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Qi Zheng,1,* Yuetong Li,1,* Wenfeng Zhu,1 Xiang Xu,2 Guoping Sheng,3 Lanjuan Li1 1State Key Laboratory for Diagnosis and Treatment of Infectious Diseases, National Clinical Research Center for Infectious Diseases, National Medical Center for Infectious Diseases, Collaborative Innovation Center for Diagnosis and Treatment of Infectious Diseases, The First Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou, People’s Republic of China; 2Zhejiang Chinese Medical University, Hangzhou, People’s Republic of China; 3Key Laboratory of Artificial Organs and Computational Medicine in Zhejiang Province, Shulan (Hangzhou) Hospital Affiliated to Zhejiang Shuren University, Shulan International Medical College, Hangzhou, People’s Republic of China*These authors contributed equally to this workCorrespondence: Guoping Sheng, Key Laboratory of Artificial Organs and Computational Medicine in Zhejiang Province, Shulan (Hangzhou) Hospital Affiliated to Shulan International Medical College, Zhejiang Shuren University, 848 Dongxin Road, Hangzhou, 310000, People’s Republic of China, Email guoping.sheng@shulan.com Lanjuan Li, State Key Laboratory for the Diagnosis and Treatment of Infectious Diseases, The First Affiliated Hospital, Zhejiang University School of Medicine, 79 Qingchun Road, Hangzhou, 310003, People’s Republic of China, Email ljli@zju.edu.cnBackground: Previous studies have indicated that human flora may affect the development of scabies, however, no studies have proven a causal relationship between human flora and scabies, which would be detrimental to future in-depth studies on human flora and scabies.Methods: Mendelian randomization (MR) was used to analyze the causal effect between human microbiota and scabies, with data on intestinal flora and skin flora from two large published studies and data on scabies from the FinnGen database. Five MR analysis methods were used to increase the reliability of the results, and sensitivity analyses were conducted to increase the robustness of the results.Results: Our results suggest that 13 intestinal flora as well as 7 skin flora can have a causal effect on scabies.Conclusion: Overall, our results demonstrate a causal relationship between intestinal and skin flora and scabies and are consistent with previous observational findings. This will contribute to the future development of probiotic agents for the prevention or treatment of scabies.Keywords: gut microbiota, skin microbiota, scabies, FinnGen, Mendelian randomization

Jiajun Qiu,1– 3,&ast; Xin Huang,1– 3,&ast; Maobin Kuang,1– 3,&ast; Ruijuan Yang,1,4 Jiachong Li,1 Guotai Sheng,5,6 Yang Zou2,3 1Jiangxi Medical College, Nanchang University, Nanchang, Jiangxi Province, People’s Republic of China; 2Jiangxi Cardiovascular Research Institute, Jiangxi Provincial People’s Hospital, Nanchang, Jiangxi Province, People’s Republic of China; 3Jiangxi Cardiovascular Research Institute, The First Affiliated Hospital of Nanchang Medical College, Nanchang, Jiangxi Province, People’s Republic of China; 4Department of Endocrinology, Jiangxi Provincial People’s Hospital, Nanchang, Jiangxi Province, People’s Republic of China; 5Jiangxi Provincial Geriatric Hospital, Jiangxi Provincial People’s Hospital, Nanchang, Jiangxi Province, People’s Republic of China; 6Jiangxi Provincial Geriatric Hospital, The First Affiliated Hospital of Nanchang Medical College, Nanchang, Jiangxi Province, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Guotai Sheng, Jiangxi Provincial Geriatric Hospital, Jiangxi Provincial People’s Hospital, No. 92 Aiguo Road, Nanchang, Jiangxi, 330006, People’s Republic of China, Email tgs200509@163.com Yang Zou, Jiangxi Cardiovascular Research Institute, Jiangxi Provincial People’s Hospital, No. 92 Aiguo Road, Nanchang, Jiangxi, 330006, People’s Republic of China, Email jxyxyzy@163.comPurpose: The association between traditional lipid parameters and non-alcoholic fatty liver disease (NAFLD) has been extensively discussed. This study aims to evaluate and compare the lipoprotein combine index (LCI) and traditional lipid parameters [total cholesterol (TC), triglycerides (TG), low-density lipoprotein cholesterol (LDL-C), and high-density lipoprotein cholesterol (HDL-C)] to identify NAFLD.Patients and Methods: The analysis included 14,251 participants from the NAfld in the Gifu Area, Longitudinal Analysis (NAGALA). Logistic regression models were employed to calculate standardized odds ratios (ORs) and 95% confidence intervals (CIs) for assessing and comparing the association of LCI and traditional lipid parameters with NAFLD. Additionally, receiver operating characteristic (ROC) curves were used to calculate the area under the curve (AUC) for LCI and traditional lipid parameters in identifying NAFLD.Results: After adjusting for various confounders, we found that LCI was positively associated with NAFLD (OR=2.25, 95% CI 1.92– 2.63), and this association was stronger than that of traditional lipid parameters [OR: TC1.23, TG1.73 LDL-C1.10]. Further subgroup analyses revealed that the association of LCI with NAFLD was stronger than other traditional lipid parameters in all subgroups, including men and women, overweight/obese [body mass index (BMI)≥ 25 kg/m2] and non-obese (BMI< 25 kg/m2), and older (age≥ 45 years) and younger (age< 45 years) participants. Additionally, ROC analysis indicated that LCI (AUC=0.8118) had significantly higher accuracy (All DeLong P< 0.05) in identifying NAFLD compared to traditional lipid parameters (AUC: TC0.6309; TG0.7969; LDL-C0.6941); HDL-C0.7587). Sensitivity analysis further confirmed the robustness of the study findings.Conclusion: This study revealed for the first time a positive correlation between LCI and NAFLD. Compared to traditional lipid parameters, LCI has a higher correlation with NAFLD. Additionally, further ROC analysis demonstrated that LCI had higher accuracy in identifying NAFLD compared to traditional lipid parameters, suggesting that LCI may be a better marker for NAFLD identification than traditional lipid parameters.Keywords: non-alcoholic fatty liver disease, lipoprotein combine index, NAFLD, traditional lipid parameters, LCI

Guotai Sheng,1,&ast; Dingyang Liu,1,&ast; Maobin Kuang,1,&ast; Yanjia Zhong,2 Shuhua Zhang,3 Yang Zou3 1Cardiology Department, Jiangxi Provincial People’s Hospital, Nanchang, Jiangxi Provincial, 330006, People’s Republic of China; 2Endocrinology Department, Jiangxi Provincial People’s Hospital, Nanchang, Jiangxi Province, 330006, People’s Republic of China; 3Jiangxi Cardiovascular Research Institute, Jiangxi Provincial People’s Hospital, Nanchang, Jiangxi Provincial, People’s Republic of China&ast;These authors have contributed equally to this workCorrespondence: Yang Zou, Jiangxi Cardiovascular Research Institute, Jiangxi Provincial People’s Hospital, Nanchang, Jiangxi Provincial, People’s Republic of China, Email jxyxyzy@163.comPurpose: Diabetes is one of the most prevalent chronic diseases in the world, and its prevalence is expected to rise further. To help understand the utility of the ratio of non-high-density lipoprotein cholesterol to high-density lipoprotein cholesterol (NHHR) in diabetes prevention, this large-scale longitudinal cohort study aims to explore the association of NHHR with diabetes risk and compare it as a risk predictor with conventional lipid parameters.Patients and Methods: This observational study extracted data from the NAGALA longitudinal cohort study conducted in Japan between 2004 and 2015. Multivariate Cox regression analysis was used to evaluate the association between NHHR and the risk of diabetes. The dose–response relationship was analyzed by restricted cubic spline (RCS) regression and the potential risk threshold was estimated. The receiver operator characteristic curve (ROC) was used to analyze and calculate the predictive value and optimal threshold of NHHR and other conventional lipids for new-onset diabetes.Results: Of the 15,464 people aged 18– 79, 373 (2.41%) were diagnosed with new-onset diabetes during the study period, with a median age of 46 years. The sensitivity analysis based on multivariate adjustment showed that the independent positive correlation between diabetes and NHHR was stable in different populations. RCS and ROC analysis indicated that the association between NHHR and diabetes was non-linear, and the NHHR was a better marker for predicting diabetes risk than other conventional lipid parameters; Additionally, it is worth noting that an NHHR of approximately 2.74 may be the optimal threshold for intervention in diabetes risk.Conclusion: In the general population, NHHR is a better marker for predicting diabetes risk than conventional lipid parameters, and an NHHR of about 2.74 may be the optimal threshold for assessing diabetes risk.Keywords: non-high-density lipoprotein cholesterol to high-density lipoprotein cholesterol, diabetes, longitudinal cohort, operator characteristic curve

Jingling Duan,1,2 Yang Yang,1,2 Zhen Wu,3 Shiang Lin,4 Chen Zhou,1,2 Guowen Sheng,1,2 Fan Yang,1,2 Lihui Bian,5 Xiaoling Zhang,6 Shengjun Xiao11Department of Pathology, The Second Affiliated Hospital, Guilin Medical University, Guilin 541199, People’s Republic of China; 2Graduate College, Guilin Medical University, Guilin 541199, People’s Republic of China; 3Xiangya School of Medicine, Central South University, Changsha 410083, People’s Republic of China; 4Department of Otorhinolaryngology, The Affiliated Hospital, Guangdong Medical University, Zhanjiang 524001, People’s Republic of China; 5Department of Pathology, The Affiliated Hospital, Hebei University, Baoding 071000, People’s Republic of China; 6Department of Physiology, Faculty of Basic Medical Science, Guilin Medical University, Guilin 541199, People’s Republic of ChinaBackground: Most Epstein-Barr virus (EBV)-positive cells lose the EBV episomes upon prolonged propagation. Purpose: The purposes of this study were to establish a simple cell model for nasopharyngeal carcinoma (NPC) research by introducing a plasmid with the EBV genome into NPC cells and then to investigate the resulting changes in malignant biological behaviour and NPC-associated signalling pathways. Methods: HONE1 NPC cells were transfected with F-factor plasmids including the EBV genome (HONE1-EBV cells). Then cell proliferation, migration, cell cycle distribution and apoptosis were evaluated in vitro by using CCK8, transwell and flow cytometry assays respectively. EBV-encoded proteins and cell signal tranducting proteins were detected by western blot assays. EBV-encoded RNAs were detected by in situ hybridization. EBV particles were assayed by transmission electron microscope (TEM). The morphology of cells were detected by immunofluorescence assays for alpha-tubulin.&#x00A0Results: Latent membrane protein 1 (LMP1), latent membrane protein 2A (LMP2A), Epstein-Barr nuclear antigen 1 (EBNA1) and EBV-encoded small RNAs (EBERs) were successfully expressed in HONE1-EBV cells. No EBV particles were founded by TEM. Introduction of the EBV genome significantly promoted proliferation, cell cycle progression and migration and inhibited apoptosis in HONE1 cells. Immunofluorescence assays showed that the morphology of HONE1-EBV cells changed into spindle. Furthermore, EBV genome introduction significantly inhibited the JAK/STAT signalling pathway, while it activated the PI3K-AKT and NF-κB signalling pathways in HONE1 cells. Conclusion: These findings suggest that F-factor plasmid-mediated EBV genome introduction was successful in constructing an EBV positive cell model, which showed deteriorated biological behavior and activated NPC-associated signalling pathways. This model can serve as a good tool for studying EBV in NPC, but the subtle differences in cancer-associated pathways must be considered.Keywords: Epstein-Barr virus, cell cycle, signal transduction, oncogenesis

We sought to identify serological markers capable of diagnosing preeclampsia (PE). We performed serum peptide analysis (liquid chromatography mass spectrometry) of 62 unique samples from 31 PE patients and 31 healthy pregnant controls, with two-thirds used

Piezoelectric materials, which convert mechanical to electrical energy and vice versa, are typically characterized by the intimate coexistence of two phases across a morphotropic phase boundary. Electrically switching one to the other yields large electromechanical coupling coefficients. Driven by global environmental concerns, there is currently a strong push to discover practical lead-free piezoelectrics for device engineering. Using a combination of epitaxial growth techniques in conjunction with theoretical approaches, we show the formation of a morphotropic phase boundary through epitaxial constraint in lead-free piezoelectric bismuth ferrite (BiFeO3) films. Electric field-dependent studies show that a tetragonal-like phase can be reversibly converted into a rhombohedral-like phase, accompanied by measurable displacements of the surface, making this new lead-free system of interest for probe-based data storage and actuator applications.

Toxic air pollutants in street canyons are important issues concerning public health especially in some large Asian cities like Guangzhou. In 1998

Lubrication and heat transfer control are two significant functions of mold fluxes. In order to coordinate the contradiction between lubrication and heat transfer, the effects of BaO and Li²O on basic characteristics of CaO-SiO² based mold fluxes were studied by hemispherical melting temperature instrument, rotating cylinder method, X-ray diffractometer (XRD) in present study. The results show that the melting temperature and viscosity at 1300°C all represent a downward trend with BaO and Li²O enhancement at different basicity, and the break temperature decrease with BaO addition while decrease and then increase with Li²O addition, which illustrates that Li2O content should be no more than 0.8 wt% for the purpose of lubrication. Meanwhile, to ensure a sufficient thickness of the liquid slag film and avoid discontinuity of the liquid slag film, the BaO content is better to be 10 wt% with low melting temperature and viscosity. The main crystalline phase in the mold fluxes is cuspidine (3CaO·2SiO2·CaF2), and the crystallization ratio rises sharply when basicity increased to 1.65. For better deal with the contradiction of lubrication and heat transfer, the mold fluxes composition w(BaO) = 10 wt%, w(Li2O) = 0.8 wt%, R ≥1.65 is reasonable, which has a profound impact on high crystallization and lubricity mold fluxes. [ABSTRACT FROM AUTHOR]

Abstract A high-level perceptual model found in the human brain is essential to guide robotic control when facing perception-intensive interactive tasks. Soft robots with inherent softness may benefit from such mechanisms when interacting with their surroundings. Here, we propose an expected-actual perception-action loop and demonstrate the model on a sensorized soft continuum robot. By sensing and matching expected and actual shape (1.4% estimation error on average), at each perception loop, our robot system rapidly (detection within 0.4 s) and robustly detects contact and distinguishes deformation sources, whether external and internal actions are applied separately or simultaneously. We also show that our soft arm can accurately perceive contact direction in both static and dynamic configurations (error below 10°), even in interactive environments without vision. The potential of our method are demonstrated in two experimental scenarios: learning to autonomously navigate by touching the walls, and teaching and repeating desired configurations of position and force through interaction with human operators.

Abstract The multifunctional proteins of class 2 CRISPR systems such as Cas9, have been employed to activate cryptic biosynthetic gene clusters (BGCs) in Streptomyces, which represent a large and hidden reservoir of natural products. However, such approaches are not applicable to most Streptomyces strains with reasons to be comprehended. Inspired by the prevalence of the class 1 subtype especially the type I-E CRISPR system in Streptomyces, here we report the development of the type I-E CRISPR system into a series of transcriptional regulation tools. We further demonstrate the effectiveness of such activators in nine phylogenetically distant Streptomyces strains. Using these tools, we successfully activate 13 out of 21 BGCs and lead to the identification and characterization of one polyketide, one Ripp and three alkaloid products. Our work is expected to have a profound impact and to facilitate the discovery of numerous structurally diverse compounds from Streptomyces.

Abstract The nucleus pulposus (NP) plays a vital role in intervertebral disc degeneration (IVDD). Previous studies have revealed cellular heterogeneity in NP tissue during IVDD progression. However, the cellular and molecular alterations of diverse cell clusters during IVDD remain to be fully elucidated. NP tissues were isolated from patients with different grades of IVDD undergoing discectomy, and then subjected to single-cell RNA sequencing (scRNA-seq). Cell subsets were identified based on unbiased clustering of gene expression profiles. Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway analyses were performed to determine the molecular features of diverse cell clusters. Monocle analysis was used to illustrate the differentiation trajectories of chondrocytes. Additionally, CellPhoneDB analysis revealed potential interactions between chondrocytes and other cells during IVDD. Based on the expression profiles of 47,610 individual cells, eight putative clusters including chondrocytes, endothelial cells, fibroblasts, macrophages, mural cells, osteoclasts, proliferating stromal cells and T cells were identified. The chondrocyte cluster was classified into three subsets, C1-C3, which were associated with stress-resistance, fibrosis and inflammatory responses, respectively. Pseudo-time trajectories suggested that chondrocytes gradually differentiated into fibroblasts during IVDD. Immune cells including cDC2s, macrophages and monocytes were identified. Further analysis showed that chondrocytes might communicate with immune cells via the MIF, TNFSF9, SPP1 and CCL4L2 signaling pathways. In addition, we found that invading endothelial cells might interact with chondrocytes through the COL4A1, CXCL12, VEGFA and SEMA3E signaling pathways. Our results reveal the cellular complexity and phenotypic characteristics of NP tissues at single-cell resolution, which will contribute to the in-depth investigation of preventative and regenerative strategies for IVDD.