Serine 85 functions as a catalytic acid in the reprotonation process during EvAS-catalyzed astellifadiene biosynthesis.

The deprotonation-reprotonation sequence introduces additional cyclization branches in terpene biosynthesis. However, the underlying mechanism remains poorly understood. In this study, we employed a combined approach of molecular dynamics (MD) simulations and site-directed mutagenesis on astellifadiene synthase EvAS from to investigate the role of a protonated S85 residue.

Comparison of the Immunogenicity of the LZ901 Vaccine and HZ/su Vaccine in a Mouse Model.

Herpes zoster (HZ) is an infectious disease caused by the reactivation of varicella zoster virus (VZV), with 68% of cases occurring in adults over 50 years of age. HZ/su (Shingrix) was approved by the Food and Drug Administration in 2017 for the prevention of HZ in individuals ≥ 50 years of age and showed very good protection from HZ. However, due to the use of the adjuvant AS01, adverse reactions caused by Shingrix are a concern.

Discovery of a SUCNR1 antagonist for potential treatment of diabetic nephropathy: In silico and in vitro studies.

Diabetic nephropathy (DN) is one of the most severe complications of diabetes mellitus. Succinate Receptor 1 (SUCNR1), a member of the G-protein-coupled receptor (GPCR) family, represents a potential target for treatment of DN. Here, utilizing multi-strategy in silico virtual screening methods containing AlphaFold2 modelling, molecular dynamics (MD) simulation, ligand-based pharmacophore screening, molecular docking and machine learning-based similarity clustering, we successfully identified a novel antagonist of SUCNR1, AK-968/12117473 (Cpd3).

Microstructure, Mechanical Properties and Wear Behaviors of Ultrafine-Grain WC-Based Cermets with Different Binder Phases Fabricated by Spark Plasma Sintering.

In this work, to explore potential substitutions for the Co binder phase, ultrafine-grain WC-based cermets with various binder phases of Co, Ni and AlCoCrNiFeCu HEA were prepared using the SPS method. Based on SPS, WC-based cermets were fabricated at higher speed, showing fine carbide particles less than 410 μm. The microstructure, mechanical properties and wear properties were systematically evaluated.

NHC-Au-Catalyzed Isomerization of Propargylic B(MIDA)s to Allenes and Double Isomerization of Alkynes to 1,3-Dienes.

The synthesis of allenyl boronates is an important yet challenging topic in organic synthesis. Reported herein is an NHC-gold-catalyzed 1,3-H shift toward allenyl boronates synthesis from simple propargylic B(MIDA)s. Mechanistic studies suggest dual roles of the boryl moiety in the reaction: to activate the substrate for isomerization and at the same time, to prevent the allene product from further isomerization.

The Immunogenicity of CpG, MF59-like, and Alum Adjuvant Delta Strain Inactivated SARS-CoV-2 Vaccines in Mice.

The continuous evolution and mutation of SARS-CoV-2 have highlighted the need for more effective vaccines. In this study, CpG, MF59-like, and Alum adjuvant Delta strain inactivated SARS-CoV-2 vaccines were prepared, and the immunogenicity of these vaccines in mice was evaluated. The Delta + MF59-like vaccine group produced the highest levels of S- and RBD-binding antibodies and live Delta virus neutralization levels after one shot of immunization, while mice in the Delta + Alum vaccine group had the highest levels of these antibodies after two doses, and the Delta + MF59-like and Delta + Alum vaccine groups produced high levels of cross-neutralization antibodies against prototype, Beta, and Gamma strain SARS-CoV-2 viruses.

Prediction of CO/NOx emissions and the smoldering characteristic of sewage sludge based on back propagation neural network.

Smoldering can achieve effective disposal of sewage sludge (SS) with high moisture content at low energy input, providing social and economic benefits. However, smoldering is accompanied by the emission of high concentrations of CO/NOx, and thus, it requires sufficient attention. This study comprehensively investigates the effects of SS characteristics and experimental parameters on CO/NOx emissions and smoldering characteristics.

Molecular insights into the catalytic promiscuity of a bacterial diterpene synthase.

Diterpene synthase VenA is responsible for assembling venezuelaene A with a unique 5-5-6-7 tetracyclic skeleton from geranylgeranyl pyrophosphate. VenA also demonstrates substrate promiscuity by accepting geranyl pyrophosphate and farnesyl pyrophosphate as alternative substrates. Herein, we report the crystal structures of VenA in both apo form and holo form in complex with a trinuclear magnesium cluster and pyrophosphate group.

The impact of ambient air pollution on an influenza model with partial immunity and vaccination.

In this paper, we investigate the effects of ambient air pollution (AAP) on the spread of influenza in an AAP-dependent dynamic influenza model. The value of this study lies in two aspects. Mathematically, we establish the threshold dynamics in the term of the basic reproduction number $ \mathcal{R}_0 $: If $ \mathcal{R}_0 < 1 $, the disease will go to extinction, while if $ \mathcal{R}_0 > 1 $, the disease will persist.

A theoretical study on the effect of C particles on the growth of coronene radical based on HACA pathway.

Soot is a pollutant caused by combustion and is harmful to the environment and human health. Polycyclic aromatic hydrocarbons (PAHs) are considered the precursors of soot, thus exploring the growth mechanism of PAHs is conducive to reducing soot release. The mechanism by which a pentagonal carbon ring triggers the formation of curved PAHs has been demonstrated but studies on subsequent growth of soot are rare due to the lack of a suitable model.

The Quantification of Spike Proteins in the Inactivated SARS-CoV-2 Vaccines of the Prototype, Delta, and Omicron Variants by LC-MS.

Developing variant vaccines or multivalent vaccines is a feasible way to address the epidemic as the SARS-CoV-2 variants of concern (VOCs) posed an increased risk to global public health. The spike protein of the SARS-CoV-2 virus was usually used as the main antigen in many types of vaccines to produce neutralizing antibodies against the virus. However, the spike (S) proteins of different variants were only differentiated by a few amino acids, making it difficult to obtain specific antibodies that can distinguish different VOCs, thereby challenging the accurate distinction and quantification of the variants using immunological methods such as ELISA.

Unnatural activities and mechanistic insights of cytochrome P450 PikC gained from site-specific mutagenesis by non-canonical amino acids.

Cytochrome P450 enzymes play important roles in the biosynthesis of macrolide antibiotics by mediating a vast variety of regio- and stereoselective oxidative modifications, thus improving their chemical diversity, biological activities, and pharmaceutical properties. Tremendous efforts have been made on engineering the reactivity and selectivity of these useful biocatalysts. However, the 20 proteinogenic amino acids cannot always satisfy the requirement of site-directed/random mutagenesis and rational protein design of P450 enzymes.

Co,N-doped carbon sheets prepared by a facile method as high-efficiency oxygen reduction catalysts.

Transition metal and nitrogen codoped carbon materials have emerged as one of the most promising candidates to replace noble metal-based oxygen reduction reaction (ORR) catalysts. However, the development of high-efficiency, stable and low-cost metal-nitrogen-carbon catalysts still remains a challenge. In this study, cobalt and nitrogen codoped carbon sheet catalysts were successfully prepared by a simple self-injected vapor phase growth and template method.

Establishment of the first Chinese national standard for protein subunit SARS-CoV-2 vaccine.

A reference standard is needed for quality control of protein subunit SARS-CoV-2 vaccines to meet urgent domestic needs. The Chinese National Institutes for Food and Drug Control (NIFDC) launched a project to establish the first reference material for the protein subunit SARS-CoV-2 vaccine to be used for calibration of antigen testing. The potency and stability of the national candidate standard (CS) were determined by collaborative calibration, and accelerated and freeze-thaw degradation studies.

Immunological evaluation of an inactivated SARS-CoV-2 vaccine in rhesus macaques.

Because of the relatively limited understanding of coronavirus disease 2019 (COVID-19) pathogenesis, immunological analysis for vaccine development is needed. Mice and macaques were immunized with an inactivated severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) vaccine prepared by two inactivators. Various immunological indexes were tested, and viral challenges were performed on day 7 or 150 after booster immunization in monkeys.

A Survey of Pharmacogenomics Testing Among Physicians, Pharmacists, and Researchers From China.

To elucidate current domestic factors influencing pharmacogenomics (PGx) implementation and its future in China, we conducted a questionnaire survey on PGx applications and testing. A questionnaire-based survey was created on the popular online professional survey platform "Wenjuanxing" (www.wjx.

Lentil lectin derived from exhibit broad antiviral activities against SARS-CoV-2 variants.

The spike (S) protein of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) mutated continuously and newly emerging variants escape from antibody-mediated neutralization raised great concern. S protein is heavily glycosylated and the glycosylation sites are relatively conserved, thus glycans on S protein surface could be a target for the development of anti-SARS-CoV-2 strategies against variants. Here, we collected 12 plant-derived lectins with different carbohydrate specificity and evaluated their anti-SARS-CoV-2 activity against mutant strains and epidemic variants using a pseudovirus-based neutralization assay.

Immunogenicity and safety of an inactivated quadrivalent influenza vaccine: A randomized, double-blind, controlled phase III study in healthy population aged ≥3 years.

Inactivated quadrivalent influenza vaccine (IIV4) containing two influenza A strains (H1N1 and H3N2) and one strain from each B lineage (Victoria and Yamagata) may offer broader protection against seasonal influenza. This study examined the immunogenicity and safety of a candidate IIV4. A randomized, double-blind, controlled phase III clinical trial was conducted in healthy subjects aged ≥3 years.

Genetic and phenotypic frequency distribution of CYP2C9, CYP2C19 and CYP2D6 in over 3200 Han Chinese.

Purpose: This retrospective study analyzed the polymorphisms and phenotypic frequencies of CYP2C9, CYP2C19 and CYP2D6 in a Han Chinese population.

Methods: Tests for polymorphisms of CYP2C9, CYP2C19 and CYP2D6 were performed in over 3000 (3099-3931) samples using an Illumina HiSeq X Ten sequencer. Following the guidance of the PharmGKB and PharmVar databases, the polymorphisms of CYP2C9, CYP2C19 and CYP2D6 were transformed into phenotypes, which included ultrarapid metabolizers (UMs), rapid metabolizers (RMs), normal metabolizers (NMs), intermediate metabolizers (IMs) and poor metabolizers (PMs).

Development of an inactivated vaccine candidate for SARS-CoV-2.

The coronavirus disease 2019 (COVID-19) pandemic caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has resulted in an unprecedented public health crisis. Because of the novelty of the virus, there are currently no SARS-CoV-2-specific treatments or vaccines available. Therefore, rapid development of effective vaccines against SARS-CoV-2 are urgently needed.

Safety and Immunogenicity of Sabin Strain Inactivated Poliovirus Vaccine Compared With Salk Strain Inactivated Poliovirus Vaccine, in Different Sequential Schedules With Bivalent Oral Poliovirus Vaccine: Randomized Controlled Noninferiority Clinical Trials in China.

Background: A new Sabin strain inactivated poliovirus vaccine (sIPV) proved to be immunogenic and safe in all IPV primary immunization in the previous study, with the corresponding profiles in sequential immunizations unclear.

Methods: Two clinical trials on the "IPV + 2 bivalent oral polio vaccine (2bOPV)" (Trial A) and "2IPV + bOPV" (Trial B) vaccination were conducted. Both clinical trials were randomized, controlled, double-blinded, noninferiority trials, and wild-strain IPV (wIPV) was adopted as the control vaccine.

mPEG-icariin nanoparticles for treating myocardial ischaemia.

Icariin (ICA), a major active ingredient from Chinese medicine, has unique pharmacological effects on ischaemic heart disease. However, its hydrophobic property limits its administration and leads to poor efficacy. This work aimed to change its hydrophobic property and improve the treatment efficacy.

A neuraminidase activity-based microneutralization assay for evaluating antibody responses to influenza H5 and H7 vaccines.

Outbreaks of the highly pathogenic avian influenza H5N1 and H7N9 viruses have spurred an unprecedented research effort to develop antivirals and vaccines against influenza. Standardized methods for vaccine evaluation are critical for facilitating vaccine development. Compared with hemagglutination inhibition assays, mounting evidence suggest that microneutralization tests (MNTs) is a better choice for the evaluation of candidate pandemic influenza vaccines because they measure neutralizing antibody activity in cell cultures and are more sensitive in detecting H5 and H7.

A simple and safe antibody neutralization assay based on polio pseudoviruses.

The evaluation of the immunogenicity of Sabin strain based Inactivated Poliovirus Vaccines (sIPV) necessitates the use of wild strains in neutralization assays to assess the potential cross-reactivity of antibodies. The live virus strains including wild and Sabin strains must be handled in level 3 biocontainment laboratories. To develop an alternative assay without the use of a live virus, we constructed Mahoney, MEF-1, and Saukett pseudovirions by inserting luciferase reporter genes into intact capsid proteins.