Publications by authors named "Haibo Wu"

188 Publications

Vasculogenic Mimicry Formation Predicts Tumor Progression in Oligodendroglioma.

Pathol Oncol Res 2021 18;27:1609844. Epub 2021 Aug 18.

Department of Pathology, the First Affiliated Hospital of USTC, Division of Life Sciences and Medicine, University of Science and Technology of China, Hefei, China.

Vasculogenic mimicry (VM) has been identified as an important vasculogenic mechanism in malignant tumors, but little is known about its clinical meanings and mechanisms in oligodendroglioma. In this study, VM-positive cases were detected in 28 (20.6%) out of 136 oligodendroglioma samples, significantly associated with higher WHO grade, lower Karnofsky performance status (KPS) scores, and recurrent tumor ( < 0.001, = 0.040, and = 0.020 respectively). Patients with VM-positive oligodendroglioma had a shorter progress-free survival (PFS) compared with those with VM-negative tumor ( < 0.001), whereas no significant difference was detected in overall survival (OS) between these patients. High levels of phosphorylate serine/threonine kinases Ataxia-telangiectasia mutated (pATM) and phosphorylate Ataxia-telangiectasia and Rad3-Related (pATR) were detected in 31 (22.8%) and 34 (25.0%), respectively out of 136 oligodendroglioma samples. Higher expressions of pATM and pATR were both associated with a shorter PFS ( < 0.001 and < 0.001). VM-positive oligodendroglioma specimens tended to exhibit higher pATM and pATR staining than VM-negative specimens (r = 0.435, < 0.001 and r = 0.317, < 0.001). Besides, Hypoxia-inducible factor-1α (HIF1α) expression was detected in 14(10.3%) samples, correlated with higher WHO grade and non-frontal lobe ( = 0.010 and = 0.029). However, no obvious connection was detected between HIF1α expression and VM formation ( = 0.537). Finally, either univariate or multivariate analysis suggested that VM was an independent unfavorable predictor for oligodendroglioma patients ( < 0.001, HR = 7.928, 95%CI: 3.382-18.584, and = 0.007, HR = 4.534, 95%CI: 1.504-13.675, respectively). VM is a potential prognosticator for tumor progression in oligodendroglioma patients. Phosphorylation of ATM and ATR linked to treatment-resistance may be associated with VM formation. The role of VM in tumor progression and the implication of pATM/pATR in VM formation may provide potential therapeutic targets for oligodendroglioma treatment.
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http://dx.doi.org/10.3389/pore.2021.1609844DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8408314PMC
August 2021

Two amide glycosides from L. and its bioactivities.

Nat Prod Res 2021 Aug 5;35(16):2655-2659. Epub 2019 Sep 5.

Sorbonne Université, CNRS, Laboratoire de Biodiversité et Biotechnologie Microbienne, Banyuls-sur-mer, France.

Two novel amide glycosides, named oleraciamide E () and oleraciamide F (), were isolated from the L. Their structures were determined by means of 1D and 2D NMR spectroscopic and UHPLC-ESI-TOF-MS methods. Oleraciamide E () exhibited anticholinesterase activity with IC values of 52.43 ± 0.33 μM, and presented scavenging activity in 1,1-diphenyl-2-picrylhydrazyl (DPPH) radical quenching assay, with the IC values of 24.64 ± 0.33 μM.
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http://dx.doi.org/10.1080/14786419.2019.1660333DOI Listing
August 2021

Clinical trial of Wenxin granules combined with aspirin in the treatment of cardiac syndrome X.

Asian J Surg 2021 Aug 6. Epub 2021 Aug 6.

Department of Cardiology, Hebei General Hospital, 348 Heping West Road, Shijiazhuang, 050051, China. Electronic address:

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http://dx.doi.org/10.1016/j.asjsur.2021.07.057DOI Listing
August 2021

Genetic analysis and biological characteristics of novel clade 2.3.4.4 reassortment H5N6 avian influenza viruses from poultry in eastern China in 2016.

Int J Infect Dis 2021 Aug 6;110:436-448. Epub 2021 Aug 6.

State Key Laboratory for Diagnosis and Treatment of Infectious Diseases, and National Clinical Research Center for Infectious Diseases, the First Affiliated Hospital, School of Medicine, Zhejiang University, Hangzhou 310003, China. Electronic address:

Objectives: The continuous evolution of highly pathogenic H5N6 avian influenza viruses (AIVs) causes outbreaks in wildfowl and poultry, and occasional human infections. The aim of this study was to better understand the genetic relationships between these H5N6 AIVs from eastern China and other AIVs.

Methods: In 2016, 1623 cloacal swabs were sampled from poultry in 18 LPMs in eastern China, and subsequently characterized systematically using gene sequencing, phylogenetic studies, and antigenic analysis. In addition, their pathogenicity in mammals was studied in BALB/c mice, which were inoculated with viruses, with survival rate and body weight recorded daily for 14 days.

Results: In total, 56 H5N6 AIVs were isolated in eastern China and five representative isolates were selected for further study. In our study, the H5N6 AIVs clustered into clade 2.3.4.4, Group C, and their six internal segments were derived from H6N6 and H9N2 viruses, or both, suggesting extensive reassortant among H5N6 AIVs with other subtypes. These H5N6 viruses could replicate in the lungs without prior adaptation, and exhibited slight-to-moderate virulence in mice.

Conclusions: The continuous circulation of these novel H5N6 viruses suggests the importance of persistent surveillance of H5N6 AIVs in poultry.
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http://dx.doi.org/10.1016/j.ijid.2021.07.074DOI Listing
August 2021

Dynamic Characteristic Analysis of Antibodies in Patients With COVID-19: A 13-Month Study.

Front Immunol 2021 20;12:708184. Epub 2021 Jul 20.

State Key Laboratory for Diagnosis and Treatment of Infectious Diseases, National Clinical Research Center for Infectious Diseases, Collaborative Innovation Center for Diagnosis and Treatment of Infectious Diseases, The First Affiliated Hospital, School of Medicine, Zhejiang University, Hangzhou, China.

There is a worldwide pandemic of Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection; yet our understanding remains limited on the characteristic of antibodies, especially for dynamic long-term tracking. Sequential serum samples were collected up to 416 days post onset of symptoms (POS) from 102 patients who were hospitalized with coronavirus disease 2019 (COVID-19). Immunoglobulin (Ig)G, IgM, and IgA levels targeting SARS-CoV-2 spike 1 receptor-binding domain (S1-RBD), spike 2 extracellular domain (S2-ECD), and nucleocapsid protein (N) were quantified as well as neutralizing activity. We were pleasantly surprised to find that the antibody remained detective and effective for more than a year POS. We also found the varied reactions of different antibodies as time passed: N-IgA rose most rapidly in the early stage of infection, while S2-IgG was present at a high level in the long time of observation. This study described the long traceable antibody response of the COVID-19 and offered hints about targets to screen for postinfectious immunity and for vaccination development of SARS-CoV-2.
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http://dx.doi.org/10.3389/fimmu.2021.708184DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8330131PMC
August 2021

MiR-342 controls Mycobacterium tuberculosis susceptibility by modulating inflammation and cell death.

EMBO Rep 2021 Sep 20;22(9):e52252. Epub 2021 Jul 20.

School of Life Sciences, Chongqing University, Chongqing, China.

Tuberculosis (TB) is an infectious disease caused by Mycobacterium tuberculosis (Mtb) that places a heavy strain on public health. Host susceptibility to Mtb is modulated by macrophages, which regulate the balance between cell apoptosis and necrosis. However, the role of molecular switches that modulate apoptosis and necrosis during Mtb infection remains unclear. Here, we show that Mtb-susceptible mice and TB patients have relatively low miR-342-3p expression, while mice with miR-342-3p overexpression are more resistant to Mtb. We demonstrate that the miR-342-3p/SOCS6 axis regulates anti-Mtb immunity by increasing the production of inflammatory cytokines and chemokines. Most importantly, the miR-342-3p/SOCS6 axis participates in the switching between Mtb-induced apoptosis and necrosis through A20-mediated K48-linked ubiquitination and RIPK3 degradation. Our findings reveal several strategies by which the host innate immune system controls intracellular Mtb growth via the miRNA-mRNA network and pave the way for host-directed therapies targeting these pathways.
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http://dx.doi.org/10.15252/embr.202052252DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8419689PMC
September 2021

Structure-Based Discovery of Novel Nonpeptide Inhibitors Targeting SARS-CoV-2 M.

J Chem Inf Model 2021 08 19;61(8):3917-3926. Epub 2021 Jul 19.

School of Pharmaceutical Sciences and Innovative Drug Research Centre, Chongqing Key Laboratory of Natural Product Synthesis and Drug Research, Chongqing University, Chongqing 401331, China.

The continual spread of novel coronavirus disease 2019 (COVID-19) is caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), posing a severe threat to the health worldwide. The main protease (M, alias 3CL) of SARS-CoV-2 is a crucial enzyme for the maturation of viral particles and is a very attractive target for designing drugs to treat COVID-19. Here, we propose a multiple conformation-based virtual screening strategy to discover inhibitors that can target SARS-CoV-2 M. Based on this strategy, nine M structures and a protein mimetics library with 8960 commercially available compounds were prepared to carry out ensemble docking for the first time. Five of the nine structures are apo forms presented in different conformations, whereas the other four structures are holo forms complexed with different ligands. The surface plasmon resonance assay revealed that 6 out of 49 compounds had the ability to bind to SARS-CoV-2 M. The fluorescence resonance energy transfer experiment showed that the biochemical half-maximal inhibitory concentration (IC) values of the six compounds could hamper M activities ranged from 0.69 ± 0.05 to 2.05 ± 0.92 μM. Evaluation of antiviral activity using the cell-based assay indicated that two compounds (Z1244904919 and Z1759961356) could strongly inhibit the cytopathic effect and reduce replication of the living virus in Vero E6 cells with the half-maximal effective concentrations (EC) of 4.98 ± 1.83 and 8.52 ± 0.92 μM, respectively. The mechanism of the action for the two inhibitors were further elucidated at the molecular level by molecular dynamics simulation and subsequent binding free energy analysis. As a result, the discovered noncovalent reversible inhibitors with novel scaffolds are promising antiviral drug candidates, which may be used to develop the treatment of COVID-19.
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http://dx.doi.org/10.1021/acs.jcim.1c00355DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8315252PMC
August 2021

The Prognostic Value of Retraction Clefts in Chinese Invasive Breast Cancer Patients.

Pathol Oncol Res 2021 21;27:1609743. Epub 2021 Apr 21.

Department of Pathology, The First Affiliated Hospital of USTC, Division of Life Sciences and Medicine, University of Science and Technology of China, Hefei, China.

Some studies reported the correlation between retraction clefts (RCs) and the clinicopathological features as well as prognosis in invasive breast carcinoma. However, limited number of investigations have been done and controversial results were reported. Larger population studies around the world might help to provide more accurate and comprehensive information. Thus, we examined the correlation between the extent of RCs and the clinicopathological features as well as the prognosis in 541 invasive breast carcinoma samples from Central China in this study. The statistical analyses were performed with the Pearson χ2 tests and univariate Cox proportional hazards regression assays. Compared with other studies, lower RCs occurrence rate (15.5%) was observed in Chinese breast cancer patients and opposite association between the presence of RCs and lymph nodes metastasis was identified, in which both progression free survival (PFS) and overall survival (OS) were improved with the presence of RCs in our study. Besides, despite some statistically significant associations between RCs and molecular subtypes, RCs and estrogen receptor status, the results were largely depending on the stratification methods. Generally, no convincing association was detected between the extent of RCs and the clinicopathological features or prognosis. In sum, the extent of RCs showed limited value as a prognostic predictor in invasive breast carcinoma patients from Central China.
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http://dx.doi.org/10.3389/pore.2021.1609743DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8262209PMC
April 2021

Evaluation of Ascending Aortic Longitudinal Strain Via Two-Dimensional Speckle Tracking Echocardiography in Hypertensive Patients Complicated by Type A Aortic Dissection.

J Ultrasound Med 2021 Jul 5. Epub 2021 Jul 5.

Department of Cardiovascular Ultrasound, the Second Affiliated Hospital of Dalian Medical University, Dalian, China.

Objective: To explore the value of ascending aortic longitudinal strain (LS) in identification of hypertensive (HP) patients with a high risk of type A aortic dissection (AAD).

Methods: Total 40 primary HP patients with AAD (group C), 80 selected age- and sex-matched primary HP patients (group A, normal-sized ascending aorta (AA), n = 40; group B, dilated AA, n = 40) and 40 healthy volunteers were enrolled in this study. Brachial blood pressures were measured, and the aortic stiffness index (β) determined by M-mode analysis was calculated as a conventional parameter of arterial stiffness. The LS of the anterior and posterior ascending aortic wall (AW-LS and PW-LS) were determined.

Results: Compared to the control group (34.21 ± 5.25%), the mean LS of AA in HP patients (group A 28.6 ± 5.95%; group B 23.64 ± 4.98%; group C 17.93 ± 3.96%; P < .001) were significantly reduced. Multivariate logistic regression analysis showed that the mean LS (OR 0.719, 95% CI 0.615-0.839, P < .001) and pulse pressure (PP) (OR 1.055, 95% CI 1.006-1.106, P = .028) were identified as independent predictors of AAD in HP patients. The AUC of mean LS combined with PP reached 0.926 (sensitivity, 95.0%; specificity, 82.5%), which was higher than the mean LS, PP, stiffness index, and ascending aortic diameter (AAd) separately. Besides, the AW-LS and PW-LS were negatively correlated with the AAd, stiffness index, stroke volume, systolic blood pressure, and PP, respectively (P < .001).

Conclusion: The LS of AA evaluated by two-dimensional speckle tracking echocardiography decreased significantly along with the expansion of aortic lumen and the occurrence of AAD in HP patients. It is also an independent predictor of AAD in HP patients.
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http://dx.doi.org/10.1002/jum.15777DOI Listing
July 2021

Development of an antigen-ELISA and a colloidal gold-based immunochromatographic strip based on monoclonal antibodies for detection of avian influenza A(H5) viruses.

J Vet Diagn Invest 2021 Sep 24;33(5):969-974. Epub 2021 Jun 24.

State Key Laboratory for Diagnosis and Treatment of Infectious Diseases, and National Clinical Research Center for Infectious Diseases, the First Affiliated Hospital, School of Medicine, Zhejiang University, Hangzhou, China.

Avian influenza A(H5) viruses (avian IAVs) pose a major threat to the economy and public health. We developed an antigen-ELISA (ag-ELISA) and a colloidal gold-based immunochromatographic strip for the rapid detection of avian A(H5) viruses. Both detection methods displayed no cross-reactivity with other viruses (e.g., other avian IAVs, infectious bursal disease virus, Newcastle disease virus, infectious bronchitis virus, avian paramyxovirus). The ag-ELISA was sensitive down to 0.5 hemagglutinin (HA) units/100 µL of avian A(H5) viruses and 7.5 ng/mL of purified H5 HA proteins. The immunochromatographic strip was sensitive down to 1 HA unit/100 µL of avian A(H5) viruses. Both detection methods exhibited good reproducibility with CVs < 10%. For 200 random poultry samples, the sensitivity and specificity of the ag-ELISA were 92.6% and 98.8%, respectively, and for test strips were 88.9% and 98.3%, respectively. Both detection methods displayed high specificity, sensitivity, and stability, making them suitable for rapid detection and field investigation of avian A(H5) viruses.
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http://dx.doi.org/10.1177/10406387211027538DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8366253PMC
September 2021

Kinetic resolution of racemic allylic alcohols iridium-catalyzed asymmetric hydrogenation: scope, synthetic applications and insight into the origin of selectivity.

Chem Sci 2020 Dec 8;12(5):1937-1943. Epub 2020 Dec 8.

Department of Organic Chemistry, Stockholm University, Arrhenius Laboratory 106 91 Stockholm Sweden

Asymmetric hydrogenation is one of the most commonly used tools in organic synthesis, whereas, kinetic resolution asymmetric hydrogenation is less developed. Herein, we describe the first iridium catalyzed kinetic resolution of a wide range of trisubstituted secondary and tertiary allylic alcohols. Large selectivity factors were observed in most cases ( up to 211), providing the unreacted starting materials in good yield with high levels of enantiopurity (ee up to >99%). The utility of this method is highlighted in the enantioselective formal synthesis of some bioactive natural products including pumiliotoxin A, inthomycin A and B. DFT studies and a selectivity model concerning the origin of selectivity are presented.
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http://dx.doi.org/10.1039/d0sc05276kDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8179068PMC
December 2020

Site- and Enantioselective Iridium-Catalyzed Desymmetric Mono-Hydrogenation of 1,4-Dienes.

Angew Chem Int Ed Engl 2021 08 20;60(35):19428-19434. Epub 2021 Jul 20.

Department of Organic Chemistry, Stockholm University, 10691, Stockholm, Sweden.

The control of site selectivity in asymmetric mono-hydrogenation of dienes or polyenes remains largely underdeveloped. Herein, we present a highly efficient desymmetrization of 1,4-dienes via iridium-catalyzed site- and enantioselective hydrogenation. This methodology demonstrates the first iridium-catalyzed hydrogenative desymmetriation of meso dienes and provides a concise approach to the installation of two vicinal stereogenic centers adjacent to an alkene. High isolated yields (up to 96 %) and excellent diastereo- and enantioselectivities (up to 99:1 d.r. and 99 % ee) were obtained for a series of divinyl carbinol and divinyl carbinamide substrates. DFT calculations reveal that an interaction between the hydroxy oxygen and the reacting hydride is responsible for the stereoselectivity of the desymmetrization of the divinyl carbinol. Based on the calculated energy profiles, a model that simulates product distribution over time was applied to show an intuitive kinetics of this process. The usefulness of the methodology was demonstrated by the synthesis of the key intermediates of natural products zaragozic acid A and (+)-invictolide.
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http://dx.doi.org/10.1002/anie.202107267DOI Listing
August 2021

Asymmetric synthesis of 1,2-fluorohydrin: iridium catalyzed hydrogenation of fluorinated allylic alcohol.

Chem Sci 2020 Sep 25;11(41):11189-11194. Epub 2020 Sep 25.

Department of Organic Chemistry, Stockholm University Svante Arrhenius väg 16C SE-10691 Stockholm Sweden

We have developed a simple protocol for the preparation of 1,2-fluorohydrin by asymmetric hydrogenation of fluorinated allylic alcohols using an efficient azabicyclo thiazole-phosphine iridium complex. The iridium-catalyzed asymmetric synthesis of chiral 1,2-fluorohydrin molecules was carried out at ambient temperature with operational simplicity, and scalability. This method was compatible with various aromatic, aliphatic, and heterocyclic fluorinated compounds as well as a variety of polyfluorinated compounds, providing the corresponding products in excellent yields and enantioselectivities.
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http://dx.doi.org/10.1039/d0sc04032kDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8162319PMC
September 2020

Analysis of vaccine-like lumpy skin disease virus from flies near the western border of China.

Transbound Emerg Dis 2021 May 25. Epub 2021 May 25.

Animal Inspection and Quarantine Laboratory, Technical Center of Chong-Qing Custom, Chongqing, China.

Lumpy skin disease (LSD) is a devastating viral disease that occurs in cattle. In China, it was first detected in the Xin-Jiang autonomous region, near the border with Kazakhstan, in August 2019. As there were no new occurrences of LSD in either country following the first detection, the initial introduction of the virus remains unknown. Arthropod vectors were considered as potential vectors. Consequently, to identify the arthropod vectors involved in transmitting LSD virus (LSDV), an insect surveillance campaign was launched at four different sites scattered along the border, and samples from 22 flying insect species were collected and subjected to PCR assays. Following the Agianniotaki LSDV vaccine and Sprygin's general LSDV assays, two kinds of non-biting flies, namely, Musca domestica L and Muscina stabulans, were positive for LSDV. However, all the other insects tested negative. Viral DNA was only detected in wash fluid, implying body surface contamination of the virus. The negative test results suggest that non-biting flies are the dominant insects involved in the observed local epidemic. Three genomic regions encoding RPO30, GPCR, and LW126 were successfully sequenced and subjected to phylogenetic analysis. The sequences shared high homology with LSDV/Russia/Saratov/2017, a recombinant vaccine-like strain formerly identified in Russia, and clustered with LSDV vaccine strains in phylogenetic trees of RPO30 and LW126. However, the GPCR gene was seen to be solely clustered with LSDV field strains, implying differences in host affinity between these closely related vaccine-like strains. Despite this, there is no direct evidence to support cross-border transmission of the vaccine-like LSDV. To our knowledge, this is the first report of vaccine-like LSDV DNA detection in non-biting flies in China.
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http://dx.doi.org/10.1111/tbed.14159DOI Listing
May 2021

Multisegmental versus monosegmental intramedullary spinal cord ependymomas: perioperative neurological functions and surgical outcomes.

Neurosurg Rev 2021 May 14. Epub 2021 May 14.

Department of Neurosurgery, Peking University Third Hospital, Peking University, Beijing, China.

Multiple factors, such as tumor size, lateralization, tumor location, accompanying syringomyelia, and regional spinal cord atrophy, may affect the resectability and clinical prognosis of intramedullary spinal cord ependymomas. However, whether long-segmental involvement of the spinal cord may impair functional outcomes remains unclear. This study was aimed to compare perioperative neurological functions and long-term surgical outcomes between multisegmental ependymomas and their monosegmental counterparts. A total of 62 patients with intramedullary spinal cord ependymoma (WHO grade II) were enrolled, and all of them underwent surgical resection. The patients were classified into the multisegmental group (n = 43) and the monosegmental group (n = 19). Perioperative and long-term (average follow-up period, 47.3 ± 21.4 months) neurological functions were evaluated using the modified McCormick (mMC) scale and the modified Japanese Orthopaedic Association (mJOA) scoring system. Preoperative neurological functions in the multisegmental group were significantly worse than those in the monosegmental group (P < 0.05). However, postoperative short-term neurological functions, as well as long-term functional outcomes, were similar between the two groups (P > 0.05). Logistic regression analysis showed that preoperative mMC and mJOA scores were significantly correlated with neurological improvement during the follow-up period (P < 0.05). Multisegmental involvement of the spinal cord is associated with worse neurological functions in patients with intramedullary spinal cord ependymoma, while the long-term prognosis is not affected. The preoperative neurological status of the patient is the only predictor of long-term functional improvement.
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http://dx.doi.org/10.1007/s10143-021-01567-5DOI Listing
May 2021

Computational design and modeling of nanobodies toward SARS-CoV-2 receptor binding domain.

Chem Biol Drug Des 2021 07 13;98(1):1-18. Epub 2021 May 13.

School of Pharmaceutical Sciences and Innovative Drug Research Centre, Chongqing Key Laboratory of Natural Product Synthesis and Drug Research, Chongqing University, Chongqing, China.

The ongoing pandemic of coronavirus disease 2019 (COVID-19) caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has become a global health concern and pose a serious threat to humanity. There is an urgent need for developing therapeutic drugs and (or) biologics to prevent the spread of the virus. The life cycle of SARS-CoV-2 shows that the virus enters host cells by first binding to angiotensin-converting enzyme 2 (ACE2) through its spike protein receptor-binding domain (RBD). Therefore, blocking the binding between of ACE2 and SARS-CoV-2 RBD can inhibit the virus infection in the host cells. In this study, by grafting the complementarity-determining regions (CDRs) of developed SARS-CoV, MERS-CoVs specific neutralizing antibodies (nAbs) include monoclonal antibodies (mAbs) as well as SARS-CoV-2 mAbs onto a known stable nanobody (Nb) scaffold, and a total of 16 Nbs sequences were designed. Five Nbs, namely CS01, CS02, CS03, CS10, and CS16, were selected based on the free energy landscape of protein docking verified by the recently reported Nb-RBD cocrystal structures. CS01, CS02, and CS03 occupied the ACE2 binding site of RBD, while CS10 and CS16 were proposed to inhibit the interaction between RBD and ACE2 through an allosteric mechanism. Based on the structures of the five Nbs in complex with RBD, seven brand-new Nbs with enhanced binding affinities (CS02_RD01, CS03_RD01, CS03_RD02, CS03_RD03, CS03_RD04, CS16_RD01, and CS16_RD02) were generated by redesign of residues on the interface of the five Nbs contact with SARS-CoV-2 RBD. In addition, the identified "hot spots" on the interface of each complex provide useful information to understand the binding mechanism of designed Nbs to SARS-CoV-2 RBD. In sum, the predicted stabilities and high binding affinities of the 11 (re)designed Nbs indicating the potential of the developed computational framework in this work to design effective agents to block the infection of SARS-CoV-2.
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http://dx.doi.org/10.1111/cbdd.13847DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8250495PMC
July 2021

Cardioprotective effect of anisodamine against ischemia/reperfusion injury through the mitochondrial ATP-sensitive potassium channel.

Eur J Pharmacol 2021 Jun 20;901:174095. Epub 2021 Apr 20.

Department of Cardiology, Hebei General Hospital, Shijiazhuang, Hebei, 050000, China. Electronic address:

Previous clinical studies have shown that anisodamine could improve no-reflow phenomenon and prevent reperfusion arrhythmias, but whether this protective effect is related to the antagonism of the M-type cholinergic receptor or other potential mechanisms is uncertain. The aim of the present study was to investigate the role of the mitochondrial ATP-sensitive potassium channel (mitoK ATP ) in cardioprotective effect of anisodamine against ischemia/reperfusion injury. Anisodamine and 5- hydroxydecanoic acid were used to explore the relationship between anisodamine and mitoK ATP . Using a Langendorff isolated heart ischemia/reperfusion injury model, hemodynamic parameters and reperfusion ventricular arrhythmia were evaluated; in addition, changes in myocardial infarct size, cTnI from coronary effluent and myocardial ultrastructure, as well as ATP, MDA and SOD in myocardial tissues, were detected. In the hypoxia/reoxygenation injury model of neonatal rat cardiomyocyte, cTnI release in the culture medium and levels of ATP, MDA and SOD in cardiomyocytes and mitochondrial membrane potential, were analyzed. Overall, anisodamine could significantly improve the hemodynamic indexes of isolated rat heart injured by ischemia/reperfusion, reduce the occurrence of ventricular reperfusion arrhythmia and myocardial infarction area, and improve the ultrastructural damage of myocardium and mitochondria. The in vitro results demonstrated that anisodamine could improve mitochondrial energy metabolism, reduce oxidative stress and stabilize mitochondrial membrane potential. The cardioprotective effects were significantly inhibited by 5-hydroxydecanoic acid. In conclusion, this study suggests that the opening of mitoK ATP could play an important role in the protective effect of anisodamine against myocardial ischemia/reperfusion injury.
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http://dx.doi.org/10.1016/j.ejphar.2021.174095DOI Listing
June 2021

Pyroptotic macrophages stimulate the SARS-CoV-2-associated cytokine storm.

Cell Mol Immunol 2021 05 19;18(5):1305-1307. Epub 2021 Mar 19.

Department of Pathology, The First Affiliated Hospital of USTC, Division of Life Sciences and Medicine, University of Science and Technology of China, Hefei, Anhui, China.

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http://dx.doi.org/10.1038/s41423-021-00665-0DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7976727PMC
May 2021

ORF8 contributes to cytokine storm during SARS-CoV-2 infection by activating IL-17 pathway.

iScience 2021 Apr 9;24(4):102293. Epub 2021 Mar 9.

School of Life Sciences, Chongqing University, Chongqing 401331, China.

Recently, COVID-19 caused by the novel coronavirus SARS-CoV-2 has brought great challenges to the world. More and more studies have shown that patients with severe COVID-19 may suffer from cytokine storm syndrome; however, there are few studies on its pathogenesis. Here we demonstrated that SARS-CoV-2 coding protein open reading frame 8 (ORF8) acted as a contributing factor to cytokine storm during COVID-19 infection. ORF8 could activate IL-17 signaling pathway and promote the expression of pro-inflammatory factors. Moreover, we demonstrated that treatment of IL17RA antibody protected mice from ORF8-induced inflammation. Our findings are helpful to understand the pathogenesis of cytokine storm caused by SARS-CoV-2 and provide a potential target for the development of COVID-19 therapeutic drugs.
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http://dx.doi.org/10.1016/j.isci.2021.102293DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7942160PMC
April 2021

Aberrant expression of thyroid transcription factor-1 in meningeal solitary fibrous tumor/hemangiopericytoma.

Brain Tumor Pathol 2021 Apr 5;38(2):122-131. Epub 2021 Mar 5.

Department of Pathology, The First Affiliated Hospital of USTC, Division of Life Sciences and Medicine, University of Science and Technology of China, Hefei, 230036, Anhui, China.

Meningeal solitary fibrous tumor (SFT) and hemangiopericytoma (HPC) were categorized as the same entity in the World Health Organization (WHO) 2016 classification of tumors of the central nervous system (CNS). Although NAB2-STAT6 fusion protein can be used to distinguish most of SFT/HPC from the other sarcomas, additional biomarkers were requested to separate meningeal SFT/HPC from meningioma and the molecular pathological difference between meningeal SFT/HPC and extra-CNS SFT/HPC still remains unclear. In this study, we evaluated the expression of TTF-1 in 67 meningeal SFT/HPC, 62 extra-CNS SFT/HPC and 201 meningiomas samples with immunohistochemistry (IHC) assays. The results showed that TTF-1 was detected in 23 of 67 (34.3%) meningeal SFT/HPC, 3 retroperitoneum SFT/HPC and none of meningiomas. Meanwhile, the copy number variation and mRNA expression of TTF-1 were measured by real-time quantitative PCR (qPCR) in meningeal SFT/HPC. These results demonstrated that TTF-1 protein expression level was significantly correlated with its transcription level, but independently related to the gene copy number variant. In conclusion, our study suggested that a large proportion of meningeal SFT/HPC was positive to TTF-1, while very few extra CNS SFT/HPC cases and no meningiomas were stained. So TTF-1 has value as an auxiliary diagnostic marker for meningeal SFT/HPC.
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http://dx.doi.org/10.1007/s10014-021-00395-1DOI Listing
April 2021

Development and application of a real-time RT-PCR assay to rapidly detect H2 subtype avian influenza A viruses.

J Vet Diagn Invest 2021 May 22;33(3):577-581. Epub 2021 Feb 22.

State Key Laboratory for Diagnosis and Treatment of Infectious Diseases, and National Clinical Research Center for Infectious Diseases, The First Affiliated Hospital, School of Medicine, Zhejiang University, Hangzhou, China.

The H2 subtypes of avian influenza A viruses (avian IAVs) have been circulating in poultry, and they have the potential to infect humans. Therefore, establishing a method to quickly detect this subtype is pivotal. We developed a TaqMan minor groove binder real-time RT-PCR assay that involved probes and primers based on conserved sequences of the matrix and hemagglutinin genes. The detection limit of this assay was as low as one 50% egg infectious dose (EID)/mL per reaction. This assay is specific, sensitive, and rapid for detecting avian IAV H2 subtypes.
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http://dx.doi.org/10.1177/1040638721994810DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8120088PMC
May 2021

Isolation and characterization of two novel reassortant H5N6 avian influenza viruses from waterfowl in eastern China.

Arch Virol 2021 Apr 17;166(4):1197-1201. Epub 2021 Feb 17.

State Key Laboratory for Diagnosis and Treatment of Infectious Diseases, National Clinical Research Center for Infectious Diseases, The First Affiliated Hospital, School of Medicine, Zhejiang University, 79 Qingchun Road, Hangzhou, 310003, Zhejiang, China.

Waterfowl are considered to be the natural hosts of avian influenza virus. In 2017, two reassortant highly pathogenic H5N6 avian influenza viruses of clade 2.3.4.4, subclade II, were identified in wild birds in eastern China. Genome sequencing and phylogenetic and antigenicity analysis showed that the viruses originated from multiple reassortments. To evaluate their pathogenicity in mammals, 15 BALB/c mice were infected with these viruses, and survival and weight loss were monitored for 14 days. Infection was associated with moderate pathogenicity in the mice, and the viruses could replicate in the lungs without prior adaptation. Thus, the existence of these viruses poses a continuous threat to both birds and humans.
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http://dx.doi.org/10.1007/s00705-021-04995-2DOI Listing
April 2021

Religious Problem-Solving Styles and Life Satisfaction: Exploring God, the Will and the Way.

J Relig Health 2021 Jan 15. Epub 2021 Jan 15.

Lingnan (University) College, Sun Yat-sen University, Guangzhou, People's Republic of China.

A proliferation of empirical studies over the past few decades has examined the connection between religiosity and health; an extension of this literature has focused on the association between three styles of religious problem-solving-collaborative, self-directing and deferring-and psychological adjustment. Few studies, however, have examined variables that may mediate this association. The present study utilized a cross-sectional design to examine the pathways (means to attain goals) and agency (goal-directed energy and determination) components of hope as mediators in the association between religious problem-solving styles and psychosocial adjustment. Students (n = 91) at a midsize Southeastern university completed a demographic questionnaire, the Religious Problem-solving Styles Scale, Adult Hope Scale, and the Life Satisfaction Scale. Mediation analyses revealed that both the collaborative and deferring religious problem-solving styles were positively associated with life satisfaction through agency thinking, but the self-directing religious problem-solving style was negatively associated with life satisfaction through agency thinking. Contrary to expectations, there was no significant indirect effect of any of the religious problem-solving styles on life satisfaction via pathways thinking. These results suggest that approaching problems within a specific religious framework is associated with psychosocial adjustment, and that each religious problem-solving style may exert its effects by either amplifying or quelling goal-directed motivation and willpower. Future studies should utilize quasi-experimental designs in order to delineate cause-and-effect relationships among religious problem-solving styles, agency and pathways thinking, and psychosocial adjustment.
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http://dx.doi.org/10.1007/s10943-020-01159-5DOI Listing
January 2021

Patient-derived SARS-CoV-2 mutations impact viral replication dynamics and infectivity in vitro and with clinical implications in vivo.

Cell Discov 2020 Oct 29;6(1):76. Epub 2020 Oct 29.

State Key Laboratory for Diagnosis and Treatment of Infectious Diseases, National Clinical Research Center for Infectious Diseases, First Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou, Zhejiang, 310009, China.

The severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has spread globally with more than 33 million patients diagnosed, taking more than a million lives. Abundant mutations were observed but the functional consequences of these mutations are largely unknown. We report the mutation spectrum, replication dynamics, and infectivity of 11 patient-derived viral isolates in diverse cell lines, including the human lung cancer cell line Calu-3. We observed 46 mutations, including 9 different mutations in the spike gene. Importantly, these viral isolates show significant and consistent variations in replication dynamics and infectivity in tested cell lines, up to a 1500-fold difference in viral titers at 24 h after infecting Calu-3 cells. Moreover, we show that the variations in viral titers among viral isolates are positively correlated with blood clotting function but inversely correlated with the amount of red blood cell and hemoglobin in patients. Therefore, we provide direct evidence that naturally occurring mutations in SARS-CoV-2 can substantially change its replication dynamics and infectivity in diverse human cell lines, with clinical implications in vivo.
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http://dx.doi.org/10.1038/s41421-020-00226-1DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7595057PMC
October 2020

Bicuspidization reconstruction for regurgitant quadricuspid pulmonary valve concomitant pulmonary artery aneurysm graft replacement.

J Card Surg 2021 Feb 7;36(2):716-719. Epub 2020 Dec 7.

Department of Cardiovascular Surgery, The Second Affiliated Hospital of Dalian Medical University, Dalian, Liaoning, China.

Large pulmonary artery aneurysm with severe pulmonary valve regurgitation due to the quadricuspid pulmonary valve (Type F) was found in a 54-year-old woman with fatigue and dyspnea on exertion, and in New York Heart Association (NYHA) functional class III. The annulus plication and bicuspidization technique were successfully used for the pulmonary valvular reconstruction. Then, the main pulmonary artery was replaced with Dacron graft and the left pulmonary arterioplasty was performed. Postoperative echocardiography confirmed a satisfactory motion of the reconstructed pulmonary valve with trivial regurgitation and no stenosis.
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http://dx.doi.org/10.1111/jocs.15211DOI Listing
February 2021

Clozapine Use in Patients with Early-Stage Schizophrenia in a Chinese Psychiatric Hospital.

Neuropsychiatr Dis Treat 2020 24;16:2827-2836. Epub 2020 Nov 24.

The First School of Clinical Medicine, Southern Medical University, Guangzhou, Guangdong, People's Republic of China.

Objective: Previous studies suggest that clozapine is commonly underutilized and that its initiation is delayed in patients with first-episode schizophrenia. Knowledge regarding clozapine use among Chinese patients with early-stage schizophrenia is limited. The aim of the present study was to investigate the point prevalence of and patterns and factors associated with clozapine use in patients with early-stage schizophrenia discharged from a psychiatric hospital in China.

Methods: A retrospective study was conducted to analyze the prescriptions of 867 consecutive patients with early-stage schizophrenia who were admitted to the Affiliated Brain Hospital of Guangzhou Medical University between Jan 1, 2011 and Dec 31, 2016.

Results: At discharge from the hospital, 114 (13.1%) patients were prescribed clozapine. Among the patients taking clozapine, 93 patients (81.6%) were prescribed clozapine polypharmacy, and only 21 patients (18.4%) were prescribed clozapine monotherapy. None of the patients were prescribed an overdose of clozapine. The mean daily dosage of clozapine was 160.97 mg, 149.05 mg and 213.69 mg among all patients taking clozapine, patients taking clozapine polypharmacy and patients taking clozapine monotherapy, respectively. The antipsychotic most frequently combined with clozapine was risperidone. Logistic regression suggested that the length of hospital stay, high school education, lower benzodiazepine use and antipsychotic polypharmacy were independently and significantly associated with clozapine use (P<0.05).

Conclusion: Although clozapine has been commonly used in China in recent years, the present study found that clozapine was not commonly used in patients with early-stage schizophrenia. An underutilization and delayed initiation of clozapine may exist in a portion of patients with early-stage schizophrenia. Given the unfavorable outcomes of underutilized and delayed clozapine use, future studies may be needed to assess and increase clozapine use in this population.
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http://dx.doi.org/10.2147/NDT.S261503DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7699990PMC
November 2020

Transcriptional changes of mouse ovary during follicle initial or cyclic recruitment mediated by extra hormone treatment.

Life Sci 2021 Jan 24;264:118654. Epub 2020 Oct 24.

Department of Assisted Reproduction, Shanghai Ninth People's Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai 200011, China. Electronic address:

Aims: Folliculogenesis contains gonadotropin-independent and -dependent stage. Disruption in any of this process would induce failure in retrieving capable oocytes during clinical treatment. However, there is still limited understanding of the molecular components specifically regulating this process.

Material And Methods: Ovaries of P3, P20 and exogenous gonadotropin-treated P22 mice were sampled and underwent RNA-seq to investigate the transcriptome variance during mouse folliculogenesis.

Key Findings: In our dataset, 1883 and 626 DEGs were captured for each stage respectively, which were further clustered into eight expression patterns. Pathway enrichment analysis identified distinct biological processes enriched in two stages, with the most prominent being the pathways related to metabolism, gene expression, cell cycle, immune system and DNA methylation. Transcriptional regulator inference yielded eight master transcription factors (i.e. Runx1, Stat3, Sox3, Pou5f1, Gata4, Foxl2, Cebpb, and Esr1) driving folliculogenesis.

Significance: Our study revealed the temporal transcriptional reprogramming and gene expression dynamics during folliculogenesis mediated by extra hormone treatment, which could provide novel insights to controlled ovarian stimulation in future infertility treatment.
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http://dx.doi.org/10.1016/j.lfs.2020.118654DOI Listing
January 2021

Immunological Effects of Aggregation-Induced Emission Materials.

Front Immunol 2020 6;11:575816. Epub 2020 Oct 6.

CAS Key Lab of Soft Matter Chemistry, University of Science and Technology of China, Hefei, China.

Nanotechnology is widely used in the fields of biology and medicine. Some special nanoparticles with good biocompatibility, hydrophilicity, and photostability can be used as ideal systems for biomedical imaging in early diagnosis and treatment of diseases. Among them, aggregation-induced emission materials are new antiaggregation-caused quenching nano-imaging materials, which have advantages in biocompatibility, imaging contrast, and light stability. Meanwhile, heterogeneity of nanoparticles may cause various adverse immune reactions. In response to the above problems, many researchers have modified nano-materials to be multifunctional nano-composites, aiming at combining diagnosis and treatment with simultaneous imaging and targeted therapy and additionally avoiding immune reactions, which is of great potential in imaging-guided therapy. This review discusses the application of aggregation-induced emission materials, and other nano-imaging materials are also mentioned. We hope to provide new ideas and methods for the imaging of nano-materials in diagnosis and treatment.
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http://dx.doi.org/10.3389/fimmu.2020.575816DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7573557PMC
June 2021

Antioxidant Polymers via the Kabachnik-Fields Reaction to Control Cellular Oxidative Stress.

Macromol Biosci 2020 12 28;20(12):e1900419. Epub 2020 Sep 28.

Key Laboratory of Bioorganic Phosphorus Chemistry and Chemical Biology (Ministry of Education), Department of Chemistry, Tsinghua University, Beijing, 100084, P. R. China.

Small molecular antioxidants are almost ineffective in regulating harmful oxidative stress in vivo because of their poor bioavailability. Polymer antioxidants are a promising alternative to address this issue, but their laborious synthetic routes limit their development. In this study, aliphatic and aromatic aldehydes are used to synthesize a family of polymers containing different α-aminophosphonate pendant groups via a facile one-pot method that combines the Kabachnik-Fields (KF) reaction and free radical polymerization. The structure-property relationship study of these polymers reveals the KF moieties in polymer structures confer radical scavenging ability on polymers. The radical scavenging ability and cytotoxicity of these polymers are evaluated in a stepwise manner to identify a biocompatible polymer antioxidant that can effectively protect the cells from H O -induced oxidative damage. This is the first attempt to develop antioxidative polymers by the KF reaction. It highlights the feasibility of synthesizing new functional polymers using multicomponent reactions, which has important implications for organic and polymer chemistry.
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http://dx.doi.org/10.1002/mabi.201900419DOI Listing
December 2020
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