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Rong Huang,1,* Jun Zeng,1,* Xiaoze Yu,1 Yunke Shi,2 Na Song,1 Jie Zhang,1 Peng Wang,1 Min Luo,1 Yiming Ma,2 Chuang Xiao,1 Lueli Wang,1 Guanhua Du,3 Hongyan Cai,4 Weimin Yang1 1School of Pharmaceutical Science & Yunnan Key Laboratory of Pharmacology for Natural Products, Kunming Medical University, Kunming, Yunnan, People’s Republic of China; 2The First Department of Cardiology, The First Affiliated Hospital of Kunming Medical University, Kunming, Yunnan, People’s Republic of China; 3Key Laboratory of Drug Target Research and Drug Screen, Institute of Materia Medica, Chinese Academy of Medical Science and Peking Union Medical College, Beijing, People’s Republic of China; 4The Second Department of Cardiology, The First Affiliated Hospital of Kunming Medical University, Kunming, Yunnan, People’s Republic of China*These authors contributed equally to this workCorrespondence: Weimin Yang, School of Pharmaceutical Science & Yunnan Key Laboratory of Pharmacology for Natural Products, Kunming Medical University, Kunming, Yunnan, 650500, People’s Republic of China, Email ywmbessie@yeah.net Hongyan Cai, The Second Department of Cardiology, The First Affiliated Hospital of Kunming Medical University, Kunming, Yunnan, 650032, People’s Republic of China, Email caihy@ydyy.cnPurpose: Luteolin is a promising candidate for diabetic nephropathy due to its potential anti-inflammatory and anti-fibrotic properties. This study explored the molecular mechanisms through which luteolin combats fibrosis in DN.Methods: Potential targets affected by luteolin and genes associated with DN were collected from databases. Overlapping targets between luteolin and diabetic nephropathy were identified through Venn analysis. A protein-protein interaction network was constructed using these common targets, and critical pathways and targets were elucidated through GO and KEGG analysis. These pathways and targets were confirmed using a streptozotocin-induced mouse model. Luteolin was administered at 45 mg/kg and 90 mg/kg. Various parameters were evaluated, including body weight, blood glucose levels, and histopathological examinations. Protein levels related to energy metabolism, inflammation, and fibrosis were quantified.Results: Fifty-three targets associated with luteolin and 36 genes related to diabetic nephropathy were extracted. The AGE-RAGE signaling pathway was the key pathway impacted by luteolin in diabetic nephropathy. Key molecular targets include TGF-β, IL-1β, and PPARG. Luteolin reduced body weight and blood glucose levels, lowered the left kidney index, and improved insulin and glucose tolerance. Furthermore, luteolin mitigated inflammatory cell infiltration, basement membrane thickening, and collagen deposition in the kidney. Luteolin up-regulated the protein expression of p-AMPKα (Th172) while simultaneously down-regulated the protein expression of p-NF-ĸB (p65), NLRP3, TGF-β 1, α-SMA, and Collagen I.Conclusion: Luteolin mitigated renal fibrosis by alleviating energy metabolism disruptions and inflammation by modulating the AMPK/NLRP3/TGF-β signaling pathway.Keywords: diabetic nephropathy, network pharmacology, inflammation, TGF-β, fibrosis

Tianzhuo Zhang,1,2,&ast; Nan Song,3,&ast; Shuo Li,2,&ast; Ling Yu,2 Yining Xie,2 Zhijie Yue,2 Rui Zhang,4 Lijie Wang,4 Hongyu Tan2 1Department of Gastroenterology, Beijing Children’s Hospital, Capital Medical University, National Center for Children’s Health, Beijing, 100045, People’s Republic of China; 2Department of Anesthesiology, Key Laboratory of Carcinogenesis and Translational Research (Ministry of Education/Beijing), Peking University Cancer Hospital & Institute, Beijing, 100142, People’s Republic of China; 3Department of Gynecology, Key laboratory of Carcinogenesis and Translational Research (Ministry of Education/Beijing), Peking University Cancer Hospital & Institute, Beijing, 100142, People’s Republic of China; 4Philips (China) Investment Co., Ltd., Beijing, 100600, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Hongyu Tan, Department of Anesthesiology, Key Laboratory of Carcinogenesis and Translational Research (Ministry of Education/Beijing), Peking University Cancer Hospital & Institute, Beijing, 100142, People’s Republic of China, Tel +86-10-88196409, Email maggitan@yeah.netPurpose: This study aims to evaluate the effect of S-ketamine on slow wave sleep (SWS) and the related changes in serum protein in gynecological patients after open abdomen surgery.Methods: This was a randomized controlled trial. One hundred gynecological patients undergoing open abdomen surgery were randomized into an S-ketamine group (group S) or placebo group (0.9% saline; group C). During operation, patients in group S received adjuvant S-ketamine infusion (0.2 mg·kg− 1·h− 1) while those in group C received 0.9% saline. All patients were connected to patient-controlled intravenous analgesia (PCIA) pump in the end of the surgery and the patients in group S with an additional S-ketamine in PCIA pump. Polysomnogram (PSG) was monitored during the next night after surgery with PCIA pump. Blood samples were collected for proteomic analysis at 6:00 AM after PSG monitoring. The primary outcome was the percentage of SWS (also known as stage 3 non-rapid eye movement sleep, stage N3) on the next night after surgery, and the secondary outcome was subjective sleep quality, pain scores, and the changes in serum proteomics.Results: Complete polysomnogram recordings were obtained from 64 study participants (31 in group C and 33 in group S). The administration of S-ketamine infusion resulted in a significant increase in the percentage of SWS/N3 compared to the control group (group C, median (IQR [range]), 8.9 (6.3, 12.5); group S, median (IQR [range]), 15.6 (12.4, 18.8), P< 0.001). However, subjective evaluations of sleep quality revealed no significant variances between the two groups. The protein affected by S-ketamine was primarily associated with posttranslational modification, protein turnover, carbohydrate transport, and metabolism.Conclusion: In patients undergoing open gynecological surgery, S-ketamine enhanced the percentage of objective sleep of SWS during the next night after surgery. Additionally, there were differences observed in serum protein levels between the two groups.Trial Registration: ChiCTR2200055180. Registered on 02/01/2022.Keywords: S-ketamine, slow wave sleep, serum proteomics, gynecologic surgery

Changzheng Song,1 Qingwei Wang,2 Nianci Song3 1Erythrocrine Research Initiative of Translational Medicine, Shandong Academy of Medical Sciences, Jinan, People’s Republic of China; 2Cancer Therapy Center, Qilu Hospital of Shandong University, Jinan, People’s Republic of China; 3Biodesign Lab, Geriatricare Biorobotics Studio, Baltimore, MD, USACorrespondence: Changzheng Song, Erythrocrine Research Initiative of Translational Medicine, Shandong Academy of Medical Sciences, N-18877 Jingshi Road, Jinan, 250062, People’s Republic of China, Email songcz@sina.cnBackground and Objective: Cupping is a time-honoured traditional healing modality for pain management and remains favoured by professionals and lay people across several cultures today. However, the analgesic mechanism of cupping is still poorly understood. In addition, clinical guidelines for standardized applications of cupping are currently lacking. The awareness of cupping marks has provoked curiosity about the connection between skin color changes and their benefit for local pain relief. Computer simulation is a promising approach for numerical modeling the cupping-evoked erythrocyte emigration. Quantitative proteomic profiling of cupping-induced blister fluid exhibited a significant decrease in the abundance of haemoglobin β subunit. This finding provides a critical clue to paint a novel picture of the mechanism behind cupping. The hemorphins are a set of non-classical opioid peptides derived from the proteolysis of haemoglobin β subunit. In the present study, a probable mechanism of hemorphin-based cupping analgesia is proposed. The hemorphin could also act as a potential biomarker for objective and timely quantitative clinical assessment of cupping in the management of pain conditions. A seminal theory may open a new avenue for future translational research on promoting the efficacy and safety of cupping analgesia.Conclusion: The local analgesic effect of cupping is probable in the context of haemoglobin degradation that bestows the appearance of hemorphins along with engaging opioid receptor signalling. Exploring the potential novel mechanism of cupping analgesia facilitates seeking non-pharmacologic pain interventions.Keywords: cupping analgesia, erythrocyte, hemorphin, cupping mark, numerical simulation

Nan Song,1,2,&ast; Xi-Sheng Shan,1,2,&ast; Yi Yang,3 Zhong Zheng,4 Wen-Cheng Shi,4 Xiao-Yan Yang,3 Yang Li,3 Ai-Ping Tan,3 Hong Liu,5 Ke Peng,1,2 Fu-Hai Ji1,2 1Department of Anesthesiology, First Affiliated Hospital of Soochow University, Suzhou, Jiangsu, People’s Republic of China; 2Institute of Anesthesiology, Soochow University, Suzhou, Jiangsu, People’s Republic of China; 3Department of Anesthesiology, the People’s Hospital of SND, Suzhou, Jiangsu, People’s Republic of China; 4Department of Anesthesiology, Taicang First People’s Hospital, Taicang, Jiangsu, People’s Republic of China; 5Department of Anesthesiology and Pain Medicine, University of California Davis Health System, Sacramento, CA, USA&ast;These authors contributed equally to this workCorrespondence: Fu-Hai Ji, Chair and Professor, Department of Anesthesiology, First Affiliated Hospital of Soochow University, 188 Shizi Street, Suzhou, Jiangsu, 215006, People’s Republic of China, Tel +86-512-67780056, Email jifuhaisuda@163.com Ke Peng, Acting Vice Chair for Research and Associate Professor, Department of Anesthesiology, First Affiliated Hospital of Soochow University, 188 Shizi Street, Suzhou, Jiangsu, 215006, People’s Republic of China, Tel +86-512-67780055, Email pengke0422@163.comBackground: Same-visit bidirectional endoscopy (esophagogastroduodenoscopy and colonoscopy) is widely performed under sedation. At present, the optimal sedation regimen remains unclear. This study aims to test the hypothesis that a low-dose esketamine added to propofol sedation reduces hemodynamic and respiratory adverse events in these procedures.Methods: In this multicenter, randomized, double-blind, placebo-controlled trial, 660 adult patients scheduled for same-visit bidirectional endoscopy under sedation from 3 teaching hospitals in China will be recruited. Patients will be randomly allocated, in a 1:1 ratio, to an esketamine group or a normal saline group (n = 330 in each group), stratified by study center. All patients will receive intravenous propofol 0.5 mg/kg and sufentanil 0.1 μg/mL for induction of sedation, followed by intravenous esketamine 0.15 mg/kg or the same volume of normal saline. Propofol will be titrated to the target sedation levels during the procedures. The primary endpoint is a composite of desaturation (peripheral oxygen saturation < 90%) and hypotension (systolic blood pressure < 80 mmHg or decrease > 30% of baseline). Secondary endpoints include desaturation, hypotension, total dose of propofol, pain scores and fatigue scores on the 0– 10 numerical rating scale, dizziness or headache, hallucination or nightmare, nausea or vomiting, endoscopist satisfaction, and patient satisfaction. All analyses will be intention-to-treat.Discussion: We expect that a low-dose esketamine adjunct to propofol-based sedation will improve cardiorespiratory stability in patients undergoing same-visit bidirectional endoscopy, providing reference for clinical sedation practice during these procedures.Trial Registration: Chinese Clinical Trial Registry (Identifier: ChiCTR-ChiCTR2200055938).Keywords: esketamine, propofol, sedation, bidirectional endoscopy, desaturation, hypotension

Xin Gao,1 Xuemei He,1 Hiroyuki Oshima,2 Daisuke Miyatake,2 Yukio Otsuka,2 Kota Kato,3 Chunxiao Cai,4 Tomasz Wojtkowski,5 Nan Song,6 Yuichiro Kaneko,7 Aixin Shi1 1Clinical Trial Center, Beijing Hospital, National Center of Gerontology; Institute of Geriatric Medicine, Chinese Academy of Medical Sciences, Beijing, People’s Republic of China; 2Clinical Pharmacology and Exploratory Development, Astellas Pharma Inc., Tokyo, Japan; 3Analysis & Pharmacokinetics Research Labs., Astellas Pharma Inc., Ibaraki, Japan; 4Development Medical Department, Astellas (China) Investment Co., Ltd, Beijing, People’s Republic of China; 5Data Science Development, Astellas Pharma US, Inc., Northbrook, IL, USA; 6Development Division Biostatistics and Statistical Programming, Astellas (China) Investment Co., Ltd, Beijing, People’s Republic of China; 7Biostatistics Group, Japan-Asia Data Science, Development, Astellas Pharma Inc, Tokyo, JapanCorrespondence: Aixin Shi, Clinical Trial Center, Beijing Hospital, National Center of Gerontology; Institute of Geriatric Medicine, Chinese Academy of Medical Science, Beijing, 100730, People’s Republic of China, Tel +86-10-85133632, Email aixins0302@126.comObjective: To investigate the pharmacokinetics and safety of peficitinib (Janus kinase inhibitor for the treatment of rheumatoid arthritis) in healthy Chinese subjects following single and multiple doses.Methods: This open-label, randomized study was conducted at one site in China. Subjects received peficitinib 50, 100 or 150 mg as a single dose on Day 1 (fasted) and once daily from Days 8 to 13 in the multiple-dose period (fed). Blood samples were collected before administration each day, and up to 72h post administration. Pharmacokinetic assessments included area under the concentration curve (AUC), half-life (t1/2), maximum concentration (Cmax), and time to maximum concentration (tmax) of peficitinib and its metabolites (H1, H2 and H4). Treatment-emergent adverse events (TEAEs) were evaluated.Results: Thirty-six subjects were enrolled (12 per dose group). After a single dose of peficitinib, median tmax was 1.0– 1.5h and mean t1/2 was 7.4– 13.0h for all doses. In the multiple-dose period, median tmax was 1.5– 2.0h. Dose-proportional increases in Cmax and AUC24h were observed for peficitinib and its metabolites following single and multiple doses, with minimal drug accumulation. The major metabolite was H2, with a systemic exposure of > 150% of the parent AUC. Drug-related TEAEs were experienced by 5 (13.9%) and 12 (33.3%) subjects in the single- and multiple-dose periods, respectively. Following multiple doses of peficitinib, TEAEs were more frequent in higher than lower dose groups but were mild in severity with no related discontinuation or death.Conclusion: Following single and multiple doses of peficitinib in healthy Chinese subjects, peficitinib demonstrated rapid absorption and was well tolerated at all doses.Clinicaltrials.gov Identifier: NCT04143477.Keywords: rheumatoid arthritis, treatment, dose-proportionality, tsDMARDs

Xiao Li,1,&ast; Zicheng Xu,1,&ast; Ting Xu,1,&ast; Feng Qi,1 Ninghong Song2 1Department of Urology, The Affiliated Cancer Hospital of Nanjing Medical University & Jiangsu Cancer Hospital & Jiangsu Institute of Cancer Research, Nanjing, 210009, People’s Republic of China; 2Department of Urology, The First Affiliated Hospital of Nanjing Medical University, Nanjing, 210029, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Feng QiDepartment of Urology, The Affiliated Cancer Hospital of Nanjing Medical University & Jiangsu Cancer Hospital & Jiangsu Institute of Cancer Research, Nanjing, 210009, People’s Republic of ChinaEmail qf199408@163.comNinghong SongDepartment of Urology, The First Affiliated Hospital of Nanjing Medical University, Nanjing, 210029, People’s Republic of ChinaEmail songninghong@126.comBackground: To explore the baseline characteristics, pathological and survival outcomes of Asian-American patients with clear cell renal cell carcinoma (ccRCC), and make comparisons with White patients.Materials and Methods: In this study, patients diagnosed with ccRCC between 2010 and 2015 were extracted from the Surveillance, Epidemiology, and End Results (SEER) database. Basic characteristics of Asian-American patients were analysed and compared with White patients. Then, proportional mortality ratio (PMR) analyses were performed in Asian population to investigate the proportions of different cause of deaths (CODs), and make comparisons with White patients. Moreover, Kaplan–Meier (KM) analyses were developed to investigate the survival disparities of ccRCC patients between Asian-Americans and White patients. Finally, a competing risk regression model was constructed to identify potential prognostic factors for ccRCC patients in the whole population.Results: A total of 1586 Asian-American patients were eventually identified, and the median age at diagnosis was 61 years old. In Asian patients, those from South Asian had the youngest age at diagnosis (P< 0.001) and the earliest stage of diseases (localized: 76.83%, T1: 70.73%, all P< 0.05) when compared with other ethnicities. No significant differences were detected in tumor characteristics between Asian-Americans and White patients. Older age (P< 0.001), earlier stage (P< 0.001) and the administration of surgery (P=0.050) were tightly associated with a lower risk of dying of RCC in Asian-American patients. Additionally, Asian-American patients had comparable survival outcomes when compared with White patients. Lastly, competing risk regression model revealed that age at diagnosis (P< 0.001), tumor grade (P< 0.001), histological stage (P< 0.001), median household income (P< 0.001) and the administration of surgery (P< 0.001) were prognostic factors for cancer-specific survival (CSS) in ccRCC patients, while died of other causes was regarded as a competing event.Conclusion: Asian-American patients had similar tumor characteristics and survival outcomes with White patients. In Asian patients, those from South Asian had the youngest age at diagnosis and the earliest stage of diseases. Age, grade, histological stage, household income and surgery were identified to be closely related to CSS in ccRCC patients. In the future, prospective and well-designed studies are needed to verify our findings.Keywords: ccRCC, Asian-American, SEER, White, prognosis

Yu-fan Yang,1,* Hui Wang,1,2,* Nan Song,1,* Ya-hui Jiang,1 Jun Zhang,1 Xiao-wen Meng,1 Xiao-mei Feng,3,4 Hong Liu,5 Ke Peng,1 Fu-hai Ji1 1Department of Anesthesiology, First Affiliated Hospital of Soochow University, Suzhou, Jiangsu, People’s Republic of China; 2Department of Anesthesiology, Wuxi People’s Hospital Affiliated to Nanjing Medical University, Wuxi, Jiangsu, People’s Republic of China; 3Department of Anesthesiology, University of Utah Health, Salt Lake City, UT, USA; 4Transitional Residency Program, Intermountain Medical Center, Murray, UT, USA; 5Department of Anesthesiology and Pain Medicine, University of California Davis Health, Sacramento, CA, USA*These authors contributed equally to this workCorrespondence: Ke Peng; Fu-hai JiDepartment of Anesthesiology, First Affiliated Hospital of Soochow University, 899 Pinghai Road, Suzhou, Jiangsu, 215006, People’s Republic of ChinaTel +86-159-6215-5989; +86-512-6797-2352Email pengke0422@163.com; jifuhaisuda@163.comBackground: Endoplasmic reticulum stress (ERS)-mediated myocardial inflammation and apoptosis plays an important role in myocardial ischemia/reperfusion (I/R) injury. Dexmedetomidine has been used clinically with sedative, analgesic, and anti-inflammatory properties. This study aimed to determine the effects of dexmedetomidine pretreatment on inflammation, apoptosis, and the expression of ERS signaling during myocardial I/R injury.Methods: Rats underwent myocardial ischemia for 30 min and reperfusion for 6 h, and H9c2 cardiomyocytes were subjected to oxygen-glucose deprivation/reoxygenation (OGD/R) injury (OGD for 12 h and reoxygenation for 3 h). Dexmedetomidine was administered prior to myocardial ischemia in rats or ODG in cardiomyocytes. In addition, the α 2-adrenergic receptor antagonist (yohimbine) or the PERK activator (CCT020312) was given prior to dexmedetomidine treatment.Results: Dexmedetomidine pretreatment decreased serum levels of cardiac troponin I, reduced myocardial infarct size, alleviated histological structure damage, and improved left ventricular function following myocardial I/R injury in rats. In addition, dexmedetomidine pretreatment increased cell viability and reduced cytotoxicity following OGD/R injury in cardiomyocytes. Mechanistically, the cardioprotection offered by dexmedetomidine was mediated via the inhibition of inflammation and apoptosis through downregulating the expression of the ERS signaling pathway, including glucose-regulated protein 78 (GRP78), protein kinase R-like endoplasmic reticulum kinase (PERK), C/EBP homologous protein (CHOP), inositol-requiring protein 1 (IRE1), and activating transcription factor 6 (ATF6). Conversely, the protective effects of dexmedetomidine were diminished by blocking the α 2 adrenergic receptors with yohimbine or promoting PERK phosphorylation with CCT020312.Conclusion: Dexmedetomidine pretreatment protects the hearts against I/R injury via inhibiting inflammation and apoptosis through downregulation of the ERS signaling pathway. Future clinical studies are needed to confirm the cardioprotective effects of dexmedetomidine in patients at risk of myocardial I/R injury.Keywords: myocardial ischemia/reperfusion injury, dexmedetomidine, endoplasmic reticulum stress, inflammation, apoptosis, GRP78/PERK/CHOP

Guangli Zhu, Yuting Zhang, Jianjun Dong, Yilin Liu, Fang Zhao, Ting Li, Zhanrong Shi, Yanping Zhang, Na Song, Wenyue Song, Yuzhen Lv Reproductive Medicine Center, Jiaozuo Women and Children’s Hospital, Jiaozuo, Henan Province, People’s Republic of ChinaCorrespondence: Yuzhen LvReproductive Medicine Center, Jiaozuo Women and Children’s Hospital, Jiaozuo, 454150, Henan, People’s Republic of ChinaTel +8613839158938Email lyz jiaozuo@126.comBackground: Although obesity may affect reproductive functions, the molecular mechanisms of apoptosis-related biomarkers remain uncertain.Objective: To examine the effects of body mass index on sperm quality and apoptosis-related factors in seminal plasma of men.Methods: Data for 54 subfertile men were collected at our reproductive medical center. The men were divided into normal weight, overweight, and obese groups based on their body mass index (BMI). Sperm DNA fragmentation (sperm chromatin structure analysis), sperm apoptosis (annexin V), and sperm apoptosis-related factors (antibody array assay) were assessed and their relationships with BMI were analyzed.Results: BMI was not significantly related to age, duration of infertility, duration of sexual abstinence, semen volume, sperm concentration, or rate of normal sperm morphology (p > 0.05). However, progressive sperm motility was significantly reduced and the rates of sperm DNA fragmentation index (DFI) and sperm apoptosis were significantly increased in overweight and obese men compared with men with normal BMI. Fas/Fasl, Bcl-2/Bax, caspase-3, caspase-8, p53, and p21 were all upregulated in the overweight and obese groups. Protein function annotation by Gene Ontology analysis and Kyoto Encyclopedia of Genes and Genomes pathway analysis revealed that apoptosis-related factors were enriched in a network associated with activation of apoptotic signaling pathways, such as apoptosis and p53 signaling.Conclusion: These data suggest that increased BMI is associated with increased sperm apoptosis and sperm DNA damage, as well as accelerated expression of apoptosis-related factors via the activation of apoptotic signaling pathways.Keywords: BMI, obesity, semen quality, sperm DNA, apoptosis-related factors, biomarker

Xiaohan Ren,1,* Shangqian Wang,1,* Xinglin Chen,1,* Xiyi Wei,1,* Guangyao Li,1,* Shancheng Ren,2 Tongtong Zhang,1 Xu Zhang,1 Zhongwen Lu,1 Zebing You,1 Zengjun Wang,1 Ninghong Song,1 Chao Qin1 1The State Key Laboratory of Reproductive; Department of Urology, The First Affiliated Hospital of Nanjing Medical University, Nanjing 210029, People’s Republic of China; 2Department of Urology, Shanghai Changhai Hospital, Second Military Medical University, Shanghai, People’s Republic of China*These authors contributed equally to this workCorrespondence: Chao Qin; Ninghong SongThe State Key Laboratory of Reproductive; Department of Urology, The First Affiliated Hospital of Nanjing Medical University, Nanjing 210029, People’s Republic of ChinaTel +86 13776678978; +86 15651728807Email nmuqinchao@163.com; songninghong_urol@163.comBackground: Since December 2019, the novel coronavirus, severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), first spread quickly in Wuhan, China, then globally. Based on previously published evidence, ACE2 and TMPRSS2 are both pivotal entry molecules that enable cellular infection by SARS-CoV-2. Also, increased expression of pro-inflammatory cytokines, or a “cytokine storm,” is associated with multiple organ dysfunction syndrome often observed in critically ill patients.Methods: We investigated the expression pattern of ACE2 and TMPRSS2 in major organs in the human body, especially in specific disease conditions. Multiple sequence alignment of ACE2 in different species was used to explain animal susceptibility. Moreover, the cell-specific expression patterns of ACE2 and cytokine receptors in the urinary tract were assessed using single-cell RNA sequencing (scRNA-seq). Additional biological relevance was determined through Gene Set Enrichment Analysis (GSEA) using an ACE2-specific signature.Results: Our results revealed that ACE2 and TMPRSS2 were highly expressed in genitourinary organs. ACE2 was highly and significantly expressed in the kidney among individuals with chronic kidney diseases or diabetic nephropathy. In single cells, ACE2 was primarily enriched in gametocytes in the testis and renal proximal tubules. The receptors for pro-inflammatory cytokines, especially IL6ST, were notably concentrated in endothelial cells, macrophages, spermatogonial stem cells in the testis, and renal endothelial cells, which suggested the occurrence of alternative damaging autoimmune mechanisms.Conclusion: This study provided new insights into the pathogenic mechanisms of SARS-CoV-2 that underlie the clinical manifestations observed in the human testis and kidney. These observations might substantially facilitate the development of effective treatments for this rapidly spreading disease.Keywords: genitourinary organs, pro-inflammatory cytokine receptors, kidney, testis, SARS-CoV-2

Sillago muktijoddhai, S. mengjialensis, S. sihama and Sillaginops macrolepis (Perciformes, Sillaginidae) are common coastal sand borers. The first three species are found in the Northeastern Indian Ocean, and the fourth one is located in the Western Central Pacific Ocean only. Molecular data applying in the prior investigations on systematics and phylogenetic relationships were not only incomplete but also uncertain for these fishes. This study sequenced their complete mitochondrial genomes using Sanger Dideoxy DNA sequencing for the first time. Their complete mitochondrial genome was a circular molecule of 17,022, 16,624, 16,825 and 16,502bp in length for S. muktijoddhai, S. mengjialensis, S. sihama and Sillaginops macrolepis, respectively. Most protein-coding genes (PCGs) were initiated with the typical ATG codon and terminated with the TAA or TAG codon and the incomplete termination codon T/TA could be detected in the four species. The majority of AT-skew and GC-skew values of the entire mitogenomes among the four species were negative. The Ka/Ks ratio analyses indicated 13 PCGs were suffering strong purifying selection. In the phylogenetic analysis, S. muktijoddhai, S. mengjialensis, and S. sihama were placed with relative species of the genus Sillago supporting morphological phylogeny. However, S. macrolepis was situated in the clade of genus Sillago that contrasted to morphological phylogeny. Divergence time analysis showed that Sillaginidae species diverged around 61 million years ago. [ABSTRACT FROM AUTHOR]

This study investigates higher-order localized waves for coupled variable-coefficient fourth-order nonlinear Schrödinger equations, which are used to describe the simultaneous propagation of optical pulses in an inhomogeneous optical fiber. Based on the seed solutions and Lax pair, the Nth-order localized wave solutions are constructed. The interactions of rogue waves with dark–bright solitons are graphically analyzed via numerical simulation. The results are helpful for studying localized wave phenomena in nonlinear optics. [ABSTRACT FROM AUTHOR]

Glycyrrhiza uralensis is an important endangered medicinal plant species and requires special conservation in China. Its relationships with environmental gradients are significant for its conservation. The responses of dominant species to environmental gradients in G. uralensis communities were simulated by using the general linear model (GLM). The data were collected from 100 quadrats of 5 m x 5 m in five sites from east to west in northern China. The results showed that GLM was very useful in modelling species responses to environmental gradients. Precipitation and soil nutrients (soil N, P, K, organic matter and pH) were the variables that correlated most to G. uralensis populations, dominant species and communities. G. uralensis showed the greatest responses to all comprehensive and single gradients, and was absolutely dominant in communities. Its response pattern was unimodal, i.e. it increased and then decreased after reaching the highest value, to almost all environmental gradients. Other four dominant species showed different response patterns with slight variation. To protect G. uralensis populations and communities, the measures of soil and water conservation, improving soil nutrients, utilization management etc., should be considered. [ABSTRACT FROM AUTHOR]