Rapid accumulation of viral proteins in host cells render viruses highly dependent on cellular chaperones including heat shock protein 90 (Hsp90). Three highly pathogenic human coronaviruses, including MERS-CoV, SARS-CoV and SARS-CoV-2, have emerged in the past 2 decades. However, there is no approved antiviral agent against these coronaviruses. We inspected the role of Hsp90 for coronavirus propagation. First, an Hsp90 inhibitor, 17-AAG, significantly suppressed MERS-CoV propagation in cell lines and physiological-relevant human intestinal organoids. Second,...

Coxsackievirus A16 (CV-A16) is a major causative pathogen of hand, foot, and mouth diseases (HFMDs). The licensed HFMD vaccine targets EV-A71 without cross-protection against CV-A16. Thus, a CV-A16 vaccine is needed. In this study, the immunogenicity and protective efficacy of a live attenuated CV-A16 candidate, K168-8Ac, were evaluated in a rhesus monkey model. Four passages of this strain (P35, P50, P60, and P70) were administered to monkeys, and its protective effect was identified. The immunized...

Replication-competent vesicular stomatitis virus (VSV)-based recombinant viruses are useful tools for studying emerging and highly pathogenic enveloped viruses in level 2 biosafety facilities. Here, we used a replication-competent recombinant VSVs (rVSVs) encoding the spike (S) protein of SARS-CoV-2 in place of the original G glycoprotein (rVSV-eGFP-SARS-CoV-2) to develop a high-throughput entry assay for SARS-CoV-2. The S protein was incorporated into the recovered rVSV-eGFP-SARS-CoV-2 particles, which could be neutralized by sera from convalescent COVID-19 patients. The...

The establishment of a simple and effective method for determination of heavy metal ions has great significance due to the high hazard of heavy metal ions to public health and environments. Herein, we developed a facile way to synthesise a nanocomposite comprised of carbon nanotubes (CNTs) and metal-organic frameworks (MOFs), and explored its application in constructing an electrochemical (EC) sensor for detection of Cd2+ in aqueous solutions. The sensing surface was simply fabricated by casting...

A versatile theranostic agent that integrated with therapeutic and diagnostic functions is extremely essential for cancer theranostic. Herein, a multifunctional theranostic nanoplatform (PFP@MPDA-DOX) based on perfluoropentane (PFP) encapsulated mesoporous polydopamine (MPDA) is elaborately designed, followed by gating of drug doxorubicin (DOX) for preventing cargo leaking. The MPDA with pH-responsive biodegradation behavior was served as nanocarrier, which also endows the nanoplatform with a large cavity for PFP filling. The nanoparticles were then gated with DOX molecule...

Stimuli-responsive drug delivery systems (DDSs) are expected to realize site-specific drug release and kill cancer cells selectively. In this study, a pH-responsive micelle was designed utilizing the pH-sensitivity of borate bonds formed between dopamine and boronic acid. First, methyl (polyethylene glycol)-block-polycaprolactone (mPEG-PCL) was conjugated with 4-cyano-4-(thiobenzoylthio)pentanoic acid (CTP) to obtain a macroinitiator. Two different segments poly(dopamine methacrylamide) (PDMA) and poly(vinylphenylboronic acid) (PVBA) were then grafted to the end of mPEG-PCL. Two triblock copolymers, mPEG-PCL-PDMA and...

One of the major goals in HIV-1 vaccine development is to achieve properly folded and stabilized envelope glycoprotein (Env) trimers that mimic the native Env on the mature virion. Here, we design and characterize uncleaved prefusion-optimized (UFO) trimers for 12 Envs currently circulating in China. Biochemical and biophysical characterization of these UFO trimers identified two subtype B/Bʹ Envs, CNE6 and MG13, which exhibited the highest trimer content and stability at a level comparable to the...

One of the major goals in HIV-1 vaccine development is to achieve properly folded and stabilized envelope glycoprotein (Env) trimers that mimic the native Env on the mature virion. Here, we design and characterize uncleaved prefusion-optimized (UFO) trimers for 12 Envs currently circulating in China. Biochemical and biophysical characterization of these UFO trimers identified two subtype B/Bʹ Envs, CNE6 and MG13, which exhibited the highest trimer content and stability at a level comparable to the...

A simple, eco-friendly and convenient procedure has been developed for the synthesis of diphenyl diselinides from readily available aryl boronic acids by reaction with SeO2 in the presence of iodine under simple conditions. The methodology is reported about 19 examples and applicable to a broad scope of aryl boronic acids containing electron-rich and electron-poor substituents. Apart from being milder and environmentally benign conditions, this synthetic protocol comprises a novel, reliable methodology to give good to...

A Bayesian group sequential design is proposed that performs survival comparisons within patient subgroups in randomized trials where treatment–subgroup interactions may be present. A latent subgroup membership variable is assumed to allow the design to adaptively combine homogeneous subgroups, or split heterogeneous subgroups, to improve the procedure’s within-subgroup power. If a baseline covariate related to survival is available, the design may incorporate this information to improve subgroup identification while basing the comparative test on the...

We studied plasma antibody responses of 35 patients about 1 month after SARS-CoV-2 infection. Titers of antibodies binding to the viral nucleocapsid and spike proteins were significantly higher in patients with severe disease. Likewise, mean antibody neutralization titers against SARS-CoV-2 pseudovirus and live virus were higher in the sicker patients, by ∼5-fold and ∼7-fold, respectively. These findings have important implications for those pursuing plasma therapy, isolation of neutralizing monoclonal antibodies, and determinants of immunity.

The global pandemic of coronavirus disease 2019 (COVID-19) is a disaster for human society. A convenient and reliable neutralization assay is very important for the development of vaccines and novel drugs. In this study, a G protein-deficient vesicular stomatitis virus (VSVdG) bearing a truncated spike protein (S with C-terminal 18 amino acid truncation) was compared to that bearing the full-length spike protein of SARS-CoV-2 and showed much higher efficiency. A neutralization assay was established based...

Rapid accumulation of viral proteins in host cells render viruses highly dependent on cellular chaperones including heat shock protein 90 (Hsp90). Three highly pathogenic human coronaviruses, including MERS-CoV, SARS-CoV and SARS-CoV-2, have emerged in the past 2 decades. However, there is no approved antiviral agent against these coronaviruses. We inspected the role of Hsp90 for coronavirus propagation. First, an Hsp90 inhibitor, 17-AAG, significantly suppressed MERS-CoV propagation in cell lines and physiological-relevant human intestinal organoids. Second,...

An ultra-sensitive spectrofluorimetry method was developed and validated for the rapid determination of ferrocyanide ions (hexacyanidoferrate(II), FeCN64-, FCNs) by using sulphur (S) and nitrogen (N) dual-doped fluorescence carbon nanoparticles (S,N-FCNPs) as nanoprobe. The fluorescence of S,N-FCNPs was strongly reduced due to the dynamic interaction between S,N-FCNPs and FeCNs. The developed method proved to be highly sensitive and selective for FeCNs detection with linearity in three concentration ranges over four orders of magnitude, covering 0.01–200.0 μg/mL....

An ultra-sensitive spectrofluorimetry method was developed and validated for the rapid determination of ferrocyanide ions (hexacyanidoferrate(II), FeCN64-, FCNs) by using sulphur (S) and nitrogen (N) dual-doped fluorescence carbon nanoparticles (S,N-FCNPs) as nanoprobe. The fluorescence of S,N-FCNPs was strongly reduced due to the dynamic interaction between S,N-FCNPs and FeCNs. The developed method proved to be highly sensitive and selective for FeCNs detection with linearity in three concentration ranges over four orders of magnitude, covering 0.01–200.0 μg/mL....

Co-occurrence of hypervirulence and KPC-2 carbapenem resistant phenotypes in a highly-transmissible ST11 clone ofKlebsiella pneumoniae has elicited deep concerns from public health stand point. To address this puzzle, we conducted a large-scale epidemiological, clinical and genomic study of K. pneumonia ST11 clones with both hypervirulence and carbapenem resistance in two tertiary hospitals in Zhejiang province. Most of the patients (15/23) were diagnosed with exclusively carbapenem-resistant K. pneumoniae (CRKP) infections. Ten death cases were reported, some...

Quantitative real time PCR (RT-PCR) is widely used as the gold standard for clinical detection of SARS-CoV-2. However, due to the low viral load specimens and the limitations of RT-PCR, significant numbers of false negative reports are inevitable, which results in failure to timely diagnose, cut off transmission, and assess discharge criteria. To improve this situation, an optimized droplet digital PCR (ddPCR) was used for detection of SARS-CoV-2, which showed that the limit of detection...

The establishment of a simple and effective method for determination of heavy metal ions has great significance due to the high hazard of heavy metal ions to public health and environments. Herein, we developed a facile way to synthesise a nanocomposite comprised of carbon nanotubes (CNTs) and metal-organic frameworks (MOFs), and explored its application in constructing an electrochemical (EC) sensor for detection of Cd2+ in aqueous solutions. The sensing surface was simply fabricated by casting...

In this work, a novel flexible photoelectrochemical immunosensor is developed to determine cardiac troponin I (cTnI) in serum. The flower-like ZnIn2S4 nanospheres (ZIS), as signal amplification material, were successfully synthesized by a solvothermal method. The ZIS and Bi2Se3 were modified on the indium tin oxide- polyethylene terephthalate (ITO-PET) electrode, which effectively accelerates the electronic transition and improved the photocurrent conversion efficiency (signal on). However, the binding of antigen–antibody proteins blocks the electron transfer, resulting in...

A Bayesian group sequential design is proposed that performs survival comparisons within patient subgroups in randomized trials where treatment–subgroup interactions may be present. A latent subgroup membership variable is assumed to allow the design to adaptively combine homogeneous subgroups, or split heterogeneous subgroups, to improve the procedure’s within-subgroup power. If a baseline covariate related to survival is available, the design may incorporate this information to improve subgroup identification while basing the comparative test on the...

A Bayesian group sequential design is proposed that performs survival comparisons within patient subgroups in randomized trials where treatment–subgroup interactions may be present. A latent subgroup membership variable is assumed to allow the design to adaptively combine homogeneous subgroups, or split heterogeneous subgroups, to improve the procedure’s within-subgroup power. If a baseline covariate related to survival is available, the design may incorporate this information to improve subgroup identification while basing the comparative test on the...

Ribosomal DNA (rDNA) transcription drives cell growth and cell proliferation via the product ribosomal RNA (rRNA), the essential component of ribosome. Given the fundamental role of rRNA in ribosome biogenesis, rDNA transcription has emerged as one of the effective targets for a number of human diseases including various types of cancers. In this study, we identify curcumin, an ancient drug, as a novel natural inhibitor of rDNA transcription. Curcumin treatment impairs the assembly of the...

To investigate the effect of sea buckthorn puree consumption on reducing blood lipid and other risk factors of CVD. A total of 111 patients with hypercholesteromia who were treated with 90 ml sea buckthorn puree or placebo for 90 days were enrolled in this trial. Physical examination and analysis of lipid markers, hsCRP concentrations and cell adhesion protein concentrations with fasting blood samples were performed at 0-day, 45-day and 90-day after treatment. We found that...

To investigate the effect of sea buckthorn puree consumption on reducing blood lipid and other risk factors of CVD. A total of 111 patients with hypercholesteromia who were treated with 90 ml sea buckthorn puree or placebo for 90 days were enrolled in this trial. Physical examination and analysis of lipid markers, hsCRP concentrations and cell adhesion protein concentrations with fasting blood samples were performed at 0-day, 45-day and 90-day after treatment. We found that...

Coxsackievirus A16 (CV-A16) is a major causative pathogen of hand, foot, and mouth diseases (HFMDs). The licensed HFMD vaccine targets EV-A71 without cross-protection against CV-A16. Thus, a CV-A16 vaccine is needed. In this study, the immunogenicity and protective efficacy of a live attenuated CV-A16 candidate, K168-8Ac, were evaluated in a rhesus monkey model. Four passages of this strain (P35, P50, P60, and P70) were administered to monkeys, and its protective effect was identified. The immunized...