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Xiaoling Shang,1,&ast; Chenyue Zhang,2,&ast; Yuanyuan Lv,3,&ast; Xiaoxiao Zhang,3,&ast; Kaiyue Guo,4 Huijuan Li,3 Haiyong Wang5 1Shandong Cancer Hospital and Institute, Shandong University, Jinan, 250117, People’s Republic of China; 2Department of Integrated Therapy, Fudan University Shanghai Cancer Center, Shanghai Medical College, Shanghai, People’s Republic of China; 3Department of Clinical Drug Research, Shandong Cancer Hospital and Institute, Shandong First Medical University and Shandong Academy of Medical Sciences, Jinan, 250117, People’s Republic of China; 4Department of Radiation Oncology, Qilu Hospital of Shandong University, Shandong University, Jinan, 250117, People’s Republic of China; 5Department of Internal Medicine-Oncology, Shandong Cancer Hospital and Institute, Shandong First Medical University and Shandong Academy of Medical Sciences, Jinan, 250117, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Huijuan Li, Department of Clinical Drug Research, Shandong Cancer Hospital and Institute, Shandong First Medical University and Shandong Academy of Medical Sciences, Jinan, 250117, People’s Republic of China, Email ywb234@126.com Haiyong Wang, Department of internal Medicine-Oncology, Shandong Cancer Hospital and Institute, Shandong First Medical University and Shandong Academy of Medical Sciences, Jinan, 250117, People’s Republic of China, Tel +860531-87984777, Fax +86531-87984079, Email wanghaiyong6688@126.comBackground: Immune checkpoint inhibitors (ICIs) has prolonged survival in patients with extensive-stage small cell lung cancer (ES-SCLC) as first-line treatment. However, whether ICI rechallenge could bring survival benefit to patients with ES-SCLC following its failure as first-line treatment remains unknown. Therefore, we aim to address the issue and identify the cohort of patients that may derive such benefit.Methods: Patients with ES-SCLC from both the IMpower133 study and Shandong Cancer Hospital and Institute (shanzhong cohort) who failed first-line ICI were included. Kaplan Meier analysis was performed to compare overall survival (OS). Both univariate and multivariate Cox regression analyses were conducted to identify factors affecting survival. Tumor immune cell infiltration was evaluated by the CIBERSORT algorithm and detected by multiplex immunofluorescence (mIF).Results: A total of 125 ES-SCLC patients undergoing atezolizumab and 161 patients undergoing ICI as first-line treatment were recruited from IMpower133 and shanzhong cohort. Those receiving ICI rechallenge had a longer OS than those without in IMpower133 (P = 0.08) and shanzhong cohort (P = 0.013). In IMpower133 cohort, subgroup analyses found that patients with < 4 metastatic sites derived more survival benefit from atezolizumab (P = 0.008). For patients with ES-SCLC harboring < 4 metastatic sites, there was significant OS difference between atezolizumab versus non-atezolizumab as retreatment (P = 0.036). Moreover, for ES-SCLC patients with < 4 metastatic sites, atezolizumab improved survival compared with non-atezolizumab (hazard ratio [HR]: 0.457; 95% CI: 0.256– 0.817; P = 0.008). These findings were confirmed in shanzhong cohort. Those harboring < 4 metastatic sites had fewer M2 macrophage and more CD4 naïve T cells infiltration, which was further confirmed by mIF of ES-SCLC samples from shanzhong cohort.Conclusion: Our study provides rationale for ICI rechallenge among ES-SCLC patients with < 4 metastatic sites, suggesting beneficial outcome by reshaping TME.Keywords: extensive stage small cell lung cancer, ICI rechallenge, survival, metastatic sites, tumor microenvironment

Yuan Liu,1,2,&ast; Xingchen Shang,1,&ast; Wenyi Du,1,&ast; Wei Shen,1 Yanfei Zhu1 1Department of General Surgery, Wuxi Medical Center of Nanjing Medical University, Wuxi, People’s Republic of China; 2Department of General Surgery, Tengzhou Central People’s Hospital, Jining Medical College, Shandong, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Wei Shen; Yanfei Zhu, Department of General Surgery, Wuxi Medical Center of Nanjing Medical University, Wuxi, People’s Republic of China, Tel +8613385110723 ; +8617852061572, Email shenweiijs@outlook.com; wxsrmyy@outlook.comPurpose: The reappearance of gastric cancer, a frequent postoperative complication following radical gastric cancer surgery, substantially impacts the near-term and far-reaching medical outlook of patients. The objective of this research was to create a machine learning algorithm that could recognize high-risk factors for gastric cancer recurrence and anticipate the correlation between gastric cancer recurrence and Helicobacter pylori (H. pylori) infection.Patients and Methods: This investigation comprised 1234 patients diagnosed with gastric cancer, and 37 characteristic variables were obtained. Four machine learning algorithms, namely, extreme gradient boosting (XGBoost), random forest (RF), k-nearest neighbor algorithm (KNN), and multilayer perceptron (MLP), were implemented to develop the models. The k-fold cross-validation technique was utilized to perform internal validation of the four models, while independent datasets were employed for external validation of the models.Results: In contrast to the other machine learning models, the XGBoost algorithm demonstrated superior predictive ability regarding high-risk factors for gastric cancer recurrence. The outcomes of Shapley additive explanation (SHAP) analysis revealed that tumor invasion depth, tumor lymph node metastasis, H. pylori infection, postoperative carcinoembryonic antigen (CEA), tumor size, and tumor number were risk elements for gastric cancer recurrence in patients, with H. pylori infection being the primary high-risk factor.Conclusion: Out of the four machine learning models, the XGBoost algorithm exhibited superior performance in predicting the recurrence of gastric cancer. In addition, machine learning models can help clinicians identify key prognostic factors that are clinically meaningful for the application of personalized patient monitoring and immunotherapy.Keywords: gastric tumor, gastrectomy, helicobacter pylori, immunotherapy, risk factor, machine learning

Xiaoqian Shang,1,&ast; Naifeisha Maimaiti,1,&ast; Jiahui Fan,1 Liang Wang,2 Yuanyuan Wang,3 Hu Sun,3 Jie Lv,1 Xiufeng Zhang,4 Jing Wang,4 Xiumin Ma1 1State Key Laboratory of Pathogenesis, Prevention and Treatment of High Incidence Diseases in Central Asia, Clinical Laboratory Center, Tumor Hospital Affiliated to Xinjiang Medical University, Urumqi, Xinjiang, 830011, People’s Republic of China; 2The Fifth Affiliated Hospital of Xinjiang Medical University, Urumqi, Xinjiang, 830011, People’s Republic of China; 3First Affiliated Hospital of Xinjiang Medical University, Urumqi, Xinjiang, 830011, People’s Republic of China; 4Department of Respiratory Medicine, Second Affiliated Hospital of Hainan Medical University, Haikou, Hainan, 570100, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Xiumin Ma, State Key Laboratory of Pathogenesis, Prevention and Treatment of High Incidence Diseases in Central Asia, Clinical Laboratory Center, Tumor Hospital Affiliated to Xinjiang Medical University, Urumqi, Xinjiang, 830011, People’s Republic of China, Email maxiumin1210@sohu.com Jing Wang, Department of Respiratory Medicine, Second Affiliated Hospital of Hainan Medical University, Haikou, Hainan, 570100, People’s Republic of China, Email tlfwj@163.comBackground: Macrophage play a significant work in the development of tuberculosis. This study aims to investigate the relationship between TREM2 and macrophage polarization, as well as the related cytokines.Methods: This study involved 43 pulmonary tuberculosis patients and 37 healthy controls. Enzyme-linked immunosorbent assay (ELISA) was used to detect the expression levels of M1/M2 macrophage-related cytokines IL-10 and IL-12 in the peripheral blood of pulmonary tuberculosis patients. The relative mRNA expression levels of TREM2, IL-10 and IL-12 were detected using quantitative real-time PCR (qRT-PCR). Additionally, Spearman rank correlation analysis was used to preliminarily assess the correlation between TREM2 and M1 / M2 macrophages. Hematoxylin-eosin (HE) staining was performed to observe the pathological manifestations of pulmonary tuberculosis lesions. Immunohistochemical (IHC) staining was used to observe the localization of the macrophage-specific molecule CD68, the M1 specific molecule iNOS, the M2 specific molecule CD163, and TREM2.Results: The lesions of pulmonary tuberculosis patients showed Langhans multinucleated macrophages and tuberculous granulomas. The ELISA results indicated that the expression levels of IL-10 and IL-12 were significantly increased in peripheral blood of pulmonary tuberculosis patients. Additionally, the relative mRNA expression levels of TREM2, IL-10 and IL-12 were also significantly higher in the pulmonary tuberculosis group. Furthermore, a positive correlation was observed between TREM2 and IL-10, which are secreted by M2 macrophages. IHC revealed significant positivity of TREM2 and macrophage-related markers in tuberculous granuloma. Specifically, TREM2 and M2 macrophage marker CD163 were significantly expressed in the cytoplasm and membrane of Langhans multinucleated macrophages.Conclusion: The role of macrophage polarization in pulmonary tuberculosis is significant, and further investigation is needed to understand relationship between TREM2 and M2 macrophages.Keywords: tuberculosis, TREM2, macrophage

Xiaokang Zheng,1,2,&ast; Yu Li,2,&ast; Xuejun Shang,3 Ranlu Liu1 1Department of Urology, Tianjin Medical University General Hospital, Tianjin Medical University, Tianjin, 300052, People’s Republic of China; 2Department of Andrology, Henan Provincial People’s Hospital; Zhengzhou University People’s Hospital; Henan University People’s Hospital, Zhengzhou, Henan, 450003, People’s Republic of China; 3Department of Urology, Jinling Hospital, Affiliated Hospital of Medical School, Nanjing University, Nanjing, 210002, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Ranlu Liu, Department of Urology, Tianjin Medical University General Hospital, Tianjin Medical University, No.154, Anshan Road, Tianjin, 300052, People’s Republic of China, Email ranluliu@126.com Yu Li, Department of Andrology, Henan Provincial People’s Hospital; Zhengzhou University People’s Hospital; Henan University People’s Hospital, No.7 Weiwu Road, Zhengzhou, Henan, 450003, People’s Republic of China, Email liyu7715@126.comPurpose: The systemic infection and inflammation can result in testes injury, whereas the exact mechanism is unknown. The lipid metabolism has a dual impact on controlling metabolism and inflammation, which is a potential pathway. The objective of this study was to determine if changes in plasma lipids during lipopolysaccharide (LPS)-induced systemic inflammation affect the dysregulation of testes lipid metabolism.Materials and Methods: LPS (5 mg/kg) was used to induce systemic inflammation in rats after a single intraperitoneal injection. After 4 weeks, the rats were sacrificed, and the serum and testes were used for laboratory measurements and histology examination. Plasma and testis were used for lipidomics analysis based the liquid chromatography-mass spectrometry. Spearman rank correlation analysis was used to compare the correlation of differential lipids in phospholipids, glycerolipids, and sphingolipids between testis and plasma.Results: LPS raised the levels of cytokines in serum and testis, decreased the activities of antioxidant enzymes, increased the levels of lipid peroxidation products, and damaged testis tissue. In testis and plasma, 146 and 401 differential lipids, mostly phosphatidylcholine, phosphatidylethanolamine an so on, were found in comparison to the control group. Correlation analysis produced a total of 2528 correlation coefficients, 1150 of which were P< 0.05 and accounted for 45.49%.Conclusion: The changes of lipid composition and content in the testis are related to cytokine overload and oxidative stress. Testis lipid metabolism disorders caused by LPS-induced systemic inflammation are lack of a correlation with plasma lipid changes, and are likely owing to interference with the testis itself.Keywords: systemic inflammation, infertility, lipidomics, oxidative stress, correlation analysis

Chunran Pan,&ast; Wenjie Hou,&ast; Xiaofeng Deng, Jiawei Liu, Ruimin Chi, Xingru Shang, Tao Xu, Xiaoxia Hao Department of Rehabilitation, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, 430030, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Xiaoxia Hao, Department of Rehabilitation, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, 1095&num;, Jie-Fang Avenue, Qiaokou District, Wuhan, 430030, People’s Republic of China, Tel +86 1-597-296-0593, Fax +86- 27-83662640, Email haoxiaoxia@hust.edu.cnAbstract: Intervertebral disc degeneration (IDD) is considered as a dominant contributor to low back pain (LBP), causing severe pain, limited range of lumbar motion, physical dysfunction, and restriction of social activity. However, the specific pathological mechanisms underlying IDD remain elusive, and effective strategies to delay the pathogenesis of IDD are still unclear and limited. In recent years, some studies have found that nuclear factor erythroid 2-related factor 2 (Nrf2), an important antioxidant transcription factor, may play crucial roles in the pathogenesis and progression of age-related diseases including IDD. Nrf2 can maintain redox homeostasis and protecting nucleus pulposus (NP) cells against oxidative stress, inflammatory response, extracellular matrix (ECM) catabolism, cell senescence and cell death involving in the progression of IDD. In this review, we aim to systematically describe the vital roles and pathological mechanism of Nrf2 signaling axis in the pathogenesis of IDD, which may put forward potential therapeutic strategies for the prevention and treatment of IDD by targeting Nrf2.Keywords: Nrf2, intervertebral disc degeneration, nucleus pulposus cells, oxidative stress

Xingchen Shang,1,2,&ast; Linfei Ye,1,&ast; Xiaohua Gu,3 Aihua Zhou,4 Yunmei Xu,5 Yiran Zhang,1 Yuexia Liao,1 Lin Li6 1School of Nursing, Yangzhou University, Yangzhou, People’s Republic of China; 2School of Nursing, Li Ka Shing Faculty of Medicine, The University of Hong Kong, Hong Kong, People’s Republic of China; 3Delivery Room, Yangzhou Maternal and Child Care Service Centre, Yangzhou, People’s Republic of China; 4Delivery Room, Taizhou Second People’s Hospital, Taizhou, People’s Republic of China; 5Obstetrics and Gynecology Department, Baoying People’s Hospital, Yangzhou, People’s Republic of China; 6Department of Nursing, The Affiliated Hospital of Yangzhou University, Yangzhou, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Lin Li, Department of Nursing, The Affiliated Hospital of Yangzhou University, No. 368, Hanjiang Middle Road, Yangzhou, 225000, People’s Republic of China, Tel +86 13585233313, Email 361350908@qq.comBackground: Most pregnant women do not reach the recommendation for physical activity (PA). As a subcategory of PA, exercise is also essential. Evidence on pregnant women’s attitudes and barriers to PA and exercise self-efficacy in China is scarce.Aim: To explore the levels and influencing factors of attitudes and barriers to PA and exercise self-efficacy among pregnant women.Methods: A cross-sectional study of 311 pregnant women was conducted from August to December 2022. Individual characteristics, pregnant women’s attitudes toward exercise, barriers to prenatal PA and exercise, and exercise self-efficacy were measured using the self-designed demographic questionnaire, pregnant women’s attitudes toward exercise questionnaire, barriers to prenatal PA and exercise questionnaire, and the pregnancy exercise self-efficacy scale, respectively.Results: More than 90% of pregnant women believed exercise benefits themselves and their babies, and 40.8% of pregnant women did not know how to exercise. Women encounter different types of barriers to PA and exercise. Intrapersonal barriers included the proportion of feelings of tiredness (56.6%), low energy (54.7%), lack of interest or motivation (49.2%), feelings of illness and morning sickness (46.6%), and large body weight (43.7%). Interpersonal barriers included pregnant women being advised to avoid PA and exercise (49.2%), lack of clear advice about the intensity and dose of exercise (41.8%), no one to exercise with (38.9%), and lack of advice from healthcare professionals (38.6%). Weather conditions were the most significant environmental barriers (41.2%). The total score of pregnancy exercise self-efficacy was (38.50± 7.33). Education level, parity, and attitudes toward exercise independently predict pregnant women’s attitudes toward exercise, barriers to prenatal PA and exercise, and exercise self-efficacy, respectively.Conclusion: Pregnant women have a favorable attitude toward exercise and relatively good exercise self-efficacy but lack knowledge of exercise. They face numerous barriers. Medical professionals should encourage pregnant women with lower levels of education to exercise and assist multipara in overcoming obstacles.Keywords: attitudes, barriers, exercise self-efficacy, physical activity, pregnancy

Jing Yang, Chengsen Shu, Xianfu Shang, Hao Xu, Ning Wei Department of Interventional Radiology, the Affiliated Hospital of Xuzhou Medical University, Xuzhou, Jiangsu, 221006, People’s Republic of ChinaCorrespondence: Ning Wei, Email weiningjieru2006@163.comPurpose: This study aimed to investigate the prognostic value of systemic immune-inflammation index (SII) in patients with extrahepatic cholangiocarcinoma (EHCC) treated by percutaneous transhepatic biliary stenting (PTBS) combined with 125I seed intracavitary irradiation and further develop a predictive model related to SII.Methods: A total of 145 patients with EHCC who received PTBS combined with 125I seed implantation were retrospectively analyzed. The optimal cut-off value of SII was identified by receiver operating characteristic (ROC) curve analysis. Kaplan–Meier curves and Cox regression were applied to estimate the prognostic value of SII and identify other significant factors of overall survival (OS). Additionally, a novel nomogram was constructed. The concordance index (C-index), calibration plots and decision curve analysis were used to evaluate the performance of the nomogram model.Results: The optimal cut-off value for preoperative SII of 890.2 stratified the patients into High-SII (H-SII) and Low-SII (L-SII) groups. Univariate and multivariate analyses demonstrated that SII was an independent factor for OS. We also found that better therapeutic effect could be obtained with combined postoperative chemotherapy (P < 0.001). Moreover, we revealed that elevated preoperative CA19-9 (P = 0.038) and TBIL level (P = 0.024) were reason for poor prognosis of EHCC. A well-discriminated and calibrated nomogram was developed to predict the 1-year and 2-year OS of EHCC (C-index: 0.709).Conclusion: The SII may be a feasible and convenient prognosis predictor for EHCC. The comprehensive nomogram based on SII presented in this study is a promising model for predicting OS in EHCC patients after PTBS combined with 125I seed intracavitary irradiation.Keywords: extrahepatic cholangiocarcinoma, biliary stenting, 125I seed, systemic immune-inflammation index, nomogram

Minerals are ubiquitous in the natural environment and have close contact with microorganisms. In various scenarios, microorganisms that harbor extracellular electron transfer (EET) capabilities have evolved a series of beneficial strategies through the mutual exchange of electrons with extracellular minerals to enhance survival and metabolism. These electron exchange interactions are highly relevant to the cycling of elements in the epigeosphere and have a profound significance in bioelectrochemical engineering applications. In this review, we summarize recent advances related to the effects of different minerals that facilitate the EET process and discuss the underlying mechanisms and outlooks for future applications. The promotional effects of minerals arise from their redox-active ability, electrical conductivity and photocatalytic capability. In mineral-promoted EET processes, various responses have concurrently arisen in microorganisms, such as stretching of electrically conductive pili (e-pili), upregulated expression of outer-membrane cytochromes (Cyts) and production of specific enzymes, and secretion of extracellular polymeric substances (EPSs). This review synthesizes the understanding of electron exchange mechanisms between microorganisms and minerals and highlights potential applications in development of renewable energy production and pollutant remediation, which are topics of particular significance to future exploitation of biotechnology.

Xingchen Shang,1,2 Linfei Ye,1 Lin Li3 1School of Nursing, Yangzhou University, Yangzhou, People’s Republic of China; 2School of Nursing, Li Ka Shing Faculty of Medicine, The University of Hong Kong, Hong Kong, People’s Republic of China; 3Department of Nursing, The Affiliated Hospital of Yangzhou University, Yangzhou, People’s Republic of ChinaCorrespondence: Xingchen Shang, Email 007210@yzu.edu.cn

Regression-based methods are commonly used for riverine constituent concentration/flux estimation, which is essential for guiding water quality protection practices and environmental decision making. This paper developed a multivariate adaptive regression splines model for estimating riverine constituent concentrations (MARS-EC). The process, interpretability and flexibility of the MARS-EC modelling approach, was demonstrated for total nitrogen in the Patuxent River, a major river input to Chesapeake Bay. Model accuracy and uncertainty of the MARS-EC approach was further analysed using nitrate plus nitrite datasets from eight tributary rivers to Chesapeake Bay. Results showed that the MARS-EC approach integrated the advantages of both parametric and nonparametric regression methods, and model accuracy was demonstrated to be superior to the traditionally used ESTIMATOR model. MARS-EC is flexible and allows consideration of auxiliary variables; the variables and interactions can be selected automatically. MARS-EC does not constrain concentration-predictor curves to be constant but rather is able to identify shifts in these curves from mathematical expressions and visual graphics. The MARS-EC approach provides an effective and complementary tool along with existing approaches for estimating riverine constituent concentrations.

In recent years, there is great concern about plastic pollution due to the identification of several environmental risks associated with microplastics (

Yu Li,1 Jinde Zhu,1 Xiaodong Zhao,2 Yi Sun,2,3 Feng Xu,1,2 Song Xu,1,2 Xuejun Shang1,2 1Department of Urology, Jinling Hospital, The First School of Clinical Medicine, Southern Medical University, Nanjing, People’s Republic of China; 2Department of Urology, Jinling Clinical Medical College of Nanjing Medical University, Nanjing, People’s Republic of China; 3Department of Pathology, Jiangsu Province Hospital of Chinese Medicine, Affiliated Hospital of Nanjing University of Chinese Medicine, Nanjing, People’s Republic of ChinaCorrespondence: Xuejun Shang, Department of Urology, Jinling Hospital, The First School of Clinical Medicine, Southern Medical University, No. 305 East Zhongshan Road, Nanjing, 210002, People’s Republic of China, Tel +8613813905418, Email shangxj98@163.comPurpose: Epididymitis histological alterations and related long-term reproductive issues cannot be cured by antibiotics alone. Few studies have been done on the effect of lycopene on epididymitis, despite the fact that it is an efficient antioxidant. The objective of this study was to assess the impact of lycopene on Lipopolysaccharide (LPS)-induced epididymis and lipid metabolism.Methods: Thirty-one 260– 290g rats were separated into the blank control group (n=10), the oil-control group (n=10), the single intraperitoneal injection of 5 mg/kg LPS (n=5), and the continuous intragastric of 5 mg/kg lycopene (n=6). The animals were euthanized after four weeks, and blood and the epididymis were removed for analysis.Results: Lycopene significantly decreased IL-1α, IL-1β, TNF-α, MCP-1, IL-6 and lipid peroxidation product Malondialdehyde in serum and epididymis. It significantly increased the epididymis’s antioxidant enzyme and total antioxidant capacity. According to LC-MS plasma lipidomics, lycopene increased phosphatidylcholine, lysophosphatidylcholine, decreased phosphatidylethanolamine, triacylglycerol, and diacylglycerol levels, changed the composition of lipids, altered metabolic pathways, and these changes were related to the mechanism of anti-inflammatory and oxidative stress. 20 lipids, including PC (20:5e) and LPC (14:0), were identified through additional Spearman correlation analysis as being related to cytokines and oxidation indices. They served as possible lipid markers that may be utilized to gauge the severity of inflammation.Conclusion: Lycopene has anti-inflammatory and antioxidant properties that improve histopathological and functional damage in LPS-induced epididymitis and is an alternate supplement for treating epididymitis. Lipidomics provide new perspectives on the possible mechanism of lycopene in protecting against LPS-induced epididymitis by integrating lipid metabolism and inflammation.Keywords: lycopene, lipidomics, inflammatory, antioxidant, lipids regulation, correlation

Semiconducting minerals are ubiquitous in soil and their association with microbes often affects the environment. In this study, the impacts of zinc sulfide (ZnS, used as a model compound for semiconducting sphalerite) on As/Fe mobility of flooded tailing soils under dark and intermittent illumination conditions were elucidated for the first time. Microbial reductive dissolution of As(V) and Fe(III) was more pronounced under intermittent illumination than under dark conditions. In ZnS-amended soils, release of As(III) and Fe(II) was 1.3 and 1.7 times higher, respectively, under intermittent illumination than the highest concentrations released from soils amended with acetate alone under dark conditions (12741.1 ± 714.3 μg/L and 37.9 ± 2.3 mg/L, respectively). However, under dark conditions in ZnS-amended soil, the release of As(III) and Fe(II) was 0.8 and 0.7 times that of the highest concentrations released from soils amended with acetate under dark conditions, respectively. Treatment with ZnS potentially decreased the abundance of several metal-reducing bacteria (e.g., Bacillus, Geobacter, Clostridium, and Desulfitobacterium), which resulted in lower As/Fe reduction than for the acetate alone treatment under dark conditions. However, under intermittent illumination, the excited mineral photoholes were scavenged by humic/fulvic acids, and photoelectrons were synchronously separated and participated in the microbial electron chain. The fortification provided by the photoelectrons subsequently boosted As/Fe reduction, even though there was a lower abundance of metal-reducing bacteria. Hence, this study provides an in-depth understanding of the impacts of semiconducting minerals on the fates of metal pollutants, microbial diversity, and the bioavailability of dissolved organic matter in flooded soils.

Xiaobin Shang,1,&ast; Yan Fang,2,&ast; Wenqiang Xin,3 Hongbo You1 1Department of Orthopaedics, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, 430030, People’s Republic of China; 2Department of Anesthesiology, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, 430030, People’s Republic of China; 3Department of Neurosurgery, Tianjin Medical University General Hospital, Tianjin, 352000, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Hongbo You, Email hongboyou2014@outlook.comAbstract: Osteoarthritis (OA) is a whole joint disease characterized by synovitis, cartilage destruction, and subchondral bone sclerosis and cyst. Despite decades’ study, effective treatment is rare for this chronic disease. Extracellular vesicles (EVs), including exosomes, microvesicles, and apoptosis bodies, are nano-sized vesicles with a cargo containing biologically active agents, such as nucleic acids, lipids, and proteins. As a group of short non-coding RNAs, microRNAs (miRNAs) can be delivered by parental cells secreted EVs. Negatively regulate the target mRNAs at the posttranscriptional level and regulate gene expression in recipient cells without modifying gene sequence. Recently, most studies focused on the function of EVs mediated miRNAs in the pathophysiological process of OA. However, all kinds of EVs specific and OA specific factors might influence the administration of EVs-miRNAs, especially the precise quantitative management. As a result, the flourishing of current research about EVs in the laboratory might not promote the relevant clinical transformation in OA treatment. In this review, we reviewed the present application of EVs-miRNAs in the therapeutic of OA and further analyzed the potential factors that might influence its application. Further progress in the quantitative management of EVs-miRNAs would accelerate the clinical transformation of miRNAs enriched EVs in the OA field.Keywords: osteoarthritis, extracellular vesicles, microRNAs, quantitative management, clinical transformation

Wenbin Qiao,1,&ast; Jiahui Fan,1,&ast; Xiaoqian Shang,1,&ast; Liang Wang,2 Bahetibieke Tuohetaerbaike,2 Ying Li,2 Li Zhang,2 YiShan Huo,1 Jing Wang,3 Xiumin Ma1,2 1State Key Laboratory of Pathogenesis, Prevention and Treatment of High Incidence Diseases in Central Asia, Clinical Laboratory Center, Tumor Hospital Affiliated to Xinjiang Medical University, Urumqi, 830000, People’s Republic of China; 2First Affiliated Hospital of Xinjiang Medical University, Urumqi, Xinjiang, 830011, People’s Republic of China; 3Respiratory Department of the Second Affiliated Hospital of Hainan Medical College, Haikou, Hainan, 570000, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Xiumin MaState Key Laboratory of Pathogenesis, Prevention and Treatment of High Incidence Diseases in Central Asia, Clinical Laboratory Center, Tumor Hospital Affiliated to Xinjiang Medical University, No. 789 Suzhou Road, Urumqi, 830011, Xinjiang Uygur Autonomous Region, People’s Republic of ChinaTel +86-13369649029Email maxiumin1210@sohu.comJing WangRespiratory Department of the Second Affiliated Hospital of Hainan Medical College, Haikou, Hainan, 570000, People’s Republic of ChinaTel +86-13629925886Email tlfwj@163.comObjective: Central nervous system tuberculosis is the most serious form of extrapulmonary tuberculosis. We aim to discover potential biomarkers involved in the development of the disease.Methods: Through gene difference analysis, construction of a protein interaction network and tissue specific analysis and other bioinformatics analysis methods, we found out the relatively high expression of important substances in the central nervous system, interferon induced protein with tetratricopeptide repeats 1. Subsequently, the lesion tissue and the resection margin tissue away from the lesion were collected from the 6 cases of central nervous system tuberculosis patients diagnosed from 2019 to 2020, and the pathological manifestations were observed by Hematoxylin and Eosin (H&E) staining, and the expression of IFIT1 was verified by immunohistochemistry.Results: A total of 101 differential genes were analyzed between extrapulmonary tuberculosis patients and normal people, and they were mainly enriched in the interferon pathway. The protein interaction network unearthed 34 key genes. Through tissue specific analysis, it was found that IFIT1 is relatively high in the central nervous system. H&E staining showed the expression of multinucleated macrophages, and immunohistochemistry showed that IFIT1 was significantly positively expressed in the lesion tissue.Conclusion: IFIT1 is an important substance involved in central nervous system tuberculosis.Keywords: central nervous system tuberculosis, biomarkers, interferon induced protein with tetratricopeptide repeats 1, hematoxylin and eosin staining, immunohistochemistry staining

Xiaojing Shang,1 Rui Zhang,2 Xiaolai Wang,1 Junxin Yao,1 Xiaoying Zhao,1 Huanming Li3 1Department of Endocrinology, Tianjin Fourth Central Hospital, Tianjin, People’s Republic of China; 2Division of Health Management, Tianjin Fourth Central Hospital, Tianjin, People’s Republic of China; 3Department of Cardiology, Tianjin Fourth Central Hospital, Tianjin, People’s Republic of ChinaCorrespondence: Huanming Li Email lihuanming0716@163.comAim: Elevated serum ferritin has been found to be closely related to type 2 diabetes mellitus. This study aimed to explore the relationship of high serum ferritin to metabolism and chronic complications in type 2 diabetes.Methods: This was a cross-sectional study. A total of 330 type 2 diabetes patients who visited an endocrine clinic were included for the analysis. Serum ferritin and metabolic parameters were recorded. The prevalence of chronic diabetic complications was evaluated. Based on serum ferritin, participants were divided into hyperferritinemia and normal-ferritin groups. Metabolic parameters and prevalence of chronic diabetic complications were compared. The relationship between hyperferritinemia and chronic diabetic complications was explored with multivariate logistic regression models. Data were statistically analyzed by sex.Results: Compared with the normal-ferritin group, the hyperferritinemia group showed higher levels of the serum inflammatory marker CRP and higher prevalence of diabetic retinopathy (DR) and coronary heart disease (CHD), regardless of sex (p< 0.05). Moreover, male patients with hyperferritinemia had increased serum triglyceride, alanine transferase, γ-glutamyltranspeptidase, urea nitrogen, creatinine, and uric acid and higher prevalence of microalbuminuria (p< 0.01). After controlling for demographics and metabolic profiles, hyperferritinemia remained an independent risk factor of DR (male OR 3.957, 95% CI 1.559– 10.041, p=0.004; female OR 2.474, 95% CI 1.127– 5.430, p=0.024) and CHD (male OR 2.607, 95% CI 1.087– 6.257, p=0.032; female OR 2.293, 95% CI 1.031– 5.096, p=0.042).Conclusion: This study found that hyperferritinemia was associated with increased CRP and higher prevalence of DR and CHD in type 2 diabetes. In men, high serum ferritin was also associated with dyslipidemia, hepatic dysfunction, and microalbuminuria.Keywords: diabetes mellitus, type 2, ferritin, metabolism, chronic complication

Conservation tillage has been widely adopted in agricultural lands worldwide and is considered a potential strategy for climate change mitigation through enhanced carbon sequestration. However, conservation tillage may alter soil N2O emissions, which may diminish the potential climate change mitigation benefits. Based on 212 observations from 40 publications, a meta-analysis was conducted to quantitatively assess the effects of climate regimes, initial soil properties, and type/duration of agricultural practices on soil N2O emission following application of conservation tillage. Overall, conservation tillage significantly increased soil N2O emission by 17.8% compared to conventional tillage. The greatest increase in N2O emission was observed from soils in tropical climates (70.1%) experiencing short-term (29.3%) application of conservation tillage. Soil pH and clay content significantly influenced N2O emission, while overall soil texture and soil organic carbon (SOC) were not effective predictors of soil N2O emission following conservation tillage. According to the categorical meta-analysis, agricultural practices, including water, residue, and rotation managements and crop types, significantly affected soil N2O emission following conservation tillage. Conservation tillage induced N2O emissions were mitigated with rain-fed cropping systems, residue removal, crop rotation and cultivation of beans and some vegetables. Significant categorical variables affecting N2O emission were mainly attributed to soil aeration and substrate availability, which were important factors affecting nitrification and denitrification processes. Overall, the conservation tillage induced N2O emission factor (EFad) increased by 0.40%, suggesting an attenuation of climate change benefits from increased N2O emission. Our meta-analysis provides a scientific basis for assessing the effects of conservation tillage on N2O emissions and provides site-specific information to mitigate N2O emissions associated with conservation tillage practices.

The persistence effect contribution of legacy nutrients is often cited as a reason for little or no improvement in water quality following extensive implementation of watershed nutrient mitigation actions, yet there is limited knowledge concerning factors influencing this response, often called the “persistence effect.” Here, we adopted detrended fluctuation analysis and Spearman analysis methods to assess the influence of land use on the watershed phosphorus (P) persistence effect, using monthly water quality records during 2010–2016 in 13 catchments within a drinking water reservoir watershed in eastern China. Detrended fluctuation analysis was used to calculate the Hurst exponent α to assess watershed legacy P characteristics (α ≈ 0.5, α > 0.5, and α

Chenyue Zhang,1,&ast;,2 Xiaoling Shang,3,4,&ast; Jian Sun,5 Zhenxiang Li,6 Jiamao Lin,7 Chenglong Zhao,8 Haiyong Wang7 1Department of Integrated Therapy, Fudan University Shanghai Cancer Center, Shanghai, 200032, People’s Republic of China; 2Department of Oncology, Shanghai Medical College, Fudan University, Shanghai, People’s Republic of China; 3Department of Clinical Laboratory, Shandong Cancer Hospital and Institute, Shandong First Medical University and Shandong Academy of Medical Sciences, Jinan, 250117, People’s Republic of China; 4Department of Clinical Laboratory, Shandong University, Jinan, 250012, People’s Republic of China; 5Department of Thoracic Surgery, Shandong Cancer Hospital and Institute, Shandong First Medical University and Shandong Academy of Medical Sciences, Jinan, 250117, People’s Republic of China; 6Department of Radiation Oncology, Shandong Cancer Hospital and Institute, Shandong First Medical University and Shandong Academy of Medical Sciences, Jinan, 250117, People’s Republic of China; 7Department of Internal Medicine-Oncology, Shandong Cancer Hospital and Institute, Shandong First Medical University and Shandong Academy of Medical Sciences, Jinan, 250117, People’s Republic of China; 8Department of Pathology, Shandong Cancer Hospital and Institute, Shandong First Medical University and Shandong Academy of Medical Sciences, Jinan, 250117, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Chenyue ZhangDepartment of Integrated Therapy, Fudan University Shanghai Cancer Center, Shanghai, 200032, People’s Republic of ChinaEmail zhangchenyue_yazi@126.comHaiyong WangDepartment of Internal Medicine-Oncology, Shandong Cancer Hospital and Institute, Shandong First Medical University and Shandong Academy of Medical Sciences, Jinan, 250117, People’s Republic of ChinaTel/Fax +86 531 67626332Email wanghaiyong6688@126.comBackground: Combined small cell lung cancer (c-SCLC) distinguishes itself from small cell lung cancer (SCLC) due to its inclusion of both SCLC and non-small cell lung cancer (NSCLC) components. Few studies have compared clinicopathological characteristics, prognosis and factors affecting survival. We therefore addressed the issues in this study.Patients and Methods: A total of 400 c-SCLC and 20,841 SCLC patients were enrolled using SEER database. Difference in clinicopathological characteristics of SCLC and c-SCLC patients was analyzed using chi-square. Kaplan–Meier was applied to compare their survival before and after propensity score matching (PSM). Cox regression model was adopted to assess the impact of different clinical variables on survival. Logistic regression was applied to identify risk factors for c-SCLC and SCLC patients.Results: Differences in race, sex, T stage, N stage, surgery, bone, brain and liver metastasis were detected between c-SCLC and SCLC patients. c-SCLC patients had better overall survival (OS) than SCLC patients before PSM. Age, race, sex, T stage, N stage, surgery, bone, brain, liver and lung metastasis were prognostic factors affecting OS for c-SCLC and SCLC (P < 0.05). However, a significant OS benefit was not observed in c-SCLC after adjusting for clinicopathological variables (HR, 0.950; 95% CI, 0.842– 1.073; P=0.411). No significant OS difference was found between c-SCLC and SCLC patients after PSM (P = 0.789). c-SCLC patients had lower risk of lymph node (OR: 0.555; 95% CI: 0.439– 0.703; P < 0.001) and liver metastasis (OR: 0.591; 95% CI: 0.448– 0.779; P < 0.001), whereas had no significant differences in bone and brain metastasis risks (P > 0.05) compared with SCLC patients.Conclusion: The prognosis of c-SCLC did not significantly differ from that of SCLC if clinicopathological characteristics are controlled. Better prognosis for c-SCLC patients over SCLC patients may be ascribed to fewer liver and lymph node metastases upon diagnosis.Keywords: prognosis, overall survival, clinicopathological features, c-SCLC, SCLC

Xin Shang, Lan-Er Shi, Dina Taule, Zhang-Zhi Zhu The First Affiliated Hospital of Guangzhou University of Chinese Medicine, Guangzhou, Guangdong, People’s Republic of ChinaCorrespondence: Zhang-Zhi ZhuThe First Affiliated Hospital of Guangzhou University of Chinese Medicine, No. 12, Jichang Road, Guangzhou, Guangdong, 510405, People’s Republic of ChinaTel +86-18620120683Fax +86- 20-36591595Email zzz@gzucm.edu.cnBackground: Currently, there is still a lack of understanding about the mechanism and therapeutic targets of pancreatic adenocarcinoma (PAAD). The potential of miRNA–mRNA networks for the identification of regulatory mechanisms involved in PAAD development remains unexplored.Methods: We compared differentially expressed miRNAs (DEMIs) and differentially expressed genes (DEGs) in PAAD and normal tissues from the Gene Expression Omnibus (GEO) database. Transcription factors (TFs) were obtained from FunRich. Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment analyses of DEGs and DEMIs were implemented using Database for Annotation, Visualization and Integrated Discovery (DAVID). Then, key miRNAs and targeted mRNAs were identified by assessment of their expression and prognosis in UALCAN and Kaplan–Meier plotters. In the last step, the candidate miRNA–mRNA selected was confirmed by real-time quantitative polymerase chain reaction (qRT-PCR).Results: We distinguished 62 significant DEMIs, 1314 upregulated DEGs, and 1110 downregulated DEGs. The top 10 TFs were identified. In total, there were 160 hub genes obtained by intersecting the set of 2224 predicted targets with the set of significant DEGs. And we selected 8 key miRNAs. Furthermore, low expression of miR-455-3p in PAAD tissue was closely connected with poor prognosis, and only 5 target mRNAs were predicted to be increased in PAAD tissue with poor prognosis. Therefore, a novel miRNA–hub gene regulatory network in PAAD was constructed. Finally, in vitro experiments indicated that miR-455-3p expression was decreased in PAAD sample. HOXC4, DLG4, DYNLL1 and FBXO45 were validated by qRT-PCR as highly probable targets of miR-455-3p.Conclusion: A novel miRNA–mRNA axis has been discovered that may be involved in the regulation of transcriptional disorders and affected the survival of PAAD patients, which would provide a novel strategy for the treatment of PAAD.Keywords: pancreatic adenocarcinoma, bioinformatics analysis, differentially expressed genes, differentially expressed microRNAs, hsa-miR-455-3p

Xiushuai Shang,1,2 Liaoran Zhang,2 Rilong Jin,1 Hu Yang,1 Hairong Tao2 1Department of Orthopedics Surgery, The First Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou, People’s Republic of China; 2Shanghai Key Laboratory of Orthopaedic Implant, Department of Orthopaedic Surgery, Shanghai Ninth People’s Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, People’s Republic of ChinaCorrespondence: Hairong TaoShanghai Key Laboratory of Orthopaedic Implants, Department of Orthopaedic Surgery, Shanghai Ninth People’s Hospital, Shanghai JiaoTong University School of Medicine, No. 639 Zhizaoju Road, Shanghai, 200011, People’s Republic of ChinaTel +86-13761221256Email doctorthr@163.comObjective: Pain is the main symptom of osteoarthritis (OA). Nerve growth factor (NGF) plays a crucial role in the generation of OA pain. And estrogen-alone used resulted in a sustained joint pain reduction in postmenopausal women. So we aim to find whether estrogen alters chondrocytes’ NGF level, affecting OA pain.Methods: Primary chondrocytes and cartilage explants isolated from Sprague Dawley rat knees were cultured with physiological concentrations of estrogen (17β-Estradiol ≥ 98%, E2), Estrogen Receptor α (ERα) inhibitor and stimulants. Then, chondrocytes NGF mRNA expression and protein release were analyzed by a quantitative real-time polymerase chain reaction (qPCR) and enzyme-linked immunosorbent assay (ELISA) respectively. Additionally, cultures were pre-incubated with MEK-ERK inhibitor to identify the signaling pathway that estrogen alters NGF mRNA and protein levels.Results: We found that chondrocytes NGF expression and release were decreased by E2. E2 also reduced chondrocytes IL-1β-stimulated or TGF-β 1-stimulated NGF expression. Phosphorylated extracellular signal-regulated kinasep1/2 (p-ERK1/2) signals were detected stronger than the control group by Western Blotting (WB). When we cultured chondrocytes with PD98059 (MEK-ERK inhibitor, PD), NGF mRNA expression was added to 1.41Ct (2.07± 0.1 fold).Conclusion: We showed that E2 reduces chondrocytes NGF expression significantly, even after stimulation by TGF-β 1 or IL-1β. MEK-ERK signaling is involved in this process.Keywords: osteoarthritis, pain, estrogens, nerve growth factor