Publications by authors named "Weidong Zhang"

652 Publications

SiamMFC: Visual Object Tracking Based on Mainfold Full Convolution Siamese Network.

Sensors (Basel) 2021 Sep 24;21(19). Epub 2021 Sep 24.

National Center for Materials Service Safety, University of Science and Technology Beijing, Beijing 100083, China.

Visual tracking task is divided into classification and regression tasks, and manifold features are introduced to improve the performance of the tracker. Although the previous anchor-based tracker has achieved superior tracking performance, the anchor-based tracker not only needs to set parameters manually but also ignores the influence of the geometric characteristics of the object on the tracker performance. In this paper, we propose a novel Siamese network framework with ResNet50 as the backbone, which is an anchor-free tracker based on manifold features. The network design is simple and easy to understand, which not only considers the influence of geometric features on the target tracking performance but also reduces the calculation of parameters and improves the target tracking performance. In the experiment, we compared our tracker with the most advanced public benchmarks and obtained a state-of-the-art performance.
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http://dx.doi.org/10.3390/s21196388DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8512198PMC
September 2021

Identification of Prognostic Factors Related to Super Enhancer-Regulated ceRNA Network in Metastatic Lung Adenocarcinoma.

Int J Gen Med 2021 1;14:6261-6275. Epub 2021 Oct 1.

Department of Thoracic Surgery, Tianjin First Central Hospital, Tianjin, People's Republic of China.

Introduction: The regulatory mechanisms of super enhancers (SEs) and ceRNA networks in LUAD progression are not well understood. We aimed to discover the prognostic-related ceRNA network regulated by SEs in metastatic LUAD.

Methods: RNA-seq data were extracted from The Cancer Genome Atlas (TCGA) database. Differentially expressed (DE) RNAs were identified by edgeR. CeRNA network was predicted and visualized using starBase and Cytoscape. H3K27ac ChIP-seq data were derived from the Gene Expression Omnibus (GEO) database, and used for SE identification. Kaplan-Meier curve and multivariate Cox model were applied for prognostic analysis. Gene Ontology (GO), Kyoto Encyclopedia of Genes and Genomes (KEGG) and protein-protein interaction (PPI) network were performed for functional analysis. SEs of AC074117.1 were verified by ChIP-qPCR in A549 and H1299 cells. MTT assay was performed to analyze cell proliferation. Luciferase activity assay was carried out to validate the target targeting relationships of ceRNA network.

Results: A total of 2355 DEmRNA, 483 DElncRNA and 155 DEmiRNA were identified between metastatic LUAD and adjacent normal tissues. CeRNA network consisting of 7 DElncRNAs, 18 DEmiRNAs and 15 DEmRNAs was constructed. Among the seven DElncRNAs in ceRNA network, only AC074117.1 was regulated by SEs. SE-regulated prognostic ceRNA sub-network consisting of FKBP3, E2F2, AC074117.1 and hsa-let-7c-5p was screened and verified. The overlapping co-expressed mRNAs of FKBP3, E2F2, AC074117.1 and hsa-let-7c-5p were mainly related to cell division and Fanconi anemia pathway. Genes in the ceRNA sub-network were correlated with DNA mismatch repair markers. Functional experiments proved that AC074117.1 was highly expressed in LUAD cells. AC074117.1 silencing notably inhibited proliferation of A549 and H1299 cells. Luciferase activity assay confirmed the direct relationship in AC074117.1-hsa-let-7c-5p-FKBP3/E2F2 network.

Conclusion: A novel prognostic ceRNA sub-network regulated by SEs was identified in metastatic LUAD. This study provided potential therapeutic targets and prognostic markers for further study of metastatic LUAD.
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http://dx.doi.org/10.2147/IJGM.S332317DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8493278PMC
October 2021

Effects of low-concentration glyphosate and aminomethyl phosphonic acid on zebrafish embryo development.

Ecotoxicol Environ Saf 2021 Oct 4;226:112854. Epub 2021 Oct 4.

School of Public Health, Hebei Medical University, Shijiazhuang, Hebei 050017, China. Electronic address:

Glyphosate (GLY) is the most widely used broad-spectrum, non-selective herbicide in the world, whose main degradation product is aminomethyl phosphonic acid (AMPA). Because of long-term and large-scale use, residual GLY and AMPA in the environment pose great environmental and human health threats. The purpose of this study is to evaluate the effects and mechanism of residual low-concentrations of GLY and AMPA in the environment on the development of zebrafish embryos. Zebrafish embryos were exposed to 0, 1, 10, 100, and 700 ng·mL GLY and AMPA for 72 h (from 2 to 74 h post-fertilization). With increasing exposure dose, heart rates of both embryos and larvae showed a rising trend and obvious arrhythmia appeared. Defects in cardiac development and function of zebrafish juveniles may be related to altered transcription levels of cardiac development genes (TBX5, NKX2.5, BMP4) and apoptosis genes (Bcl-2, Bax). In addition, pericardial edema and bone deformation of zebrafish embryos may be caused by inhibition of Na/K-ATPase and Ca-ATPase after exposure to GLY and AMPA. The present results demonstrated that at typical environmental residual concentrations of GLY and AMPA had similar developmental toxicity in zebrafish embryos.
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http://dx.doi.org/10.1016/j.ecoenv.2021.112854DOI Listing
October 2021

A Single-cell Transcriptome Atlas of Cashmere Goat Hair Follicle Morphogenesis.

Genomics Proteomics Bioinformatics 2021 Sep 14. Epub 2021 Sep 14.

Key Laboratory of Animal Genetics, Breeding and Reproduction of Shaanxi Province, College of Animal Science and Technology, Northwest A&F University, Yangling 712100, China. Electronic address:

Cashmere, also known as soft gold, is produced from the secondary hair follicles (SHFs) of cashmere goats. The number of SHFs determines the yield and quality of cashmere, therefore, it is of interest to investigate the transcriptional profiles present during cashmere goat hair follicle development. However, mechanisms underlying this development remain largely unexplored and studies regarding hair follicle development mostly use a murine research model. To provide a comprehensive understanding of cellular heterogeneity and cell fate decisions, single-cell RNA sequencing was performed on 19,705 single cells of the dorsal skin from cashmere goat fetuses at induction (embryonic day 60), organogenesis (embryonic day 90), and cytodifferentiation (embryonic day 120) stages. For the first time, unsupervised clustering analysis identified 16 cell clusters, and their corresponding cell types were also characterized. Based on lineage inference, a detailed molecular landscape was revealed along the dermal and epidermal cell lineage developmental pathways. Notably, our current data also confirmed the heterogeneity of dermal papilla cells from different hair follicle types, which was further validated by immunohistochemical staining analysis. The current study identifies different biomarkers during cashmere goat hair follicle development and has implications for cashmere goat breeding in the future.
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http://dx.doi.org/10.1016/j.gpb.2021.07.003DOI Listing
September 2021

Plasmonic enhanced enzyme activity by catalytic cascade induced mutual benefit tumor starvation/immune/photothermal therapy.

Biomater Sci 2021 Sep 14;9(18):6116-6125. Epub 2021 Sep 14.

State Key Laboratory of Metastable Materials Science and Technology, Key Laboratory of Nanobiotechnology of Hebei Province, Applying Chemistry Key Lab of Hebei Province, Yanshan University, Qinhuangdao 066004, China.

Single tumor starvation therapy can activate other signaling pathways in tumor cells and easily induce tumor cell metastasis. This research proposes an intelligent nanoparticle, which is effectively combined with plasmonic and immunotherapy to realize a new strategy of "upstream consumption and downstream blocking" of nutrients in tumor sites. The intelligent nanoparticle (Ag-G/[email protected]) was composed of Ag NCs loaded with glucose oxidase (GOx), catalase (CAT) and coated with the tumor cytomembrane (M). Homologous targeting of tumor cytomembrane facilitated more delivery of Ag-G/[email protected] to tumor sites and then the plasmonic excited from Ag-G/[email protected] can increase the catalytic efficiency of the enzymatic reaction. Hydrogen peroxide (HO) produced by Ag-G/[email protected] through the consumption of glucose is further catalyzed by CAT to produce oxygen (O). This self-reinforcing cascade reaction not only consumes the nutrients of tumor cells, but also the plasmonic-induced photothermal therapy can further stimulate the immune system to produce interferon-γ (IFN-γ), blocking angiogenesis and restricting the nutrient supply of tumor cells. This strategy takes the nutrition necessary for cell survival as the entry point, through endogenous continuous consumption of intracellular nutrients and containment of exogenous supplementation, combined with plasmonic thermal effect and immunotherapy to kill tumor cells, which provides a new way of treating cancer safely and effectively.
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http://dx.doi.org/10.1039/d1bm00551kDOI Listing
September 2021

Naringin Exerts Therapeutic Effects on Mice Colitis: A Study Based on Transcriptomics Combined With Functional Experiments.

Front Pharmacol 2021 24;12:729414. Epub 2021 Aug 24.

Comparative Medicine Department of Researching and Teaching, Dalian Medical University, Dalian, China.

Naringin has been shown to exert protective effects in an animal model of ulcerative colitis, but detailed mechanisms remain unclear. This study aimed to investigate function and signaling mechanisms underlying naringin-induced therapeutic effects on colitis. Two mouse models were established to mimic human Inflammatory bowel disease (IBD) by treating drinking water with dextran sodium sulphate or intra-colonic administration of 2, 4, 6-trinitrobenzene sulfonic acid. Transcriptomics combined with functional experiments were used to investigate underlying mechanisms. Colitis symptoms, including weight loss and high disease activity index were significantly reversed by naringin. The inflammatory response, oxidative reactions, and epithelial cell apoptosis that occur with colitis were also alleviated by naringin. After naringin treatment, transcriptomics results identified 753 differentially expressed mRNAs that were enriched in signaling pathways, including the neuroactive ligand-receptor interaction, calcium signaling, and peroxisome proliferator-activated receptor (PPAR) signaling. The naringin-induced alleviation of colitis was significantly inhibited by the PPAR-γ inhibitor BADGE. In IEC-6 and RAW264.7 cells incubated with lipopolysaccharide (LPS), NF-κB-p65, a downstream protein of PPAR-γ, was significantly increased. Naringin suppressed LPS-induced high expression of NF-κB-p65, which was inhibited by small interfering RNA targeting PPAR-γ. Our study clarifies detailed mechanisms underlying naringin-induced therapeutic effects on mice colitis, and PPAR-γ was found to be the main target of naringin by functional experiments both and . Our study supplies new scientific information for the use of naringin in colitis treatment.
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http://dx.doi.org/10.3389/fphar.2021.729414DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8421552PMC
August 2021

Dietary fructose intake is correlated with fat distribution in the Newfoundland population.

Nutrition 2021 Jul 25;93:111434. Epub 2021 Jul 25.

Faculty of Medicine, Memorial University, St. John's, Newfoundland, Canada. Electronic address:

Objective: Increased dietary fructose intake is associated with elevated body weight and body mass index. Few studies are available regarding the relationship between fat distribution and dietary fructose intake. The aim of this study was to investigate the association between dietary fructose intake and fat distribution in adults in a large Newfoundland cohort.

Methods: We analyzed 2298 adults from CODING (Complex Diseases in the New found land Population: Environment and Genetics) study. Intake of dietary fructose was evaluated from the Willett food frequency questionnaire. Fat distribution was estimated by dual-energy x-ray absorptiometry. Partial correlation analysis was used to determine the correlations of dietary fructose intake with fat distribution adjusted for major confounding factors.

Results: Daily dietary fructose intake was negatively associated with arm fat in postmenopausal women (r = -0.080, P < 0.05), but positively associated with arm fat in premenopausal women after adjusting for age, total calorie intake, and physical activity levels (r = 0.079, P < 0.05). Dietary fructose intake was negatively correlated with both arm fat (r = -0.131, P < 0.05) and visceral fat (r = -0.124 measured in mass, r = -0.124 measured in volume respectively; P < 0.05) in men <45 y of age, not in men ≥45 y.

Conclusion: This study demonstrated that dietary fructose intake is significantly correlated with arm fat in both women and men, and visceral fat in men in the Newfoundland free-living population. The correlations are sex- and menopause-status dependent.
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http://dx.doi.org/10.1016/j.nut.2021.111434DOI Listing
July 2021

Case Report: Rare Pulmonary Sclerosing Pneumocytoma: Large, Multiple, Metastatic, and Fatal.

Front Med (Lausanne) 2021 16;8:661032. Epub 2021 Aug 16.

Department of Thoracic Surgery, Henan Provincial Chest Hospital, Zhengzhou, China.

Pulmonary sclerosing pneumocytoma (PSP) is a rare benign or low-grade malignant tumor, but it has the potential to present with multiple lesions, lymph node metastasis, extra-pulmonary metastasis, recurrence and even cause death. Herein, a case of PSP that was huge, presented with multiple lesions and had lymph node as well as extrapulmonary metastases (liver, abdominal cavity, bones) is reported for the first time. This patient was also the first one to die of respiratory and circulatory failure caused by the PSP tumor and its metastases which compressed the mediastinal tissue.
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http://dx.doi.org/10.3389/fmed.2021.661032DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8415542PMC
August 2021

Qing-Fei-Pai-Du decoction and wogonoside exert anti-inflammatory action through down-regulating USP14 to promote the degradation of activating transcription factor 2.

FASEB J 2021 09;35(9):e21870

Suzhou Institute of Systems Medicine, Chinese Academy of Medical Science and Peking Union Medical College, Suzhou, China.

COVID-19 is often characterized by dysregulated inflammatory and immune responses. It has been shown that the Traditional Chinese Medicine formulation Qing-Fei-Pai-Du decoction (QFPDD) is effective in the treatment of the disease, especially for patients in the early stage. Our network pharmacology analyses indicated that many inflammation and immune-related molecules were the targets of the active components of QFPDD, which propelled us to examine the effects of the decoction on inflammation. We found in the present study that QFPDD effectively alleviated dextran sulfate sodium-induced intestinal inflammation in mice. It inhibited the production of pro-inflammatory cytokines IL-6 and TNFα, and promoted the expression of anti-inflammatory cytokine IL-10 by macrophagic cells. Further investigations found that QFPDD and one of its active components wogonoside markedly reduced LPS-stimulated phosphorylation of transcription factor ATF2, an important regulator of multiple cytokines expression. Our data revealed that both QFPDD and wogonoside decreased the half-life of ATF2 and promoted its proteasomal degradation. Of note, QFPDD and wogonoside down-regulated deubiquitinating enzyme USP14 along with inducing ATF2 degradation. Inhibition of USP14 with the small molecular inhibitor IU1 also led to the decrease of ATF2 in the cells, indicating that QFPDD and wogonoside may act through regulating USP14 to promote ATF2 degradation. To further assess the importance of ubiquitination in regulating ATF2, we generated mice that were intestinal-specific KLHL5 deficiency, a CUL3-interacting protein participating in substrate recognition of E3s. In these mice, QFPDD mitigated inflammatory reaction in the spleen, but not intestinal inflammation, suggesting CUL3-KLHL5 may function as an E3 for ATF2 degradation.
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http://dx.doi.org/10.1096/fj.202100370RRDOI Listing
September 2021

Emerging protein degradation strategies: expanding the scope to extracellular and membrane proteins.

Theranostics 2021 13;11(17):8337-8349. Epub 2021 Jul 13.

Institute of Interdisciplinary Integrative Medicine Research and Shuguang Hospital, Shanghai University of Traditional Chinese Medicine, Shanghai, 201203, China.

Classic small molecule inhibitors that directly target pathogenic proteins typically rely on the accessible binding sites to achieve prolonged occupancy and influence protein functions. The emerging targeted protein degradation (TPD) strategies exemplified by PROteolysis TArgeting Chimeras (PROTACs) are revolutionizing conventional drug discovery modality to target proteins of interest (POIs) that were categorized as "undruggable" before, however, these strategies are limited within intracellular POIs. The novel new degrader technologies such as LYsosome-TArgeting Chimaeras (LYTACs) and Antibody-based PROTACs (AbTACs) have been successfully developed to expand the scope of TPD to extracellular and membrane proteins, fulfilling huge unmet medical needs. Here, we systematically review the currently viable protein degradation strategies, emphasize that LYTACs and AbTACs turn a new avenue for the development of TPD, and highlight the potential challenges and directions in this vibrant field.
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http://dx.doi.org/10.7150/thno.62686DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8344007PMC
July 2021

Calcium phosphate bone cement with enhanced physicochemical properties via in situ formation of an interpenetrating network.

J Mater Chem B 2021 Sep 4;9(34):6802-6810. Epub 2021 Aug 4.

College of Chemistry, Chemical Engineering and Materials Science, Department of Orthopaedic Surgery, Orthopaedic Institute, The First Affiliated Hospital, Soochow University, Suzhou, Jiangsu, China.

Calcium phosphate cement (CPC), which exhibits excellent biocompatibility and bioactivity, is a well-established material for the repair of bone defects. However, its disadvantages such as poor washout resistance and low mechanical strength limit its clinical applications. In this study, CPC with enhanced washout resistance and mechanical properties has been developed by the in situ crosslinking of glycidyl methacrylate modified γ-polyglutamic acid (m-PGA) within the cement matrix, forming an interpenetrating network. Compared with unmodified CPC, the final setting time of the composite cements was shortened and its washout resistance was significantly improved. In addition, the composite cements showed enhanced mechanical strength and degradation properties. An in vitro study demonstrated that the composite cements exhibited good biocompatibility. The in vivo results showed that the composite cements promoted bone formation. These results suggest that the biocompatible, injectable α-tricalcium phosphate (α-TCP)/m-PGA cements may have the potential to be used as bone filling materials for future clinical applications.
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http://dx.doi.org/10.1039/d1tb00867fDOI Listing
September 2021

Language and Communication Impact of Hypertension: A Qualitative Study.

Int J Hypertens 2021 8;2021:9931873. Epub 2021 Jul 8.

Department of Epidemiology and Biostatistics, College of Public Health, Zhengzhou University, Zhengzhou, Henan 450001, China.

. Hypertension (HTN) is the second main source of outpatient morbidity in Ghana, and the understanding of a disease is necessary for its prevention and management. Language and communication are contributing factors to HTN in Ghana. No studies have been conducted to assess knowledge/awareness of HTN (in the context of its understanding) among students in Ghana. Following a local name for HTN in Ghana, researchers interviewed students through a focus group to assess their understanding/perception (meaning, cause, and prevention) of the disease. Available literature has concerned itself with clients' knowledge of their condition (diagnosis) rather than their comprehension of the true nature of what HTN is. The objective of this study is to assess the knowledge/awareness of HTN in the context of its understanding of the meaning, perception, causes, and prevention of hypertension among students of Ghana's Senior High School (Second Cycle). Semistructured interviews with the use of the theme lists were employed. Focus group conversations and interviews were held in the local Akan (Twi) language, which was later translated, interpreted, and analyzed. Overall, 25 second-cycle students participated. 60% were between 15 and 17 years, 24% were ≥18 years, and 16% were <15 years of age. Males were 44% and females were 56%. Students gave diverse perceptions of their knowledge of HTN. The local language's translation of HTN has influenced and affected its meaning/understanding among some, thus affecting their perception of causes and prevention.
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http://dx.doi.org/10.1155/2021/9931873DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8282399PMC
July 2021

Fabrication of Functionally Graded Diamond/Al Composites by Liquid-Solid Separation Technology.

Materials (Basel) 2021 Jun 10;14(12). Epub 2021 Jun 10.

National Center for Materials Service Safety, University of Science and Technology Beijing, Beijing 100083, China.

The electronic packaging shell, the necessary material for hermetic packaging of large microelectronic device chips, is made by mechanical processing of a uniform block. However, the property variety requirements at different positions of the shell due to the performance have not been solved. An independently developed liquid-solid separation technology is applied to fabricate the diamond/Al composites with a graded distribution of diamond particles. The diamond content decreases along a gradient from the bottom of the shell, which houses the chips, to the top of the shell wall, which is welded with the cover plate. The bottom of the shell has a thermal conductivity (TC) of 169 W/mK, coefficient of thermal expansion (CTE) of 11.0 × 10/K, bending strength of 88 MPa, and diamond content of 48 vol.%. The top of the shell has a TC of 108 W/mK, CTE of 19.3 × 10/K, bending strength of 175 MPa, and diamond content of 15 vol.%, which solves the special requirements of different parts of the shell and helps to improve the thermal stability of packaging components. Moreover, the interfacial characteristics are also investigated. This work provides a promising approach for the preparation of packaging shells by near-net shape forming.
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http://dx.doi.org/10.3390/ma14123205DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8230396PMC
June 2021

Alpha neural oscillation of females in the luteal phase is sensitive to high risk during sequential risk decisions.

Behav Brain Res 2021 Sep 25;413:113427. Epub 2021 Jun 25.

School of Psychology and Cognitive Science, East China Normal University, China. Electronic address:

Risk taking is a non-negligible component in decision-making. Previous behavioral studies have demonstrated that female's risk decisions vary along with their menstrual cycle phases. However, little is known how females' neural processes of risk stimuli change in different menstrual cycle phases. To address this, the present study adopted a sequential economic risk-taking task and EEG technique. Thirty eligible female participants completed the task twice with EEG recordings, once in the late follicular phase and once in the midluteal phase, separately. We found that the risk stimuli induced an evident frontal N1 in the early time window of 90-180 ms. The results on N1 showed no significant difference between two phases for low- and medium-risk stimuli; whereas, for high-risk stimuli, females in midluteal phase exhibited a significantly larger N1 than that in late follicular phase. Further, by exploiting time-frequency transformation, we observed a pronounced low alpha (∼8 Hz) activity in frontal area from stimuli onset to 175 ms. The results indicated that, only for high-risk stimuli, the alpha power was significantly greater in midluteal phase than that in late follicular phase. Our neural results demonstrated a stronger early neural response to high-risk stimuli of females in midluteal phase, which suggests women are more sensitive to high risk in midluteal than in late follicular phase.
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http://dx.doi.org/10.1016/j.bbr.2021.113427DOI Listing
September 2021

Roles of Melatonin in Goat Hair Follicle Stem Cell Proliferation and Pluripotency Through Regulating the Wnt Signaling Pathway.

Front Cell Dev Biol 2021 4;9:686805. Epub 2021 Jun 4.

College of Animal Science and Technology, Northwest A&F University, Yangling, China.

Emerging studies show that melatonin promotes cashmere development through hypodermic implantation. However, the impact and underlying mechanisms are currently unknown. study has previously demonstrated that melatonin induces cashmere growth by regulating the proliferation of goat secondary hair follicle stem cells (gsHFSCs), but there is limited information concerning the effects of melatonin on cell pluripotency. It is also known that Wnt signaling may actively participate in regulating cell proliferation and stem cell pluripotency. Therefore, in the current investigation, goat hair follicle stem cells were exposed to multiple concentrations of melatonin and different culture times to reveal the relationship between melatonin and the activation of Wnt signaling. A proportionally high Catenin beta-1 (CTNNB1) response was induced by 500 ng/L of melatonin, but it was then suppressed with the dosages over 1,000 ng/L. Greater amounts of CTNNB1 entered the cell nuclei by extending the exposure time to 72 h, which activated transcription factor 4/lymphoid enhancer-binding factor 1 and promoted the expression of the proliferation-related genes , , and . Moreover, nuclear receptor ROR-alpha (RORα) and bone morphogenetic protein 4 (BMP4) were employed to analyze the underlying mechanism. RORα presented a sluggish concentration/time-dependent rise, but BMP4 was increased dramatically by melatonin exposure, which revealed that melatonin might participate in regulating the pluripotency of hair follicle stem cells. Interestingly, NOGGIN, which is a BMP antagonist and highly relevant to cell stemness, was also stimulated by melatonin. These findings demonstrated that melatonin exposure and/or NOGGIN overexpression in hair follicle stem cells might promote the expression of pluripotency markers Homeobox protein NANOG, Organic cation/carnitine transporter 4, and Hematopoietic progenitor cell antigen CD34. Our findings here provided a comprehensive view of Wnt signaling in melatonin stimulated cells and melatonin mediated stemness of gsHFSCs by regulating NOGGIN, which demonstrates a regulatory mechanism of melatonin enhancement on the growth of cashmere.
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http://dx.doi.org/10.3389/fcell.2021.686805DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8212062PMC
June 2021

Catechol-driven self-assembly to fabricate highly ordered and SERS-active glycoadjuvant patterns.

J Mater Chem B 2021 06;9(25):5039-5042

Center for Soft Condensed Matter Physics and Interdisciplinary Research & Jiangsu Key Laboratory of Thin Films, School of Physical Science and Technology, Soochow University, Suzhou, 215006, P. R. China. and State and Local Joint Engineering Laboratory for Novel Functional Polymeric Materials, Soochow University, Suzhou 215123, China.

Detection of vaccine (adjuvant and antigen) is crucial for the fundamental studies of immunotherapy. In this work, the catechol-containing glycopolymer obtained by sunlight-induced RAFT polymerization was first designed to generate [email protected] Then, a simple and general self-assembled technique, catechol-driven self-assembly (CDSA), was developed to fabricate AuNP-based glycoadjuvant patterns, regardless of the size, shape and synthetic method of AuNPs. More importantly, highly ordered glycoadjuvant patterns could be easily formed by catechol-driven self-assembly under confinement, which exhibit a higher SERS signal amplification ability for the detection of carbohydrates (glycoadjuvant).
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http://dx.doi.org/10.1039/d1tb00833aDOI Listing
June 2021

Design, synthesis, and biological evaluation of novel sulindac derivatives as partial agonists of PPARγ with potential anti-diabetic efficacy.

Eur J Med Chem 2021 Oct 24;222:113542. Epub 2021 May 24.

School of Pharmaceutical Sciences, Fujian Provincial Key Laboratory of Innovative Drug Target Research, Xiamen University, Xiamen, Fujian, 361102, China; High Throughput Drug Screening Platform, Xiamen University, Xiamen, Fujian, 361102, China. Electronic address:

Peroxisome proliferator-activated receptor gamma (PPARγ) is a valuable drug target for diabetic treatment and ligands of PPARγ have shown potent anti-diabetic efficacy. However, to overcome the severe side effects of current PPARγ-targeted drugs, novel PPARγ ligands need to be developed. Sulindac, an identified ligand of PPARγ, is widely used in clinic as a non-steroidal anti-inflammatory drug. To explore its potential application for diabetes, we designed and synthesized a series of sulindac derivatives to investigate their structure-activity relationship as PPARγ ligand and potential anti-diabetic effect. We found that meta-substitution in sulindac's benzylidene moiety was beneficial to PPARγ binding and transactivation. Z rather than E configuration of the benzylidene double bond endowed derivatives with the selectivity of PPARγ activation. The indene fluorine is essential for binding and regulating PPARγ. Compared with rosiglitazone, compound 6b with benzyloxyl meta-substitution and Z benzylidene double bond weakly induced adipogenesis and PPARγ-targeted gene expression. However, 6b potently improved glucose tolerance in a diabetic mice model. Unlike rosiglitazone, 6b was devoid of apparent toxicity to osteoblastic formation. Thus, we provided some useful guidelines for PPARγ-based optimization of sulindac and an anti-diabetic lead compound with less side effects.
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http://dx.doi.org/10.1016/j.ejmech.2021.113542DOI Listing
October 2021

Low vision rehabilitation in improving the quality of life for patients with impaired vision: A systematic review and meta-analysis of 52 randomized clinical trials.

Medicine (Baltimore) 2021 05;100(19):e25736

Department of Rehabilitation and Treatment, Wangjing Hospital, Chinese Academy of Traditional Chinese Medicine.

Background Aim: Low vision rehabilitation optimizes the use of residual vision after severe vision loss, but also teaches skills to improve visual functioning in daily life. These skills promote independence and active participation in society. This meta-analysis was designed to evaluate the efficacy of low vision rehabilitation in improving the quality of life (QoL) in visually impaired adults.

Methods: We searched the Cochrane Library, PubMed, EMBASE, and Web of Science up to January 1, 2020. Randomized controlled trials (RCTs) that compared rehabilitation interventions with active or inactive controls were included. The standardized mean difference (SMD) with a 95% confidence interval (CI) was estimated to compare outcomes. Two reviewers extracted data and assessed trial quality independently. All statistical analyses were performed using the standard statistical procedures of RevMan 5.2.

Results: A total of 52 RCTs with 6,239 participants were included in this meta-analysis. Compared to inactive comparators including waiting list or no care, low vision rehabilitation improved vision-related QoL, visual functioning (QoL: psychological aspect), and self-efficacy or self-esteem (QoL: psychological aspect), with pooled SMDs of -0.61 (95% CI -0.95 to -0.26; P = .0006), -1.14 (95% CI -1.69 to -0.59; P < .0001), and -0.84 (95% CI -1.47 to -0.22; P < .0001), respectively. Compared to active comparators, low vision rehabilitation improved vision-related QoL (SMD -0.26; 95% CI -0.46 to -0.06; P = .01) and activities of daily living (QoL: physical aspect) (SMD -0.39; 95% CI -0.67 to -0.12 P < .0001). However, no significant difference in health-related QoL and adaptation to vision loss (QoL: psychological aspect) was found between low vision rehabilitation and inactive comparators.

Conclusions: This meta-analysis indicated that low vision rehabilitation interventions, particularly psychological therapies and methods of enhancing vision, may improve vision-related QoL and visual functioning in people with sight loss compared to usual care. Further studies should explore longer maintenance effects and the costs of several types of low vision rehabilitation. Studies characterizing the mechanisms of rehabilitation interventions in different settings, including low-income countries, are also required.
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http://dx.doi.org/10.1097/MD.0000000000025736DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8133190PMC
May 2021

Pneumonia, pleurisy, mediastinitis, and mediastinal cyst infection secondary to endobronchial ultrasound-guided transbronchial needle aspiration: A case report.

Medicine (Baltimore) 2021 May;100(20):e25973

Department of Pulmonary and Critical Care Medicine, Hunan Provincial People's Hospital, The First Affiliated Hospital of Hunan Normal University, Changsha.

Introduction: Endobronchial ultrasound-guided transbronchial needle aspiration (EBUS-TBNA) is less commonly used in nonmalignant diseases. In particular, its application in mediastinal cystic lesions has been reported less frequently. EBUS-TBNA is a reassuringly safe procedure with an overall complication rate less than 2%, and serious adverse event rate of 0.14% to 0.16%. The most common complications are infections (mediastinal cyst infection most seen).

Patient Concerns: A 28-year-old male presented to the hospital with mediastinal cyst that was incidentally discovered by computed tomography. There was no past history of the patient reviewed.

Diagnosis: The cyst was identified as a round, anechoic structure by EBUS and serous fluid was aspirated. The carcino-embryonic antigen, mycobacterium tuberculosis DNA and cultures in the fluid were negative. Cytology analysis showed lots of lymphocytes and no malignant cells. The diagnosis of lymphangioma was confirmed based on the computed tomography and EBUS presentation, the nature of the aspirated fluid and the large number of mature lymphocytes within the cystic fluid.

Interventions: Twenty-six hours after EBUS-TBNA, the patient complained of a fever with the highest temperature of 39°C, accompanied by a right-side chest pain, no other symptoms of were reported. The following examinations confirmed the diagnosis of pneumonia, pleurisy, mediastinitis and mediastinal cyst infection, while cultures from cyst and right pleural effusion were both negative. The patient was treated with Teicoplanin+Imipenem/cilastatin, and ultrasound guided transcutaneous catheterization drainage of mediastinal cyst and pleural effusion were performed.

Outcomes: Seven days after the treatments, the patient's symptoms resolved, the complete blood count, C-reactive protein, erythrocyte sedimentation rate were lowered. The size of the cyst was slightly reduced on 17 June compared to that before EBUS-TBNA. Although the surgical resection of the cyst was recommended, the patient declined. After extracted the two drainage tubes, the patient was discharged on June 22. The patient was followed up by telephone 6 months after discharge and he remained asymptomatic.

Conclusions: EBUS-TBNA is a useful diagnostic and therapeutic tool for the management of mediastinal cysts. However, considering the possibility of serious complications, the clinical procedure should be carried out scrupulously with appropriate patient selection and strict aseptic principles.
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http://dx.doi.org/10.1097/MD.0000000000025973DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8137064PMC
May 2021

Absolute protein assay for the simultaneous quantification of two epoxide hydrolases in rats by mass spectrometry-based targeted proteomics.

J Sep Sci 2021 Jul 12;44(14):2754-2763. Epub 2021 Jun 12.

Department of Clinical Pharmacology, Affiliated Hospital of Nanjing University of Chinese Medicine, Jiangsu Provincial Hospital of Traditional Chinese Medicine, Nanjing, P. R. China.

Epoxide hydrolases catalyze the hydrolysis of both exogenous and endogenous epoxides to the corresponding vicinal diols by adding water. Microsomal and soluble epoxide hydrolase are two main mammalian enzymes that have been intensely characterized. The purpose of this investigation was to develop and validate a proteomics assay allowing the simultaneous quantification of microsomal and soluble epoxide hydrolase in rats. Protein quantification was realized through targeted proteomics using liquid chromatography with tandem mass spectrometry for the determination of trypsin-specific surrogate peptides after digestion. Stable isotope-labeled peptides were used as the internal standards. The chromatography of the surrogate peptides was performed on an Agilent SB C column (100 mm × 4.6 mm, 1.8 µm) with gradient elution. Acetonitrile containing 0.1% formic acid and 0.1% formic acid aqueous solution were used as mobile phases. A multiple reaction monitoring method in a positive ionization mode was used for the simultaneous detection of the peptides. The method was validated concerning the specificity, linearity, within-day and between-day accuracy and precision, matrix effect, stability, and digestion efficiency. The developed assay was successfully used to quantify the protein levels of microsomal and soluble epoxide hydrolase in rat liver, kidney, and heart S9 samples.
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http://dx.doi.org/10.1002/jssc.202100066DOI Listing
July 2021

Development of Piezoelectric Energy Harvester System through Optimizing Multiple Structural Parameters.

Sensors (Basel) 2021 Apr 20;21(8). Epub 2021 Apr 20.

Joint USTB Virginia Tech Lab Multifunctional Materials, USTB, Department Civil & Environmental Engineering, Virginia Tech, Blacksburg, VA 24061, USA.

Road power generation technology is of significance for constructing smart roads. With a high electromechanical conversion rate and high bearing capacity, the stack piezoelectric transducer is one of the most used structures in road energy harvesting to convert mechanical energy into electrical energy. To further improve the energy generation efficiency of this type of piezoelectric energy harvester (PEH), this study theoretically and experimentally investigated the influences of connection mode, number of stack layers, ratio of height to cross-sectional area and number of units on the power generation performance. Two types of PEHs were designed and verified using a laboratory accelerated pavement testing system. The findings of this study can guide the structural optimization of PEHs to meet different purposes of sensing or energy harvesting.
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http://dx.doi.org/10.3390/s21082876DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8073095PMC
April 2021

Genotoxicity of chloroacetamide herbicides and their metabolites and .

Int J Mol Med 2021 Jun 28;47(6). Epub 2021 Apr 28.

School of Public Health, Hebei Medical University, Shijiazhuang, Hebei 050017, P.R. China.

The toxicity of chloroacetamide herbicide in embryo development remains unclear. Acetochlor (AC) is a chloroacetamide that metabolizes into 2‑ethyl‑6‑methyl-2-chloroacetanilide (CMEPA) and 6‑ethyl‑o‑toluidine (MEA). The present study determined the potential effect of AC and its metabolites on embryo development. Both HepG2 cells and zebrafish embryos were exposed to AC, CMEPA and MEA in the presence or absence of co‑treatment with anti‑reactive oxygen species (ROS) reagent N‑acetylcysteine. The generation of ROS, levels of superoxide dismutase (SOD) and glutathione (GSH) in HepG2 cells and lactate dehydrogenase (LDH) leakage from HepG2 cells were investigated. The effects of AC, CMEPA and MEA on DNA breakage, MAPK/ERK pathway activity, viability and apoptosis of HepG2 cells were examined by comet assay, western blotting, MTT assay and flow cytometry, respectively. Levels of LDH, SOD and GSH in zebrafish embryos exposed to AC, CMEPA and MEA were measured. The hatching and survival rates of zebrafish embryos exposed to AC, CMEPA and MEA, were determined, and apoptosis of hatched fish was investigated using acridine orange staining. The present data showed AC, CMEPA and MEA induced generation of ROS and decreased levels of SOD and GSH in HepG2 cells, which in turn promoted DNA breakage and LDH leakage from cells, ultimately inhibiting cell viability and inducing apoptosis, as well as phosphorylation of JNK and P38. However, co‑treatment with N‑acetylcysteine alleviated the pro‑apoptosis effect of AC and its metabolites. Moreover, exposure to AC, CMEPA and MEA lead to toxicity of zebrafish embryos with decreased SOD and GSH and increased LDH levels and cell apoptosis, ultimately decreasing the hatching and survival rates of zebrafish, all of which was attenuated by treatment with N‑acetylcysteine. Therefore, AC and its metabolites (CMEPA and MEA) showed cytotoxicity and embryo development toxicity.
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http://dx.doi.org/10.3892/ijmm.2021.4936DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8054635PMC
June 2021

Comprehensive bioinformatics analysis reveals kinase activity profiling associated with heart failure.

J Cell Biochem 2021 Apr 25. Epub 2021 Apr 25.

School of Pharmacy, Second Military Medical University, Shanghai, China.

Heart failure is a complex clinical syndrome originating from cardiac injury, which leads to considerable morbidity and mortality. Among the dynamic molecular adaptations occurring in heart failure development, aggravation of the disease is often attributed to global or local abnormality of the kinase. Therefore, the overall monitoring of kinase activity is indispensable. In this study, a bioinformatics analysis method was developed to conduct deep mining of transcriptome and phosphoproteome in failing heart tissue. A total of 982 differentially expressed genes and 9781 phosphorylation sites on 3252 proteins were identified. Via upstream regulator relations and kinase-substrate relations, a dendrogram of kinases can be constructed to monitor its abnormality. The results show that, on the dendrogram, the distribution of kinases demonstrated complex kinase activity changes and certain rules that occur during heart failure. Finally, we also identified the hub kinases in heart failure and verified the expression of these kinases by reverse-transcription polymerase chain reaction and Western blot analysis. In conclusion, for the first time, we have systematically analyzed the differences in kinases during heart failure and provided an unprecedented breadth of multi-omics data. These results can bring about a sufficient data foundation and novel research perspectives.
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http://dx.doi.org/10.1002/jcb.29935DOI Listing
April 2021

A Comprehensive Investigation to Reveal the Relationship Between Plasmacytoid Dendritic Cells and Breast Cancer by Multiomics Data Analysis.

Front Cell Dev Biol 2021 1;9:640476. Epub 2021 Apr 1.

School of Pharmacy, Second Military Medical University, Shanghai, China.

Plasmacytoid dendritic cells (pDC) are an essential immune microenvironment component. They have been reported for crucial roles in linking the adaptive and immune systems. However, the prognostic role of the pDC in breast cancer (BRCA) was controversial. In this work, we collected large sample cohorts and did a comprehensive investigation to reveal the relationship between pDC and BRCA by multiomics data analysis. Elevated pDC levels were correlated with prolonged survival outcomes in BRCA patients. The distinct mutation landscape and lower burden of somatic copy number alterations (SCNA) and lower intratumoral heterogeneity were observed in the high pDC abundance group. Additionally, a more sensitive immune response and chemotherapies response were observed in the high pDC group, which implicates that patients with high pDC abundance can be benefited from the combination of chemotherapy and immunotherapy. In conclusion, the correlation between pDC abundance and BRCA patients' overall survival (OS) was found to be positive. We identified the molecular profiles of BRCA patients with pDC abundance. Our findings may be beneficial in aiding in the development of immunotherapy and elucidating on the precision treatment for BRCA.
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http://dx.doi.org/10.3389/fcell.2021.640476DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8047150PMC
April 2021

Moderate mechanical stimulation rescues degenerative annulus fibrosus by suppressing caveolin-1 mediated pro-inflammatory signaling pathway.

Int J Biol Sci 2021 3;17(5):1395-1412. Epub 2021 Apr 3.

Department of Orthopaedic Surgery, Orthopaedic Institute, The First Affiliated Hospital, Soochow University, Suzhou, Jiangsu, China.

Mechanical loading can induce or antagonize the extracellular matrix (ECM) synthesis, proliferation, migration, and inflammatory responses of annulus fibrosus cells (AFCs), depending on the loading mode and level. Caveolin-1 (Cav1), the core protein of caveolae, plays an important role in cellular mechanotransduction and inflammatory responses. In the present study, we presented that AFCs demonstrated different behaviors when subjected to cyclic tensile strain (CTS) for 24 h at a magnitude of 0%, 2%, 5% and 12%, respectively. It was found that 5% CTS had positive effects on cell proliferation, migration and anabolism, while 12% CTS had the opposite effects. Besides, cells exposed to interleukin-1β stimulus exhibited an increase expression in inflammatory genes, and the expression of these genes decreased after exposure to moderate mechanical loading with 5% CTS. In addition, 5% CTS decreased the level of Cav1 and integrin β1 and exhibited anti-inflammatory effects. Moreover, the expression of integrin β1 and p-p65 increased in AFCs transfected with Cav1 plasmids. results revealed that moderate mechanical stimulation could recover the water content and morphology of the discs. In conclusion, moderate mechanical stimulation restrained Cav1-mediated signaling pathway and exhibited anti-inflammatory effects on AFCs. Together with results, this study expounds the underlying molecular mechanisms on the effect of moderate mechanical stimulation on intervertebral discs (IVDs) and may provide a new therapeutic strategy for the treatment of IVD degeneration.
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http://dx.doi.org/10.7150/ijbs.57774DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8040478PMC
April 2021

Giant Ferroelectric Resistance Switching Controlled by a Modulatory Terminal for Low-Power Neuromorphic In-Memory Computing.

Adv Mater 2021 May 15;33(21):e2008709. Epub 2021 Apr 15.

Physical Sciences and Engineering Division, King Abdullah University of Science and Technology, Thuwal, 23955-6900, Saudi Arabia.

Ferroelectrics have been demonstrated as excellent building blocks for high-performance nonvolatile memories, including memristors, which play critical roles in the hardware implementation of artificial synapses and in-memory computing. Here, it is reported that the emerging van der Waals ferroelectric α-In Se can be used to successfully implement heterosynaptic plasticity (a fundamental but rarely emulated synaptic form) and achieve a resistance-switching ratio of heterosynaptic memristors above 10 , which is two orders of magnitude larger than that in other similar devices. The polarization change of ferroelectric α-In Se channel is responsible for the resistance switching at various paired terminals. The third terminal of α-In Se memristors exhibits nonvolatile control over channel current at a picoampere level, endowing the devices with picojoule read-energy consumption to emulate the associative heterosynaptic learning. The simulation proves that both supervised and unsupervised learning manners can be implemented in α-In Se neutral networks with high image recognition accuracy. Moreover, these heterosynaptic devices can naturally realize Boolean logic without an additional circuit component. The results suggest that van der Waals ferroelectrics hold great potential for applications in complex, energy-efficient, brain-inspired computing systems and logic-in-memory computers.
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http://dx.doi.org/10.1002/adma.202008709DOI Listing
May 2021

Neuromedin U uses Gαi2 and Gαo to suppress glucose-stimulated Ca2+ signaling and insulin secretion in pancreatic β cells.

PLoS One 2021 15;16(4):e0250232. Epub 2021 Apr 15.

Division of Neurology, Respirology, Endocrinology and Metabolism, Department of Internal Medicine, Faculty of Medicine, University of Miyazaki, Miyazaki, Japan.

Neuromedin U (NMU), a highly conserved peptide in mammals, is involved in a wide variety of physiological processes, including impairment of pancreatic β-cell function via induction of mitochondrial dysfunction and endoplasmic reticulum (ER) stress, ultimately suppressing insulin secretion. NMU has two receptors, NMU receptor 1 (NMUR1) and NMUR2, both of which are G-protein-coupled receptors (GPCRs). Only NMUR1 is expressed in mouse islets and β cell-derived MIN6-K8 cells. The molecular mechanisms underlying the insulinostatic action mediated by NMUR1 in β cells have yet to be elucidated. In this study, we explored the molecular mechanism driving impairment of insulin secretion in β cells by the NMU-NMUR1 axis. Pretreatment with the Gαi/o inhibitor Bordetella pertussis toxin (PTX), but not the Gαq inhibitor YM254890, abolished NMU-induced suppression of glucose-stimulated insulin secretion and calcium response in β cells. Knockdown of Gαi2 and Gαo in β cells counteracted NMU-induced suppression of insulin secretion and gene alterations related to mitochondrial fusion (Mfn1, Mfn2), fission (Fis1, Drp1), mitophagy (Pink1, Park2), mitochondrial dynamics (Pgc-1α, Nrf1, and Tfam), ER stress (Chop, Atp2a3, Ryr2, and Itpr2), intracellular ATP level, and mitochondrial membrane potential. NMU decreased forskolin-stimulated intracellular cAMP in both mouse and human islets. We concluded that NMUR1 coupled to PTX-sensitive Gαi2 and Gαo proteins in β cells reduced intracellular Ca2+ influx and cAMP level, thereby causing β-cell dysfunction and impairment. These results highlight a novel signaling mechanism of NMU and provide valuable insights into the further investigation of NMU functions in β-cell biology.
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http://journals.plos.org/plosone/article?id=10.1371/journal.pone.0250232PLOS
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8049253PMC
September 2021

Stapled Wasp Venom-Derived Oncolytic Peptides with Side Chains Induce Rapid Membrane Lysis and Prolonged Immune Responses in Melanoma.

J Med Chem 2021 05 12;64(9):5802-5815. Epub 2021 Apr 12.

Institute of Interdisciplinary Integrative Medicine Research, Shanghai University of Traditional Chinese Medicine, Shanghai 201203, China.

Peptide stapling chemistry represents an attractive strategy to promote the clinical translation of protein epitope mimetics, but its use has not been applied to natural cytotoxic peptides (NCPs) to produce new oncolytic peptides. Based on a wasp venom peptide, a series of stapled anoplin peptides (StAnos) were prepared. The optimized stapled Ano-3/3s were shown to be protease-resistant and exerted superior tumor cell-selective cytotoxicity by rapid membrane disruption. In addition, Ano-3/3s induced tumor ablation in mice through the direct oncolytic effect and subsequent stimulation of immunogenic cell death. This synergistic oncolytic-immunotherapy effect is more remarkable on melanoma than on triple-negative breast cancer . The efficacies exerted by Ano-3/3s on melanoma were further characterized by CD8+ T cell infiltration, and the addition of anti-CD8 antibodies diminished the long-term antitumor effects. In summary, these results support stapled peptide chemistry as an advantageous method to enhance the NCP potency for oncolytic therapy.
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http://dx.doi.org/10.1021/acs.jmedchem.0c02237DOI Listing
May 2021

Upregulation of mmu_circ_0001066 attenuates the inhibitory effect of bisphosphonates on osteoclastogenesis.

Oral Dis 2021 Apr 9. Epub 2021 Apr 9.

Department of Oral and Maxillofacial Surgery, The Affiliated Hospital of Qingdao University, Qingdao, China.

Objective: Medication-related osteonecrosis of the jaw (MRONJ) is the main adverse side effect of bisphosphonates (BPs), mainly owing to the inhibitory effect of BPs on osteoclastogenesis. CircRNAs were identified to be an important factor in regulating cellular processes. The aim of this study was to explore the effect of mmu_circ_0001066 on BP-inhibited osteoclastogenesis.

Materials And Methods: The expression of MRONJ-related miRNA in RANKL-induced RAW264.7 cells treated with BP was analyzed using qRT-PCR analysis. Bioinformatics techniques were applied to screen potential circRNAs. Tartrate-resistant acid phosphatase (TRAP) staining and bone resorption assays were used to examine the effect of mmu_circ_0001066 on osteoclastogenesis. Bioinformatics analysis, luciferase reporter assays, and Western blotting assays were performed to investigate the underlying mechanism.

Results: Four MRONJ-related miRNAs were upregulated in BP-treated RAW264.7 cells, and the expression of mmu_circ_0001066 was negatively correlated with those of MRONJ-related miRNAs. Furthermore, the upregulation of mmu_circ_0001066 partially attenuated the inhibitory effect of BP on osteoclastogenesis in RAW264.7 cells. Mechanistically, upregulated miR-16 suppressed osteoclastogenesis and miR-16 inhibitor increased osteoclastogenesis. Furthermore, we have identified that miR-16 is a downstream effector of mmu_circ_0001066.

Conclusion: Our results suggest that mmu_circ_0001066 played an important role in the BP-mediated suppression of osteoclastogenesis, which lays a foundation for identifying mmu_circ_0001066 as a potential biomarker for MRONJ.
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http://dx.doi.org/10.1111/odi.13871DOI Listing
April 2021
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