A micro-sized vaccine based on recombinant Lactiplantibacillus plantarum fights against SARS-CoV-2 infection via intranasal immunization.

COVID-19 has globally spread to burden the medical system. Even with a massive vaccination, a mucosal vaccine offering more comprehensive and convenient protection is imminent. Here, a micro-sized vaccine based on recombinant Lactiplantibacillus plantarum (rLP) displaying spike or receptor-binding domain (RBD) was characterized as microparticles, and its safety and protective effects against SARS-CoV-2 were evaluated. We found a 66.7% mortality reduction and 100% protection with rLP against SARS-CoV-2 in a mouse model. The histological analysis showed decreased hemorrhage symptoms and increased leukocyte infiltration in the lung. Especially, rLP:RBD significantly decreased pulmonary viral loads. For the first time, our study provides a Lactiplantibacillus plantarum-vectored vaccine to prevent COVID-19 progress and transmission via intranasal vaccination.

Preparation of Nylon-6 micro-nanofiber composite membranes with 3D uniform gradient structure for high-efficiency air filtration of ultrafine particles

[Display omitted] • Nylon-6 micro-nanofiber composite membranes had uniform space gradient structure. • Composite membranes had good filtration performance against ultrafine particles. • The masks had stable protection performance and comfortable wearing experience. Compared of traditional melt-blown nonwoven materials, micro-nanofiber composite membranes with uniform spatial gradient structure will be the development trend of high efficiency and low resistance filtration materials, especially against ultrafine particles with kinetic diameter less than 0.25 (PM 0.25). Herein, Nylon-6 micro-nanofiber composite membranes (Nylon-6 FCMs) with three-dimensional (3D) uniform gradient structure were prepared by air jet spinning under the help of PEO. The fluffy 3D gradient structure possessed a uniform gradual pore gradient from large to small, ensuring the PM 0.25 were captured by exact grading under high gas flow due to the form of special "trumpet-like" gas passage inside the membranes. The structure of Nylon-6 FCMs could be controlled and exhibited high tensile strength, good moisture permeability, excellent filtration performance. Among them, the FCM-1 with a uniform gradual pore gradient could achieve the optimal filtering performance with filtration efficiency (99.99 %) and pressure drop (144 Pa). The mask prepared using this Nylon-6 FCMs also displayed good protective effect with comparable air permeability (221.84 mm·s−1) and moisture permeability (181.84 g·m−2·h−1) compared of commercial melt-blown masks. Most importantly, this mask prepared still could maintain good filtration performance even in high temperature and high humidity environment, providing users more comfortable wearing experience and stable protection performance, especially under the current COVID-19 outbreak. [ FROM AUTHOR]

Preparation of Nylon-6 micro-nanofiber composite membranes with 3D uniform gradient structure for high-efficiency air filtration of ultrafine particles

Compared of traditional melt-blown nonwoven materials, micro-nanofiber composite membranes with uniform spatial gradient structure will be the development trend of high efficiency and low resistance filtration materials, especially against ultrafine particles with kinetic diameter less than 0.25 (PM0.25). Herein, Nylon-6 micro-nanofiber composite membranes (Nylon-6 FCMs) with three-dimensional (3D) uniform gradient structure were prepared by air jet spinning under the help of PEO. The fluffy 3D gradient structure possessed a uniform gradual pore gradient from large to small, ensuring the PM0.25 were captured by exact grading under high gas flow due to the form of special "trumpet-like” gas passage inside the membranes. The structure of Nylon-6 FCMs could be controlled and exhibited high tensile strength, good moisture permeability, excellent filtration performance. Among them, the FCM-1 with a uniform gradual pore gradient could achieve the optimal filtering performance with filtration efficiency (99.99%) and pressure drop (144 Pa). The mask prepared using this Nylon-6 FCMs also displayed good protective effect with comparable air permeability (221.84 mm·s-1) and moisture permeability (181.84 g·m-2·h-1) compared of commercial melt-blown masks. Most importantly, this mask prepared still could maintain good filtration performance even in high temperature and high humidity environment, providing users more comfortable wearing experience and stable protection performance, especially under the current COVID-19 outbreak.

Contribution of PEPFAR-Supported HIV and TB Molecular Diagnostic Networks to COVID-19 Testing Preparedness in 16 Countries.

The US President's Emergency Plan for AIDS Relief (PEPFAR) supports molecular HIV and tuberculosis diagnostic networks and information management systems in low- and middle-income countries. We describe how national programs leveraged these PEPFAR-supported laboratory resources for SARS-CoV-2 testing during the COVID-19 pandemic. We sent a spreadsheet template consisting of 46 indicators for assessing the use of PEPFAR-supported diagnostic networks for COVID-19 pandemic response activities during April 1, 2020, to March 31, 2021, to 27 PEPFAR-supported countries or regions. A total of 109 PEPFAR-supported centralized HIV viral load and early infant diagnosis laboratories and 138 decentralized HIV and TB sites reported performing SARS-CoV-2 testing in 16 countries. Together, these sites contributed to >3.4 million SARS-CoV-2 tests during the 1-year period. Our findings illustrate that PEPFAR-supported diagnostic networks provided a wide range of resources to respond to emergency COVID-19 diagnostic testing in 16 low- and middle-income countries.

Industries' heterogeneous reactions during the COVID‐19 outbreak: Evidence from Chinese stock markets

This study examines the heterogeneous effects of the COVID-19 outbreak on stock prices in China. We confirm what is already known, that the pandemic has had a significant negative impact on stock market returns. Additionally, we find, this effect is heterogeneous across industries. Second, fear sentiment can directly cause stock prices to fall and panic exacerbates the negative impact of the pandemic on stock returns. Third, and most importantly, we demonstrate the underlying mechanisms of four firm characteristics and find that those with high asset intensity, low labor intensity, high inventory-to-revenue ratio, and small market value are more negatively affected than others. For labor-intensive state-owned firms, in particular, stock performance worsened because of higher idle labor costs. Finally, we created an index to measure the relative position of an industry in the supply chain, which shows that downstream companies were more vulnerable to the effects of the pandemic.

Design and production of environmentally degradable quaternary ammonium salts

Quaternary ammonium compounds (QACs) are a class of cationic surfactants routinely used for the disinfection of industries, institutions and households, and have seen a sharp increase in use during the COVID-19 pandemic. However, current commercial QACs consist of only stable chemical bonds such as C-N, C-C, and C-H, which makes their natural degradation rather difficult. Recent studies suggest that emerging negative environmental impacts, such as systemic antibiotics resistance and toxicity to living organisms, are directly associated with prolonged exposure to QACs. Here we report a new class of QAC which contains relatively volatile chemical functional groups such as ester and thioether bonds. Degradation kinetics in aqueous solutions suggests that the stability of these QACs depends not only on their intrinsic hydrophobicity but also on external environmental factors such as pH, temperature and ion presence. The microbicidal effects of QACs containing carbon chains with various lengths were also tested, one of which, named "Ephemora", is highly active against a broad spectrum of microbes including fungi, bacteria and viruses, for instance, methicillin-resistant Staphylococcus aureus (MRSA). The easy synthesis and purification of Ephemora starting from inexpensive commercially available reagents, together with its excellent antimicrobial activity and ability to degrade in natural waters over time, make its large-scale commercial production possible.

Linking genomic and epidemiologic information to advance the study of COVID-19.

The outbreak of Coronavirus Disease 2019 (COVID-19) at the end of 2019 turned into a global pandemic. To help analyze the spread and evolution of the virus, we collated and analyzed data related to the viral genome, sequence variations, and locations in temporal and spatial distribution from GISAID. Information from the Wikipedia web page and published research papers were categorized and mined to extract epidemiological data, which was then integrated with the public dataset. Genomic and epidemiological data were matched with public information, and the data quality was verified by manual curation. Finally, an online database centered on virus genomic information and epidemiological data can be freely accessible at https://www.biosino.org/kgcov/ , which is helpful to identify relevant knowledge and devising epidemic prevention and control policies in collaboration with disease control personnel.

Coronavirus GenBrowser for monitoring the transmission and evolution of SARS-CoV-2.

Genomic epidemiology is important to study the COVID-19 pandemic, and more than two million severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) genomic sequences were deposited into public databases. However, the exponential increase of sequences invokes unprecedented bioinformatic challenges. Here, we present the Coronavirus GenBrowser (CGB) based on a highly efficient analysis framework and a node-picking rendering strategy. In total, 1,002,739 high-quality genomic sequences with the transmission-related metadata were analyzed and visualized. The size of the core data file is only 12.20 MB, highly efficient for clean data sharing. Quick visualization modules and rich interactive operations are provided to explore the annotated SARS-CoV-2 evolutionary tree. CGB binary nomenclature is proposed to name each internal lineage. The pre-analyzed data can be filtered out according to the user-defined criteria to explore the transmission of SARS-CoV-2. Different evolutionary analyses can also be easily performed, such as the detection of accelerated evolution and ongoing positive selection. Moreover, the 75 genomic spots conserved in SARS-CoV-2 but non-conserved in other coronaviruses were identified, which may indicate the functional elements specifically important for SARS-CoV-2. The CGB was written in Java and JavaScript. It not only enables users who have no programming skills to analyze millions of genomic sequences, but also offers a panoramic vision of the transmission and evolution of SARS-CoV-2.

The healthcare supply location-inventory-routing problem: A robust approach

Motivated by a real-world healthcare supply case of a medical implant company, this paper studies a supply network configuration problem that integrates warehouse selections for vendor managed inventory (VMI), inventory policy, and delivery routing optimization together. The problem is a variant of the classic location-inventory-routing problem (LIRP) with both deterministic demand and uncertain demand, where multi-product, multi-period, multi-type delivery, delivery time limit and VMI are considered. Two types of delivery are used: one is the scheduled bulk delivery to the VMI warehouses and the other is direct shipping for hospitals. To address the problem, first, a deterministic MILP model is presented for the integrated LIRP. Then, to deal with the uncertainty in demand, we propose a robust optimization model and transform it into a tractable linear equivalent formulation. Further, considering the effect of COVID-19 pandemic on the demand and delivery time, a new robust model is proposed to account for this special situation. Numerical experiments are conducted to verify the advantage of the proposed robust optimization models. The sensitivity analysis provides some interesting managerial insights, and a real-world case of medical implant supply configuration with 78 hospitals is solved.

SAS: A Platform of Spike Antigenicity for SARS-CoV-2.

Since the outbreak of SARS-CoV-2, antigenicity concerns continue to linger with emerging mutants. As recent variants have shown decreased reactivity to previously determined monoclonal antibodies (mAbs) or sera, monitoring the antigenicity change of circulating mutants is urgently needed for vaccine effectiveness. Currently, antigenic comparison is mainly carried out by immuno-binding assays. Yet, an online predicting system is highly desirable to complement the targeted experimental tests from the perspective of time and cost. Here, we provided a platform of SAS (Spike protein Antigenicity for SARS-CoV-2), enabling predicting the resistant effect of emerging variants and the dynamic coverage of SARS-CoV-2 antibodies among circulating strains. When being compared to experimental results, SAS prediction obtained the consistency of 100% on 8 mAb-binding tests with detailed epitope covering mutational sites, and 80.3% on 223 anti-serum tests. Moreover, on the latest South Africa escaping strain (B.1.351), SAS predicted a significant resistance to reference strain at multiple mutated epitopes, agreeing well with the vaccine evaluation results. SAS enables auto-updating from GISAID, and the current version collects 867K GISAID strains, 15.4K unique spike (S) variants, and 28 validated and predicted epitope regions that include 339 antigenic sites. Together with the targeted immune-binding experiments, SAS may be helpful to reduce the experimental searching space, indicate the emergence and expansion of antigenic variants, and suggest the dynamic coverage of representative mAbs/vaccines among the latest circulating strains. SAS can be accessed at https://www.biosino.org/sas.

Design and production of environmentally degradable quaternary ammonium salts (Electronic supplementary information (ESI) available: Synthesis, characterization, 1H NMR, spectroscopic data and other materials. See DOI: 10.1039/d1gc01525g)

Quaternary ammonium compounds (QACs) are a class of cationic surfactants routinely used for the disinfection of industries, institutions and households, and have seen a sharp increase in use during the COVID-19 pandemic. However, current commercial QACs consist of only stable chemical bonds such as C–N, C–C, and C–H, which makes their natural degradation rather difficult. Recent studies suggest that emerging negative environmental impacts, such as systemic antibiotics resistance and toxicity to living organisms, are directly associated with prolonged exposure to QACs. Here we report a new class of QAC which contains relatively volatile chemical functional groups such as ester and thioether bonds. Degradation kinetics in aqueous solutions suggests that the stability of these QACs depends not only on their intrinsic hydrophobicity but also on external environmental factors such as pH, temperature and ion presence. The microbicidal effects of QACs containing carbon chains with various lengths were also tested, one of which, named “Ephemora”, is highly active against a broad spectrum of microbes including fungi, bacteria and viruses, for instance, methicillin-resistant Staphylococcus aureus (MRSA). The easy synthesis and purification of Ephemora starting from inexpensive commercially available reagents, together with its excellent antimicrobial activity and ability to degrade in natural waters over time, make its large-scale commercial production possible.

Identifying potential anti-COVID-19 pharmacological components of traditional Chinese medicine Lianhuaqingwen capsule based on human exposure and ACE2 biochromatography screening.

Lianhuaqingwen (LHQW) capsule, a herb medicine product, has been clinically proved to be effective in coronavirus disease 2019 (COVID-19) pneumonia treatment. However, human exposure to LHQW components and their pharmacological effects remain largely unknown. Hence, this study aimed to determine human exposure to LHQW components and their anti-COVID-19 pharmacological activities. Analysis of LHQW component profiles in human plasma and urine after repeated therapeutic dosing was conducted using a combination of HRMS and an untargeted data-mining approach, leading to detection of 132 LHQW prototype and metabolite components, which were absorbed via the gastrointestinal tract and formed via biotransformation in human, respectively. Together with data from screening by comprehensive 2D angiotensin-converting enzyme 2 (ACE2) biochromatography, 8 components in LHQW that were exposed to human and had potential ACE2 targeting ability were identified for further pharmacodynamic evaluation. Results show that rhein, forsythoside A, forsythoside I, neochlorogenic acid and its isomers exhibited high inhibitory effect on ACE2. For the first time, this study provides chemical and biochemical evidence for exploring molecular mechanisms of therapeutic effects of LHQW capsule for the treatment of COVID-19 patients based on the components exposed to human. It also demonstrates the utility of the human exposure-based approach to identify pharmaceutically active components in Chinese herb medicines.

A combined abiotic oxidation-precipitation process for rapid As removal from high-As(III)-Mn(II) acid mine drainage and low As-leaching solid products

A combination process of Fenton-like and catalytic Mn(II) oxidation via molecular oxygen-induced abio-oxidation of As(III)-Mn(II)-rich acid mine drainage (AMD) is developed to rapidly and efficiently remove As and obtain low As-leaching solids in this study. The effect of pH, temperature, oxygen flow rate and neutralization reagent on As removal was investigated. The results showed that pH was important to As removal efficiency, which achieved maximum in 0.25-2 h, but decreased from ∼100 % to ∼92.6 % with the increase of pH 5-9. pH, temperature and oxygen flow rate played key roles in As(III) oxidation. The increase of As(III) oxidized from 16.8 to 67.1% to 98.6-99.0 % occurred as increasing the pH 5-9, 25-95 °C and oxygen flow rate of 0-2.4 L min-1. NaOH or Ca(OH)2 as base was less important to As removal. The mechanism involved Fenton-like reaction between Fe(II) and O2 for produced Fe(III) (oxy)hydroxide association with As(III + V) and Mn(II), catalytic Mn(II) oxidation for the formation of Mn(III, IV) oxides, and further As(III) oxidation by Mn(III, IV) oxides. As-bearing six-line ferrihydrite was the main solid product for low As-leaching fixation. pH 8, 95 °C and oxygen flow rate of 1.6 L min-1 were optimal for As removal.