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Benjin Xu,1– 3,* Zhuru Hou,2,4,* Ling Liu,1– 3,* Rongrong Yan,3 Jinjing Zhang,3 Jianhong Wei,4 Miao Du,1,2 Yan Xuan,1,2 Lei Fan,2,4 Zhuoxi Li2,4 1Department of Medical Laboratory Science, Fenyang College of Shanxi Medical University, Fenyang, People’s Republic of China; 2Key Laboratory of Lvliang for Clinical Molecular Diagnostics, Fenyang, People’s Republic of China; 3Department of Clinical Laboratory, Fenyang Hospital of Shanxi Province, Fenyang, People’s Republic of China; 4Department of Basic Medicine, Fenyang College of Shanxi Medical University, Fenyang, People’s Republic of China*These authors contributed equally to this workCorrespondence: Ling Liu; Benjin Xu, Department of Medical Laboratory Science, Fenyang College of Shanxi Medical University, Fenyang, 032200, People’s Republic of China, Email ll772x@sxmu.edu.cn; bj0726@sxmu.edu.cnObjective: This paper explores the drug resistance, genome and proteome expression characteristics of Salmonella from a food poisoning event.Methods: A multidrug-resistant Salmonella Enteritidis strain, labeled as 27A, was isolated and identified from a food poisoning patient. Antimicrobial susceptibility testing determined the resistance of 27A strain to 14 antibiotics. Then, WGS analysis and comparative genomics analysis were performed on 27A, and the functional annotation of resistance genes, virulence genes were performed based on VFDB, ARDB, COG, CARD, GO, KEGG, and CAZY databases. Meanwhile, based on iTRAQ technology, quantitative proteomic analysis was conducted on 27A to analyze the functions and interactions of differentially expressed proteins related to bacterial resistance and pathogenicity.Results: Strain 27A belonged to ST11 S. Enteritidis and was resistant to levofloxacin, ciprofloxacin, ampicillin, piperacillin, and ampicillin/sulbactam. There were 33 drug resistance genes, 384 virulence genes and 2 plasmid replicon, IncFIB(S) and IncFII(S), annotated by WGS. Proteomic analysis revealed significant changes in virulence and drug proteins, which were mainly involved in bacterial pathogenicity and metabolic processes. PPI prediction showed the relationship between virulence proteins and T3SS proteins, and PagN cooperated with proteins related to T3SS to jointly mediate the invasion of 27A strain on the human body. Phylogenetic analysis indicated that S. Enteritidis has potential transmission in humans, food, and animals.Conclusion: This study comprehensively analyzed the drug resistance and virulence phenotypes of S. Enteritidis 27A using genomic and proteomic approaches. These helps reveal the drug resistance and virulence mechanisms of S. Enteritidis, and provides important information for the source tracing and the prevention of related diseases, which lays a foundation for research on food safety, public health monitoring, and the drug resistance and pathogenicity of S. Enteritidis.Keywords: Salmonella, WGS, quantitative proteomics, resistance, virulence, evolution

Yaowei Xuan,1,* Lin Li,2,* Chenping Zhang,3,4 Min Zhang,1 Junkai Cao,1 Zhen Zhang3,4 1Department of Stomatology, The First Medical Centre, Chinese PLA General Hospital, Beijing, People’s Republic of China; 2State Key Laboratory of Military Stomatology & National Clinical Research Center for Oral Diseases & Shaanxi Clinical Research Center for Oral Diseases, Department of Periodontology, School of Stomatology, Fourth Military Medical University, Xi’an, People’s Republic of China; 3Department of Oral Maxillofacial-Head Neck Oncology, Shanghai Ninth People’s Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, People’s Republic of China; 4College of Stomatology, Shanghai Jiao Tong University, National Center for Stomatology, National Clinical Research Center for Oral Diseases, Shanghai Key Laboratory of Stomatology, Shanghai, People’s Republic of China*These authors contributed equally to this workCorrespondence: Zhen Zhang; Junkai Cao, Tel/Fax +86 153-1779-7335 ; +86 139-0129-0992, Email zz_nirvana@163.com; caojk301@163.comBackground: Repairing critical-sized bone defects secondary to traumatic or tumorous damage is a complex conundrum in clinical practice; in this case, artificial scaffolds exhibited preferable outcomes. Bredigite (BRT, Ca7MgSi4O16) bioceramic possesses excellent physicochemical properties and biological activity as a promising candidate for bone tissue engineering.Methods: Structurally ordered BRT (BRT-O) scaffolds were fabricated by a three-dimensional (3D) printing technique, and the random BRT (BRT-R) scaffolds and clinically available β-tricalcium phosphate (β-TCP) scaffolds were compared as control groups. Their physicochemical properties were characterized, and RAW 264.7 cells, bone marrow mesenchymal stem cells (BMSCs), and rat cranial critical-sized bone defect models were utilized for evaluating macrophage polarization and bone regeneration.Results: The BRT-O scaffolds exhibited regular morphology and homogeneous porosity. In addition, the BRT-O scaffolds released higher concentrations of ionic products based on coordinated biodegradability than the β-TCP scaffolds. In vitro, the BRT-O scaffolds facilitated RWA264.7 cells polarization to pro-healing M2 macrophage phenotype, whereas the BRT-R and β-TCP scaffolds stimulated more pro-inflammatory M1-type macrophages. A conditioned medium derived from macrophages seeding on the BRT-O scaffolds notably promoted the osteogenic lineage differentiation of BMSCs in vitro. The cell migration ability of BMSCs was significantly enhanced under the BRT-O-induced immune microenvironment. Moreover, in rat cranial critical-sized bone defect models, the BRT-O scaffolds group promoted new bone formation with a higher proportion of M2-type macrophage infiltration and expression of osteogenesis-related markers. Therefore, in vivo, BRT-O scaffolds play immunomodulatory roles in promoting critical-sized bone defects by enhancing the polarization of M2 macrophages.Conclusion: 3D-printed BRT-O scaffolds can be a promising option for bone tissue engineering, at least partly through macrophage polarization and osteoimmunomodulation.Graphical Abstract: Keywords: bredigite, three-dimensional printing, osteoimmunomodulation, macrophage polarization, tissue engineering

Yan Xuan,1,2 Wen Zhang,1 Yuying Wang,1 Bin Wang,1 Fangzhen Xia,1 Kun Zhang,1 Qing Li,1 Ningjian Wang,1 Yingli Lu1 1Institute and Department of Endocrinology and Metabolism, Shanghai Ninth People’s Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, People’s Republic of China; 2Department of Endocrinology, Luwan Branch, Ruijin Hospital, School of Medicine, Shanghai Jiaotong University, Shanghai, 200020, People’s Republic of ChinaCorrespondence: Yingli Lu, Institute and Department of Endocrinology and Metabolism, Shanghai Ninth People’s Hospital, Shanghai JiaoTong University School of Medicine, Shanghai, 200011, People’s Republic of China, Tel +86-13636352507, Fax +86-21-63136856, Email luyingli2008@126.comAim: Previous studies have implicated the uric acid to high-density lipoprotein cholesterol (HDL-C) ratio (UHR) was associated with type 2 diabetes. However, the association between UHR and diabetes-related vascular damages is still unclear.Methods: The total of 4551 patients with type 2 diabetes from the cross-sectional Environmental Pollutant Exposure and Metabolic Diseases in Shanghai study (METAL study) were enrolled. UHR was calculated as uric acid to HDL-C ratio. Cardiovascular disease (CVD) was defined as previously diagnosed with stroke, coronary heart disease, or peripheral arterial disease. Chronic kidney disease (CKD) was defined as estimated glomerular filtration rate ≤ 60 mL/min/1.73 m2 and/or urinary albumin to creatinine ratio ≥ 30 mg/g. Fundus image was examined by trained individuals and degree of diabetic retinopathy (DR) was evaluated.Results: UHR was positively correlated with CVD (OR = 1.28, 95% CI: 1.02– 1.61) and CKD (OR = 1.78, 95% CI: 1.39– 2.27) after adjusting for all confounders. No association was found between UHR and DR. In stratified analyses, UHR was predominantly correlated with CVD in diabetic patients with age older than 65 (OR = 1.41, 95% CI: 1.08– 1.85), female (OR = 1.43, 95% CI: 1.06– 1.94) and BMI≥ 24kg/m2 (OR = 1.57, 95% CI: 1.17– 2.11). A 1-SD increment of UHR was also positively associated with CVD (OR 1.26, 95% CI 1.03, 1.15) and CKD (OR 1.28, 95% CI 1.20,1.39). UHR was positively associated with CKD in all subgroups analysis. No significant interaction effect was observed between UHR and all subgroup variables in CVD and CKD risk.Conclusion: Our study reported a positive association between the UHR and diabetic-related vascular complications in men and postmenopausal women. The relationship between the UHR and DR seems to be uncertain and requires further investigation. And no significant interaction effect was observed between the UHR and all subgroup variables in CVD and CKD risk.Keywords: type 2 diabetes, uric acid to HDL cholesterol ratio, cardiovascular disease, chronic kidney disease, diabetic retinopathy, inflammation

Jing Mao,1,* Ya Li,2– 4,* Qingqing Bian,3 Yinshuang Xuan,3 Jingmei Li,3 Zhikun Wang,3 Suxiang Feng,1,2,4 Xuefang Liu,2,4 Yange Tian,2,4 Suyun Li2– 4 1College of Pharmacy, Henan University of Chinese Medicine, Zhengzhou, People’s Republic of China; 2Henan Key Laboratory of Chinese Medicine for Respiratory Disease, Henan University of Chinese Medicine, Zhengzhou, People’s Republic of China; 3Institute for Respiratory Diseases, The First Affiliated Hospital, Henan University of Chinese Medicine, Zhengzhou, People’s Republic of China; 4Co-Construction Collaborative Innovation Center for Chinese Medicine and Respiratory Disease by Henan & Education Ministry of P.R. China, Henan University of Chinese Medicine, Zhengzhou, People’s Republic of China*These authors contributed equally to this workCorrespondence: Suyun Li, Email lisuyun2000@126.comPurpose: Bufei Jianpi formula (BJF), a traditional Chinese medicine, is an effective and safe therapeutic formula for chronic obstructive pulmonary disease (COPD). BJF treatment is known to reduce the incidence of loose stools in rats with COPD. It is unclear whether BJF regulates gut microbiota. This study examined whether BJF improved mucosal immune function by remodeling the gut microbiota and modulating metabolites in COPD rats.Methods: Sixty Sprague Dawley (SD) rats were randomized into control, model, BJF, aminophylline (APL), and probiotics (PBT) groups. The stable COPD rat model was duplicated using repeated cigarette smoke inhalation and lipopolysaccharide (LPS) injection. Normal saline, BJF, APL, or PBT were intragastrically administered from weeks eight to twelve, and then the rats were sacrificed at week thirteen. Lung and colon tissues were removed; feces were collected. Pulmonary function, histopathology, levels of inflammatory factors, and activation of NF-κB in the lung tissues were evaluated. Gut microbiota were analyzed using 16S rRNA gene sequencing; fecal short-chain fatty acid (SCFA) concentrations were determined using gas chromatography/mass spectrometry. Mucosal immune response-related genes and proteins were determined using quantitative polymerase chain reaction and Western blotting.Results: BJF improved pulmonary function and reduced lung inflammation. Further, BJF treatment altered the gut microbiota composition and significantly increased the abundance of Firmicutes and the ratio of Firmicutes to Bacteroides, raising SCFA levels, including acetate, butyrate, and propionate levels. However, the abundance of Bacteroidetes, Proteobacteria, Spirochaetes, Clostridiaceae, and Treponema decreased after BJF administration. BJF decreased the gene and protein expression of NLRP3, Caspase-1, IL-8, and IL-1β, and increased GPR43 expression.Conclusion: Overall, BJF administration improved mucosal immune function by remodeling the gut microbiota and suppressing the SCFAs/GPR43/NLRP3 pathway in COPD rats. This study provides evidence for the mechanisms underlying BJF-induced improvements in COPD and supports clinical application of BJF.Keywords: Bufei Jianpi formula, chronic obstructive pulmonary disease, gut microbiota, gut-lung axis, short-chain fatty acids, mucosal immune function

Yan Xuan,1,2,* Wen Zhang,1,* Yuying Wang,1 Bin Wang,1 Yi Chen,1 Fangzhen Xia,1 Kun Zhang,1 Qing Li,1 Ningjian Wang,1 Yingli Lu1 1Institute and Department of Endocrinology and Metabolism, Shanghai Ninth People’s Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, People’s Republic of China; 2Department of Endocrinology, Luwan Branch, Ruijin Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, 200020, People’s Republic of China*These authors contributed equally to this workCorrespondence: Yingli Lu, Institute and Department of Endocrinology and Metabolism, Shanghai Ninth People’s Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, 200011, People’s Republic of China, Tel +86-13636352507, Fax +86-21-63136856, Email luyingli2008@126.comBackground: The aim of this study was measuring the association between the hypertriglyceridemic-waist (HTGW) phenotype and chronic kidney disease in a large type 2 diabetes population.Methods: A total of 4254 diabetic patients from the cross-sectional Environmental Pollutant Exposure and Metabolic Diseases in Shanghai (METAL) study were enrolled. The hypertriglyceridemic-waist (HTGW) phenotype was defined as the presence of an elevated waist circumference (WC) and elevated triglyceride (TG) concentration. Chronic kidney disease (CKD) was defined as an estimated glomerular filtration rate (eGFR) less than 60 mL/min/1.73 m2 or urinary albumin creatinine ratio (uACR) more than 30 mg/g. Linear and multiple logistic regression models were used for measuring the association between HTGW phenotype and chronic kidney disease.Results: The prevalence of CKD was 29% and 35.8% in total participants and participants with HTGW phenotype, respectively. Subjects in the HTGW phenotype group were more likely to have CKD (OR 1.47, 95% CI: 1.11, 1.95) compared with subjects in the normal waist circumference and normal triglycerides (NTNW) group. HTGW phenotype was both associated with the increasing risk of decreased eGFR (OR 1.31, 95% CI: 1.02, 1.75) and elevated uACR (OR 1.57, 95% CI: 1.18, 2.11). Furthermore, the stratified analysis showed that the strongest positive association between HTGW phenotype and CKD presence was found in the subgroup of presence of hypertension. The associations were all fully adjusted for age, sex, BMI, current smoking, current drinking and other confounding factors.Conclusion: Our study suggested a positive association between the HTGW phenotype and CKD in Chinese type 2 diabetes patients. Further prospective studies are needed to confirm our findings and to investigate the underlying biological mechanisms.Keywords: central obesity, type 2 diabetes mellitus, hypertriglyceridemia waist phenotype, chronic kidney disease

Kai Ma,* Jing Li,* Guoqi Shen, Di Zheng, Yongli Xuan, Yuan Lu, Wenhua Li Department of Cardiology, The Affiliated Hospital of Xuzhou Medical University, Xuzhou, Jiangsu, 221004, People’s Republic of China*These authors contributed equally to this workCorrespondence: Wenhua Li, Tel +86 18052268293, Email xzwenhua0202@163.comObjective: To establish a nomogram model to predict the risk of contrast-induced acute kidney injury (CI-AKI) by analyzing the risk factors of CI-AKI and to evaluate its effectiveness.Methods: Retrospectively analyze the clinical data of non-ST-elevation acute coronary syndrome (NSTE-ACS) patients who underwent percutaneous coronary intervention (PCI) in our cardiology department from September 2018 to June 2021. Of these, patients who underwent PCI in an earlier period formed the training cohort (70%; n = 809) for nomogram development, and those who underwent PCI thereafter formed the validation cohort (30%; n = 347) to confirm the model’s performance. The independent risk factors of CI-AKI were determined by LASSO regression and multivariable logistic regression analysis. By using R software from which nomogram models were subsequently generated. The nomogram was developed and evaluated based on discrimination, calibration, and clinical efficacy using the concordance statistic (C-statistic), calibration plot, and decision curve analysis (DCA), respectively.Results: The nomogram consisted of six variables: age > 75, left ventricular ejection fraction, diabetes mellitus, fibrinogen-to-albumin ratio, high-sensitive C-reactive protein, and lymphocyte count. The C-index of the nomogram is 0.835 (95% CI: 0.800– 0.871) in the training cohort and 0.767 (95% CI: 0.711– 0.824) in the validation cohort, respectively. The calibration plots exhibited that the nomogram was in good agreement between prediction and observation in the training and validation cohorts. Decision curve analysis and clinical impact curve suggested that the predictive nomogram had clinical utility.Conclusion: The nomogram model established has a good degree of differentiation and accuracy, which is intuitively and individually to screen high-risk groups and has a certain predictive value for the occurrence of CI-AKI in NSTE-ACS patients after PCI.Keywords: nomogram, risk forecasting model, non-ST-elevation acute coronary syndrome, percutaneous coronary intervention, contrast-induced acute kidney injury

Yuanbo Fu,1,* Mina Wang,1,2,* Bingcong Zhao,1,* Baoli Liu,3 Jie Sun,4 Yaohui Feng,3 Zhengfang Wang,3 Qian Li,3 Chunhong Shi,3 Yabo Xuan,3 Siqi Long,3 Huan Liu,4 Tiange Chi,5 Zehuan Liao,6,7 Bin Li,1 Qingquan Liu3 1The Department of Acupuncture and Moxibustion, Beijing Hospital of Traditional Chinese Medicine, Capital Medical University, Beijing Key Laboratory of Acupuncture Neuromodulation, Beijing 100010, People’s Republic of China; 2Beijing University of Chinese Medicine, Beijing 100029, People’s Republic of China; 3Beijing Hospital of Traditional Chinese Medicine, Capital Medical University, Beijing 100010, People’s Republic of China; 4Beijing Xiao Tang Shan Hospital, Beijing 102200, People’s Republic of China; 5The First Clinical Medical School, Beijing University of Chinese Medicine, Beijing 100029, People’s Republic of China; 6School of Biological Sciences, Nanyang Technological University, Singapore 637551, Singapore; 7Department of Microbiology, Tumor and Cell Biology (MTC), Karolinska Institutet, Stockholm 17177, Sweden*These authors contributed equally to this workCorrespondence: Bin LiBeijing Hospital of Traditional Chinese Medicine, Capital Medical University, Beijing Key Laboratory of Acupuncture Neuromodulation, No. 23 Gallery Street, Beijing 100010, People’s Republic of ChinaEmail libin0314a@126.comQingquan LiuBeijing Hospital of Traditional Chinese Medicine, Capital Medical University, No. 23 Gallery Street, Beijing 100010, People’s Republic of ChinaEmail liuqingquan2003@126.comPurpose: To investigate the psychological impact of cases of coronavirus disease 19 (COVID-19) on medical staff of Beijing Xiaotangshan Hospital.Methods: The 287 online questionnaires were distributed to medical staff working at Beijing Xiaotangshan Hospital, comprising three main sections and 17 questions: basic information, current departmental position, and the 12-item General Health Questionnaire (GHQ-12). The threshold for emotional distress was defined to be a total score of 4 on the GHQ-12 and above.Results: A total of 255 members of medical staff participating in this study presented an emotional distress rate of 17%. Members who were male, aged 50– 59, married with children, positioned as doctors, and in administration were the population with the highest rate of emotional distress. Furthermore, the severity of emotional distress among those under 30 was significantly lower than those aged 30– 39 and 50– 59. Doctors and other occupations shared a lower level of satisfaction on routine activities compared with nurses, so did staff in the administration compared with those who were working in screening or logistic departments. Besides, males and staff of the confirmation department had more difficulty in concentrating than females and those of the screening department, respectively.Conclusion: Medical staff working at Xiaotangshan Hospital underwent relatively low levels of emotional distress thanks to sufficient medical and psychological preparations. However, special attention should be paid to those who were male, married with children, senior, doctors, in administration, and in the confirmation department.Keywords: COVID-19, psychological impact, medical staff, Beijing, GHQ-12

Xin Tian, Ying Xuan, Rong Wu, Song Gao Department of Clinical Oncology, Shengjing Hospital of China Medical University, Shenyang, Liaoning 110004, People’s Republic of ChinaCorrespondence: Song GaoDepartment of Clinical Oncology, Shengjing Hospital of China Medical University, 36 San Hao Street, Shenyang 110004, People’s Republic of ChinaEmail gaogao0229@hotmail.comObjective: To investigate the curative and adverse effects (AEs) of additional use of nimotuzumab combined with induction chemotherapy and concurrent chemoradiotherapy in unresectable locoregionally advanced hypopharyngeal carcinoma.Patients and Methods: We retrospectively evaluated 36 patients with stage III or IVA hypopharyngeal carcinoma who received induction chemotherapy followed by concurrent chemoradiotherapy with or without nimotuzumab. The induction chemotherapy included two or three cycles of TPF regimen. The intensity-modulated radiation therapy (IMRT) dose was 70 Gy to the planning target volume. Concurrent with radiotherapy, patients received chemotherapy consisting of cisplatin q3w. Adjuvant chemotherapy consisting of TPF regimen was administered 1 month later after concurrent chemoradiotherapy. Nimotuzumab (200 mg day 1, q3w) was given to patients concurrently with induction chemotherapy and was administered concurrently with IMRT at a weekly dose of 200 mg.Results: After induction chemotherapy, the objective response rate in patients treated with nimotuzumab (group A) versus those treated without nimotuzumab (group B) was 91.7% versus 58.3% (p=0.029). After concurrent chemoradiotherapy, the objective response rate was 95.8% in group A versus 83.3% in group B (p=0.253). The median follow-up was 22.6 months (range 8.9– 39.5 months). The 2-year OS rate in group A and group B were 62.5% (95% CI 55– 70%) and 51.8% (95% CI 45– 59%), respectively, the 2-year OS rate in group A was better than group B, P< 0.05. PFS was 23 months (95% CI 19– 27) in group A versus 18 months (95% CI 12– 22) in group B, PFS was longer in group A than group B, P< 0.05. There was no significant difference in AEs between the two groups.Conclusion: Additional use of nimotuzumab combined with induction chemotherapy and concurrent chemoradiotherapy in unresectable locoregionally advanced hypopharyngeal carcinoma yielded better short-term efficacy, also may improve overall survival and progression-free survival than patients without using nimotuzumab. The toxicity was tolerable.Keywords: nimotuzumab, induction chemotherapy, chemoradiotherapy, unresectable, locoregionally advanced, hypopharyngeal carcinoma

Lihua Piao,1 Haoyue Li,1,2 Ying Feng,1,2 Xiaogang Li,3 Yan Cui,4 Yanhua Xuan1,2 1Institute for Regenerative Medicine, Yanbian University College of Medicine, Yanji 133002, Jilin Province, People’s Republic of China; 2Department of Pathology, Yanbian University College of Medicine, Yanji 133002, Jilin Province, People’s Republic of China; 3Department of Urology, Yanbian University Affiliated Hospital, Yanji 133002, Jilin Province, People’s Republic of China; 4Department of Oncology, Yanbian University Affiliated Hospital, Yanji 133002, Jilin Province, People’s Republic of ChinaCorrespondence: Yanhua XuanDepartment of Pathology, Yanbian University College of Medicine, No. 977, Gongyuan Road, Yanji City 133002, People’s Republic of ChinaTel +86-433-2435107Fax +86-433-2732456Email xuanyh1@ybu.edu.cn Yan CuiDepartment of Oncology, Yanbian University Affiliated Hospital, No. 977, Gongyuan Road, Yanji City 133002, People’s Republic of ChinaTel +86-433-2435107Fax +86-433-2732456Email cuiyan2005@hotmail.comPurpose: The leucine zipper-EF-hand containing transmembrane protein 1 (LETM1) is a mitochondrial protein that has been associated with the occurrence and development of malignant tumors. Previous studies have shown that LETM1 expression is increased in several types of human cancer and is associated with a poor clinical outcome. However, the role of LETM1 in prostate cancer (PCa) has not yet been determined. In this study, we investigated the clinicopathological significance of LETM1 expression and its role in PCa progression.Methods: We assessed the expression of LETM1 and genes related to cancer stemness, epithelial-mesenchymal transition (EMT), cell cycle, and PI3K/Akt signaling in 133 paraffin-embedded PCa tissue samples and cancer cells by using immunohistochemistry, immunofluorescence, and Western blotting.Results: LETM1 expression was significantly increased in PCa, and it was positively correlated with Gleason score, pathologic tumor (pT) stage, clinical stage, and high microvessel density. Survival analysis showed that patients with PCa with a high level of LETM1 expression exhibited a low overall survival. Cox regression analysis indicated that LETM1 is an independent poor prognostic PCa factor. Additionally, the expression of LETM1 was correlated with cancer cell stemness-associated genes, EMT-related genes, cell cycle regulatory genes, and PI3K/Akt signaling gene expression in PCa. Furthermore, knocking down LETM1 expression down-regulated the expression of stemness-related proteins, while inhibiting tumor spheroid formation, EMT-like changes, cell proliferation, migration, and invasion in PCa cells. Importantly, the PI3K inhibitor LY294002 strongly inhibited the expression of LETM1, pPI3K-p85, and pAkt (Thr308, Ser473) in PCa cells.Conclusion: These results indicate that LETM1 expression is associated with cancer cell stemness, promotes EMT-like changes and cell proliferation and is a potential prognostic biomarker for PCa.Keywords: prostate cancer, leucine zipper-EF-hand containing transmembrane protein 1, epithelial-mesenchymal transition, prognosis

Pin Li,1,2,* Cheng Peng,3,* Yongpeng Xie,4,* Lei Wang,5 Liangyou Gu,1 Shengpan Wu,1 Donglai Shen,1 Yundong Xuan,1 Xin Ma,1 Xu Zhang1 1Department of Urology, State Key Laboratory of Kidney Diseases, The First Medical Center of Chinese PLA General Hospital, Beijing, People’s Republic of China; 2Department of Pediatric Urology, Bayi Children’s Hospital Affiliated to the Seventh Medical Center of Chinese PLA General Hospital, Beijing, People’s Republic of China; 3Department of Urology, The Seventh Medical Center of Chinese PLA General Hospital, Beijing, People’s Republic of China; 4Department of Urology, The First Affiliated Hospital of Chongqing Medical University, Chongqing, People’s Republic of China; 5Chinese PLA 534 Hospital, Luoyang, People’s Republic of China*These authors contributed equally to this workCorrespondence: Xu Zhang; Xin MaDepartment of Urology, Chinese PLA General Hospital, Beijing 100853, People’s Republic of ChinaTel +86-10-6693-8211; +86-10-6693-8008Fax +86-10-6822-3567; +86-10-6822-3575Email xzhang@tjh.tjmu.edu.cn; urologist@foxmail.comObjective: To provide a preoperative predictive model to support clinical decision-making regarding the selection of in renal cell carcinoma (RCC) patients who will benefit the most from lymph node dissection.Methods: This retrospective analysis enrolled 374 RCC patients without distant metastasis who underwent surgical treatment from January 2006 to December 2017. The relationships between lymph node invasion (LNI) and age at surgery; gender; body mass index(BMI); the presence of clinical symptoms such as flank pain, hematuria or a palpable mass; clinical T stage (cT stage); clinical N stage (cN stage); and the results of routine hematological and serum biochemical analyses were investigated. All the variables were included in univariate and multivariate logistic regression analyses, and the significant variables were then included in a novel nomogram to predict the probability of LNI. Then, we calibrated the nomogram with an internal validation set.Results: Six of eighteen variables were significant in the univariate logistic regression analysis. After multivariate logistic regression analysis, age at surgery (OR=0.643, 95% CI: 0.421–0.975), cT stage (OR=3.034, 95% CI: 1.541–5.926), cN stage (OR=6.353, 95% CI: 3.273–12.456), lymphocyte percentage (OR=0.481, 95% CI: 0.256–0.894), and the presence of clinical symptoms (OR=2.045, 95% CI: 1.065–3.924) were independent predictors of LNI and were included in the nomogram. The C-index of this nomogram was 0.824.Conclusion: Preoperative basic laboratory findings combined with the results of a physical examination and radiological examination can indicate the probability of LNI in RCC patients.Keywords: kidney cancer, renal cell carcinoma, lymph node invasion, predictive nomogram

Junyao Duan,1 Xin Ma,2 Jing Shi,1 Yundong Xuan,2 Hanfeng Wang,2 Pin Li,3 Yu Zhang,2 Yang Fan,2 Huijie Gong,1 Xuetao Ma,1 Yuewen Pang,1 Ling Wang,1 Yongji Yan,1 Xu Zhang21Department of Urology, Dongzhimen Hospital Affiliated to Beijing University of Chinese Medicine, Beijing 100700, People’s Republic of China; 2Department of Urology, State Key Laboratory of Kidney Diseases, PLA Medical School, Chinese People’s Liberation Army General Hospital, Beijing 100853, People’s Republic of China; 3School of Medicine, Nankai University, Tianjin 300071, People’s Republic of ChinaBackground: Renal cell carcinoma (RCC) is one of the most common types of urological malignant tumors. Despite recent advances in diagnosis and management of RCC, its prognosis remains poor. Emerging evidence has shown that long noncoding RNAs (lncRNAs) play crucial regulatory roles in cancer biology.Materials and methods: The most abundant transcript of long intergenic non-protein coding RNA p53 induced transcript (LINC-PINT) in clear cell RCC (ccRCC) was determined by RT-PCR. Quantitative real-time PCR was performed to examine LINC-PINT expression in paired ccRCC samples and cell lines. The relationship of LINC-PINT expression with clinicopathologic characteristics and clinical outcome was analyzed. The biological function of LINC-PINT was studied by MTS and colony formation. The flow cytometry was used to analyze cell cycle distribution and apoptosis. The subcelluar fractionation and RIP assay was performed to explore the molecular mechanism of LINC-PINT. Western blotting and immunofluorescence was carried out to examine EZH2 and p53. Results: We found that the LINC-PINT was frequently upregulated in ccRCC samples. Furthermore, we observed that the level of LINC-PINT depended on gender as well as on pT and TNM stage of patients with ccRCC. Moreover, patients with high LINC-PINT expression had poor disease-free survival and overall survival. Functionally, overexpression of LINC-PINT promoted ccRCC cell proliferation, induced cell cycle progression, and inhibited apoptosis. LINC-PINT was primarily located in cell nuclei and interacted with EZH2. When EZH2 was knocked down in 769P and OS-RC-2 cells overexpressing LINC-PINT, the effect of LINC-PINT on cell proliferation, cell cycle, and apoptosis was partially reversed. Additionally, inducing p53 by doxorubicin (Dox) promoted LINC-PINT expression.Conclusion: Collectively, our results provide novel insights into the important role of LINC-PINT in ccRCC development and indicate that LINC-PINT may serve as a valuable prognostic biomarker for ccRCC.Keywords: long noncoding RNA, LINC-PINT, clear cell renal cell carcinoma, prognosis, cell proliferation, EZH2

Yong Tang,1,2,* Yiwen Xuan,2,* Guibin Qiao,3 Zhu’an Ou,2 Zhe He,2 Qihang Zhu,2 Ming Liao,2 Guilin Yin1 1Southern Medical University, Guangzhou, China; 2Department of Thoracic Surgery, General Hospital of Southern Theatre Command of PLA, Guangzhou, China; 3Department of Thoracic Surgery, Guangdong General Hospital, Guangdong Academy of Medical Sciences, Guangzhou, China *These authors contributed equally to this work Background: Mouse double minute 2 (MDM2) contributes to cancer metastasis and epithelial–mesenchymal transition (EMT). This study aimed to investigate small mothers against decapentaplegic (Smad) signaling in MDM2-mediated EMT in lung adenocarcinoma (LAC). Materials and methods: Expression patterns of MDM2 in LAC tissues, adjacent tissues, and cell lines (BEAS-2B, PC9, H1975, and A549) were detected. We then overexpressed MDM2 in PC9 cells and knocked it down in H1975 cells. To explore whether MDM2 activates EMT through the Smad2/3 signaling pathway, Smad2 and Smad3 were also silenced by siRNA in H1975 cells. Male BALB/c nude mice were used in in vivo model to validate the effects of MDM2 on LAC cells. Results: MDM2 was significantly upregulated in LAC tissues compared with adjacent tissues. The expression of MDM2 was relatively higher in PC9 cells and relatively lower in H1975 cells compared with A549 cells. Overexpression of MDM2 significantly increased cell proliferation, migration, and invasion in LAC cells, while inhibiting apoptosis in PC9 cells. On the contrary, silencing of MDM2 significantly inhibited the expression of EMT-related genes N-cadherin and vimentin, while promoting the expression of E-cadherin and β-catenin. In vivo, MDM2 knockdown inhibited tumor growth. In addition, the expression of Smad2/3 was correlated with MDM2 in H1975 cells transfected with Smad2 and Smad3 siRNAs, which inhibited EMT progress. Conclusion: MDM2 can activate the Smad2/3 signaling pathway, which promotes the proliferation and EMT progress of LAC cells. Keywords: lung adenocarcinoma, epithelial–mesenchymal transition, Smad signaling pathway, cell metastasis, MDM2

Shicheng Li,1,* Yunpeng Xuan,1,* Bing Gao,2 Xiao Sun,1 Shuncheng Miao,1 Tong Lu,1 Yuanyong Wang,1 Wenjie Jiao1 1Department of Thoracic Surgery, Affiliated Hospital of Qingdao University, Qingdao, China; 2School of Basic Medicine, Qingdao University, Qingdao, China *These authors contributed equally to this work Background: Lung adenocarcinoma (LUAD) is the leading cause of cancer-related death worldwide. The main obstacle to early diagnosis or monitoring of patients at high risk of poor survival has been the lack of essential predictive biomarkers.Methods: RNA-sequencing was performed on LUAD affected tissue and paired adjacent to noncancerous tissue samples and Gene Expression Omnibus dataset GSE19188 and GSE33532 were used to obtain an intersection of differential expressed genes and construct a protein–protein interaction network to get hub genes. Then corresponding overall survival information of two cohorts of LUAD patients from our hospital and The Cancer Genome Atlas project-LUAD were included in the present study. An analysis of the Kyoto Encyclopedia of Genes and Genomes database and Gene Ontology were carried out to study the signature mechanism.Results: In our study, we identified eight candidate genes (DLGAP5, KIF11, RAD51AP1, CCNB1, AURKA, CDC6, OIP5 and NCAPG) closely related to survival in LUAD. A linear prognostic model of the eight genes was constructed and weighted by the regression coefficient (β) from the multivariate Cox regression analysis of The Cancer Genome Atlas-LUAD cohort to divide patients into low- and high-risk groups. The prognostic ability of the signature was validated in LUAD patients at our hospital. Patients assigned to the high-risk group exhibited poor overall survival compared to patients in the low-risk group. Finally, functional enrichment analysis showed that cell division played a vital role in the development of LUAD.Conclusion: The study identified an mRNA signature including eight genes, which may serve as a potential prognostic marker of LUAD. Keywords: RNA-seq, prognostic, signature, lung adenocarcinoma

Yong Tang,1,2,* Guibin Qiao,1,2,* Enwu Xu,2 Yiwen Xuan,2 Ming Liao,2 Guilin Yin1 1Southern Medical University, Guangzhou, Guangdong Province, China, 2Department of Thoracic Surgery, General Hospital of Guangzhou Military Command of PLA, Yuexiu District, Guangzhou City, Guangdong Province, China *These authors contributed equally to this work Abstract: Despite advances in the management of non-small cell lung cancer, it remains to be the leading cause of cancer-related deaths worldwide primarily because of diagnosis at a late stage with an overall 5-year survival rate of 17%. A reduction in mortality was achieved by low-dose computed tomography screening of high-risk patients. However, the benefit was later challenged by the high false positive rate, resulting in unnecessary follow-ups, thus entailing a burden on both the health care system and the individual. The diagnostic dilemma imposed by imaging modalities has created a need for the development of biomarkers capable of differentiating benign nodules from malignant ones. In the past decade, with the advancements in high-throughput profiling technologies, a huge amount of work has been done to derive biomarkers to supplement clinical diagnosis. However, only a few of them have efficient sensitivity and specificity to be utilized in clinical settings. Therefore, there is an urgent need for the development of sensitive and specific means to detect and diagnose lung cancers at an early stage, when curative interventions are still possible. Due to the invasiveness of tissue biopsies and inability to capture tumor heterogeneity, nowadays enormous efforts have been invested in the development of technologies and biomarkers that enable sensitive and cost-effective testing using substrates that can be obtained in a noninvasive manner. This review, primarily focusing on liquid biopsy, summarizes all documented potential biomarkers for diagnosis, monitoring recurrence treatment response. Keywords: liquid biopsy, circulating-tumor DNA, circulating tumor cells, non-small cell lung cancer, exosomes, biomarkers

Atmospheric rivers (ARs) are narrow, elongated belts of intense water vapor transport that often occur in mid‐latitude areas and are the primary drivers of heavy precipitation in these regions. This study investigates the impact of ARs on precipitation patterns in the Jianghuai River Basin during the Mei‐yu period. Focusing on a specific rainstorm event on June 27, 2022, we analyze atmospheric circulation, water vapor attributes, and transport trajectories. Three distinct classes of grids (Class A, significantly influenced by ARs; Class B, moderately affected; and Class C, untouched by ARs) are identified based on their response to ARs. Class A grids, located centrally, experience substantial precipitation, with a higher probability of rainstorm events. Class B grids, situated at a distance from ARs, exhibit moderate precipitation and a longer duration of rainy days. Class C grids, minimally affected by ARs, experience minimal precipitation with almost no chance of rainstorm events. The results from grid‐based analysis emphasize the localized influence of ARs, indicating a 8–30 times increase in precipitation intensity of Class A compared to Class C. The 23‐day Mei‐yu period is further categorized into AR days and non‐AR days, revealing that ARs amplify precipitation intensity by 2–5 times on average. Grid‐based and day‐based analyses provide complementary insights, with the former offering a broader spatial perspective and the latter emphasizing temporal distinctions. These findings underscore the nuanced influence of ARs on precipitation, emphasizing their role in extreme events and highlighting the importance of considering both spatial and temporal factors in understanding precipitation variability. [ABSTRACT FROM AUTHOR]

Large genomic datasets in combination with clinical data can be used as an unbiased tool to identify genes important in patient survival and discover potential therapeutic targets. We used a genome-wide screen to identify 587 genes significantly and robustly deregulated across four independent breast cancer (BC) datasets compared to normal breast tissue. Gene expression of 381 genes was significantly associated with relapse-free survival (RFS) in BC patients. We used a gene co-expression network approach to visualize the genetic architecture in normal breast and BCs. In normal breast tissue, co-expression cliques were identified enriched for cell cycle, gene transcription, cell adhesion, cytoskeletal organization and metabolism. In contrast, in BC, only two major co-expression cliques were identified enriched for cell cycle-related processes or blood vessel development, cell adhesion and mammary gland development processes. Interestingly, gene expression levels of 7 genes were found to be negatively correlated with many cell cycle related genes, highlighting these genes as potential tumor suppressors and novel therapeutic targets. A forward-conditional Cox regression analysis was used to identify a 12-gene signature associated with RFS. A prognostic scoring system was created based on the 12-gene signature. This scoring system robustly predicted BC patient RFS in 60 sampling test sets and was further validated in TCGA and METABRIC BC data. Our integrated study identified a 12-gene prognostic signature that could guide adjuvant therapy for BC patients and includes novel potential molecular targets for therapy.

Musculoskeletal disorders (MSD) are a collection of degenerative conditions impacting the body's bones, joints, muscles, tendons, ligaments, and nerves. MSDs affect approximately 1.71 billion individuals worldwide and are a significant cause of disability. Curcumin is a polyphenolic compound with anti-inflammatory, antioxidant, and antitumor properties. In this review, we will discuss the research progress of structural analogs, derivatives, and nanomaterials that can improve the bioavailability of this natural drug. Curcumin may potentially retard the progression of osteoporosis, osteoarthritis, and rheumatoid arthritis. These effects may be related to curcumin's targeting of multiple signalling pathways. [ABSTRACT FROM AUTHOR]

A study was conducted to compare the efficacy and safety of home-based 590nm light-emitting diodes (LEDs) and in-hospital 1064nm Q-switched Nd:YAG laser in the treatment of facial melasma. Fifty patients were randomly assigned to either the LEDs group or the QSNY group and were followed up for 16 weeks. The results showed that both treatments significantly reduced the melasma area severity index (mMASI) scores, melanin index (MI), and erythema index (EI) in both groups. No statistical differences were found between the two groups, suggesting that home-based LEDs could be a promising alternative for melasma treatment due to its portability and low cost. The study was funded by the Medical Innovation Research Special Project of Shanghai Science and Technology Commission, the National Natural Science Foundation of China, and the Natural Science Foundation of Shanghai. No conflicts of interest were declared, and the data are available upon request. [Extracted from the article]

Abstract PANoptosis induces programmed cell death (PCD) through extensive crosstalk and is associated with development of cancer. However, the functional mechanisms, clinical significance, and potential applications of PANoptosis-related genes (PRGs) in colorectal cancer (CRC) have not been fully elucidated. Functional enrichment of key PRGs was analyzed based on databases, and relationships between key PRGs and the immune microenvironment, immune cell infiltration, chemotherapy drug sensitivity, tumor progression genes, single-cell cellular subgroups, signal transduction pathways, transcription factor regulation, and miRNA regulatory networks were systematically explored. This study identified 5 key PRGs associated with CRC: BCL10, CDKN2A, DAPK1, PYGM and TIMP1. Then, RT-PCR was used to verify expression of these genes in CRC cells and tissues. Clinical significance and prognostic value of key genes were further verified by multiple datasets. Analyses of the immune microenvironment, immune cell infiltration, chemotherapy drug sensitivity, tumor progression genes, single-cell cellular subgroups, and signal transduction pathways suggest a close relationship between these key genes and development of CRC. In addition, a novel prognostic nomogram model for CRC was successfully constructed by combining important clinical indicators and the key genes. In conclusion, our findings offer new insights for understanding the pathogenesis of CRC, predicting CRC prognosis, and identifying multiple therapeutic targets for future CRC therapy.

Abstract Background Perioperative reflux aspiration presents a grave concern during sedation or general anesthesia, particularly when solid gastric contents prompt acute upper respiratory obstruction, potentially resulting in fatal consequences for patients. Currently, there are limited means for promptly assessing solid gastric contents in clinical settings. Therefore, this study examined the efficacy of ultrasound assessment for solid gastric contents, offering a rapid and non-invasive approach for early detection and decision-making regarding interventions. Methods The study included 400 patients scheduled for upper endoscopy procedures, which encompassed both gastroscope and gastroscope combined colonoscopy examinations with sedation. Ultrasound scanning of the antrum was performed while patients were positioned semi-sitting or in the right lateral decubitus (RLD) posture. The evaluation of solid gastric contents relied on direct visual observation during endoscopy. Gastric volume measurement occurred subsequent to endoscopic suction of gastric contents. Receiver operating characteristic curves were utilized to assess the effectiveness of ultrasonography in discerning solid contents. Result Seven patients undergoing gastroscope with sedation were found to have solid gastric contents. The sensitivity, specificity, positive predictive value, and negative predictive value of the ultrasound qualitative evaluation of solid contents were 85.7%, 99%, 60%, and 99.7%, respectively. Conclusion Solid stomach contents can be evaluated qualitatively with reasonable accuracy using ultrasonography. Additionally, in patients undergoing upper endoscopy and assessed to have solid gastric contents with ultrasound, administration of mild sedation is recommended. Trial registration www.chictr.org.cn (ChiCTR2100048994); registered 19/07/2021.

Abstract Background Brassica napus L. (B. napus) is susceptible to waterlogging stress during different cultivation periods. Therefore, it is crucial to enhance the resistance to waterlogging stress to achieve a high and stable yield of B. napus. Results Here we observed significant differences in the responses of two B. napus varieties in root under waterlogging stress. The sensitive variety (23651) exhibited a more pronounced and rapid reduction in cell wall thickness and root integrity compared with the tolerant variety (Santana) under waterlogging stress. By module clustering analysis based on transcriptome data, we identified that cell wall polysaccharide metabolism responded to waterlogging stress in root. It was found that pectin content was significantly reduced in the sensitive variety compared with the tolerant variety. Furthermore, transcriptome analysis revealed that the expression of two homologous genes encoding polygalacturonase-inhibiting protein 2 (PGIP2), involved in polysaccharide metabolic pathways, was highly upregulated in root of the tolerant variety under waterlogging stress. BnaPGIP2s probably confer waterlogging resistance by inhibiting the activity of polygalacturonases (PGs), which in turn reduces the degradation of the pectin backbone polygalacturonic acid. Conclusions Our findings demonstrate that cell wall polysaccharides in root plays a vital role in response to the waterlogging stress and provide a theoretical foundation for breeding waterlogging resistance in B. napus varieties.

AIM: To investigate whether retinal nerve fiber layer defects (RNFLDs) is a potential risk factor for chronic kidney disease (CKD) in Chinese adults. METHODS: The Kailuan Eye Study was a population-based study that included 14 440 participants. All participants underwent detailed assessments, RNFLDs were diagnosed using color fundus photographs. RESULTS: Overall, 12 507 participants [8533 males (68.23%)] had complete systemic examination data and at least one evaluable fundus photograph. RNFLDs were found in 621 participants [5.0%; 95% confidence interval (CI): 4.6%-5.34%], and 70 cases of multiple RNFLDs were found (11.27%). After adjusting multiple factors, RNFLDs was significantly associated with CKD severity, the ORs of CKD stage 3, stage 4 and stage 5 were 1.698, 4.167, and 9.512, respectively. Multiple RNFLDs were also associated with CKD severity after adjusting multiple factors, the ORs of CKD stage 3 and stage 5 were 4.465 and 11.833 respectively. Furthermore, 2294 participants had CKD (18.34%, 95%CI: 17.68%-18.99%). After adjusting for other factors, CKD presence was significantly correlated with the presence of RNFLDs. CONCLUSION: The strongest risk factors for RNFLDs are CKD and hypertension. Conversely, RNFLDs can be an ocular feature in patients with CKD. Fundoscopy can help detect systemic diseases, and assessment for RNFLDs should be considered in CKD patients.

Abstract To date, the types of fuels used in pottery kilns during the Western Zhou Dynasty have not been adequately addressed. Samples from updraft kilns and semi-downdraft kilns at the Fengjing site, the capital in the late Western Zhou period, were selected for analysis. Through phytolith and wood charcoal analysis, various grasses mainly Panicoideae, Pooideae, and Eragrostidoideae, as well as millet, rice, and wheat crops were identified. Additionally, wood primarily from trees of the Quercus, Ulmus, and Liquidambar taxa was found. These findings suggest that different pottery kilns used similar fuels, demonstrating a broad-spectrum rather than specialized fuel utilization during the Zhou period.

Thermal management of nanoscale quantum dots (QDs) in light-emitting devices is a long-lasting challenge. The existing heat transfer reinforcement solutions for QDs-polymer composite mainly rely on thermal-conductive fillers. However, this strategy failed to deliver the QDs’ heat generation across a long distance, and the accumulated heat still causes considerable temperature rise of QDs-polymer composite, which eventually menaces the performance and reliability of light-emitting devices. Inspired by the radially aligned fruit fibers in oranges, we proposed to eliminate this heat dissipation challenge by establishing long-range ordered heat transfer pathways within the QDs-polymer composite. Ultrahigh molecular weight polyethylene fibers (UPEF) were radially aligned throughout the polymer matrix, thus facilitating massive efficient heat dissipation of the QDs. Under a UPEF filling fraction of 24.46 vol%, the in-plane thermal conductivity of QDs-radially aligned UPEF composite (QDs-RAPE) could reach 10.45 W m−1 K−1, which is the highest value of QDs-polymer composite reported so far. As a proof of concept, the QDs’ working temperature can be reduced by 342.5 °C when illuminated by a highly concentrated laser diode (LD) under driving current of 1000 mA, thus improving their optical performance. This work may pave a new way for next generation high-power QDs lighting applications.

Abstract Background Phosphorus is a macronutrient necessary for plant growth and development and its availability and efficient use affect crop yields. Leaves are the largest tissue that uses phosphorus in plants, and membrane phospholipids are the main source of cellular phosphorus usage. Results Here we identify a key process for plant cellular phosphorus recycling mediated by membrane phospholipid hydrolysis during leaf senescence. Our results indicate that over 90% of lipid phosphorus, accounting for more than one-third of total cellular phosphorus, is recycled from senescent leaves before falling off the plants. Nonspecific phospholipase C4 (NPC4) and phospholipase Dζ2 (PLDζ2) are highly induced during leaf senescence, and knockouts of PLDζ2 and NPC4 decrease the loss of membrane phospholipids and delay leaf senescence. Conversely, overexpression of PLDζ2 and NPC4 accelerates the loss of phospholipids and leaf senescence, promoting phosphorus remobilization from senescent leaves to young tissues and plant growth. We also show that this phosphorus recycling process in senescent leaves mediated by membrane phospholipid hydrolysis is conserved in plants. Conclusions These results indicate that PLDζ2- and NPC4-mediated membrane phospholipid hydrolysis promotes phosphorus remobilization from senescent leaves to growing tissues and that the phospholipid hydrolysis-mediated phosphorus recycling improves phosphorus use efficiency in plants.

Abstract Background Aldehyde dehydrogenase 2 (ALDH2) is critical for alcohol metabolism by converting acetaldehyde to acetic acid. In East Asian descendants, an inactive genetic variant in ALDH2, rs671, triggers an alcohol flushing response due to acetaldehyde accumulation. As alcohol flushing is not exclusive to those of East Asian descent, we questioned whether additional ALDH2 genetic variants can drive facial flushing and inefficient acetaldehyde metabolism using human testing and biochemical assays. Methods After IRB approval, human subjects were given an alcohol challenge (0.25 g/kg) while quantifying acetaldehyde levels and the physiological response (heart rate and skin temperature) to alcohol. Further, by employing biochemical techniques including human purified ALDH2 proteins and transiently transfected NIH 3T3 cells, we characterized two newly identified ALDH2 variants for ALDH2 enzymatic activity, ALDH2 dimer/tetramer formation, and reactive oxygen species production after alcohol treatment. Results Humans heterozygous for rs747096195 (R101G) or rs190764869 (R114W) had facial flushing and a 2-fold increase in acetaldehyde levels, while rs671 (E504K) had facial flushing and a 6-fold increase in acetaldehyde levels relative to wild type ALDH2 carriers. In vitro studies with recombinant R101G and R114W ALDH2 enzyme showed a reduced efficiency in acetaldehyde metabolism that is unique when compared to E504K or wild-type ALDH2. The effect is caused by a lack of functional dimer/tetramer formation for R101G and decreased Vmax for both R101G and R114W. Transiently transfected NIH-3T3 cells with R101G and R114W also had a reduced enzymatic activity by ~ 50% relative to transfected wild-type ALDH2 and when subjected to alcohol, the R101G and R114W variants had a 2-3-fold increase in reactive oxygen species formation with respect to wild type ALDH2. Conclusions We identified two additional ALDH2 variants in humans causing facial flushing and acetaldehyde accumulation after alcohol consumption. As alcohol use is associated with a several-fold higher risk for esophageal cancer for the E504K variant, the methodology developed here to characterize ALDH2 genetic variant response to alcohol can lead the way precision medicine strategies to further understand the interplay of alcohol consumption, ALDH2 genetics, and cancer.

Abstract Objectives Lung cancer is an independent risk factor for pulmonary complications following HIV infection. This study aimed to examine the expression and clinical significance of Cathepsin G (CTSG) protein in both non-HIV and HIV-related lung cancers. Methods The data related to lung adenocarcinoma (LUAD) and lung squamous carcinoma (LUSC) in the TCGA dataset and the data related to healthy individuals in the GTEx dataset, the GEPIA2 database was used to excavate the distinction in the expression of CTSG protein in non-small cell lung cancer (NSCLC) tissues versus normal non-cancerous tissues. The Ualcan database was used to compare the differences in CTSG expression at different stages of LUAD and LUSC. Immunohistochemistry (IHC) was used to detect the expression of CTSG proteins in the pathological tissues of patients with HIV-related lung cancer and patients with lung cancer without co-infection, the Kaplan-Meier method was used for survival analysis. Results We observed that CTSG expression in NSCLC is lower compared to adjacent non-tumor tissues and correlates with NSCLC clinical stage. CTSG protein expression in HIV-related lung cancer tissues was lower than in adjacent tissues and lower than in lung cancer tissues without HIV infection, with a statistically significant difference (P

Abstract The educational environment plays a vital role in the development of students who participate in athletic pursuits both in terms of their physical health and their ability to detect fatigue. As a result of recent advancements in deep learning and biosensors benefitting from edge computing resources, we are now able to monitor the physiological fatigue of students participating in sports in real time. These devices can then be used to analyze the data using contemporary technology. In this paper, we present an innovative deep learning framework for forecasting fatigue in athletic students following physical exercise. It addresses the issue of lack of precision computational models and extensive data analysis in current approaches to monitoring students’ physical activity. In our study, we classified fatigue and non-fatigue based on photoplethysmography (PPG) signals. Several deep learning models are compared in the study. Using limited training data, determining the optimal parameters for PPG presents a significant challenge. For datasets containing many data points, several models were trained using PPG signals: a deep residual network convolutional neural network (ResNetCNN) ResNetCNN, an Xception architecture, a bidirectional long short-term memory (BILSTM), and a combination of these models. Training and testing datasets were assigned using a fivefold cross validation approach. Based on the testing dataset, the model demonstrated a proper classification accuracy of 91.8%.

Food taste-modulating peptides mainly interact with salt taste receptor ENaC, TRPV1 or TMC4, umami receptor T1R1/T1R3, sweet receptor T1R2/T1R3, bitter receptor T2R and kokumi receptor CaSR to induce PLCβ2/IP3 or cAMP/PKA pathway to achieve taste transduction. Computer aided analysis techniques such as molecular docking, dynamic simulation, virtual screening and deep learning can efficiently, accurately and widely identify and develop novel taste-modulating peptides, which can effectively promote the high-quality development of nutrition and health food industry. This paper aims to present the latest research progress in the field of taste-modulating peptides, including the human taste perception mechanism, the taste mechanism of food taste-modulating peptides, as well as computer aided analysis techniques. This provides ideas for cost reduction, efficiency enhancement, and subsequent in-depth research in the era of Big Compute and development of new taste-modulating peptide products in the field of food taste-modulating peptides development.

The synchronized development of mineralized bone and blood vessels is a fundamental requirement for successful bone tissue regeneration. Adequate energy production forms the cornerstone supporting new bone formation. ETS variant 2 (ETV2) has been identified as a transcription factor that promotes energy metabolism reprogramming and facilitates the coordination between osteogenesis and angiogenesis. In vitro molecular experiments have demonstrated that ETV2 enhances osteogenic differentiation of dental pulp stem cells (DPSCs) by regulating the ETV2- prolyl hydroxylase 2 (PHD2)- hypoxia-inducible factor-1α (HIF-1α)- vascular endothelial growth factor A (VEGFA) axis. Notably, ETV2 achieves the rapid reprogramming of energy metabolism by simultaneously accelerating mitochondrial aerobic respiration and glycolysis, thus fulfilling the energy requirements essential to expedite osteogenic differentiation. Furthermore, decreased α-ketoglutarate release from ETV2-modified DPSCs contributes to microcirculation reconstruction. Additionally, we engineered hydroxyapatite/chitosan microspheres (HA/CS MS) with biomimetic nanostructures to facilitate multiple ETV2-DPSC functions and further enhanced the osteogenic differentiation. Animal experiments have validated the synergistic effect of ETV2-modified DPSCs and HA/CS MS in promoting the critical-size bone defect regeneration. In summary, this study offers a novel treatment approach for vascularized bone tissue regeneration that relies on energy metabolism activation and the maintenance of a stable local hypoxia signaling state.