Publications by authors named "Zhiwei Wu"

137 Publications

Characterization of the interactions of ADAMTS13 CUB1 domain to WT- and GOF-Spacer domain by molecular dynamics simulation.

J Mol Graph Model 2021 Sep 6;109:108029. Epub 2021 Sep 6.

Research Department of Medical Sciences, Guangdong Provincial People's Hospital, Guangdong Academy of Medical Sciences, Guangzhou, 510080, China. Electronic address:

Metalloprotease ADAMTS13 specifically cleaves VWF (von Willebrand Factor) to prevent excessive platelet aggregation and thrombus formation at the sites of vascular injury. To avoid non-specific cleavage, ADAMTS13 has the auto-inhibition effect in which the Spacer domain in N-terminal interacts with the CUB1 domain in C-terminal, resulting in decreased proteolytic activity. Previous studies reported that exosite-3 in the Spacer domain was a key binding site in the Spacer-CUB1 interaction. When exosite-3 was mutated (R660K/F592Y/R568K/Y661F/Y665F, GOF), the auto-inhibition of ADAMTS13 was disrupted and the enzymatic activity was markedly increased. However, the characteristics of the Spacer-CUB1 interaction is not fully understood. Here, we constructed the model of Spacer-CUB1 complex by homologous modeling and molecular docking to characterize the Spacer-CUB1 binding and predict key amino acid residues via molecular dynamics simulation. Our data showed that G607-S610 was a non-reported potential binding site in the Spacer domain; GOF mutation attenuated the formation of hydrogen bond between exosite-3 and the CUB1 domain; Residues E1231, R1251, L1258, D1259 and T1261 in the CUB1 domain might play an important role in the Spacer-CUB1 interaction. Our study advances the understanding of the structural basis of the auto-inhibition of ADAMTS13 and provides information about the key residues in the binding interface.
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http://dx.doi.org/10.1016/j.jmgm.2021.108029DOI Listing
September 2021

Mechanical Properties and Heat Transfer Performance of Conically Corrugated Tube.

Materials (Basel) 2021 Aug 28;14(17). Epub 2021 Aug 28.

Shandong Meiling Chemical Equipment Co., Ltd., Zibo 255430, China.

Conically corrugated tube is a new type of high-efficiency heat exchange tube. In this paper, the mechanical and heat transfer properties of conically corrugated tubes formed by the cold rolling of smooth tubes are studied through experimental measurement and numerical simulation to lay the foundations for applying the tubes in heat exchangers. The results show that while conically corrugated tube has a lower axial elastic stiffness compared with smooth tube, conically corrugated tube has a higher yield strength and ultimate strength. Unlike smooth tubes, conically corrugated tubes develop three-dimensional stresses when an axial tensile load is applied to them. In addition, the heat transfer coefficient of conically corrugated tube is 15%, 17%, and 115% higher than that of spiral grooved tube, convergent divergent tube, and smooth tube, respectively. Finally, the correlation equations of the axial stress concentration factor, stiffness equivalent coefficient, Nusselt number, and flow resistance coefficient of conically corrugated tubes are obtained for engineering application.
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http://dx.doi.org/10.3390/ma14174902DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8432666PMC
August 2021

DEAD-Box Helicase DDX6 Facilitated RIG-I-Mediated Type-I Interferon Response to EV71 Infection.

Front Cell Infect Microbiol 2021 13;11:725392. Epub 2021 Aug 13.

Center for Public Health Research, Medical School, Nanjing University, Nanjing, China.

Previous studies have shown that DEAD (Glu-Asp-Ala-Glu)-box RNA helicases play important roles in viral infection, either as cytosolic sensors of pathogenic molecules or as essential host factors against viral infection. In the current study, we found that DDX6, an RNA helicase belonging to the DEAD-box family of helicase, exhibited anti-Enterovirus 71 activity through augmenting RIG-I-mediated type-I IFN response. Moreover, DDX6 binds viral RNA to form an RNA-protein complex to positively regulate the RIG-I-mediated interferon response; however, EV71 has evolved a strategy to antagonize the antiviral effect of DDX6 by proteolytic degradation of the molecule through its non-structural protein 2A, a virus-encoded protease.
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http://dx.doi.org/10.3389/fcimb.2021.725392DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8414799PMC
August 2021

The power of imaging to understand extracellular vesicle biology in vivo.

Nat Methods 2021 Sep 26;18(9):1013-1026. Epub 2021 Aug 26.

Université de Paris, Institute of Psychiatry and Neuroscience of Paris (IPNP), INSERM U1266, Paris, France.

Extracellular vesicles (EVs) are nano-sized lipid bilayer vesicles released by virtually every cell type. EVs have diverse biological activities, ranging from roles in development and homeostasis to cancer progression, which has spurred the development of EVs as disease biomarkers and drug nanovehicles. Owing to the small size of EVs, however, most studies have relied on isolation and biochemical analysis of bulk EVs separated from biofluids. Although informative, these approaches do not capture the dynamics of EV release, biodistribution, and other contributions to pathophysiology. Recent advances in live and high-resolution microscopy techniques, combined with innovative EV labeling strategies and reporter systems, provide new tools to study EVs in vivo in their physiological environment and at the single-vesicle level. Here we critically review the latest advances and challenges in EV imaging, and identify urgent, outstanding questions in our quest to unravel EV biology and therapeutic applications.
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http://dx.doi.org/10.1038/s41592-021-01206-3DOI Listing
September 2021

Applicability of TIVAP versus PICC in non-hematological malignancies patients: A meta-analysis and systematic review.

PLoS One 2021 3;16(8):e0255473. Epub 2021 Aug 3.

Department of Geratic Surgery, Xiangya Hospital of Central South University, Changsha, Hunan, China.

Background: Applicability of totally implantable venous access port (TIVAP) and peripherally inserted central venous catheter (PICC) in non-hematological malignancies patients remains controversial.

Methods: A systematic studies search in the public databases PubMed, EMBASE, Wan Fang, CNKI (China National Knowledge Infrastructure), the Cochrane Library and Google Scholar (updated to May 1, 2020) was performed to identify eligible researches. All statistical tests in this meta-analysis were performed using Stata 12.0 software (Stata Corp, College Station, TX). A P value less than 0.05 was considered statistically significant.

Results: Thirteen studies were included in this final meta-analysis. The pooled data showed that compared with PICC, TIVAP was associated with a higher first-puncture success rate (OR:2.028, 95%CI:1.25-3.289, P<0.05), a lower accidental removal rate (OR:0.447, 95%CI:0.225-0.889, P<0.05) and lower complication rates, including infection (OR:0.570, 95%CI: 0.383-0.850, P<0.05), occlusion (OR:0.172, 95%CI:0.092-0.324, P<0.05), malposition (OR:0.279, 95%CI:0.128-0.608, P<0.05), thrombosis (OR:0.191, 95%CI, 0.111-0.329, P<0.05), phlebitis (OR:0.102, 95%CI, 0.038-0.273, P<0.05), allergy (OR:0.155, 95%CI:0.035-0.696, P<0.05). However, no difference was found in catheter life span (P>0.05) and extravasation (P>0.05). Moreover, TIVAP is more expensive compared with PICC in six-month use (weighted mean difference:3.132, 95%CI:2.434-3.83, P<0.05), but is much similar in 12 months use (P>0.05).

Conclusion: For the patients with non-hematological malignancies, TIVAP was superior to PICC in the data related to placement and the incidence of complications. Meanwhile, TIVAP is more expensive compared with PICC in six-month use, but it is much similar in twelve-month use.
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http://journals.plos.org/plosone/article?id=10.1371/journal.pone.0255473PLOS
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8330915PMC
August 2021

The efficacy of Tuina with herbal ointment for patients with post-stroke depression: study protocol for a randomized controlled trial.

Trials 2021 Jul 28;22(1):504. Epub 2021 Jul 28.

Yueyang Hospital of Integrated Traditional Chinese and Western Medicine, Shanghai University of Traditional Chinese Medicine, 110 Ganhe Road, Hongkou District, Shanghai, 200437, China.

Background: Post-stroke depression (PSD) is a common complication after stroke which hinders functional recovery and return to social participation of stroke patients. Efficacy of conventional drug therapies for patients with PSD is still uncertain. Therefore, many patients prefer to use complementary and alternative therapies for PSD. Tuina (traditional Chinese manual manipulation) with herbal ointment is an integration of manual therapy, and ointment is an important part of traditional Chinese medicine (TCM) therapy. Preliminary experiments have shown that the Tuina with herbal ointment can improve the mental state of patients with PSD. The purpose of this study is to observe and verify the efficacy of Tuina combined with herbal ointment for patients with post-stroke depression, and to lay a foundation for further research on its mechanism of action.

Methods/design: In this study, a randomized controlled trial will be conducted in parallel, including two intervention groups: Tuina with herbal ointment group and herbal ointment for control group. A total of 84 eligible participants will be randomly assigned to the groups in a 1:1 ratio. All participants will receive conventional antidepressant venlafaxine treatment (75 mg QD), on which they received two different interventions. The interventions for both groups will be carried out 5 times each week for a period of 2 weeks. The primary outcome will be the Hamilton Rating Scale for Depression (HAMD). Secondary outcomes will include transcranial magnetic stimulation (TMS), as well as 36-item Short-Form Health Survey (SF-36) and Treatment Emergent Symptom Scale (TESS). They will be assessed at the baseline, at the end of the intervention (2 weeks), and during the 1 month and 3 months of follow-up by repeated measures analysis of variance. The significance level is 5%. Adverse events will be monitored at each visit to assess safety. All outcomes will be assessed and analyzed by researchers blinded to the treatment allocation. The purpose of this study will focus on observing the efficacy of Tuina with herbal ointment for patients with post-stroke depression, and to explore further the mechanisms of its effects.

Discussion: This study may evaluate clinical application value and safety of Tuina with herbal ointment in PSD patients, which can provide basis for clinical research and mechanism exploration of PSD.

Trial Registration: Chinese Clinical Trial Registry ChiCTR2000033887 . Registered on 15 June 2020.

Dissemination: The results will be published in peer-reviewed journals and disseminated through the study's website and conferences.
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http://dx.doi.org/10.1186/s13063-021-05469-1DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8320029PMC
July 2021

Potent Neutralizing Humanized Antibody With Topical Therapeutic Potential Against HPV18-Related Cervical Cancer.

Front Immunol 2021 24;12:678318. Epub 2021 Jun 24.

Center for Public Health Research, Medical School, Nanjing University, Nanjing, China.

Cervical cancer caused by human papillomavirus (HPV) infections is the fourth most common cancer in women worldwide. Current prophylactic HPV vaccines have achieved promising success in preventing HPV infection. However, still 570,000 new cases were reported in 2018. The current primary treatment for the patient with cervical cancer is either surgery or chemoradiotherapy. Cervical cancer still lacks standard medical therapy. HPV18 induced cervical cancer has the worst prognosis and high mortality compared to other HPV infections. The development of HPV18 related with cervical malignancy requires the persistent infection of cervical-vaginal epithelium by HPV18 subtype, which can take years to transform the epithelium. This period of repeated infection provides a window for therapeutic intervention. Neutralizing antibodies formulated as topical agents that inhibit HPV18 infection should reduce the chance of cervical malignancy. We previously demonstrated that potent neutralizing anti-sera against HPV18 infection were induced by HPV18 viral like particle (VLP) generated in mammalian cells. We, therefore, isolated two potent neutralizing antibodies, 2A12 and 8H4, from over 3,810 hybridomas prepared from mice immunized with HPV18 VLP. 2A12 and 8H4 exhibited excellent potency, with 50% virus-inhibitory concentrations (IC) of 0.4 and 0.9 ng/ml, respectively. Furthermore, 2A12 and 8H4 recognized distinct and non-overlapping quaternary epitopes and bound specifically with HPV18. Humanized 2A12 (Hu2A12) retained comparable neutralizing activity against HPV18 infection in various acidic pH settings and in hydrogel formulation with IC values of 0.04 to 0.77 ng/ml, indicating that Hu2A12 will be a promising candidate for clinical development as a topical vaginal biopharmaceutical agent against HPV18 infection.
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http://dx.doi.org/10.3389/fimmu.2021.678318DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8264373PMC
June 2021

Nonstructural Protein NSs Hampers Cellular Antiviral Response through LSm14A during Severe Fever with Thrombocytopenia Syndrome Virus Infection.

J Immunol 2021 Jul 9. Epub 2021 Jul 9.

Center for Public Health Research, Medical School, Nanjing University, Nanjing, People's Republic of China;

The nonstructural protein (NSs) of severe fever with thrombocytopenia syndrome virus (SFTSV) plays multiple functions in the virus life cycle. Proteomic screening for host proteins interacting with NSs identified the cellular protein LSm14A. LSm14A, a member of the LSm family involved in RNA processing in the processing bodies, binds to viral RNA or synthetic homolog and mediates IFN regulatory factor 3 activation and IFN-β induction. NSs interacted with and colocalized with LSm14A, and this interaction effectively inhibited downstream phosphorylation and dimerization of IFN regulatory factor 3, resulting in the suppression of antiviral signaling and IFN induction in several cell types of human origin. Knockdown of NSs resulted in the suppression of SFTSV replication in host cells. Viral RNA bound to LSm14A-NSs protein complex during the interaction. A newly discovered motif of NSs functioned to interact with LSm14A. Altogether, our data demonstrated a mechanism used by SFTSV to inhibit host innate immune response.
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http://dx.doi.org/10.4049/jimmunol.2100148DOI Listing
July 2021

Safety, tolerability, and immunogenicity of an inactivated SARS-CoV-2 vaccine (CoronaVac) in healthy children and adolescents: a double-blind, randomised, controlled, phase 1/2 clinical trial.

Lancet Infect Dis 2021 Jun 28. Epub 2021 Jun 28.

Sinovac Life Sciences, Beijing, China. Electronic address:

Background: A vaccine against SARS-CoV-2 for children and adolescents will play an important role in curbing the COVID-19 pandemic. Here we aimed to assess the safety, tolerability, and immunogenicity of a candidate COVID-19 vaccine, CoronaVac, containing inactivated SARS-CoV-2, in children and adolescents aged 3-17 years.

Methods: We did a double-blind, randomised, controlled, phase 1/2 clinical trial of CoronaVac in healthy children and adolescents aged 3-17 years old at Hebei Provincial Center for Disease Control and Prevention in Zanhuang (Hebei, China). Individuals with SARS-CoV-2 exposure or infection history were excluded. Vaccine (in 0·5 mL aluminum hydroxide adjuvant) or aluminum hydroxide only (alum only, control) was given by intramuscular injection in two doses (day 0 and day 28). We did a phase 1 trial in 72 participants with an age de-escalation in three groups and dose-escalation in two blocks (1·5 μg or 3·0 μg per injection). Within each block, participants were randomly assigned (3:1) by means of block randomisation to receive CoronaVac or alum only. In phase 2, participants were randomly assigned (2:2:1) by means of block randomisation to receive either CoronaVac at 1·5 μg or 3·0 μg per dose, or alum only. All participants, investigators, and laboratory staff were masked to group allocation. The primary safety endpoint was adverse reactions within 28 days after each injection in all participants who received at least one dose. The primary immunogenicity endpoint assessed in the per-protocol population was seroconversion rate of neutralising antibody to live SARS-CoV-2 at 28 days after the second injection. This study is ongoing and is registered with ClinicalTrials.gov, NCT04551547.

Findings: Between Oct 31, 2020, and Dec 2, 2020, 72 participants were enrolled in phase 1, and between Dec 12, 2020, and Dec 30, 2020, 480 participants were enrolled in phase 2. 550 participants received at least one dose of vaccine or alum only (n=71 for phase 1 and n=479 for phase 2; safety population). In the combined safety profile of phase 1 and phase 2, any adverse reactions within 28 days after injection occurred in 56 (26%) of 219 participants in the 1·5 μg group, 63 (29%) of 217 in the 3·0 μg group, and 27 (24%) of 114 in the alum-only group, without significant difference (p=0·55). Most adverse reactions were mild and moderate in severity. Injection site pain was the most frequently reported event (73 [13%] of 550 participants), occurring in 36 (16%) of 219 participants in the 1·5 μg group, 35 (16%) of 217 in the 3·0 μg group, and two (2%) in the alum-only group. As of June 12, 2021, only one serious adverse event of pneumonia has been reported in the alum-only group, which was considered unrelated to vaccination. In phase 1, seroconversion of neutralising antibody after the second dose was observed in 27 of 27 participants (100·0% [95% CI 87·2-100·0]) in the 1·5 μg group and 26 of 26 participants (100·0% [86·8-100·0]) in the 3·0 μg group, with the geometric mean titres of 55·0 (95% CI 38·9-77·9) and 117·4 (87·8-157·0). In phase 2, seroconversion was seen in 180 of 186 participants (96·8% [93·1-98·8]) in the 1·5 μg group and 180 of 180 participants (100·0% [98·0-100·0]) in the 3·0 μg group, with the geometric mean titres of 86·4 (73·9-101·0) and 142·2 (124·7-162·1). There were no detectable antibody responses in the alum-only groups.

Interpretation: CoronaVac was well tolerated and safe and induced humoral responses in children and adolescents aged 3-17 years. Neutralising antibody titres induced by the 3·0 μg dose were higher than those of the 1·5 μg dose. The results support the use of 3·0 μg dose with a two-immunisation schedule for further studies in children and adolescents.

Funding: The Chinese National Key Research and Development Program and the Beijing Science and Technology Program.
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http://dx.doi.org/10.1016/S1473-3099(21)00319-4DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8238449PMC
June 2021

AAV-mediated in vivo CAR gene therapy for targeting human T-cell leukemia.

Blood Cancer J 2021 Jun 23;11(6):119. Epub 2021 Jun 23.

Center for Public Health Research, Medical School, Nanjing University, Nanjing, People's Republic of China.

Chimeric antigen receptor (CAR) T-cell therapy is the most active field in immuno-oncology and brings substantial benefit to patients with B cell malignancies. However, the complex procedure for CAR T-cell generation hampers its widespread applications. Here, we describe a novel approach in which human CAR T cells can be generated within the host upon injecting an Adeno-associated virus (AAV) vector carrying the CAR gene, which we call AAV delivering CAR gene therapy (ACG). Upon single infusion into a humanized NOD.Cg-Prkd Il2rg/Nju tumor mouse model of human T-cell leukemia, AAV generates sufficient numbers of potent in vivo CAR cells, resulting in tumor regression; these in vivo-generated CAR cells produce antitumor immunological characteristics. This instantaneous generation of in vivo CAR T cells may bypass the need for patient lymphodepletion, as well as the β processes of traditional CAR T-cell production, which may make CAR therapy simpler and less expensive. It may allow the development of intricate, individualized treatments in the form of on-demand and diverse therapies.
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http://dx.doi.org/10.1038/s41408-021-00508-1DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8222347PMC
June 2021

NSC23766 and Ehop016 Suppress Herpes Simplex Virus-1 Replication by Inhibiting Rac1 Activity.

Biol Pharm Bull 2021 Sep 23;44(9):1263-1271. Epub 2021 Jun 23.

Center for Public Health Research, Medical School of Nanjing University.

Herpes simplex virus-1 (HSV-1) infection of the eyes leads to herpes simplex virus keratitis (HSK), the main cause of infectious blindness in the world. As the current therapeutics for HSV-1 infection are rather limited and prolonged use of acyclovir (ACV)/ganciclovir (GCV) and in immunocompromised patients lead to the rise of drug resistant mutants, it underlines the urgent need for new antiviral agents with distinct mechanisms. Our study attempted to establish ras-related C3 botulinum toxin substrate 1 (Rac1) as a new therapeutic target for HSV-1 infection by using Rac1-specific inhibitors to evaluate the in vitro inhibition of virus growth. Our results showed that increased Rac1 activity facilitated HSV-1 replication and inhibition of Rac1 activity by NSC23766 and Ehop016 significantly reduced HSV-1 replication. Thus, we identified NSC23766 and Ehop016 as possessing potent anti-HSV-1 activities by suppressing the Rac1 activity, suggesting that Rac1 is a potential target for treating HSV-1-related diseases.
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http://dx.doi.org/10.1248/bpb.b21-00054DOI Listing
September 2021

A serpin (CvT-serpin15) of teratocytes contributes to microbial-resistance in Plutella xylostella during Cotesia vestalis parasitism.

Pest Manag Sci 2021 Oct 7;77(10):4730-4740. Epub 2021 Aug 7.

Institute of Insect Sciences, Zhejiang University, Hangzhou, China.

Background: Parasitic wasps are an important group of entomophagous insects for pest control. As parasitic wasps often lay eggs on or into their associated hosts, parasitoids evolve to utilize several factors including venom, polydnavirus (PDV) to alter host physiology for successful parasitism. Some taxa of endoparasitoids produce teratocytes, which are a type of cell that is released into host insects when wasp eggs hatch. Teratocytes display multifunction in parasitism such as host nutritional exploration, immune and developmental regulation, by secreting plenty of proteins into host hemocoel.

Results: A serpin (CvT-serpin15) secreted by teratocytes was characterized. QPCR results showed the expressional level of CvT-serpin15 was upregulated following bacterial challenges. Enzyme activity experiment indicated the recombinant CvT-serpin15 protein could interfere with the growth of Gram-positive bacteria Staphylococcus aureus. The survival rate assay demonstrated CvT-serpin15 increased survival rate of Plutella xylostella infected by S. aureus.

Conclusion: CvT-serpin15 secreted by teratocytes would boost the host immune system when pathogens invade host hemocoel during parasitism, and ultimately protect the development of wasp larva from bacterial infection. © 2021 The Authors. Pest Management Science published by John Wiley & Sons Ltd on behalf of Society of Chemical Industry.
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http://dx.doi.org/10.1002/ps.6515DOI Listing
October 2021

Enterovirus 71 infection induced Aquaporin-4 depolarization by increasing matrix metalloproteinase-9 activity.

Neurosci Lett 2021 08 12;759:136049. Epub 2021 Jun 12.

Center for Public Health Research, Medical School, Nanjing University, Nanjing, China; State Key Lab of Analytical Chemistry for Life Science, Nanjing University, Nanjing, China; Jiangsu Key Laboratory of Molecular Medicine, Medical School, Nanjing University, Nanjing, China. Electronic address:

Aquaporin-4 (AQP4) is the key water channel protein that regulates brain water homeostasis. Polarized expression of AQP4 on the astroglial endfeet facilitates its role in bi-directional brain water flux control. In the current study, we found that enterovirus 71 (EV71) infection induced depolarization of AQP4 in mouse brain, and demonstrated that β-dystroglycan (β-DG), the key component of dystrophin glycoprotein complex (DGC) that anchors AQP4 to the astroglial endfeet, was degraded upon infection. Elevated activity or expression of matrix metalloproteinase 9 (MMP9) upon infection was found in both mouse brains and patient cerebrospinal fluid (CSF) samples. Inhibiting MMP9 activity by SB-3CT rescued the decay of β-DG and reduced the depolarization of AQP4. Brain edema induced by viral infection was also ameliorated by SB-3CT treatment in mice.
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http://dx.doi.org/10.1016/j.neulet.2021.136049DOI Listing
August 2021

Infection of humanized mice with a novel phlebovirus presented pathogenic features of severe fever with thrombocytopenia syndrome.

PLoS Pathog 2021 05 11;17(5):e1009587. Epub 2021 May 11.

School of Life Sciences, Ningxia University, Yinchuan, P.R. China.

Severe fever with thrombocytopenia syndrome virus (SFTSV) is a tick-borne emerging phlebovirus with high mortality rates of 6.0 to 30%. SFTSV infection is characterized by high fever, thrombocytopenia, leukopenia, hemorrhage and multiple organ failures. Currently, specific therapies and vaccines remain elusive. Suitable small animal models are urgently needed to elucidate the pathogenesis and evaluate the potential drug and vaccine for SFTSV infection. Previous models presented only mild or no pathogenesis of SFTS, limiting their applications in SFTSV infection. Therefore, it is an urgent need to develop a small animal model for the investigation of SFTSV pathogenesis and evaluation of therapeutics. In the current report, we developed a SFTSV infection model based on the HuPBL-NCG mice that recapitulates many pathological characteristics of SFTSV infection in humans. Virus-induced histopathological changes were identified in spleen, lung, kidney, and liver. SFTSV was colocalized with macrophages in the spleen and liver, suggesting that the macrophages in the spleen and liver could be the principle target cells of SFTSV. In addition, histological analysis showed that the vascular endothelium integrity was severely disrupted upon viral infection along with depletion of platelets. In vitro cellular assays further revealed that SFTSV infection increased the vascular permeability of endothelial cells by promoting tyrosine phosphorylation and internalization of the adhesion molecule vascular endothelial (VE)-cadherin, a critical component of endothelial integrity. In addition, we found that both virus infection and pathogen-induced exuberant cytokine release dramatically contributed to the vascular endothelial injury. We elucidated the pathogenic mechanisms of hemorrhage syndrome and developed a humanized mouse model for SFTSV infection, which should be helpful for anti-SFTSV therapy and pathogenesis study.
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http://dx.doi.org/10.1371/journal.ppat.1009587DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8139491PMC
May 2021

White Matter Structural Network Analysis to Differentiate Alzheimer's Disease and Subcortical Ischemic Vascular Dementia.

Front Aging Neurosci 2021 31;13:650377. Epub 2021 Mar 31.

Department of Radiology, The First Affiliated Hospital of Soochow University, Suzhou City, China.

To explore the evaluation of white matter structural network analysis in the differentiation of Alzheimer's disease (AD) and subcortical ischemic vascular dementia (SIVD), 67 participants [31 AD patients, 19 SIVD patients, and 19 normal control (NC)] were enrolled in this study. Each participant underwent 3.0T MRI scanning. Diffusion tensor imaging (DTI) data were analyzed by graph theory (GRETNA toolbox). Statistical analyses of global parameters [gamma, sigma, lambda, global shortest path length (Lp), global efficiency (E), and local efficiency (E)] and nodal parameters [betweenness centrality (BC)] were obtained. Network-based statistical analysis (NBS) was employed to analyze the group differences of structural connections. The diagnosis efficiency of nodal BC in identifying different types of dementia was assessed by receiver operating characteristic (ROC) analysis. There were no significant differences of gender and years of education among the groups. There were no significant differences of sigma and gamma in AD vs. NC and SIVD vs. NC, whereas the E values of AD and SIVD were statistically decreased, and the lambda values were increased. The BC of the frontal cortex, left superior parietal gyrus, and left precuneus in AD patients were obviously reduced, while the BC of the prefrontal and subcortical regions were decreased in SIVD patients, compared with NC. SIVD patients had decreased structural connections in the frontal, prefrontal, and subcortical regions, while AD patients had decreased structural connections in the temporal and occipital regions and increased structural connections in the frontal and prefrontal regions. The highest area under curve (AUC) of BC was 0.946 in the right putamen for AD vs. SIVD. White matter structural network analysis may be a potential and promising method, and the topological changes of the network, especially the BC change in the right putamen, were valuable in differentiating AD and SIVD patients.
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http://dx.doi.org/10.3389/fnagi.2021.650377DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8044349PMC
March 2021

Circular RNA_0000190 and its target microRNA-767-5p are dysregulated, and they are related to risk stratification as well as prognosis in multiple myeloma patients.

Ir J Med Sci 2021 Apr 16. Epub 2021 Apr 16.

Department of Hematology, The First People's Hospital of Jingmen, No. 67 Xiangshan Avenue, Jingmen, 448000, People's Republic of, China.

Background: This study aimed to explore the correlation between circular RNA_0000190 (circ_0000190) and microRNA-767-5p (miR-767-5p), and their correlations with biochemical indices, risk stratification, treatment response, and survival in multiple myeloma (MM) patients.

Methods: Bone marrow (BM) plasma cells of 86 MM patients (during standard diagnostic procedures) and 30 healthy donors (HDs) (examination of the eligibility for BM transplantation) were obtained, among which circ_0000190 and miR-767-5p expressions were detected using reverse transcription quantitative polymerase chain reaction. In MM patients, Durie-Salmon stage and International Staging System (ISS) stage were assessed. Clinical responses (including complete response (CR) and objective response rate (ORR)) were assessed. The progression-free survival (PFS) and overall survival (OS) were calculated.

Results: Circ_0000190 was decreased, but miR-767-5p was increased in MM patients compared with HDs. Circ_0000190 was negatively correlated with miR-767-5p in both HDs and MM patients. In MM patients, circ_0000190 was negatively correlated with ISS stage, serum creatinine, beta-2-microglobulin, and lactate dehydrogenase but was positively correlated with albumin. Whereas an opposite trend in miR-767-5p was observed. Regarding clinical response, circ_0000190 had the value for predicting increased ORR, while miR-767-5p had the value for predicting decreased CR and ORR. Circ_0000190 high expression was correlated with better PFS and OS, while miR-767-5p high expression was correlated with worse PFS and OS. Multivariate Cox's analyses revealed circ_0000190 high expression as an independent factor predicting better OS.

Conclusion: Circ_0000190 and its target miR-767-5p are dysregulated, and they are related to risk stratification and prognosis in MM patients.
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http://dx.doi.org/10.1007/s11845-021-02586-3DOI Listing
April 2021

Structural, dielectric, magnetic and optical properties of double perovskite oxide SmNiMnOnanoparticles synthesized by a sol-gel process.

Nanotechnology 2021 Apr 22;32(28). Epub 2021 Apr 22.

National Laboratory of Solid State Microstructures, School of Physics, Nanjing University, Nanjing 210093, People's Republic of China.

Here we report on the structural, dielectric, magnetic and optical properties of double perovskite SmNiMnO(SNMO) nanoparticles synthesized by a sol-gel method. Structural Reitveld refinements on x-ray powder diffraction data revealed that the SNMO nanoparticles crystallized in a monoclinic crystal structure with2/space group. SEM and (HR)TEM images revealed the phase purity and single-crystalline nature of the SNMO nanoparticles. XPS spectra confirmed the presence of Sm, Niand Mnions in the SNMO nanoparticles and oxygen in the forms of lattice oxygen and the hydroxyls species. SNMO ceramics exhibited relaxor-type dielectric behavior, well fitted by modified Curie-Weiss law. Such dielectric behavior originated from the interactions of random dipoles arisen from the B-site cations disorder accompanied with the variations in local electric fields and local strain fields due to the different radii of B-site cations, and/or the virtual electrons hopping between the Niand Mncations. Magnetic data demonstrate the variations of the magnetic transitions at low temperatures and the spin glass-like behavior below 11 K, which is attributed to the spin fluctuations induced by the competing interactions between the ferromagnetic (FM) and antiferromagnetic phases. Large positive Curie-Weiss temperature () indicates the dominant FM super-exchange interactions in the SNMO samples. The SNMO nanoparticles have a direct optical band gap of 1.42 eV, close to 1.34 eV in a single junction solar cell. That enables the SNMO nanoparticles to be useful for solar cell absorbers.
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http://dx.doi.org/10.1088/1361-6528/abf59fDOI Listing
April 2021

Safety, tolerability, and immunogenicity of an inactivated SARS-CoV-2 vaccine (CoronaVac) in healthy adults aged 60 years and older: a randomised, double-blind, placebo-controlled, phase 1/2 clinical trial.

Lancet Infect Dis 2021 06 3;21(6):803-812. Epub 2021 Feb 3.

Sinovac Biotech, Beijing, China. Electronic address:

Background: A vaccine against COVID-19 is urgently needed for older adults, in whom morbidity and mortality due to the disease are increased. We aimed to assess the safety, tolerability, and immunogenicity of a candidate COVID-19 vaccine, CoronaVac, containing inactivated SARS-CoV-2, in adults aged 60 years and older.

Methods: We did a randomised, double-blind, placebo-controlled, phase 1/2 clinical trial of CoronaVac in healthy adults aged 60 years and older in Renqiu (Hebei, China). Vaccine or placebo was given by intramuscular injection in two doses (days 0 and 28). Phase 1 comprised a dose-escalation study, in which participants were allocated to two blocks: block 1 (3 μg inactivated virus in 0·5 mL of aluminium hydroxide solution per injection) and block 2 (6 μg per injection). Within each block, participants were randomly assigned (2:1) using block randomisation to receive CoronaVac or placebo (aluminium hydroxide solution only). In phase 2, participants were randomly assigned (2:2:2:1) using block randomisation to receive either CoronaVac at 1·5 μg, 3 μg, or 6 μg per dose, or placebo. All participants, investigators, and laboratory staff were masked to treatment allocation. The primary safety endpoint was adverse reactions within 28 days after each injection in all participants who received at least one dose. The primary immunogenicity endpoint was seroconversion rate at 28 days after the second injection (which was assessed in all participants who had received the two doses of vaccine according to their random assignment, had antibody results available, and did not violate the trial protocol). Seroconversion was defined as a change from seronegative at baseline to seropositive for neutralising antibodies to live SARS-CoV-2 (positive cutoff titre 1/8), or a four-fold titre increase if the participant was seropositive at baseline. This study is ongoing and is registered with ClinicalTrials.gov (NCT04383574).

Findings: Between May 22 and June 1, 2020, 72 participants (24 in each intervention group and 24 in the placebo group; mean age 65·8 years [SD 4·8]) were enrolled in phase 1, and between June 12 and June 15, 2020, 350 participants were enrolled in phase 2 (100 in each intervention group and 50 in the placebo group; mean age 66·6 years [SD 4·7] in 349 participants). In the safety populations from both phases, any adverse reaction within 28 days after injection occurred in 20 (20%) of 100 participants in the 1·5 μg group, 25 (20%) of 125 in the 3 μg group, 27 (22%) of 123 in the 6 μg group, and 15 (21%) of 73 in the placebo group. All adverse reactions were mild or moderate in severity and injection site pain (39 [9%] of 421 participants) was the most frequently reported event. As of Aug 28, 2020, eight serious adverse events, considered unrelated to vaccination, have been reported by seven (2%) participants. In phase 1, seroconversion after the second dose was observed in 24 of 24 participants (100·0% [95% CI 85·8-100·0]) in the 3 μg group and 22 of 23 (95·7% [78·1-99·9]) in the 6 μg group. In phase 2, seroconversion was seen in 88 of 97 participants in the 1·5 μg group (90·7% [83·1-95·7]), 96 of 98 in the 3 μg group (98·0% [92·8-99·8]), and 97 of 98 (99·0% [94·5-100·0]) in the 6 μg group. There were no detectable antibody responses in the placebo groups.

Interpretation: CoronaVac is safe and well tolerated in older adults. Neutralising antibody titres induced by the 3 μg dose were similar to those of the 6 μg dose, and higher than those of the 1·5 μg dose, supporting the use of the 3 μg dose CoronaVac in phase 3 trials to assess protection against COVID-19.

Funding: Chinese National Key Research and Development Program and Beijing Science and Technology Program.
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http://dx.doi.org/10.1016/S1473-3099(20)30987-7DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7906628PMC
June 2021

Synthesis of π-Conjugated Polymers Containing Benzotriazole Units via Palladium-Catalyzed Direct C-H Cross-Coupling Polycondensation for OLEDs Applications.

Polymers (Basel) 2021 Jan 14;13(2). Epub 2021 Jan 14.

School of Materials Science & Engineering, Tianjin University of Technology, Tianjin 300384, China.

Four D-π-A conjugated polymers, namely P1-P4, which contain benzotriazole building blocks in their backbone as acceptor, are synthesized via palladium-catalyzed direct C-H cross-coupling polycondensation of 5,6-difluorobenzotriazole with different thiophene derivatives, including 3-octylthiophene, 2,2'-bithiophene, thieno[3,4-b][1,4]dioxine, and 4,4-dioctyl-4H-silolo-[3,2-b:4,5-b']dithiophene as donor units, respectively. Taking the polymer P1 as an example, the chemical structure of the polymer is demonstrated by H and F NMR spectra. The optical, electrochemical, and thermal properties of these polymers are assessed by UV-vis absorption and fluorescence spectroscopy, cyclic voltammetry (CV), and thermal gravimetric analysis (TGA), respectively. DFT simulations of all polymers are also performed to understand their physicochemical properties. Furthermore, P1 and P2, which have relatively higher molecular weights and better fluorescent quantum efficiency than those of P3 and P4, are utilized as lighting emitters for organic light-emitting diodes (OLEDs), affording promising green and red luminescence with 0.07% and 0.14% of maximum external quantum efficiency, respectively, based on a device with an architecture of ITO/PEDOT:PSS/PTAA/the polymer emitting layer/TPBi/LiF/Al.
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http://dx.doi.org/10.3390/polym13020254DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7828650PMC
January 2021

Insights Into Immunothrombosis: The Interplay Among Neutrophil Extracellular Trap, von Willebrand Factor, and ADAMTS13.

Front Immunol 2020 2;11:610696. Epub 2020 Dec 2.

Research Department of Medical Sciences, Guangdong Provincial People's Hospital, Guangdong Academy of Medical Sciences, Guangzhou, China.

Both neutrophil extracellular traps (NETs) and von Willebrand factor (VWF) are essential for thrombosis and inflammation. During these processes, a complex series of events, including endothelial activation, NET formation, VWF secretion, and blood cell adhesion, aggregation and activation, occurs in an ordered manner in the vasculature. The adhesive activity of VWF multimers is regulated by a specific metalloprotease ADAMTS13 (a disintegrin and metalloproteinase with thrombospondin type 1 motifs, member 13). Increasing evidence indicates that the interaction between NETs and VWF contributes to arterial and venous thrombosis as well as inflammation. Furthermore, contents released from activated neutrophils or NETs induce the reduction of ADAMTS13 activity, which may occur in both thrombotic microangiopathies (TMAs) and acute ischemic stroke (AIS). Recently, NET is considered as a driver of endothelial damage and immunothrombosis in COVID-19. In addition, the levels of VWF and ADAMTS13 can predict the mortality of COVID-19. In this review, we summarize the biological characteristics and interactions of NETs, VWF, and ADAMTS13, and discuss their roles in TMAs, AIS, and COVID-19. Targeting the NET-VWF axis may be a novel therapeutic strategy for inflammation-associated TMAs, AIS, and COVID-19.
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http://dx.doi.org/10.3389/fimmu.2020.610696DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7738460PMC
December 2020

The Effect of miR-361-3p Targeting TRAF6 on Apoptosis of Multiple Myeloma Cells.

J Microbiol Biotechnol 2021 Feb;31(2):197-206

Department of Hematology, The First People's Hospital of Jingmen, No. 67 Xiangshan Avenue, Jingmen, Hubei Province 448000, P.R. China.

microRNA-361-3p (miR-361-3p) is involved in the carcinogenesis of oral cancer and pancreatic catheter adenocarcinoma, and has anti-carcinogenic effects on non-small cell lung cancer (NSCLC). However, its effect on multiple myeloma (MM) is less reported. Here, we found that upregulating the expression of miR-361-3p inhibited MM cell viability and promoted MM apoptosis. We measured expressions of tumor necrosis factor receptor-associated factor 6 (TRAF6) and miR-361-3p in MM cells and detected the viability, colony formation rate, and apoptosis of MM cells. In addition, we measured expressions of apoptosis-related genes Bcl-2, Bax, and Cleaved caspase-3 (C caspase-3). The binding site between miR-361-3p and TRAF6 was predicted by TargetScan. Our results showed that miR-361-3p was low expressed in the plasma of MM patients and cell lines, while its overexpression inhibited viability and colony formation of MM cells and increased the cell apoptosis. Furthermore, TRAF6, which was predicted to be a target gene of miR-361-3p, was highexpressed in the plasma of patients and cell lines with MM. Rescue experiments demonstrated that the effect of TRAF6 on MM cells was opposite to that of miR-361-3p. Upregulation of miR-361-3p induced apoptosis and inhibited the proliferation of MM cells through targeting TRAF6, suggesting that miR-361-3p might be a potential target for MM therapy.
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http://dx.doi.org/10.4014/jmb.2010.10059DOI Listing
February 2021

Calculating the Wasserstein Metric-Based Boltzmann Entropy of a Landscape Mosaic.

Entropy (Basel) 2020 Mar 26;22(4). Epub 2020 Mar 26.

State Key Laboratory of Earth Surface Processes and Resource Ecology, Beijing Normal University, Beijing 100875, China.

Shannon entropy is currently the most popular method for quantifying the disorder or information of a spatial data set such as a landscape pattern and a cartographic map. However, its drawback when applied to spatial data is also well documented; it is incapable of capturing configurational disorder. In addition, it has been recently criticized to be thermodynamically irrelevant. Therefore, Boltzmann entropy was revisited, and methods have been developed for its calculation with landscape patterns. The latest method was developed based on the Wasserstein metric. This method incorporates spatial repetitiveness, leading to a Wasserstein metric-based Boltzmann entropy that is capable of capturing the configurational disorder of a landscape mosaic. However, the numerical work required to calculate this entropy is beyond what can be practically achieved through hand calculation. This study developed a new software tool for conveniently calculating the Wasserstein metric-based Boltzmann entropy. The tool provides a user-friendly human-computer interface and many functions. These functions include multi-format data file import function, calculation function, and data clear or copy function. This study outlines several essential technical implementations of the tool and reports the evaluation of the software tool and a case study. Experimental results demonstrate that the software tool is both efficient and convenient.
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http://dx.doi.org/10.3390/e22040381DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7516855PMC
March 2020

EVs Containing Host Restriction Factor IFITM3 Inhibited ZIKV Infection of Fetuses in Pregnant Mice through Trans-placenta Delivery.

Mol Ther 2021 01 20;29(1):176-190. Epub 2020 Sep 20.

Center for Public Health Research, Medical School, Nanjing University, Nanjing, China; State Key Laboratory of Analytical Chemistry for Life Science, Nanjing University, Nanjing, China; Medical School, Jiangsu Key Laboratory of Molecular Medicine, Nanjing University, Nanjing, China. Electronic address:

Zika virus (ZIKV) infection can lead to neurological complications and fetal defects, and it has attracted global public health concerns. Effective treatment for ZIKV infection remains elusive, and a preventative vaccine is not yet available. Therapeutics for fetuses need to overcome placenta barriers to reach the fetuses and require higher safety standards. In the present study, we engineered mammalian extracellular vesicles (EVs) to deliver a host restriction factor, interferon-induced transmembrane protein 3 (IFITM3), for the treatment of ZIKV infection. Our results demonstrated that the IFITM3-containing EVs (IFITM3-Exos) suppressed ZIKV viremia by a 2-log reduction in pregnant mice. Moreover, the engineered EVs effectively delivered IFITM3 protein across the placental barrier and suppressed ZIKV in the fetuses with significant reduction of viremia in key fetal organs as measured by quantitative real-time PCR. Mechanistic study showed that IFITM3 was delivered to late endosomes/lysosomes where it inhibited viral entry into the host cells. Our study demonstrated that EVs could act as a cross-placenta drug delivery vehicle to the fetus, and IFITM3, an endogenous restriction factor, is a potential treatment for ZIKV infection during pregnancy.
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http://dx.doi.org/10.1016/j.ymthe.2020.09.026DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7791082PMC
January 2021

Effects of Wuqinxi in the Patients with Chronic Low Back Pain: A Randomized Controlled Trial.

Evid Based Complement Alternat Med 2020 18;2020:1428246. Epub 2020 Aug 18.

School of Rehabilitation Science, Shanghai University of Traditional Chinese Medicine, No. 1200 Cai Lun Road, Pudong New District, Shanghai 201203, China.

Low back pain (LBP) is one of the major concerns of the current health care. The guidelines for chronic LBP recommend traditional Chinese exercise as an effective treatment. As one of the representatives of traditional Chinese exercise, Wuqinxi has been famous in China for its effects on improving health and treating chronic diseases for thousands of years. The objectives of the study were to assess the effects of Wuqinxi in the patients with chronic LBP on pain intensity, trunk muscle strength, and quality of life. The primary outcome measure was assessed by the Short-Form McGill Pain Questionnaire (SF-MPQ), including the Visual Analog Scale (VAS) and Present Pain Intensity (PPI) as the subtables. The effects of Wuqinxi on the quality of life were also assessed by the Short-Form Health Survey (SF-36) and the Pittsburgh Sleep Quality Index (PSQI) from physical component summary (PCS), mental component summary (MCS), and sleep quality. Besides, the electrical activities of the rectus abdominis (RA), obliquus externus abdominis (OEA), lumbar erector spinae (ES), and multifidus (MF) were assessed by integrated electromyogram (iEMG) after the end of the intervention. Both the groups showed statistically significant improvement in SF-MPQ, SF-36, PSQI, and iEMG at 12 weeks and 24 weeks when compared with baseline ( < 0.05). However, Wuqinxi demonstrated better effects in SF-MPQ and MCS after 24 weeks of intervention compared with the general exercise ( < 0.05). The patients in the Wuqinxi group (WQXG) also showed a significantly higher iEMG on OEA than the general exercise group (GEG) in 30°/s and 90°/s ( < 0.05). Our results showed that Wuqinxi had better effects on chronic LBP for a long time compared with general exercise, including pain intensity and quality of life. Thus, Wuqinxi should be recognized as a possible standalone therapy and self-management skill in chronic LBP, which is suitable for long-term practice.
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http://dx.doi.org/10.1155/2020/1428246DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7450356PMC
August 2020

Contribution of Northeastern Asian stratospheric warming to subseasonal prediction of the early winter haze pollution in Sichuan Basin, China.

Sci Total Environ 2021 Jan 21;751:141823. Epub 2020 Aug 21.

Shanghai Typhoon Institute, Shanghai Meteorological Service, Shanghai 200030, China; Shanghai Key Laboratory of Meteorology and Health, Shanghai 200030, China; Anhui Province Key Laboratory of Atmospheric Science and Satellite Remote Sensing, Heifei 200030, China.

Predicting the interannual (IA) variability of the early winter haze pollution (HP) in Sichuan Basin (SCB) and analyzing the contribution of the complex terrain are of great significance and challenge as well. For one thing, this study finds that the second mode of early winter IA variations of the HP in Central Eastern China (CEC) is dominated by the pollutant pattern of SCB, characterized by an extreme value center located over SCB. For another, the mode accounts for 15.1% of the total variance and well represents the IA variability of the areal mean HP in SCB. Furthermore, the anomalous circulations conducive to the severe HP in SCB consist of the strengthened (weakened) north (south) branch of Tibetan Plateau (TP) bypassing westerlies at 700 hPa, enhanced descents over SCB, and a strong inversion layer at 750 hPa, suppressing the precipitation and the development of the planetary boundary layer (PBL) in SCB. As a result, dispersion and wet deposition conditions are poor, favorable for the occurrence of the HP in SCB. Observed evidences show that the regional warming in the upper stratosphere over Northeastern Asia in November can be a possible subseasonal precursory signal for the SCB mode. Above all, the warming at upper stratosphere will propagate downward and arrive at the lower stratosphere in 3-4 weeks. Followed by the southward and downward propagation through the longitudinal tilted isothermal surface, the warming arrives at the tropospheric mid-low latitudes in 2-3 weeks, leading to anomalous warming and descents over TP and SCB. Consequently, SCB sees the aforementioned three-dimensional anomalous circulations. For this reason, a physical-empirical subseasonal prediction model for the IA variability of the early winter HP in SCB is established in terms of the regional stratospheric temperature in November. Apparently, the hindcast shows a promising prediction skill.
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http://dx.doi.org/10.1016/j.scitotenv.2020.141823DOI Listing
January 2021

Seismic Behavior of Extended End-Plate Connections Subjected to Cyclic Loading on the Top-Side of the Column.

Materials (Basel) 2020 Aug 23;13(17). Epub 2020 Aug 23.

South China University of Technology, Guangzhou 510641, China.

The extended end-plate connections provide excellent performance in resisting seismic loads in high-risk areas. Most scholars' experiments and finite element studies on this type of joint are focused on the method of applying displacement loads on the beam tip, while the method of applying displacement on the column side has not been the subject of further study. However, the load transmission mechanism of this type of connection is not completely consistent in actual engineering, as the design concept of "strong column weak beam" does not apply to all joints. Therefore, in this paper, the lateral displacement of the applied column is used to simulate the seismic horizontal force to study the mechanical properties of the connection joints of the "weak column and strong beam" under the limit state of earthquake action. Based on the two internal columns (IC-EP1/2) and two edge columns (EC-EP1/2), the failure modes, strength, stiffness, moment-rotation curve, skeleton curve, ductility, and energy dissipation of this type of connection were studied. Experiment results indicated that this type of connection features semi-rigid and partial strength joints. The connection rotation angle of all specimens in the test exceeds 0.05 rad, which suggests it is an ideal seismic joints. Besides, the relationship between the thickness of the end-plate and the diameter of the bolt has a greater impact on the failure mode of the joint. The finite element (FE) analysis models were established for the above connection. The numerical model was validated against experimental results and showed acceptable consistency.
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http://dx.doi.org/10.3390/ma13173724DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7504020PMC
August 2020

Wogonin inhibits in vitro herpes simplex virus type 1 and 2 infection by modulating cellular NF-κB and MAPK pathways.

BMC Microbiol 2020 07 28;20(1):227. Epub 2020 Jul 28.

Clinical Laboratory, Wujin Hospital Affiliated with Jiangsu University, Wujin Clinical College of Xuzhou Medical University, Changzhou, 213017, China.

Background: Wogonin, a natural flavonoid-like chemical compound, exhibits anti-inflammatory, antitumor, antiviral, neuroprotective, and anxiolytic effects by modulating a variety of cellular signaling pathways including PI3K-Akt, p53, nuclear factor κB (NF-κB), mitogen-activated protein kinase (MAPK) pathways. In this study, its antiviral effect against herpes simplex virus (HSV) type 1 and 2 (HSV-1 and HSV-2) replication was investigated.

Results: Wogonin suppressed HSV-2-induced cytopathic effect (CPE) and reduced viral mRNA transcription, viral protein synthesis, and infectious virion particle titers in a dose-dependent manner. A time-of-drug-addition assay demonstrated that wogonin acted as a postentry viral inhibitor. Wogonin also significantly reduced HSV-induced NF-κB and MAPK pathway activation, which has previously been demonstrated to be important for viral replication.

Conclusions: Our results suggest that the anti-herpes effect of wogonin may be mediated by modulation of cellular NF-κB and JNK/p38 MAPK pathways and imply that wogonin may be useful as an anti-HSV agent.
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http://dx.doi.org/10.1186/s12866-020-01916-2DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7388529PMC
July 2020

Altered complexity of resting-state BOLD activity in Alzheimer's disease-related neurodegeneration: a multiscale entropy analysis.

Aging (Albany NY) 2020 07 10;12(13):13571-13582. Epub 2020 Jul 10.

Shenzhen Mental Health Center, Shenzhen, Guangdong, China.

Brain complexity, which reflects the ability of the brain to adapt to a changing environment, has been found to be significantly changed with age. However, there is less evidence on the alterations of brain complexity in neurodegenerative disorders such as Alzheimer's disease (AD). Here we investigated the altered complexity of resting-state blood oxygen level-dependent signals in AD-related neurodegeneration using multiscale entropy (MSE) analysis. All participants were recruited from the Alzheimer's Disease Neuroimaging Initiative, including healthy controls (HC, n=62), amnestic mild cognitive impairment (aMCI, n =81) patients, and Alzheimer's disease (AD, n=25) patients. Our results showed time scale-dependent MSE differences across the three groups. In scale=1, significantly changed MSE patterns (HC>aMCI>AD) were found in four brain regions, including the hippocampus, middle frontal gyrus, intraparietal lobe, and superior frontal gyrus. In scale=4, reversed MSE patterns (HC
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http://dx.doi.org/10.18632/aging.103463DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7377896PMC
July 2020

A single-domain antibody inhibits SFTSV and mitigates virus-induced pathogenesis in vivo.

JCI Insight 2020 07 9;5(13). Epub 2020 Jul 9.

School of Life Sciences, Ningxia University, Yinchuan, China.

Severe fever with thrombocytopenia syndrome virus (SFTSV) is a novel tick-borne bunyavirus that recently emerged in East Asian countries. SFTS is characterized by high fever, thrombocytopenia, leukopenia, multiorgan failure, and hemorrhage with case fatality rates of 6.3% to 30%. Neither antivirals nor vaccines are available at present. We previously demonstrated that neutralizing antibodies specific for SFTSV glycoprotein (Gn) played a vital role in the survival of patients with SFTS. Nanobodies from camels present unique properties, such as thermostability, high affinity, and low immunogenicity. In the current study, mammalian expressed SFTSV Gn was used to immunize a camel, and functional nanobodies were isolated from the B cell nanobody library constructed from the immunized animal. Clone SNB02 was selected for in-depth analysis for its inhibition of SFTSV replication both in vitro and in vivo. We showed that SNB02 potently inhibited SFTSV infection and prevented thrombocytopenia in a humanized mouse model and is a potential candidate for therapeutics.
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http://dx.doi.org/10.1172/jci.insight.136855DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7406269PMC
July 2020

Enhancing PPARγ by HDAC inhibition reduces foam cell formation and atherosclerosis in ApoE deficient mice.

Pharmacol Res 2020 10 1;160:105059. Epub 2020 Jul 1.

Center for Organ Fibrosis and Remodeling, Jiangsu Key Lab of Molecular Medicine, Nanjing University Medical School, Nanjing, 210093, China. Electronic address:

Atherosclerosis (AS) is a risky cardiovascular disease with limited treatment options. Various pan or type-selective histone deacetylase (HDAC) inhibitors are reportedly atheroprotective against atherosclerosis (AS); however, the key effectors and the main cellular processes that mediate the protective effects remain poorly defined. Here, we report that PPARγ (Peroxisome proliferator-activated receptor gamma), a transcription factor actively involved in lipid metabolism with strong tissue protective and anti-inflammation properties, is a critical mediator of the anti-AS effects by HDAC inhibition. We showed that a well-known pan-HDAC inhibitor TSA (Trichostatin A) reduced foam cell formation of macrophages that is accompanied by a marked elevation of PPARγ and its downstream cholesterol efflux transporter ABCA1 (ATP-binding membrane cassette transport protein A1) and ABCG1. In an AS model of ApoE mice fed on high-fat diet, TSA treatment alleviated AS lesions, similarly increased PPARγ and the downstream cholesterol transporters and mitigated the induction of inflammatory cytokine TNFα and IL-1β. Exploring the potential cause of PPARγ elevation revealed that TSA induced the acetylation of C/EBPα (CCAAT enhancer binding protein alpha), the upstream regulator of PPARγ, through which it increased PPARγ transactivation. More importantly, we generated a strain of PPARγ/ApoE double knockout mice and demonstrated that lack of PPARγ abrogated the protective effects of TSA on foam cell formation of peritoneal macrophages and the AS pathogenesis. Taken together, these results unravel that C/EBPα and PPARγ are the HDAC-sensitive components of an epigenetic signaling pathway mediating foam cell formation and AS development, and suggest that targeting C/EBPα/PPARγ axis by HDAC inhibitors possesses therapeutic potentials in retarding the progression of AS and the related cardiovascular diseases.
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http://dx.doi.org/10.1016/j.phrs.2020.105059DOI Listing
October 2020
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