The nucleoprotein (NP) is a highly conserved internal protein of the influenza virus, a major target for universal influenza vaccine. Our previous studies have proven NP-based subunit vaccine can provide partial protection in mice. It is reported that the protein transduction domain (PTD) TAT protein from human immunodeficiency virus-1 (HIV-1) is able to penetrate cells when added exogenous protein and could effectively enhance the immune response induced by the exogenous protein. In present study, the...

Critically ill patients with coronavirus diseases 2019 (COVID-19) are of grave concern. Those patients usually underwent a stage of excessive inflammation before developing acute respiratory distress syndrome. In this study, we test the hypothesis that short-term, low-to-moderate-dose corticosteroids would benefit patients when used in the early phase of excessive inflammation, namely, the therapeutic window. Among a Shanghai cohort and a validation cohort, we enrolled COVID-19 patients showing marked radiographic progression. Short-term, low-to-moderate-dose corticosteroids were considered...

Structural basis of HCoV-19 fusion core and an effective inhibition peptide against virus entry

Under the ongoing COVID-19 prevention and control measures in China, increasing the laboratory severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) nucleic acid testing capacity has become the top priority. Since the COVID-19 outbreak in Xinfadi market in Beijing in June 2020, large-scale screening of key populations has been carried out, challenging the nucleic acid testing capabilities of hospital laboratories. Therefore, within 48 hours, Peking University People’s Hospital (PKUPH) transformed a non-nucleic acid testing laboratory into...

Supplemental Material, CONSORT_a for Effectiveness of Continuous Positive Airway Pressure Versus Mandibular Advancement Device in Severe Obstructive Sleep Apnea Patients With Mandibular Retrognathia: A Prospective Clinical Trial by Haichun Lai, Wei Huang, Wei Chen and Desheng Wang in Ear, Nose & Throat Journal

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...

Obtaining ideal gene delivery vectors is still a major goal in cancer gene therapy. CAMEL, a short hybrid antimicrobial peptide, can kill cancer cells by membrane lysis. In this study, we constructed a series of non-viral vectors by attaching fatty acids with different chain lengths to the N-terminus of CAMEL. Our results showed that the cellular uptake and transfection efficiency of acyl-CAMEL started to significantly increase from a chain length of 12 carbons. C18-CAMEL was...

The combined chemotherapy and photodynamic therapy have significant advantages for cancer treatments, which have higher therapeutic effects compared with other medicines. Herein, we focused on the synthesis of carbon quantum dot (CQD) based nanocarrier system. CQD and 5-aminolevulinic acid (5-ALA) were conjugated with mono-(5-BOC-protected-glutamine-6-deoxy) β-cyclodextrin (CQD-Glu-β-CD) moiety, and finally, the anticancer chemotherapy doxorubicin (DOX) drug was loaded in the 5-ALA-CQD-Glu-β-CD system. The stepwise physicochemical changes for the preparation of the DOX loaded 5-ALA-CQD-Glu-β-CD system were...

The accumulation and penetration of antitumor drugs in tumor tissues are directly related to their antitumor effects. The particle size of the nanodrug delivery system is one of the most important factors for the accumulation and penetration of antitumor drugs within tumor tissues. Generally, nanodelivery systems of intermediate size (100–120 nm) are capable of efficient accumulation owing to prolonged circulation and enhanced permeability and retention (EPR) effect; however, smaller ones (20–40 nm) are effective for...

Reactive oxygen species (ROS)-induced neuronal mitochondrial dysfunction is a key pathologic factor in sporadic Alzheimer’s disease (AD). Neuronal mitochondria have been proposed to be a promising therapeutic target for AD, especially for the failures of phase III clinical trials on conventional amyloid-β (Aβ) targeted therapy. However, the efficient intravenous delivery of therapeutic agents to neuronal mitochondria in the brain remains a major challenge due to the complicated physiological environment. Recently, biomaterials-based nanomedicine has been widely...

Hepatic stellate cells (HSCs) play a crucial role in the progression of liver fibrosis, which can be considered as the specific therapeutic target of anti-fibrotic treatment. Targeted induction of HSCs to hepatocytes via delivery of clustered regularly interspaced short palindromic repeats (CRISPR)/CRISPR-associated protein 9 (dCas9) system holds promise for hepatic fibrosis treatment. Our study here revealed that CRISPR/dCas9-VP64 system encapsulated in AML12 cell-derived exosomes could efficiently and successfully be delivered into the HSCs. In turn,...

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...

Since the outbreak of coronavirus disease 2019 (COVID-19) in Wuhan, China, it has rapidly spread across many other countries. While the majority of patients were considered mild, critically ill patients involving respiratory failure and multiple organ dysfunction syndrome are not uncommon, which could result death. We hypothesized that cytokine storm is associated with severe outcome. We enrolled 102 COVID-19 patients who were admitted to Renmin Hospital (Wuhan, China). All patients were classified into moderate, severe...

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...

Supplemental Material, CONSORT_b for Effectiveness of Continuous Positive Airway Pressure Versus Mandibular Advancement Device in Severe Obstructive Sleep Apnea Patients With Mandibular Retrognathia: A Prospective Clinical Trial by Haichun Lai, Wei Huang, Wei Chen and Desheng Wang in Ear, Nose & Throat Journal

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,...

Nanomaterials with various dimensionalities (e.g., nanowires, nanofilms, two-dimensional materials, and three-dimensional nanostructures) have shown great potential in the recent development of flexible electronics. Conventionally, organic solvents are inevitable while integrating nanomaterials onto flexible substrates, where polymer mediator-assisted transfer techniques are involved. This often damages the flexible substrate and thus hamper the large-scale application of nanomaterials. Here we report a method using water-soluble sugar as a mediator to facilely transfer nanomaterials onto rigid or flexible substrates....

Several dehydroabietylamine derivatives containing heterocyclic moieties such as thiophene and pyrazine ring were successfully synthesized. The antiproliferative activities of these thiophene-based Schiff-bases, thiophene amides, and pyrazine amides were investigated in vitro against Hela (cervix), MCF-7 (breast), A549 (lung), HepG2 (liver), and HUVEC (umbilical vein) cells by MTT assay. The toxicity of L1−L10 (IC50 = 5.92− >100 μM) was lower than L0 (1.27 μM) and DOX (4.40 μM) in every case. Compound L1 had higher anti-HepG2...

To improve synergistic anticancer efficacy and minimize the adverse effects of chemotherapeutic drugs, temozolomide (TMZ) and curcumin (CUR) co-loaded nanostructured lipid carriers (NLCs) were prepared by microemulsion in this study. And the physicochemical properties, drug release behavior, intracellular uptake efficiency, in vitro and in vivo anticancer effects of TMZ/CUR-NLCs were evaluated. TMZ/CUR-NLCs showed enhanced inhibitory effects on glioma cells compared to single drug loaded NLCs, which may be owing to that the quickly released CUR...

A novel approach to 3-benzyl-2,5-diarylpyrazine derivatives from α-amino ketones hydrochloride and arylaldehydes in the presence of Na2CO3 has been developed. In contrast with the classic synthetic methods of pyrazines, this protocol does not need additional oxidants and is more friendly to environment.

Structural basis of HCoV-19 fusion core and an effective inhibition peptide against virus entry

Scabies remains a significant public health concern globally, affecting people of all ages, races, and socioeconomic groups. The epidemic characteristics of scabies are yet unravelled, especially in high-income countries and elderly population. In this study, we sought to investigate incidence and prevalence and their trends of scabies worldwide from 1990 to 2017 via the Global Burden of Disease (GBD) Study 2017. The prevalence and incidence of scabies tend to a moderate increase after age 70....

The source of secondary lower respiratory tract bacterial infections in influenza patients is not fully understood. A case–control study was conducted during the 2017–2018 influenza epidemic period in Beijing, China. Nasopharyngeal swabs were collected from 52 virologically confirmed influenza patients and 24 healthy medical staff. The nasopharyngeal microbiota taxonomic composition was analysed using high-throughput sequencing of the 16S rRNA gene V3–V4 regions. The super-dominant pathobiontic bacterial genus (SDPG) was defined as that accounting for >50%...

Since the outbreak of coronavirus disease 2019 (COVID-19) in Wuhan, China, it has rapidly spread across many other countries. While the majority of patients were considered mild, critically ill patients involving respiratory failure and multiple organ dysfunction syndrome are not uncommon, which could result death. We hypothesized that cytokine storm is associated with severe outcome. We enrolled 102 COVID-19 patients who were admitted to Renmin Hospital (Wuhan, China). All patients were classified into moderate, severe...

Critically ill patients with coronavirus diseases 2019 (COVID-19) are of grave concern. Those patients usually underwent a stage of excessive inflammation before developing acute respiratory distress syndrome. In this study, we test the hypothesis that short-term, low-to-moderate-dose corticosteroids would benefit patients when used in the early phase of excessive inflammation, namely, the therapeutic window. Among a Shanghai cohort and a validation cohort, we enrolled COVID-19 patients showing marked radiographic progression. Short-term, low-to-moderate-dose corticosteroids were considered...