Publications by authors named "Zhou Yu"

2,362 Publications

  • Page 1 of 1

The changing landscape of anti-lymphoma drug clinical trials in mainland China in the past 15 years (2005-2020): A systematic review.

Lancet Reg Health West Pac 2021 Mar 5;8:100097. Epub 2021 Feb 5.

Department of Medical Oncology, National Cancer Center/National Clinical Research Center for Cancer/Cancer Hospital, Chinese Academy of Medical Sciences & Peking Union Medical College, Beijing Key Laboratory of Clinical Study on Anticancer Molecular Targeted Drugs, No. 17 Panjiayuan Nanli, Chaoyang District, Beijing 100021, China.

Background: To depict a comprehensive changing landscape of anti-lymphoma drug clinical trials in mainland China from 2005 to 2020.

Methods: A systematic review was conducted on the China National Medical Products Administration Center for Drug Evaluation platform, the Chinese Clinical Trial Registry and ClinicalTrials.gov websites.

Findings: A total of 797 anti-lymphoma drug clinical trials registered from Jan 1st, 2005 to Aug 1st, 2020 were identified. The number of trials increased gradually over time, and a notable increase was observed in 2016, with the number growing from 29 in 2015 to 72 in 2016. Trials in phase I (26•1%) and phase II (26•6%) represented the majority, followed by phase III (12•5%) and phase IV (7•4%). Regarding sponsorship, industry-sponsored trials (53•2%) accounted for a slightly larger proportion than investigator-initiated trials (IITs) (46•8%). A dramatic growth for IITs was seen during 2017-2020, with the number increasing from 36 in 2017 to 96 in 2020. Additionally, the proportion of trials involving targeted agents (50•2%) accounted for the largest, followed by trials involving immunotherapy agents (41•0%), and cytotoxic agents (8•0%). Besides, a sustainable growth was observed in the number of leading anti-lymphoma drug clinical trial units in mainland China over the past 15 years. The majority of leading principal units (60•8%) were from Beijing, Shanghai, Guangdong and Jiangsu.

Interpretation: In the past 15 years, the research and development of drugs and clinical trials for lymphoma in mainland China has achieved much progression. Future efforts are needed for improving innovation and sustainability of pharmaceutical research and development.

Funding: China National Major Project for New Drug Innovation (2017ZX09304015); Chinese Academy of Medical Sciences (CAMS) Innovation Fund for Medical Sciences (CIFMS) (2016-I2M-1-001).
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1016/j.lanwpc.2021.100097DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8315394PMC
March 2021

The changing landscape of anti-lung cancer drug clinical trials in mainland China from 2005 to 2020.

Lancet Reg Health West Pac 2021 Jun 27;11:100151. Epub 2021 Apr 27.

Department of Medical Oncology, National Cancer Center/National Clinical Research Center for Cancer/Cancer Hospital, Chinese Academy of Medical Sciences & Peking Union Medical College, Beijing Key Laboratory of Clinical Study on Anticancer Molecular Targeted Drugs, No. 17 Panjiayuan Nanli, Chaoyang District, Beijing 100021, China.

Background: In recent years, new drug development on lung cancer is in full swing in China. The aim of this study was to overview the changing landscape of anti-lung cancer drug clinical trials in mainland China from 2005 to 2020.

Methods: We analysed anti-lung cancer drug clinical trials registered on three websites including the China National Medical Products Administration Centre for Drug Evaluation platform, the Chinese Clinical Trial Registry and ClinicalTrials.gov.

Findings: A total of 1595 anti-lung cancer drug clinical trials from Jan 1st, 2005 to Dec 31st, 2020 were extracted, which included 630 (39•5%) investigator-initiated trials (IITs), 698 (43•8%) domestic industry-sponsored trials (ISTs), and 267 (16•7%) international ISTs. During the past 16 years, the number of anti-lung cancer clinical trials including IITs and domestic ISTs had a remarkable growth, however, the number of international ISTs increased slowly. The number of principal clinical trial units also increased significantly over time. Of the 1595 trials, the largest growth was observed in phase I trials during 2013-2020, with an average annual growth rate of 38•6%. 278 trials were led by principal investigators (PI) from Guangdong, followed by Beijing (=273) and Shanghai (=257). Among the 965 ISTs, clinical trials involving targeted drugs (588, 60•9%) accounted for the largest proportion, followed by immunotherapeutic drugs (284, 29•4%), cytotoxic drugs (75, 7•8%), and traditional Chinese medicine (18, 1•9%). In terms of targeted drugs, EGFR-TKIs remained the most studied drugs (225/588, 38•27%). As for immunotherapy, 125 out of 284 (44•01%) trials involved PD-1 inhibitors, 60 (21•13%) trials involved PD-L1 inhibitors, and seven (2•46%) trials involved CTLA-4 inhibitors.

Interpretation: In the past 16 years, the development of anti-lung cancer drug clinical trials has achieved much progress in mainland China. The most progress lied in targeted therapy and immunotherapy.

Funding: This work was financially supported in part by China National Major Project for New Drug Innovation (2017ZX09304015) and Chinese Academy of Medical Sciences (CAMS) Innovation Fund for Medical Sciences (CIFMS) (2016-I2M-1-001).
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1016/j.lanwpc.2021.100151DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8315452PMC
June 2021

LncRNA HOTAIR promotes proliferation and inhibits apoptosis by sponging miR-214-3p in HPV16 positive cervical cancer cells.

Cancer Cell Int 2021 Jul 28;21(1):400. Epub 2021 Jul 28.

Demonstration Center for Experimental Basic Medicine Education, Wuhan University, Wuhan, Hubei, 430071, People's Republic of China.

Background: Cervical cancer (CC) is one of the most common gynaecological malignancies all around the world. The mechanisms of cervical carcinoma formation remain under close scrutiny. The long non-coding RNAs (lncRNA) and microRNAs (miRNAs) play important roles in controlling gene expression and promoting the development and progression of cervical cancer by acting as competitive endogenous RNA (ceRNA). However, the roles of lncRNA associated with ceRNAs in cervical carcinogenesis remains unknown. In this study, the expression of long non-coding RNA HOTAIR was investigated in HPV16 positive cervical cancer cells, the candidate miRNAs and target genes were identified to clarify putative ceRNAs of HOTAIR/miRNA in cervical cancer cells.

Methods: The proliferation ability of cells was measured by CCK8 and EdU incorporation assays and cell apoptosis was analyzed by flow cytometry. The expression of HOTAIR, miR-214-3p, HPV16 E7 mRNA were detected by qRT-PCR. As for searching for the interaction between miR-214-3p and HOTAIR, the binding sites for miR-214-3p on HOTAIR was predicted by starbase v2.0 database, then dual-luciferase assay was used to verify the binding sites. In addition, Gene Ontology (GO) and protein-protein interaction (PPI) network analysis of target genes of miR-214-3p were performed with bioinformatics analysis. The potential signal pathway regulated by HOTAIR/miR-214-3p was predicted by KEGG enrichment analysis and confirmed by qPCR and WB analysis in cervical cancer cells.

Results: Our results showed that expression of HOTAIR was up-regulated, while that of miR-214-3p was down-regulated in HPV16-positive cervical cancer cells. The expression status of HPV16 E7 played an important role in regulating expression of HOTAIR or miR-214-3p in cervical cancer cells. HOTAIR knockdown could significantly inhibited cell proliferate ability and promote cellular apoptosis, whereas the inhibition of miR-214-3p expression partially reversed such results. Bioinformatics analysis identified 1451 genes as target genes of miR-214-3p. The Gene ontology (GO) and KEGG Pathway enrichment analysis showed that these target genes were mainly related to regulation of cell communication, protein binding, enzyme binding and transferase activity, and Wnt ligand biogenesis. Pathway enrichment analysis results showed that the predicted target genes were significantly enriched in Wnt/β-catenin signaling pathway. Finally, our results confirmed that miR-214-3p could significantly inhibit β-catenin expression in HPV16 positive cancer cells by qPCR and WB analysis.

Conclusion: HOTAIR could act as a ceRNA through binding to miR-214-3p, promote cell proliferation and inhibit the apoptosis of HPV16 positive cervical cancer. HOTAIR/miR-214-3p/Wnt/β-catenin signal pathway might played important regulated roles in HPV16 positive cervical cancer. Our results provided new insight into defining novel biomarkers for cervical cancer.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1186/s12935-021-02103-7DOI Listing
July 2021

A Novel α-Globin Chain Variant, Hb Nanchang [: c.46G>A, Codon 15 (GT>GT) (Gly→Ser)], Detected by Matrix-Assisted Laser Desorption Ionization-Time of Flight Mass Spectrometry.

Hemoglobin 2021 Jul 26:1-4. Epub 2021 Jul 26.

Department of Laboratory Medicine, Peking University Shenzhen Hospital, Shenzhen, People's Republic of China.

Here we report a new α chain variant accidentally discovered during Hb A measurement by matrix-assisted laser desorption ionization-time of flight (MALDI-TOF) mass spectrometry (MS) that revealed the presence of a variant α chain with a mass of 15155 Da. However, this hemoglobin (Hb) variant cannot be detected by the first-line methods such as cation exchange high performance liquid chromatography (HPLC) and capillary electrophoresis (CE). Sanger sequencing confirmed the presence of a heterozygous missense mutation [: c.46G>A, codon 15 (GT>GT), (Gly→Ser)]. The theoretical mass difference (30 Da) due to the substitution of amino acid glycine to serine matched the actual measured mass difference (29 Da). As this is the first report of the mutation, we named it Hb Nanchang after the place of residence of the proband.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1080/03630269.2021.1956946DOI Listing
July 2021

cGAS Is a Negative Regulator of RIG-I-Mediated IFN Response in Cyprinid Fish.

J Immunol 2021 08 21;207(3):784-798. Epub 2021 Jul 21.

State Key Laboratory of Agricultural Microbiology, College of Fisheries, Huazhong Agricultural University, Wuhan, China;

In mammals, cyclic GMP-AMP synthase (cGAS) recognizes cytosolic dsDNA to induce the type I IFN response. However, the functional role of cGAS in the IFN response of fish remains unclear or controversial. In this study, we report that cGAS orthologs from crucian carp (cGAS) and grass carp (cGAS) target the dsRNA sensor retinoic acid-inducible gene I (RIG-I) for negative regulation of the IFN response. First, poly(deoxyadenylic-deoxythymidylic) acid-, polyinosinic-polycytidylic acid-, and spring viremia of carp virus-induced IFN responses were impaired by overexpression of cGAS and cGAS. Then, cGAS and cGAS interacted with RIG-I and MAVS and inhibited RIG-I- and MAVS-mediated IFN induction. Moreover, the K63-linked ubiquitination of RIG-I and the interaction between RIG-I and MAVS were attenuated by cGAS and cGAS. Finally, cGAS and cGAS decreased RIG-I-mediated the cellular antiviral response and facilitated viral replication. Taken together, data in this study identify cGAS and cGAS as negative regulators in RIG-I-like receptor signaling, which extends the current knowledge regarding the role of fish cGAS in the innate antiviral response.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.4049/jimmunol.2100075DOI Listing
August 2021

Quick Annotator: an open-source digital pathology based rapid image annotation tool.

J Pathol Clin Res 2021 Jul 19. Epub 2021 Jul 19.

Department of Biomedical Engineering, Case Western Reserve University, Cleveland, OH, USA.

Image-based biomarker discovery typically requires accurate segmentation of histologic structures (e.g. cell nuclei, tubules, and epithelial regions) in digital pathology whole slide images (WSIs). Unfortunately, annotating each structure of interest is laborious and often intractable even in moderately sized cohorts. Here, we present an open-source tool, Quick Annotator (QA), designed to improve annotation efficiency of histologic structures by orders of magnitude. While the user annotates regions of interest (ROIs) via an intuitive web interface, a deep learning (DL) model is concurrently optimized using these annotations and applied to the ROI. The user iteratively reviews DL results to either (1) accept accurately annotated regions or (2) correct erroneously segmented structures to improve subsequent model suggestions, before transitioning to other ROIs. We demonstrate the effectiveness of QA over comparable manual efforts via three use cases. These include annotating (1) 337,386 nuclei in 5 pancreatic WSIs, (2) 5,692 tubules in 10 colorectal WSIs, and (3) 14,187 regions of epithelium in 10 breast WSIs. Efficiency gains in terms of annotations per second of 102×, 9×, and 39× were, respectively, witnessed while retaining f-scores >0.95, suggesting that QA may be a valuable tool for efficiently fully annotating WSIs employed in downstream biomarker studies.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1002/cjp2.229DOI Listing
July 2021

High Dimensional Functionomic Analysis of Human Hematopoietic Stem and Progenitor Cells at a Single Cell Level.

Bio Protoc 2018 May 20;8(10):e2851. Epub 2018 May 20.

Department of Microbiology and Immunology, Columbia University Medical Center, New York, New York, USA.

The ability to conduct investigation of cellular transcription, signaling, and function at the single-cell level has opened opportunities to examine heterogeneous populations at unprecedented resolutions. Although methods have been developed to evaluate high-dimensional transcriptomic and proteomic data (relating to cellular mRNA and protein), there has not been a method to evaluate corresponding high-dimensional functionomic data (relating to cellular functions) from single cells. Here, we present a protocol to quantitatively measure the differentiation potentials of single human hematopoietic stem and progenitor cells, and then cluster the cells according to these measurements. High dimensional functionomic analysis of cell potential allows cell function to be linked to molecular mechanisms within the same progenitor population.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.21769/BioProtoc.2851DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8275246PMC
May 2018

Polymer-Derived Lightweight SiBCN Ceramic Nanofibers with High Microwave Absorption Performance.

ACS Appl Mater Interfaces 2021 Jul 20;13(29):34889-34898. Epub 2021 Jul 20.

Institut für Materialwissenschaft, Technische Universität Darmstadt, D-64287 Darmstadt, Germany.

Lightweight SiBCN ceramic nanofibers were prepared by a combination of electrostatic spinning and high-temperature annealing techniques, showing tunable electromagnetic wave absorption. By controlling the annealing temperature, the nanoscale architectures and atomic bonding structures of as-prepared nanofibers could be well regulated. The resulting SiBCN nanofibers ∼300 nm in diameter, which were composed of an amorphous matrix, β-SiC, and free carbon nanocrystals, were defect-free after annealing at 1600 °C. SiBCN nanofibers annealed at 1600 °C exhibited good microwave absorption, obtaining a minimum reflection coefficient of -56.9 dB at 10.56 GHz, a sample thickness of 2.6 mm with a maximum effective absorption bandwidth of 3.45 GHz, and a maximum dielectric constant of 0.44. Owing to the optimized A + B + C microstructure, SiBCN ceramic nanofibers with satisfying microwave absorption properties endowed the nanofibers with the potential to be used as lightweight, ultrastrong radar wave absorbers applied in military and the commercial market.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1021/acsami.1c07912DOI Listing
July 2021

Lymphocyte-Related Immunological Indicators for Stratifying Infection.

Front Immunol 2021 30;12:658843. Epub 2021 Jun 30.

Department of Laboratory Medicine, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China.

Background: Easily accessible tools that reliably stratify (MTB) infection are needed to facilitate the improvement of clinical management. The current study attempts to reveal lymphocyte-related immune characteristics of active tuberculosis (ATB) patients and establish immunodiagnostic model for discriminating ATB from latent tuberculosis infection (LTBI) and healthy controls (HC).

Methods: A total of 171 subjects consisted of 54 ATB, 57 LTBI, and 60 HC were consecutively recruited at Tongji hospital from January 2019 to January 2021. All participants were tested for lymphocyte subsets, phenotype, and function. Other examination including T-SPOT and microbiological detection for MTB were performed simultaneously.

Results: Compared with LTBI and HC, ATB patients exhibited significantly lower number and function of lymphocytes including CD4 T cells, CD8 T cells and NK cells, and significantly higher T cell activation represented by HLA-DR and proportion of immunosuppressive cells represented by Treg. An immunodiagnostic model based on the combination of NK cell number, HLA-DRCD3 T cells, Treg, CD4 T cell function, and NK cell function was built using logistic regression. Based on receiver operating characteristic curve analysis, the area under the curve (AUC) of the diagnostic model was 0.920 (95% CI, 0.867-0.973) in distinguishing ATB from LTBI, while the cut-off value of 0.676 produced a sensitivity of 81.48% (95% CI, 69.16%-89.62%) and specificity of 91.23% (95% CI, 81.06%-96.20%). Meanwhile, AUC analysis between ATB and HC according to the diagnostic model was 0.911 (95% CI, 0.855-0.967), with a sensitivity of 81.48% (95% CI, 69.16%-89.62%) and a specificity of 90.00% (95% CI, 79.85%-95.34%).

Conclusions: Our study demonstrated that the immunodiagnostic model established by the combination of lymphocyte-related indicators could facilitate the status differentiation of MTB infection.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.3389/fimmu.2021.658843DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8278865PMC
June 2021

Analog memristive synapse based on topotactic phase transition for high-performance neuromorphic computing and neural network pruning.

Sci Adv 2021 Jul 16;7(29). Epub 2021 Jul 16.

School of Integrated Circuits, Beijing National Research Center for Information Science and Technology (BNRist), Tsinghua University, Beijing 100084, China.

Inspired by the human brain, nonvolatile memories (NVMs)-based neuromorphic computing emerges as a promising paradigm to build power-efficient computing hardware for artificial intelligence. However, existing NVMs still suffer from physically imperfect device characteristics. In this work, a topotactic phase transition random-access memory (TPT-RAM) with a unique diffusive nonvolatile dual mode based on SrCoO is demonstrated. The reversible phase transition of SrCoO is well controlled by oxygen ion migrations along the highly ordered oxygen vacancy channels, enabling reproducible analog switching characteristics with reduced variability. Combining density functional theory and kinetic Monte Carlo simulations, the orientation-dependent switching mechanism of TPT-RAM is investigated synergistically. Furthermore, the dual-mode TPT-RAM is used to mimic the selective stabilization of developing synapses and implement neural network pruning, reducing ~84.2% of redundant synapses while improving the image classification accuracy to 99%. Our work points out a new direction to design bioplausible memristive synapses for neuromorphic computing.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1126/sciadv.abh0648DOI Listing
July 2021

A prognostic and predictive computational pathology image signature for added benefit of adjuvant chemotherapy in early stage non-small-cell lung cancer.

EBioMedicine 2021 Jul 12;69:103481. Epub 2021 Jul 12.

Center for Computational Imaging and Personalized Diagnostics, Case Western Reserve University, OH, USA; Louis Stokes Cleveland Veterans Administration Medical Center, Cleveland, OH, USA. Electronic address:

Background: We developed and validated a prognostic and predictive computational pathology risk score (CoRiS) using H&E stained tissue images from patients with early-stage non-small cell lung cancer (ES-NSCLC).

Methods: 1330 patients with ES-NSCLC were acquired from 3 independent sources and divided into four cohorts D. D comprised 100 surgery treated patients and was used to identify prognostic features via an elastic-net Cox model to predict overall and disease-free survival. CoRiS was constructed using the Cox model coefficients for the top features. The prognostic performance of CoRiS was evaluated on D (N=331), D (N=657) and D (N=242). Patients from D and D which comprised surgery + chemotherapy were used to validate CoRiS as predictive of added benefit to adjuvant chemotherapy (ACT) by comparing survival between different CoRiS defined risk groups.

Findings: CoRiS was found to be prognostic on univariable analysis, D (hazard ratio (HR) = 1.41, adjusted (adj.) P = .01) and D (HR = 1.35, adj. P < .001). Multivariable analysis showed CoRiS was independently prognostic, D (HR = 1.41, adj. P < .001) and D (HR = 1.35, adj. P < .001), after adjusting for clinico-pathologic factors. CoRiS was also able to identify high-risk patients who derived survival benefit from ACT D (HR = 0.42, adj. P = .006) and D (HR = 0.46, adj. P = .08).

Interpretation: CoRiS is a tissue non-destructive, quantitative and low-cost tool that could potentially help guide management of ES-NSCLC patients.

Funding: Data collection, anlaysis, and computation resources of the research reported in this publication was supported by the National Cancer Institute of the National Institutes of Health under award numbers: 1U24CA199374-01, R01CA202752-01A1, R01CA208236-01A1, R01 CA216579-01A1, R01 CA220581-01A1, 1U01 CA239055-01. National Center for Research Resources under award number 1 C06 RR12463-01. VA Merit Review Award IBX004121A from the United States Department of Veterans Affairs Biomedical Laboratory Research and Development Service, the DOD Prostate Cancer Idea Development Award (W81XWH-15-1-0558), the DOD Lung Cancer Investigator-Initiated Translational Research Award (W81XWH-18-1-0440), the DOD Peer Reviewed Cancer Research Program (W81XWH-16-1-0329), the Ohio Third Frontier Technology Validation Fund, the Wallace H. Coulter Foundation Program in the Department of Biomedical Engineering and the Clinical and Translational Science Award Program (CTSA) at Case Western Reserve University.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1016/j.ebiom.2021.103481DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8282972PMC
July 2021

GABAergic Neurons in the Dorsal-Intermediate Lateral Septum Regulate Sleep-Wakefulness and Anesthesia in Mice.

Anesthesiology 2021 Jul 13. Epub 2021 Jul 13.

Background: The γ-aminobutyric acid-mediated (GABAergic) inhibitory system in the brain is critical for regulation of sleep-wake and general anesthesia. The lateral septum contains mainly GABAergic neurons, being cytoarchitectonically divided into the dorsal, intermediate, and ventral parts. This study hypothesized that GABAergic neurons of the lateral septum participate in the control of wakefulness and promote recovery from anesthesia.

Methods: By employing fiber photometry, chemogenetic and optogenetic neuronal manipulations, anterograde tracing, in vivo electrophysiology, and electroencephalogram/electromyography recordings in adult male mice, the authors measured the role of lateral septum GABAergic neurons to the control of sleep-wake transition and anesthesia emergence and the corresponding neuron circuits in arousal and emergence control.

Results: The GABAergic neurons of the lateral septum exhibited high activities during the awake state by in vivo fiber photometry recordings (awake vs. non-rapid eye movement sleep: 3.3 ± 1.4% vs. -1.3 ± 1.2%, P < 0.001, n = 7 mice/group; awake vs. anesthesia: 2.6 ± 1.2% vs. -1.3 ± 0.8%, P < 0.001, n = 7 mice/group). Using chemogenetic stimulation of lateral septum GABAergic neurons resulted in a 100.5% increase in wakefulness and a 51.2% reduction in non-rapid eye movement sleep. Optogenetic activation of these GABAergic neurons promoted wakefulness from sleep (median [25th, 75th percentiles]: 153.0 [115.9, 179.7] s to 4.0 [3.4, 4.6] s, P = 0.009, n = 5 mice/group) and accelerated emergence from isoflurane anesthesia (514.4 ± 122.2 s vs. 226.5 ± 53.3 s, P < 0.001, n = 8 mice/group). Furthermore, the authors demonstrated that the lateral septum GABAergic neurons send 70.7% (228 of 323 cells) of monosynaptic projections to the ventral tegmental area GABAergic neurons, preferentially inhibiting their activities and thus regulating wakefulness and isoflurane anesthesia depth.

Conclusions: The results uncover a fundamental role of the lateral septum GABAergic neurons and their circuit in maintaining awake state and promoting general anesthesia emergence time.

Editor’s Perspective:
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1097/ALN.0000000000003868DOI Listing
July 2021

An IoT-Based Motion Tracking System for Next-Generation Foot-Related Sports Training and Talent Selection.

J Healthc Eng 2021 25;2021:9958256. Epub 2021 Jun 25.

College of Computer Science and Software Engineering, Shenzhen University, Shenzhen, China.

Motion tracking in different fields (medical, military, film, etc.) based on microelectromechanical systems (MEMS) sensing technology has been attracted by world's leading researchers and engineers in recent years; however, there is still a lack of research covering the sports field. In this study, we propose a new AIoT (AI + IoT) paradigm for next-generation foot-driven sports (soccer, football, takraw, etc.) training and talent selection. The system built is cost-effective and easy-to-use and requires much fewer computational resources than traditional video-based analysis on monitoring motions of players during training. The system built includes a customized wireless wearable sensing device (WWSDs), a mobile application, and a data processing interface-based cloud with an ankle attitude angle analysis model. Eleven right-foot male participators wore the WWSD on their ankle while each performed 20 instances of different actions in a formal soccer field. The experimental outcome demonstrates the proposed motion tracking system based on AIoT and MEMS sensing technologies capable of recognizing different motions and assessing the players' skills. The talent selection function can partition the elite and amateur players at an accuracy of 93%. This intelligent system can be an emerging technology based on wearable sensors and attain the experience-driven to data-driven transition in the field of sports training and talent selection and can be easily extended to analyze other foot-related sports motions (e.g., taekwondo, tumble, and gymnastics) and skill levels.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1155/2021/9958256DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8253628PMC
June 2021

Single dynamic covalent bond tailored responsive molecular junctions.

Angew Chem Int Ed Engl 2021 Jul 12. Epub 2021 Jul 12.

Xiamen University, College of Chemistry and Chemical Engineering, Siming south road 422, 3012, Xiamen, CHINA.

Responsive molecular devices are one of the core units for molecular electronics, and dynamic covalent bonds (DCBs) provide the opportunity for the fabrication of responsive molecular devices. Herein we employ a single dynamic acyl hydrazone bond to fabricate tailored molecular devices using the scanning tunneling microscopy break-junction technique (STM-BJ) and the eutectic Ga-In technique (EGaIn). We found that the single-DCB-tailored molecular devices exhibited acid-base and/or photo-thermal response with three well-defined molecular conductance states. The reversible switching has the ON/OFF ratio of ~10 between each state for single-molecule junctions and ~3 for the SAMs-based molecular junctions. Combined with the density functional theory calculations, we revealed that the multiple conductance states of these molecular junctions originate from the dynamic acyl hydrazone bond exchange and C=N isomerization. Our work opens the avenue towards the design of tailored single-molecule electrical devices by implanting dynamic covalent bonds in molecular architectures.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1002/anie.202106666DOI Listing
July 2021

OX40 agonist combined with irreversible electroporation synergistically eradicates established tumors and drives systemic antitumor immune response in a syngeneic pancreatic cancer model.

Am J Cancer Res 2021 15;11(6):2782-2801. Epub 2021 Jun 15.

Department of Radiology, Ruijin Hospital, Shanghai Jiao Tong University School of Medicine No. 197, Ruijin Er Road, Shanghai 200025, China.

In this study, we intended to explore a novel combination treatment scheme for pancreatic cancer, using irreversible electroporation (IRE) and OX40 agonist. We further aimed to investigate the capacity and mechanism of this combination treatment using an mouse aggressive pancreatic cancer model. To this end, mice subcutaneously injected with KPC1199 pancreatic tumor cells were treated with IRE, followed by intraperitoneal injection of OX40 agonist. Tumor growth and animal survival were observed. Flow cytometry analysis, immunohistochemistry, and immunofluorescence were used to evaluate the immune cell populations within the tumors. The tumor-specific immunity was assessed using ELISpot assay. Besides, the cytokine patterns both in serum and tumors were identified using Luminex assay. After combination therapy with IRE and OX40 agonist, 80% of the mice completely eradicated the established subcutaneous tumors, during the 120 days observation period. Rechallenging these tumor-free mice at day 120 with KPC1199 tumor cells leads to complete resistance to tumor growth, suggesting that the combination therapy generated long-term-specific antitumor immune memory. Moreover, combination therapy significantly delayed the growth of contralateral untreated tumors, and significantly prolonged animal survival, suggesting that a potent systematic anti-tumor immunity was induced by combination therapy. Mechanically, combination therapy amplified antitumor immune response induced by IRE, as manifested by the increased quality and quantity of CD8 T cells trigged by IRE. Together, these results provide strong evidence for the clinical assessment of the combination of IRE and OX40 agonist in patients with pancreatic cancer.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8263674PMC
June 2021

Perturbations in nitric oxide homeostasis promote Arabidopsis disease susceptibility towards Phytophthora parasitica.

Mol Plant Pathol 2021 Jul 9. Epub 2021 Jul 9.

The Key Laboratory of Biotechnology for Medicinal Plant of Jiangsu Province, School of Life Science, Jiangsu Normal University, Xuzhou, China.

Phytophthora species can infect hundreds of different plants, including many important crops, causing a number of agriculturally relevant diseases. A key feature of attempted pathogen infection is the rapid production of the redox active molecule nitric oxide (NO). However, the potential role(s) of NO in plant resistance against Phytophthora is relatively unexplored. Here we show that the level of NO accumulation is crucial for basal resistance in Arabidopsis against Phytophthora parasitica. Counterintuitively, both relatively low or relatively high NO accumulation leads to reduced resistance against P. parasitica. S-nitrosylation, the addition of a NO group to a protein cysteine thiol to form an S-nitrosothiol, is an important route for NO bioactivity and this process is regulated predominantly by S-nitrosoglutathione reductase 1 (GSNOR1). Loss-of-function mutations in GSNOR1 disable both salicylic acid accumulation and associated signalling, and also the production of reactive oxygen species, leading to susceptibility towards P. parasitica. Significantly, we also demonstrate that secreted proteins from P. parasitica can inhibit Arabidopsis GSNOR1 activity.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1111/mpp.13102DOI Listing
July 2021

Reversible regulation of metallo-base-pair interactions for DNA dehybridization by ultrasound.

Chem Commun (Camb) 2021 Jul;57(60):7438-7440

DWI - Leibniz Institute for Interactive Materials, Forckenbeckstr. 50, 52056 Aachen, Germany. and Institute of Technical and Macromolecular Chemistry, RWTH Aachen University, Worringerweg 1, 52074 Aachen, Germany and Zernike Institute for Advanced Materials, University of Groningen, Nijenborgh 4, 9747 AG Groningen, The Netherlands.

Mechanical force applied by ultrasound in solution leads to the dissociation of DNA metallo-base-pair interactions when these motifs are functionalized with oligodeoxynucleotide sequences of sufficient length. The annealing and force-induced denaturing process is followed by the attachment of distance-sensitive fluorescent probes and is found to be reversible.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1039/d1cc02402gDOI Listing
July 2021

lncRNAs as Hallmarks for Individualized Treatment of Gastric Cancer.

Anticancer Agents Med Chem 2021 Jul 5. Epub 2021 Jul 5.

Key Laboratory of Tumor Cellular & Molecular Pathology (University of South China),College of Hunan Province, Cancer Research Institute, Hengyang Medical College, University of South China, Hengyang, Hunan 421001, China.

Gastric cancer is global cancer with a high mortality rate. A growing number of studies have found the abnormal expression of lncRNA (long noncoding RNA) in many tumors, which plays a role in promoting or inhibiting cancer. Similarly, lncRNA abnormal expression plays an essential biological function in gastric cancer. This article focuses on lncRNA involvement in the development of gastric cancer in terms of cell cycle disorder, apoptosis inhibition, metabolic remodeling, promotion of tumor inflammation, immune escape, induction of angiogenesis, and epithelial mesenchymal transition (EMT). The involvement of lncRNA in the development of gastric cancer is related to drug resistance, such as cisplatin and multi-drug resistance. It can also be used as a potential marker for the diagnosis and prognosis of gastric cancer and a target for the treatment. With an in-depth understanding of the mechanism of lncRNA in gastric cancer, new ideas for personalized treatment of gastric cancer are expected.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.2174/1871520621666210706113102DOI Listing
July 2021

Ultra-broadband metamaterial absorbers from long to very long infrared regime.

Light Sci Appl 2021 Jul 5;10(1):138. Epub 2021 Jul 5.

Center for Advanced Optoelectronic Functional Materials Research and Key Laboratory of UV Light-Emitting Materials and Technology of Ministry of Education, College of Physics, Northeast Normal University, 130024, Changchun, China.

Broadband metamaterials absorbers with high absorption, ultrathin thickness and easy configurations are in great demand for many potential applications. In this paper, we first analyse the coupling resonances in a Ti/Ge/Ti three-layer absorber, which can realise broadband absorption from 8 to 12 μm. Then we experimentally demonstrate two types of absorbers based on the Ti/Ge/SiN/Ti configuration. By taking advantage of coupling surface plasmon resonances and intrinsic absorption of lossy material SiN, the average absorptions of two types of absorbers achieve almost 95% from 8 to 14 μm (experiment result: 78% from 6.5 to 13.5 μm). In order to expand the absorption bandwidth, we further propose two Ti/Si/SiO/Ti absorbers which can absorb 92% and 87% of ultra-broadband light in the 14-30 μm and 8-30 μm spectral range, respectively. Our findings establish general and systematic strategies for guiding the design of metamaterial absorbers with excellent broadband absorption and pave the way for enhancing the optical performance in applications of infrared thermal emitters, imaging and photodetectors.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1038/s41377-021-00577-8DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8257711PMC
July 2021

Development of DNA Biosensors Based on DNAzymes and Nucleases.

Crit Rev Anal Chem 2021 Jul 6:1-16. Epub 2021 Jul 6.

College of Life Science, Yangtze University, Jingzhou, Hubei, China.

DNA biosensors play important roles in environmental, medical, industrial and agricultural analysis. Many DNA biosensors have been designed based on the enzyme catalytic reaction. Because of the importance of enzymes in biosensors, we present a review on this topic. In this review, the enzymes were divided into DNAzymes and nucleases according to their chemical nature. Firstly, we introduced the DNAzymes with different function inducing cleavage, metalation, peroxidase, ligation and allosterism. In this section, the G-quadruplex DNAzyme, as a hot topic in recent years, was described in detail. Then, the nucleases-assisted signal amplification method was also reviewed in three categories including exonucleases, endonucleases and other nucleases according to the digestion sites in DNA substrates. In exonucleases section, the Exo I and Exo III were selected as examples. Then, the DNase I, BamH I, nicking endonuclease, S1 nuclease, the duplex specific nuclease (DSN) and RNases were chosen to illustrate the application of endonucleases. In other nucleases section, DNA polymerases and DNA ligases were detailed. Last, the challenges and future perspectives in the field were discussed.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1080/10408347.2021.1944046DOI Listing
July 2021

Lactoferrin ameliorates pathological cardiac hypertrophy related to mitochondrial quality control in aged mice.

Food Funct 2021 Jul 5. Epub 2021 Jul 5.

School of Pharmacy, Fujian Medical University, Fuzhou, China.

Pathological myocardial hypertrophy, which lacks effective prevention and treatment strategies, makes the elderly susceptible to various cardiovascular diseases. Based on the beneficial attributes of lactoferrin in aging-related diseases, we aimed to investigate whether lactoferrin could exert protection against aging-related cardiac hypertrophy and further explore the underlying mechanisms. Here, we assessed the effects of lactoferrin on myocardial pathology, apoptotic proteins, mitochondrial morphology, kinetics, autophagy, and aging-related markers, including lipofuscin deposition, overloaded iron, and oxidative stress, which are known to destabilize the mitochondrial-lysosomal axis in aged mice. Upon the administration of lactoferrin, aged hearts showed amelioration of pathological cardiac hypertrophy, which was associated with decreased apoptosis, improved morphology, rearrangement of mitochondrial dynamics, increased lysosome-dependent autophagy, and inhibition of factors detrimental to the mitochondrial-lysosomal axis. In conclusion, lactoferrin ameliorated pathological cardiac hypertrophy, potentially by improving the mitochondrial quality related to mitochondrial dynamics and the mitochondrial-lysosomal axis, thus reducing mitochondria-dependent apoptosis, which is the pivotal factor for cardiac hypertrophy in aged mice.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1039/d0fo03346dDOI Listing
July 2021

Hb adaptation to hypoxia in high-altitude fishes: Fresh evidence from schizothoracinae fishes in the Qinghai-Tibetan Plateau.

Int J Biol Macromol 2021 Jun 29;185:471-484. Epub 2021 Jun 29.

The Key Laboratory of Aquatic Biodiversity and Conservation of Chinese Academy of Sciences, Institute of Hydrobiology, Chinese Academy of Sciences, Wuhan 430072, China; Center for Excellence in Animal Evolution and Genetics, Chinese Academy of Sciences, Kunming 650223, China. Electronic address:

Uncovering the genetic basis of hypoxic adaptation is one of the most active research areas in evolutionary biology. Among air-breathing vertebrates, modifications of hemoglobin (Hb) play a pivotal role in mediating an adaptive response to high-altitude hypoxia. However, the relative contributions in water-breathing organisms are still unclear. Here, we tested the Hb concentration of fish at different altitudes. All species showed species-specific Hb concentration, which has a non-positive correlation with altitude. Moreover, we investigated the expression of Hb genes by the RNA-seq and quantitative real-time PCR (qRT-PCR), and Hb composition by two-dimensional electrophoresis (2-DE). The results showed that the multiple Hb genes and isoforms are co-expressed in schizothoracinae fishes endemic to the Qinghai-Tibetan Plateau (QTP). Phylogenetic analyses of Hb genes indicated that the evolutionary relationships are not easily reconciled with the organismal phylogeny. Furthermore, evidence of positive selection was found in the Hb genes of schizothoracinae fishes through the selection pressure analysis. We demonstrated that positively selected sites likely facilitated the functional divergence of Hb isoforms. Taken together, this study indicated that the long-term maintenance of high Hb concentration may be a disadvantage for physiologically acclimating to high altitude hypoxia. Meanwhile, the genetically based modification of Hb-O affinity in schizothoracinae fishes might facilitate the evolutionary adaptation to Tibetan aqueous environments.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1016/j.ijbiomac.2021.06.186DOI Listing
June 2021

Problematic Internet Use Was Associated With Psychological Problems Among University Students During COVID-19 Outbreak in China.

Front Public Health 2021;9:675380. Epub 2021 Jun 15.

Department of Maternal and Child Health and MOE (Ministry of Education) Key Lab of Environment and Health, School of Public Health, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China.

As the coronavirus disease 2019 (COVID-19) pandemic progressed globally, school closures and home quarantine may cause an increase in problematic Internet use among students in universities. Such a traumatic stress event may also contribute to the development of posttraumatic stress disorder (PTSD), depressive, and anxiety symptoms. This study aimed to evaluate the prevalence of PTSD, depressive, and anxiety symptoms as well as the predictive role of problematic Internet use in the above-mentioned psychological problems in university students. A cross-sectional study was conducted through an online survey of 8,879 students in China between April 20 and April 26, 2020. The presence of PTSD, depressive, and anxiety symptoms and problematic Internet use were evaluated using PTSD Checklist for DSM-5, the Center for Epidemiologic Studies Depression 9-item scale, the generalized anxiety disorder 7-item scale, and the Young diagnostic questionnaire, respectively. Sociodemographic information and the knowledge, attitude, and practice (KAP) toward COVID-19 data were also collected. A total of 4,834 (54.4%) participants were female, and 7,564 (85.2%) were undergraduate students. A total of 615 students (6.9%) reported PTSD symptoms; 5.2% (465) and 10.1% (896) reported moderate to severe depressive and anxiety symptoms, respectively. The problematic Internet use was significantly associated with higher risk of PTSD, depressive, and anxiety symptoms (odds ratio 2.662 [95% CI, 2.239-3.165], odds ratio 4.582 [95% CI, 3.753-5.611], odds ratio 3.251 [95% CI, 2.814-3.757], respectively; all < 0.001). Lower attitude and practice scores also contributed to the risk of depressive, anxiety, and PTSD symptoms ( < 0.05). Psychological problems should be paid more attention, and problematic Internet use may be a predictor when screening high-risk students for psychological problems. Our results will aid in timely psychological screening, which is meaningful in the prevention and intervention of psychological problems.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.3389/fpubh.2021.675380DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8239128PMC
July 2021

Uniaxial Compression Mechanical Properties of Foam Nickel/Iron-Epoxy Interpenetrating Phase Composites.

Materials (Basel) 2021 Jun 24;14(13). Epub 2021 Jun 24.

School of Civil Engineering and Mechanics, Yanshan University, Qinhuangdao 066004, China.

The damage process and failure mechanisms were analyzed by a series of quasi-static compressive experiments of seven materials including pure epoxy (EP), three different PPI (pores per linear inch) foam nickel-iron, and three different PPI foam nickel/iron-epoxy interpenetrating phase composites (IPC). Plotting the stress-strain curves of different materials, their change rules are discussed, then the effective elastic modulus and yield limit of the materials are provided, and the energy absorption properties of different materials are analyzed by the stress-strain curves. It was found that the effective elastic modulus and specific stiffness of the three IPC materials were higher than pure foam nickel-iron. The brittleness of epoxy can be obviously changed by selecting a suitable PPI foam nickel-iron composited with it. The unit volume energy absorption rate of foam nickel/iron-epoxy was significantly higher than pure epoxy and pure foam nickel-iron. It was also found that the energy absorption rate decreased with the increase in PPI. The stress relaxation rate decreased first and then increased with the increase in PPI. The creep behavior of the three composites was obvious in the creep elastic stage, and the creep rate increased with the increase in PPI. The creep rate decreased with the increase in PPI in the creep transition stage.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.3390/ma14133523DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8269595PMC
June 2021

Mode division multiplexing for multiple particles noncontact simultaneous trap.

Opt Lett 2021 Jul;46(13):3017-3020

We propose and demonstrate an optical trap on the basis of a normal single-mode fiber (SMF), which is used to trap two particles in the axial direction at the same time without contact based on mode division multiplexing technology. We design and manufacture a tapered fiber probe. The mode beam is excited by docking a normal SMF to a 980 nm SMF with a 2 µm offset. Then the beams of and are both transmitted in the fiber. To converge the mode beam, a SMF with a tapered end is used to produce a cage for trapping the first microparticle. This particle acts as a lens to converge the mode beam to trap the second microparticle. We verify the feasibility of trapping two particles simultaneously through simulation. With this function, the proposed optical trap is easier to manipulate different individual particles for comparison and testing, which can promote the development of the biological, biophysical, colloidal, and soft matter fields.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1364/OL.426229DOI Listing
July 2021

Zebrafish Uba1 Degrades IRF3 through K48-Linked Ubiquitination to Inhibit IFN Production.

J Immunol 2021 Jun 30. Epub 2021 Jun 30.

Institute of Hydrobiology, Chinese Academy of Sciences, Wuhan, China;

Fish IFN regulatory factor 3 (IRF3) is a crucial transcription factor in the IFN activation signaling pathway, which leads to IFN production and a positive cycle. Unrestricted IFN expression results in hyperimmune responses and therefore, IFN must be tightly regulated. In the current study, we found that zebrafish Ub-activating enzyme (Uba1) negatively regulated IRF3 via the K-48 ubiquitin proteasome degradation of IRF3. First, expression stimulated by spring viraemia of carp virus infection was blunted by the overexpression of Uba1 and enhanced by Uba1 knockdown. Afterward, we found that Uba1 was localized in the cytoplasm, where it interacted with and degraded IRF3. Functional domains analysis revealed that the C-terminal ubiquitin-fold domain was necessary for IRF3 degradation by Uba1 and the N-terminal DNA-binding domain of IRF3 was indispensable for the degradation by Uba1.The degradation of IRF3 was subsequently impaired by treatment with MG132, a ubiquitin proteasome inhibitor. Further mechanism analysis revealed that Uba1 induced the K48-linked Ub-proteasomal degradation of IRF3. Finally, the antiviral capacity of IRF3 was significantly attenuated by Uba1. Taken together, our study reveals that zebrafish Uba1 interacts with and activates the ubiquitinated degradation of IRF3, providing evidence of the IFN immune balance mechanism in fish.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.4049/jimmunol.2100125DOI Listing
June 2021

Development of a simple nomogram to estimate risk for intraoperative complications before partial nephrectomy based on the Mayo Adhesive Probability score combined with the RENAL nephrometry score.

Investig Clin Urol 2021 Jul;62(4):455-461

Department of Urology, Nanchong Central Hospital, the Second Clinical Medical College, North Sichuan Medical University, Nanchong, Sichuan, China.

Purpose: This study aimed to develop a simple nomogram based on the Mayo Adhesive Probability (MAP) score combined with the RENAL nephrometry score (RNS) to predict intraoperative complications before partial nephrectomy (PN) in Asian populations.

Materials And Methods: This study retrospectively collected patients undergoing PN at three medical centers. Each component of the MAP score and the RNS (6 variables) was evaluated to assess its association with intraoperative complications by multivariable logistic regression with backward elimination.

Results: A total of 46 cases (7.2%) with intraoperative complications were identified among 637 patients. After backward elimination, three variables, including tumor diameter (4-7 cm vs. ≤4 cm: odds ratio [OR], 4.339; 95% confidence interval [CI], 1.943-9,692; ≥7 cm vs. ≤4 cm: OR, 8.434; 95% CI, 1.225-58.090), nearness to the collecting system (4-7 mm vs. ≥7 mm: OR, 2.988; 95% CI, 1.293-6.907; ≤4 mm vs. ≥7 mm: OR, 21.394; 95% CI, 6.122-74.756), and perirenal fat stranding type (type 1 vs. no stranding: OR, 3.119; 95% CI, 1.079-9.017; type 2 vs. no stranding: OR, 18.722; 95% CI, 6.757-51.868), were retained. The predictive power (measured by area under the curve [AUC]) of the nomogram was observed to be superior to the RNS or MAP score alone (RNS: 0.686, MAP score: 0.729, the nomogram: 0.837), but comparable to their combination (0.813).

Conclusions: The simple nomogram contains fewer components than the combination of the RNS and MAP scores yet demonstrates equivalent predictive power for intraoperative complications.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.4111/icu.20210025DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8246018PMC
July 2021

Catalytic System-Controlled Divergent Reaction Strategies for the Construction of Diversified Spiropyrazolone Skeletons from Pyrazolidinones and Diazopyrazolones.

Angew Chem Int Ed Engl 2021 Jun 28. Epub 2021 Jun 28.

Shanghai Institute of Materia Medica, Chinese Academy of Sciences, DDDC, 555 Zuchongzhi Road, Zhangjiang Hi-Tech, 201203, Shanghai, CHINA.

A catalytic system-controlled divergent reaction strategy was here reported to construct four types of intriguing spiroheterocyclic skeletons from simple and readily available starting materials via a precise chemical bond activation/[n+1] annulation cascade. The tetraazaspiroheterocyclic and trizazspiroheterocyclic scaffolds could be independently constructed by a selective N-N bond activation/[n+1] annulation cascade, a C(sp 2 )-H activation/[4+1] annulation and a novel tandem C(sp 2 )-H/C(sp 3 )-H bond activation/[4+1] annulation strategy, along with a broad scope of substrates, moderate to excellent yields and value transformations. More importantly, in these transformations, we are the first time to capture a N-N bond activation and a C(sp 3 )-H bond activation of pyrazolidinones under different catalytic system.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1002/anie.202105857DOI Listing
June 2021

Gender Expression among Transgender Women in Japan: Support Is Needed to Improve Social Passing as a Woman.

Acta Med Okayama 2021 Jun;75(3):323-334

Graduate School of Health Sciences, Okayama University.

Gender expression is important for transgender women to improve their social passing as women. Herein, a questionnaire about the status of gender expression and support needs was distributed to 54 transgender women aged 17-71 in Japan. Most of the respondents noted that they had found it relatively difficult to handle physical changes and weight gain due to hormone treatment. They also found it difficult to enact and sustain practices such as a feminine use of voice and to use women-only services, whereas practicing and continuing with routine skin and hair care and feminine mannerisms were relatively easy for them. In the questionnaire regarding the support for gender transitioning, many items showed only a small percentage of the transgender women had received the support that they were looking for, and most of their needs for support were not addressed. Some of the factors that increased the respondents' needs and achievement of gender expression as women included estrogen treatment, sex reassignment surgery, and living as a woman; these aspects met their support needs as well. Gender support professionals need to coordinate and collaborate with specialists in areas such as nutritional guidance and voice training to enable transgender women to improve the extent to which they can socially 'pass' as women.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.18926/AMO/62227DOI Listing
June 2021

Divanillyl sulfone suppresses NLRP3 inflammasome activation via inducing mitophagy to ameliorate chronic neuropathic pain in mice.

J Neuroinflammation 2021 Jun 24;18(1):142. Epub 2021 Jun 24.

State Key Laboratory of Bioactive Substances and Functions of Natural Medicines, Institute of Materia Medica, Chinese Academy of Medical Sciences & Peking Union Medical College, Beijing, 100050, China.

Background: Chronic neuropathic pain is a frequent sequel to peripheral nerve injury and maladaptive nervous system function. Divanillyl sulfone (DS), a novel structural derivative of 4,4'-dihydroxydibenzyl sulfoxide from a traditional Chinese medicine Gastrodia elata with anti-nociceptive effects, significantly alleviated neuropathic pain following intrathecal injection. Here, we aimed to investigate the underlying mechanisms of DS against neuropathic pain.

Methods: A chronic constrictive injury (CCI) mouse model of neuropathic pain induced by sciatic nerve ligation was performed to evaluate the effect of DS by measuring the limb withdrawal using Von Frey filament test. Immunofluorescence staining was used to assess the cell localizations and expressions of Iba-1, ASC, NLRP3, and ROS, the formation of autolysosome. The levels of NLRP3-related proteins (caspase-1, NLRP3, and IL-1β), mitophagy-related proteins (LC3, Beclin-1, and p62), and apoptosis-related proteins (Bcl-XL and Bax) were detected by Western blotting. The apoptosis of BV-2 cell and caspase activity were evaluated by flow cytometry.

Results: DS significantly alleviated the neuropathic pain by increasing the mechanical withdrawal threshold and inhibiting the activation of NLRP3 in CCI-induced model mice. Our findings indicated that DS promoted the mitophagy by increasing the LC3II and Beclin 1 and decreasing the levels of p62 protein in BV-2 cell. This is accompanied by the inhibition of NLRP3 activation, which was shown as inhibited the expression of NLRP3 in lysates as well as the secretion of mature caspase-1 p10 and IL-1β p17 in supernatants in cultured BV-2 microglia. In addition, DS could promote mitophagy-induced improvement of dysfunctional mitochondria by clearing intracellular ROS and restoring mitochondrial membrane potential.

Conclusion: Together, our findings demonstrated that DS ameliorate chronic neuropathic pain in mice by suppressing NLRP3 inflammasome activation induced by mitophagy in microglia. DS may be a promising therapeutic agent for chronic neuropathic pain.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1186/s12974-021-02178-zDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8223331PMC
June 2021
-->