. Genomic, transcriptomic data from 952 TCGA NSCLC patients, and immunofluorescence (IF) assessment with the local cohort supported mechanism analysis. Results Utilizing the random forest algorithm, a 15-gene VAF-related model was established, differentiating patients with durable clinical benefit (DCB) from no durable benefit (NDB). The model demonstrated robust performance, with ROC-AUC values of 0.905, 0.737, and 0.711 across training (n = 313), internal validation (n = 133), and external validation (n = 157) cohorts. Stratification by the model into high- and low-score groups correlated significantly with both progression-free survival (PFS) (training: P

Abstract Background Diffuse large B-cell lymphoma (DLBCL) is a heterogeneous malignancy characterized by varied responses to treatment and prognoses. Understanding the metabolic characteristics driving DLBCL progression is crucial for developing personalized therapies. Methods This study utilized multiple omics technologies including single-cell transcriptomics (n = 5), bulk transcriptomics (n = 966), spatial transcriptomics (n = 10), immunohistochemistry (n = 34), multiple immunofluorescence (n = 20) and to elucidate the metabolic features of highly malignant DLBCL cells and tumor-associated macrophages (TAMs), along with their associated tumor microenvironment. Metabolic pathway analysis facilitated by scMetabolism, and integrated analysis via hdWGCNA, identified glycolysis genes correlating with malignancy, and the prognostic value of glycolysis genes (STMN1, ENO1, PKM, and CDK1) and TAMs were verified. Results High-glycolysis malignant DLBCL tissues exhibited an immunosuppressive microenvironment characterized by abundant IFN_TAMs (CD68+CXCL10+PD-L1+) and diminished CD8+ T cell infiltration. Glycolysis genes were positively correlated with malignancy degree. IFN_TAMs exhibited high glycolysis activity and closely communicating with high-malignancy DLBCL cells identified within datasets. The glycolysis score, evaluated by seven genes, emerged as an independent prognostic factor (HR = 1.796, 95% CI: 1.077–2.995, p = 0.025 and HR = 2.631, 95% CI: 1.207–5.735, p = 0.015) along with IFN_TAMs were positively correlated with poor survival (p

Due to lithological and environmental differences, the weathering degree of stone heritage varies even within the same area. Various factors dominate the weathering process at different stages. Implementing preventive measures has reduced the impact of controllable factors such as human activities. However, salt weathering caused by atmospheric pollutants, water, and salt migration in rock formations has emerged as a major contributor to the deterioration of stone heritage. Understanding the re-weathering characteristics of stone cultural heritage at different weathering degrees is crucial for preventive protection. This study investigated the weathering status of Nanshiku Temple and designed an experimental scheme based on field monitoring data. By controlling the number of freeze-thaw cycles, stones with different weathering degrees were prepared, and sulfate weathering simulations were conducted. The results revealed severe damage to sandstone due to Na2SO4 crystallization. Higher initial weathering degrees resulted in more pronounced deterioration and faster weathering rates. Surface hardness analysis approximated the decay process using a logarithmic function within a certain range but could not fully capture the overall weathering of the stone. Uniaxial compressive strength showed a strong correlation with weathering indices like p-wave velocity. These findings provide a theoretical basis for preventive protection efforts in stone cultural heritage.

Objectives: To investigate prognostic factors in patients with head and neck Mucoepidermoid Carcinoma (MEC), especially the impact of treatment modalities on survival. Methods: Patients with primary head and neck MEC between 2000 and 2015 were obtained from the Surveillance, Epidemiology, and End Results (SEER) database. Prognostic factors related to Overall Survival (OS) and Cancer-Specific Survival (CSS), as well as the impact of treatments, were evaluated by multivariable Cox regression analysis. Results: We identified 2692 patients diagnosed with head and neck MEC, of whom 1397 (51.89%) had a parotid gland primary, 569 (22.14%) died, and 341 (12.67%) died of MEC. Older age (≥53 years), males, unmarried, lower income, tumor site in other head and neck areas, higher tumor grade, larger tumor size, and higher stage were related to poorer OS and CSS. Patients who did not undergo surgery (HR = 3.20, 95% CI 2.45‒4.18) had worse OS, while no significant difference was detected between partial and total organ excision on patients’ OS (p = 0.729). For combination therapy, patients who received radiotherapy only (HR = 3.21, 95% CI 2.27–4.53) or no surgery and no radiotherapy (HR = 2.59, 95% CI 1.83–3.67) were correlated with worse OS (vs. surgery only), but no significant difference was detected between surgery only and surgery combined with radiotherapy on patients’ OS (p = 0.218). For CSS, the corresponding results were consistent with OS. Conclusion: Surgical resection only may be a better survival option for head and neck MEC.

The elders in China’s rural areas are facing challenges in maintaining agricultural production due to the outflow of rural laborers. The Transfer of land could alleviate the burden of land-based livelihoods for rural elders, but their decisions regarding land transfer are influenced by their social networks within the context of Chinese rural society. This study investigates how social networks impact the willingness of rural elders to transfer land. Using survey data from 782 rural elders in 32 villages across 11 provinces in China, this paper applies multilinear and binary logistic regression models. The results indicate that the willingness of rural elders to transfer land is affected by their social neteork: (1) Internal network scale, network heterogeneity, and frequency of external network relationships have a significantly positive influence on rural elders’ willingness to transfer land, while frequency of internal network relationships has a significantly negative influence. (2) There are group differences in the above impacts, and these significant impacts occur only among male elderly individuals aged 60–69 years old or living in central and western regions. (3) Social networks primarily influence rural elders’ willingness to transfer land through three mechanisms: information consultation, interpersonal trust, and material resource acquisition. A larger internal social network scale, higher heterogeneity within the network, and more frequent interactions with members of external networks lead to greater access to useful information, higher levels of trust in others, increased material resources availability, and an increased likelihood of transferring land. These findings can inform government policies aimed at improving practices related to land transfers and old age security for rural elders.

Abstract In hepatocellular carcinoma (HCC), classical cancer stem cells (CSC) markers were shared by normal stem cells, targeting which may hinder hepatic regeneration and cause liver failure. Additionally, the spatial structure of CSC still remained elusive. To address these limitations, we undertook a comprehensive study combining single-cell data (56,022 cells from 20 samples) and spatial data (38,191 spots from eight samples) to obtain CSC signature and uncover its spatial structure. Utilizing the CytoTRACE algorithm, we discretely identified CSC, which displayed upregulated proliferation pathways regulated by HIF1A. A CSC signature of 107 genes was then developed using Weighted Gene Co-expression Network Analysis (WGCNA). Notably, HCC patients with high CSC levels exhibited an accumulation of SPP1+ macrophages (Macro_SPP1) expressing metalloproteinases (MMP9, MMP12, and MMP7) regulated by HIF1A, suggesting a hypoxic tumor region connecting Macro_SPP1 and CSC. Both CSC and Macro_SPP1 correlated with worse prognosis and undesirable immunotherapy response. Spatial analysis revealed the co-location of CSC and Macro_SPP1, with CD8 T cells excluded from the tumor region. The co-location area and non-tumor area of boundary exhibited a high level of hypoxia, with the HAVRC2 checkpoint highly expressed. Within the co-location area, the SPP1 signaling pathway was most active in cell-cell communication, with SPP1-CD44 and SPP1-ITGA/ITGB identified as the main ligand-receptor pairs. This study successfully constructed a CSC signature and demonstrated the co-location of CSC and Macro_SPP1 in a hypoxic region that exacerbates the tumor microenvironment in HCC.

Breast cancer is the most prevalent malignancy and the most significant contributor to mortality in female oncology patients. Potassium Two Pore Domain Channel Subfamily K Member 1 (KCNK1) is differentially expressed in a variety of tumors, but the mechanism of its function in breast cancer is unknown. In this study, we found for the first time that KCNK1 was significantly up-regulated in human breast cancer and was correlated with poor prognosis in breast cancer patients. KCNK1 promoted breast cancer proliferation, invasion, and metastasis in vitro and vivo. Further studies unexpectedly revealed that KCNK1 increased the glycolysis and lactate production in breast cancer cells by binding to and activating lactate dehydrogenase A (LDHA), which promoted histones lysine lactylation to induce the expression of a series of downstream genes and LDHA itself. Notably, increased expression of LDHA served as a vicious positive feedback to reduce tumor cell stiffness and adhesion, which eventually resulted in the proliferation, invasion, and metastasis of breast cancer. In conclusion, our results suggest that KCNK1 may serve as a potential breast cancer biomarker, and deeper insight into the cancer-promoting mechanism of KCNK1 may uncover a novel therapeutic target for breast cancer treatment.

Abstract Wound healing is a tandem process involving inflammation, proliferation, and remodeling, through which damage is repaired and ultimately scar tissue is formed. This process mainly relies on the complex and extensive interaction of growth factors and cytokines, which coordinate the synthesis of various cell types. The loss of normal regulation in any part of this process can lead to excessive scarring or unhealed wounds. Recent studies have shown that it is possible to improve wound healing and even achieve scar-free wound healing through proper regulation of cytokines and molecules in this process. In recent years, many studies have focused on accelerating wound healing and reducing scar size by regulating the molecular mechanisms related to wound healing and scar formation. We summarized the role of these factors in wound healing and scar formation, to provide a new idea for clinical scar-free healing treatment of uterine incisions.

Abstract Background The aim of the study was to explore the efficacy and safety of immune checkpoint inhibitor (ICI) rechallenge in patients with non‐small cell lung cancer (NSCLC). Methods Studies that enrolled NSCLC patients treated with two lines of ICIs were included using four databases. The initial line (1L‐) and subsequent lines (2L‐) of ICIs were defined as 1L‐ICI and 2L‐ICI, respectively. Results A total of 17 studies involving 2100 patients were included. The pooled objective response rate (ORR), disease control rate (DCR), median progression‐free survival (mPFS), and median overall survival (mOS) for 2L‐ICIs were 10%, 50%, 3.0 months, and 13.1 months, respectively. The 2L‐ICI discontinuation rates caused by toxicities ranged from 0% to 23.5%. Original data were extracted from six studies, covering 89 patients. Patients in whom 1L‐ICIs were discontinued following clinical decision (the mPFS of 2L‐ICIs was not reach) achieved a more prolonged mPFS of 2L‐ICIs than those due to toxicity (5.2 months) and progressive disease (2.1 months) (p

Abstract Background Observational studies have reported controversial results on the association between obesity and head and neck cancer risk. This study aimed to perform a two-sample Mendelian randomization (MR) analysis to assess the causal association between obesity and head and neck cancer risk using publicly available genome-wide association studies (GWAS) summary statistics. Methods Single-nucleotide polymorphisms (SNPs) for obesity [body mass index (BMI), waist-to-hip ratio (WHR), whole body fat mass, lean body mass, and trunk fat mass] and head and neck cancer (total head and neck cancer, oral cavity cancer, oropharyngeal cancer, and oral cavity and oropharyngeal cancer) were retrieved from published GWASs and used as genetic instrumental variables. Five methods including inverse-variance-weighted (IVW), weighted-median, MR–Egger, weighted mode, and MR-PRESSO were used to obtain reliable results, and odds ratio with 95% confidence interval (CI) were calculated. Tests for horizontal pleiotropy, heterogeneity, and sensitivity were performed separately. Results Genetically predicted BMI was negatively associated with the risk of total head and neck cancer, which was significant in the IVW [OR (95%CI), 0.990 (0.984–0.996), P = 0.0005], weighted-median [OR (95%CI), 0.984 (0.975–0.993), P = 0.0009], and MR-PRESSO [OR (95%CI), 0.990 (0.984–0.995), P = 0.0004] analyses, but suggestive significant in the MR-Egger [OR (95%CI), 0.9980 (0.9968–0.9991), P 0.05). In addition, no causal associations were observed for other exposures and outcomes (all P > 0.05). Conclusion This MR analysis supported the causal association of BMI-related obesity with decreased risk of total head and neck cancer. However, the effect estimates from the MR analysis were close to 1, suggesting a slight protective effect of BMI-related obesity on head and neck cancer risk.

Modern pharmacological studies have elucidated the presence of aconitine (AC) alkaloids, polysaccharides, and saponins as the primary bioactive constituents of Fuzi. Among these, benzoylaconine, a pivotal active compound, demonstrates notable pharmacological properties including antitumor, anti-inflammatory, and cardiovascular protective effects. In recent years, benzoylaconine has garnered significant attention in basic research on heart diseases, emerging as a focal point of investigation. This paper presents a comprehensive review of the pharmacological effects of benzoylaconine, alongside an overview of advancements in metabolic characterization. The objective is to furnish valuable insights that can serve as a cornerstone for further exploration, utilization, and advancement of benzoylaconine in pharmacological research.

Purpose To investigate the diagnostic value of anti-Mullerian hormone (AMH) and Inhibin B (InhB) in menopausal women with osteoporosis from the Chinese Daur ethnic group. Methods A total of 175 menopausal women were selected and divided into the osteoporosis group ( N = 90) and the control group ( N = 85). BMD was measured by dual-energy X-ray absorptiometry, and laboratory indicators of osteoporosis, for example, serum osteocalcin (OC), β-collagen special sequence (β-CTX), and procollagen type I amino-terminal propeptide (PINP), bone alkaline phosphatase (BALP), AMH, and InhB were measured by commercial kits. The relationship between osteoporosis and AMH or InhB was analyzed. The predictive values of AMH and InhB were reflected by the ROC curve and logistic regression. Results The level of BMD was decreased and the levels of OC, β-CTX, PINP, and BALP of the menopausal osteoporosis group were increased. The concentration of AMH and InhB in the menopausal osteoporosis group was decreased and they had connections with each other. AMH and InhB could be used as independent indicators for the occurrence of osteoporosis in menopausal women and their combination had a higher diagnostic value. Conclusion AMH and InhB measurements in menopausal women had a certain clinical significance in the detection of osteoporosis. The occurrence of osteoporosis was related to BMD, OC, β-CTX, BALP, AMH, and InhB.

Abstract Seismic anisotropy in the upper mantle reveals geodynamic processes and the tectonic evolution of the Earth. The two most powerful methods, surface wave tomography, and shear‐wave splitting observations, cannot investigate the deep local anisotropy with good vertical and lateral resolution, resulting in poor constraints on plate deformation processes of the complex plate boundary beneath the Southern California region. Here, we show that the amplitude ratio of translational displacement and rotation makes it possible to retrieve the local anisotropy in the upper mantle. Azimuthal anisotropy in the asthenosphere is well determined and resolved in lateral and vertical directions. The fast axis retrieved from amplitude observations indicates the local rapid changes in plate deformation and complex pattern of mantle flow, which is compatible with the distributions of horizontal mantle flow illuminated by geodetic measurements, providing new insights on geodynamic processes of the Southern California region.

Background Research on immunogenicity after 3rd SARS-CoV-2 vaccine in elder hepatocellular carcinoma (HCC) was limited. This study aimed to investigate the efficacy and influencing factors of inactivated SARS-CoV-2 vaccine in elder HCC. Research design and methods We assessed total antibodies, anti-RBD IgG, and neutralizing antibodies (NAb) toward SARS-CoV-2 wild type (WT) as well as BA.4/5 in 304 uninfected HCC, 147 matched healthy control (HC), and 53 SARS-CoV-2 infected HCC, all aged over 60 years. The levels of antibodies were compared in the period 7-90, 91-180, and >180 days after 2nd or 3rd vaccination, respectively. Results HCC had lower seropositivity than HC after 2nd dose (total antibodies, 64%vs.92%,P 0.9999). Booster effect of 3rd dose can persist >180 days in HCC (2ndvs.3rd: total antibodies, 0.60vs.3.20,P

Abstract Background Pulmonary large cell neuroendocrine carcinoma (LCNEC) and small cell lung cancer (SCLC) are two types of high-grade neuroendocrine carcinomas of the lung with poor prognosis. LCNEC has not been thoroughly studied due to its rarity, data are also lacking regarding the survival comparison and prognosis analysis of patients with locally advanced or metastatic LCNEC and SCLC. Methods Data of patients with LCNEC, SCLC, and other NSCLC who were diagnosed from 1975 to 2019 were extracted from the Surveillance, Epidemiology and End Results (SEER) database to estimate incidence. Those in stage III-IV and being diagnosed from 2010 to 2015 were utilized further to investigate their clinical characteristics and prognosis. Propensity score matching (PSM) analyses at a ratio of 1:2 was used to compare their survival outcomes. Nomograms of LCNEC and SCLC were established with internal validation, and the nomogram of SCLC was externally validated by 349 patients diagnosed in Cancer hospital, Chinese Academy of Medical Sciences & Peking Union Medical College from January 1, 2012 to December 31, 2018. Results The incidence of LCNEC has been increasing in recent decades, meanwhile that of SCLC and other types of NSCLC were decreasing. A total of 91,635 lung cancer patients, including 785 with LCNEC, 15,776 with SCLC, and 75,074 with other NSCLC were enrolled for further analysis. The survival of stage III-IV LCNEC resembles that of SCLC, and significantly worse than other types of NSCLC before and after PSM analysis. In pretreatment prognostic analysis, age, T stage, N stage, M stage, bone metastasis, liver metastasis, and brain metastasis were found to be associated with the survival of both LCNEC and SCLC, besides sex, bilaterality, and lung metastasis were additional prognostic factors for SCLC. Two nomograms and convenient online tools respectively for LCNEC and SCLC were established accordingly with favorable predicting accuracy of

This study aims to summarize the available data and determine if the presence of venous thromboembolism (VTE) immune-related adverse event (irAE) in patients with immune checkpoint inhibitor (ICI) therapy is associated with improved treatment efficacy and clinical outcomes, which in turn was used to help optimize patient selection for anticoagulation therapy and inform rational treatment strategies for overcoming the mechanisms of ICI resistance. PubMed, Embase, Web of Science, and Cochrane Library were searched up to March 18, 2023, for studies assessing the relationship between VTE irAE development during ICI therapy and cancer outcomes. Seven primary articles with a total of 4437 patients were included in the overall survival (OS) meta-analysis. Patients with VTE had a significant increase in overall mortality compared to patients without VTE in adjusted hazard ratios (HRs 1.36, 95% confidence interval [CI] 1.06-1.75, P = .02). In the studies where immortal time bias (ITB) was accounted for, patients with VTE irAE also had poor OS than those without. HR and the corresponding 95% CI values in the non-ITB group were 2.53 (1.75-3.66, P

Continuous self-renewal and differentiation of spermatogonial stem cells (SSCs) is vital for maintenance of adult spermatogenesis. Although several spermatogonial stem cell regulators have been extensively investigated in rodents, regulatory mechanisms of human SSC self-renewal and differentiation have not been fully established. We analyzed single-cell sequencing data from the human testis and found that forkhead box P4 (FOXP4) expression gradually increased with development of SSCs. Further analysis of its expression patterns in human testicular tissues revealed that FOXP4 specifically marks a subset of spermatogonia with stem cell potential. Conditional inactivation of FOXP4 in human SSC lines suppressed SSC proliferation and significantly activated apoptosis. FOXP4 expressions were markedly suppressed in tissues with dysregulated spermatogenesis. These findings imply that FOXP4 is involved in human SSC proliferation, which will help elucidate on the mechanisms controlling the fate decisions in human SSCs.

Abstract Background Real‐world application of osimertinib with antiangiogenic agents in non‐small cell lung cancer (NSCLC) is common, but the efficacy data are rarely reported. Methods To obtain an objective efficacy report of different real‐world treatment models of osimertinib and antiangiogenic agents. Results A total of 54 patients with NSCLC were enrolled into the study. Twelve (22.2%) who received a combination of antiangiogenic agents, when there was a trend of osimertinib resistance but did not reach imageology progressive disease (PD), were assigned to Group A, with a median overall survival (OS) and progression‐free survival (PFS) of 48.0 (95% CI, not reached) and 21.0 (95% CI: 16.7–25.3) months, respectively. Thirty (55.6%) who received a combination of antiangiogenic agents when there was imageology PD during treatment with osimertinib were assigned to Group B, with a median OS and PFS of 31.8 (95% CI: 26.6–37.1) and 9.2 (95% CI: 5.9–12.6) months, respectively. Twelve (22.2%) who received a combination of antiangiogenic agents at the initial treatment with osimertinib were assigned to Group C, with a median OS and PFS of 28.5 (95% CI: 15.2–41.8) and 15.3 (95% CI: 7.9–22.7) months, respectively. Patients in Group A achieved a significant prolonged median PFS (p

The aim of this study is to explore the active components and potential molecular mechanism of action of Rubia cordifolia L. against nasopharyngeal carcinoma (NPC). We used network pharmacology, molecular docking, and bioinformatics analysis to identify the active components and their role against NPC. The experimental verification was detected by MTT, AnnexinV-FITC/PI double fluorescence staining and Western blotting method. Network pharmacology identified that mollugin is one of the most effective components inRubia cordifolia L. Important NPC targets included HSP90AA1, CDK1, EGFR, PIK3CA, MAPK14, and CDK2. Molecular docking revealed considerable binding activity of mollugin with either of the 6 important NPC targets. Bioinformatics analysis showed that these 6 important targets were mutated in NPC, and the expression of HSP90AA1, PIK3CA, and CDK2 in cancer tissues was significantly different from that in normal tissues. MTT detection and AnnexinV-FITC/PI double fluorescence staining showed that mollugin inhibited the proliferation and induced apoptosis of NPC cells. Western blotting indicated that the molecular mechanism of mollugin against NPC was related to the regulation of the expression of Survivin and XIAP. This study predicted and partially verified the pharmacological and molecular mechanism of action of Rubia cordifolia L. against NPC. Mollugin was identified as a potential active ingredient against NPC. These results prove the reliability of network pharmacology approaches and provide a basis for further research and application of Rubia cordifolia L. against NPC.

Abstract Ferroptosis is a type of cell death that depends on iron and reactive oxygen species (ROS). The accumulation of iron and lipid peroxidation primarily initiates oxidative membrane damage during ferroptosis. The core molecular mechanism of ferroptosis includes the regulation of oxidation and the balance between damage and antioxidant defense. Tumor cells usually contain a large amount of H2O2, and ferrous/iron ions will react with excessive H2O2 in cells to produce hydroxyl radicals and induce ferroptosis in tumor cells. Here, we reviewed the latest studies on the regulation of ferroptosis in tumor cells and introduced the tumor-related signaling pathways of ferroptosis. We paid particular attention to the role of noncoding RNA, nanomaterials, the role of drugs, and targeted treatment using ferroptosis drugs for mediating the ferroptosis process in tumor cells. Finally, we discussed the currently unresolved problems and future research directions for ferroptosis in tumor cells and the prospects of this emerging field. Therefore, we have attempted to provide a reference for further understanding of the pathogenesis of ferroptosis and proposed new targets for cancer treatment.

Abstract Aim There are still patients of stage I lung adenocarcinoma (ADC) suffering from local or distant recurrence. Herein we conducted a meta‐analysis to investigate the prognostic value of tumor spread through air space (STAS), a new form of invasion pattern, in patients with pathologically confirmed stage I lung ADC. Methods Related literature was searched using PubMed, Embase, Cochrane Library, and Web of Science databases from the inception dates to September 4, 2021. Recurrence‐free survival (RFS) and overall survival (OS) were set as primary outcome endpoints. In addition, subgroup analyses on operation mode, edition of the American Joint Committee on Cancer TNM staging, sample size, and research regions were also investigated. Results A total of 17 studies involving 9785 patients were included. The presence of STAS was detected in 31.2% of patients and was associated with poor RFS (adjusted hazard ratio [HR] = 1.93, p

Tiliroside, a natural flavonoid, has various biological activities and improves several inflammatory diseases in rodents. However, the effect of Tiliroside on lipopolysaccharide (LPS)-induced acute kidney injury (AKI) and the underlying mechanisms are still unclear. This study aimed to evaluate the potential renoprotective effect of Tiliroside on LPS-induced AKI in mice. Male C57BL/6 mice were intraperitoneally injected with LPS (a single dose, 3 mg/kg) with or without Tiliroside (50 or 200 mg/kg/day for 8 days). Tiliroside administration protected against LPS-induced AKI, as reflected by ameliorated renal dysfunction and histological alterations. LPS-stimulated renal expression of inflammatory cytokines, fibrosis markers, and kidney injury markers in mice was significantly abolished by Tiliroside. This flavonoid also stimulated autophagy flux but inhibited oxidative stress and tubular cell apoptosis in kidneys from LPS-injected mice. Mechanistically, our study showed the regulation of Tiliroside on the intrarenal renin-angiotensin system in LPS-induced AKI mice. Tiliroside treatment suppressed intrarenal AGT, Renin, ACE, and Ang II, but upregulated intrarenal ACE2 and Ang1-7, without affecting plasma Ang II and Ang1-7 levels. Collectively, our data highlight the renoprotective action of Tiliroside on LPS-induced AKI by suppressing inflammation, oxidative stress, and tubular cell apoptosis and activating autophagy flux via the shift towards the intrarenal ACE2/Ang1-7 axis and away from the intrarenal ACE/Ang II axis.

The detection of polycyclic aromatic hydrocarbons (PAHs) on fruit and vegetable surfaces is important for protecting human health and ensuring food safety. In this study, a method for the in situ detection and identification of PAH residues on fruit and vegetable surfaces was developed using surface-enhanced Raman spectroscopy (SERS) based on a flexible substrate and lightweight deep learning network. The flexible SERS substrate was fabricated by assembling β-cyclodextrin-modified gold nanoparticles (β-CD@AuNPs) on polytetrafluoroethylene (PTFE) film coated with perfluorinated liquid (β-CD@AuNP/PTFE). The concentrations of benzo(a)pyrene (BaP), naphthalene (Nap), and pyrene (Pyr) residues on fruit and vegetable surfaces could be detected at 0.25, 0.5, and 0.25 μg/cm2, respectively, and all the relative standard deviations (RSD) were less than 10%, indicating that the β-CD@AuNP/PTFE exhibited high sensitivity and stability. The lightweight network was then used to construct a classification model for identifying various PAH residues. ShuffleNet obtained the best results with accuracies of 100%, 96.61%, and 97.63% for the training, validation, and prediction datasets, respectively. The proposed method realised the in situ detection and identification of various PAH residues on fruit and vegetables with simplicity, celerity, and sensitivity, demonstrating great potential for the rapid, nondestructive analysis of surface contaminant residues in the food-safety field.

BackgroundExperimental and clinical evidence has demonstrated a pivotal role of inflammation in the pathogenesis of ischemic heart disease, and targeting inflammation has been shown to provide clinical benefits for patients with coronary disease. Endothelial cells constitute the majority of non-cardiomyocytes in the heart. Endothelial pro-inflammatory activation is recognized as a critical component in the pathophysiology of cardiovascular disease. The dried flowers of Edgeworthia gardneri (Wall.) Meisn. (EG) have been widely used as Tibetan folk medicine to ameliorate a range of metabolic disorders, such as diabetes mellitus, hyperlipidemia, hypertension, and obesity. However, its role in modulating endothelial inflammation and ischemic heart disease has not been evaluated.Methods and resultsHerein, using a preclinical rat model of coronary artery ligation-induced myocardial infarction (MI), we demonstrated that systemic administration of EG extract (EEEG) attenuated ischemic cardiac injury. EEEG reduced myocardial infarct size, improved cardiac function, and ameliorated adverse cardiac remodeling. Moreover, the cardioprotective effects of EEEG were associated with decreased MI-induced myocardial inflammation. Consistent with the anti-inflammatory role of EEEG in vivo, EEEG attenuated TNF-α-stimulated human umbilical vein endothelial cells (HUVECs) activation and monocyte-endothelial cell firm adhesion in vitro. Mechanistically, our data showed that EEEG’s mode of action suppresses the activation of NF-κB, ERK, and p38 MAPK signaling pathways in ECs. Importantly, we demonstrated that EEEG inhibits endothelial inflammation in an NF-κB- and p38 MAPK-dependent manner using pharmacological inhibitors.ConclusionCollectively, this study identified EG as a potential therapeutic agent in attenuating endothelial inflammation and managing ischemic cardiovascular disease.

IntroductionAtherosclerotic cardiovascular disease is the leading cause of death worldwide. The Edgeworthia gardneri (Wall.) Meisn is a Tibetan medicine commonly used to prepare herbal tea to alleviate the local people's metabolic diseases. However, the anti-atherosclerotic effect of ethanol extract of the flower of E. gardneri (Wall.) Meisn (EEEG) and its underlying mechanism remain unknown.MethodsEEEG was used to treat low-density lipoprotein (ox-LDL)-induced macrophages to detect macrophage foaminess, cholesterol binding and uptake, and lipid transport-related gene expression. eEEG treated ApoE−/− mice fed a high-fat diet for 16 weeks to detect atherosclerotic plaque area, macrophage infiltration, and liver and small intestine lipid transport-related gene expression.ResultsEEEG inhibited macrophage-derived foam cell formation induced by oxidized low-density lipoprotein (ox-LDL) by reducing CD36-mediated lipoprotein uptake. EEEG significantly alleviated atherosclerosis in ApoE−/− mice fed a high-fat diet for 16 weeks. EEEG treatment significantly decreased atherosclerotic plaque area, macrophage infiltration, and increased collagen content. Moreover, EEEG treatment significantly downregulated mRNA expression of hepatic Srb1 and intestinal Npc1l1 and increased expression of hepatic Cyp7a1.ConclusionOur study highlighted that EEEG played a role in attenuating atherosclerotic plaque formation by reducing macrophage foam cell formation.

Least-squares reverse-time migration (LSRTM) can overcome the problems of low resolution and unbalanced amplitude energy of deep formation imaging in reverse-time migration (RTM); hence, it can obtain a more accurate imaging profile. In the conventional conjugate gradient LSRTM, the gradient is obtained based on cross correlation without a precondition operator, and the source has a great influence on the gradient, causing the convergence rate to be slow. In the framework of conventional conjugate gradient LSRTM, a normalized cross-correlation of the source wavefield was used in this study to effectively weaken the influence of the source effect and reduce the low-frequency noise. The idea of normalized cross-correlation of the source wavefield was adopted to improve the steepest descent gradient to further accelerate the iterative convergence speed and complete the final migration imaging. Model and field data examples verify the advantages of the proposed methods over conventional methods in reducing source effects, improving convergence speed, and enhancing underground deep illumination.

The incidence of testicular germ cell tumor (TGCT) is currently on the rise worldwide, of which 15%-30% of patients have occur recurrence and metastasis. However, clinical methods for diagnosing TGCT and judging its prognosis remained inadequate. In this study, we aimed to explore the possibility of testis-specific long-chain non-coding RNA (lncRNA) Ret finger protein-like 3S (RFPL3S) as a biomarker for TGCT diagnosis, prognosis, and treatment response by reviewing the TGCT gene expression data in Gene Expression Omnibus (GEO) and The Cancer Genome Atlas (TCGA) databases. The cohort data and DNA methylation data of TGCT in TCGA were downloaded from TGCA, UCSC XENA, and GEO. The bioinformatic tools were used, including GEPIA2, Kaplan-Meier Plotter, LinkedOmics, UCSC XENA, Sangerbox Tools, GSCA, and Tumor Immune Dysfunction and Exclusion. Compared with normal testicular tissues, the RFPL3S expression was significantly reduced in TGCT, and was significantly negatively correlated with the patient’s Tumor, Node, Metastasis stage. Hypermethylation and low copy number of RFPL3S were present in TGCT, and low RFPL3S was associated with short disease-free and progression-free intervals. Silencing RFPL3S significantly enhanced the invasion ability and proliferation ability of TGCT cells as evaluated by Transwell and CCK-8 experiments. Additionally, RFPL3S expression was positively correlated with the infiltration of immune-activating cells such as B cells, CD8+ T cells, cytotoxic T cells, and natural killer cells, and negatively correlated with the infiltration of immunosuppressive cells such as Th17 and Th2. Higher RFPL3S expression was present in patients with immunotherapy benefits. In conclusion, we determined that the testis-specific lncRNA RFPL3S functioned as a tumor suppressor in TGCT and could be used as a prognostic predictor of TGCT, as well as a marker to predict the effect of TGCT immunotherapy.

Semiconductiong polymer nanoparticles (Pdots) have a wide range of applications in biomedical fields including biomolecular probes, tumor imaging, and therapy. However, there are few systematic studies on the biological effects and biocompatibility of Pdots in vitro and in vivo. The physicochemical properties of Pdots, such as surface modification, are very important in biomedical applications. Focusing on the central issue of the biological effects of Pdots, we systematically investigated the biological effects and biocompatibility of Pdots with different surface modifications and revealed the interactions between Pdots and organisms at the cellular and animal levels. The surfaces of Pdots were modified with different functional groups, including thiol, carboxyl, and amino groups, named Pdots@SH, Pdots@COOH, and Pdots@NH2, respectively. Extracellular studies showed that the modification of sulfhydryl, carboxyl, and amino groups had no significant effect on the physicochemical properties of Pdots, except that the amino modification affected the stability of Pdots to a certain extent. At the cellular level, Pdots@NH2 reduced cellular uptake capacity and increased cytotoxicity due to their instability in solution. At the in vivo level, the body circulation and metabolic clearance of Pdots@SH and Pdots@COOH were superior to those of Pdots@NH2. The four kinds of Pdots had no obvious effect on the blood indexes of mice and histopathological lesions in the main tissues and organs. This study provides important data for the biological effects and safety assessment of Pdots with different surface modifications, which pave the way for their potential biomedical applications.

Land urbanization is a comprehensive mapping of the relationship between urban production, life and ecology in urban space and a spatial carrier for promoting the modernization of cities. Based on the remote sensing monitoring data of the land use status of the Yangtze River Delta urban agglomeration collected in 2010 and 2020, the spatial differentiation characteristics and influencing factors of land urbanization in the area were analyzed comprehensively using hot spot analysis, kernel density estimation, the multi-scale geographically weighted regression (MGWR) model and other methods. The results indicated the following: (1) From 2010 to 2020, the average annual growth rate of land urbanization in the Yangtze River Delta urban agglomeration was 0.50%, and nearly 64.28% of the counties had an average annual growth rate that lagged behind the overall growth rate. It exhibited dynamic convergence characteristics. (2) The differentiation pattern of land urbanization in the Yangtze River Delta urban agglomeration was obvious from the southeast to the northwest. The hot spots of land urbanization were consistently concentrated in the southeastern coastal areas and showed a trend of spreading, while the cold spots were concentrated in the northwest of Anhui Province, showing a shrinking trend. (3) Compared with the GWR model and the OLS model, the MGWR model has a better fitting effect and is more suitable for studying the influencing factors of land urbanization. In addition, there were significant spatial differences in the scale and degree of influence of different influencing factors. Analyzing and revealing the spatiotemporal characteristics and driving mechanism of land urbanization in the Yangtze River Delta urban agglomeration has important theoretical value and practical significance for the scientific understanding of new-type urbanization and the implementation of regional integration and rural revitalization strategies.

Detection of infected kernels is important for Fusarium head blight (FHB) prevention and product quality assurance in wheat. In this study, Raman spectroscopy (RS) and deep learning networks were used for the determination of FHB-infected wheat kernels. First, the RS spectra of healthy, mild, and severe infection kernels were measured and spectral changes and band attribution were analyzed. Then, the Inception network was improved by residual and channel attention modules to develop the recognition models of FHB infection. The Inception–attention network produced the best determination with accuracies in training set, validation set, and prediction set of 97.13%, 91.49%, and 93.62%, among all models. The average feature map of the channel clarified the important information in feature extraction, itself required to clarify the decision-making strategy. Overall, RS and the Inception–attention network provide a noninvasive, rapid, and accurate determination of FHB-infected wheat kernels and are expected to be applied to other pathogens or diseases in various crops.

The formation process of reactive materials shaped charge is investigated by X-ray photographs and numerical simulation. In order to study the formation process, a trans-scale discretization method is proposed. A two-dimensional finite element model of shaped charge and reactive material liner is established and the jet formation process, granule size difference induced particle dispersion and granule distribution induced jet particle distribution are analyzed based on Autodyn-2D platform and Euler solver. The result shows that, under shock loading of shaped charge, the Al particle content decreases from the end to the tip of the jet, and increases as the particle size decreases. Besides, the quantity of Al particles at the bottom part of the liner has more prominent influence on the jet head density than that in the other parts, and the Al particle content in the high-speed section of jet shows inversely proportional relationship to the ratio of the particle quantity in the top area to that in the bottom area of liner.