Predicting the effect of confinement on the COVID-19 spread using machine learning enriched with satellite air pollution observations.

The real-time monitoring of reductions of economic activity by containment measures and its effect on the transmission of the coronavirus (COVID-19) is a critical unanswered question. We inferred 5,642 weekly activity anomalies from the meteorology-adjusted differences in spaceborne tropospheric NO2 column concentrations after the 2020 COVID-19 outbreak relative to the baseline from 2016 to 2019. Two satellite observations reveal reincreasing economic activity associated with lifting control measures that comes together with accelerating COVID-19 cases before the winter of 2020/2021. Application of the near-real-time satellite NO2 observations produces a much better prediction of the deceleration of COVID-19 cases than applying the Oxford Government Response Tracker, the Public Health and Social Measures, or human mobility data as alternative predictors. A convergent cross-mapping suggests that economic activity reduction inferred from NO2 is a driver of case deceleration in most of the territories. This effect, however, is not linear, while further activity reductions were associated with weaker deceleration. Over the winter of 2020/2021, nearly 1 million daily COVID-19 cases could have been avoided by optimizing the timing and strength of activity reduction relative to a scenario based on the real distribution. Our study shows how satellite observations can provide surrogate data for activity reduction during the COVID-19 pandemic and monitor the effectiveness of containment to the pandemic before vaccines become widely available.

AI-powered omics-based drug pair discovery for pyroptosis therapy targeting triple-negative breast cancer.

Due to low success rates and long cycles of traditional drug development, the clinical tendency is to apply omics techniques to reveal patient-level disease characteristics and individualized responses to treatment. However, the heterogeneous form of data and uneven distribution of targets make drug discovery and precision medicine a non-trivial task. This study takes pyroptosis therapy for triple-negative breast cancer (TNBC) as a paradigm and uses data mining of a large TNBC cohort and drug databases to establish a biofactor-regulated neural network for rapidly screening and optimizing compound pyroptosis drug pairs. Subsequently, biomimetic nanococrystals are prepared using the preferred combination of mitoxantrone and gambogic acid for rational drug delivery. The unique mechanism of obtained nanococrystals regulating pyroptosis genes through ribosomal stress and triggering pyroptosis cascade immune effects are revealed in TNBC models. In this work, a target omics-based intelligent compound drug discovery framework explores an innovative drug development paradigm, which repurposes existing drugs and enables precise treatment of refractory diseases.

More collaboration, less seriousness: Investigating new strategies for promoting youth engagement in government-generated videos during the COVID-19 pandemic in China.

Effectively engaging citizens during crises is critical for governments to disseminate timely information and help the public to adjust to the constantly changing conditions. In particular, promoting youth engagement not only enhances crisis awareness and resilience among the young generation, but also has a positive impact on youths' social participation and responsibility. With the increasing popularity of online video services, leveraging online videos to disseminate authoritative information has become a method widely adopted by government. To enhance youth awareness and engagement, two new video-based crisis communication strategies have been utilized on a popular youth-targeted video platform Bilibili in China: creating recreational videos such as animation and music videos, and collaborating with individual video-uploaders in video making. However, their impacts and results are largely unknown, which motivates our study. Guided by Entertainment Education (EE) and Collaborative Governance (CG), we report, to our best knowledge, the first systematic study on how recreational video category and government-citizen collaboration would influence youth engagement focusing on 3347 COVID-19-related government-generated videos on Bilibili. This study reveals that recreational videos successfully promote youth engagement including interaction, feedback and sharing. Collaboration with individual uploaders in video making also has a substantially positive impact on youth engagement. Through an in-depth qualitative content analysis of user-generated commentaries, we further unpacked the unique values (e.g., trust work for youth participation) as well as latent limitations (e.g., imbalanced topic distribution) of the two new strategies. We discuss how the findings enrich EE and CG theoretically, and provide practical implications to effective and engaging communication strategies during crises.

A comparative reverse docking strategy to identify potential antineoplastic targets of tea functional components and binding mode.

The main functional components of green tea, such as epigallocatechin gallate (EGCG), epigallocatechin (EGC), epicatechin gallate (ECG) and epicatechin (EC), are found to have a broad antineoplastic activity. The discovery of their targets plays an important role in revealing the antineoplastic mechanism. Therefore, to identify potential target proteins for tea polyphenols, we have taken a comparative virtual screening approach using two reverse docking systems, one based on Autodock software and the other on Tarfisdock. Two separate in silico workflows were implemented to derive a set of target proteins related to human diseases and ranked by the binding energy score. Several conventional clinically important proteins with anti-tumor effects are screened out from the PDTD protein database as the potential receptors by both procedures. To further analyze the validity of docking results, we study the binding mode of EGCG and the potential target protein Leukotriene A4 hydrolase in detail. We indicate that interactions mediated by electrostatic and hydrogen bond play a key role in ligand binding. EGCG binds to the enzyme with certain orientation and conformation that is suitable for nucleophilic attacks by several electrical residues inside the enzyme's activity cavity. This study provides useful information for studying the antitumor mechanism of tea's functional components. The comparative reverse docking strategy presented generates a tractable set of antineoplastic proteins for future experimental validation as drug targets against tumors.

Quantum States of hydrogen and its isotopes confined in single-walled carbon nanotubes: dependence on interaction potential and extreme two-dimensional confinement.

Quantum mechanical energy levels are computed for the hydrogen molecule and its homonuclear isotopes confined within carbon nanotubes of various sizes and structures using three different interaction potentials. Two translational and two rotational degrees of freedom are treated explicitly. We study the dependence on the interaction potential and the size of the nanotube of several features, including zero-pressure quantum sieving selectivities, ortho-para energy splittings, and wave function characteristics. We show that large quantum sieving selectivities, as well as large deviations from gas phase ortho-para splittings, occur only under the condition of extreme two-dimensional confinement, when the characteristic length of the hydrogen-carbon interaction potential is nearly equal to the radius of the nanotube.

Hexagonal boron nitride nanoplates as emerging biological nanovectors and their potential applications in biomedicine.

The application of nanomaterials in the biological and medical areas has attracted great attention. Cytotoxicity, stability and solubility are the prerequisites for a nanomaterial to be considered for application in the field of biomedicine. Here, we suggest a simple method to produce highly dispersed water-soluble ultrathin h-BN nanoplates whose size measures ca. 30-60 nm in diameter and 1.6 nm in thickness. Moreover, we demonstrate that h-BN nanoplates can act as a reliable biological nanovector to carry proteins by cross-linking immobilization. Furthermore, the biocompatibility of h-BN nanoplates has also been explored via an apoptosis assay. In addition, a successful attempt has been made to investigate the potency of h-BN nanoplates as an immunostimulating adjuvant in a mouse immunization experiment. Preliminary results show that the level of antibody response stimulated by an antigen protein (bovine serum albumin) linked with h-BN is ca. 4 times higher than that by the antigen protein alone. This work gives evidence that water-soluble h-BN nanoplates are of high biocompatibility and low reactogenicity and therefore they can serve as an excellent biomedical platform for nanoparticle-biomolecular interactions. They preserve and even enhance the bioacitivities of the cross-linked antigen proteins, which strongly suggests their use in nanoparticle vaccine design.

Screening of drug target proteins by 2D ligand matching approach.

Drugs interacting with off-target proteins would bring about side-effects. The identification of the proteins that a drug can bind is thus valuable for evaluating its side-effects. We established a system based on PDB database for screening for proteins a drug could bind. Firstly, all complexes in the PDB database were sorted by species; then, a ligand database was established by extracting ligands from the structure data files. Secondly, all proteins were clustered according to their sequence similarity with the protein originally bound with the ligand in PDB. To search the potential target proteins of a drug, the query drug structure is compared with all ligands in the database to obtain similar scores. Ligands with similar sores greater than a certain threshold were flagged. Protein clusters associating with these ligands would be considered as potential targets of the query drug. To test the reliability of this approach, three drugs from DrugBank were used to search for their binding proteins by our method. The results showed that all the corresponding target proteins were found. The method presented here was rapid, scalable and could be used for high efficient drug side-effects analysis.

Construction of a single chain variable fragment antibody (scFv) against tetrodotoxin (TTX) and its interaction with TTX.

Tetrodotoxin (TTX) is a small molecular weight neurotoxin that occludes voltage-gated sodium channels in nerve and muscle tissue, resulting in respiratory paralysis and death. A high affinity antibody that can neutralize the toxicity of TTX is still lacking, so it is very important to prepare an antibody for TTX therapy and detection. In the present study, a chemical method was used to prepare the tetrodotoxin complete antigen, and a small amount, repeatedly immunity way was carried to immunize 4 mice. The amplified genes encoding monoclonal antibodies against TTX were used to construct the phage display library. After six rounds of biopanning, an antibody named scFv-T53 was characterized from clones showing high affinity and specific to TTX, and its affinity constant was 1.1 × 10(6) L/mol. Three dimensional structure of the scFv-T53 was constructed by computer modeling, and TTX was docked to the scFv-T53 model to obtain the structure of the binding complex. Two predicted essential amino acids, K183 and I189, were mutated to verify the theoretical model. Both mutants lost binding activity significantly against TTX as predicted by the theoretical model. Hence, the above results will be useful for screening the high affinity anti-TTX scFv mutants.

A study of the mechanism of the chaperone-like function of an scFv of human creatine kinase by computer simulation.

A new application of antibodies is to use them as macromolecular chaperones. Protein antigens usually have multiple epitopes, thus, there may be a plurality of antibodies binding to one antigen. However, not all antibodies that bind to one antigen could act as a chaperone. Experiments show that some screened anti-human creatine kinase single chain antibodies (scFV) could assist in the folding and stabilizing of the enzyme, while others could not. We built the model of the single chain antibody (scFv-A4) that increased the stability of human creatine kinase (HCK) by the homology modeling method. Epitopes of human creatine kinase were predicted by computer and then the binding of scFv-A4 and HCK was modeled with computer. The calculation results were further combined with the peptide array membrane experiment results to obtain reliable models for the scFv-A4-HCK complex. Based on the above study we gave an explanation about how scFv-A4 could act as a macromolecular chaperone assisting the folding of HCK. This study provides an approach for predicting antigen-antibody binding mode and also a useful theoretical guidance for the study of antibodies' chaperone-like function.

Myeloperoxidase interaction with peroxynitrite: chloride deficiency and heme depletion.

Myeloperoxidase (MPO) is a hemoprotein involved in the leukocyte-mediated defense mechanism and uses hydrogen peroxide (H2O2) and chloride (Cl(-)) to produce hypochlorous acid. In human saliva and in hypochloremic alkalosis syndrome occurring in breast-fed infants, the MPO-H2O2 system functions in a lower Cl(-) concentration (10-70 mM) compared to plasma levels (100 mM) as part of the antibacterial defense system. The impact of low Cl(-) concentration and exposure to high peroxynitrite (ONOO(-)) synthesized from cigarette smoke or oxidative stress on MPO function is still unexplored. Rapid mixing of ONOO(-) and MPO caused immediate formation of a transient intermediate MPO Compound II, which then decayed to MPO-Fe(III). Double mixing of MPO with ONOO(-) followed by H2O2 caused immediate formation of Compound II, followed by MPO heme depletion, a process that occurred independent of ONOO(-) concentration. Peroxynitrite/H2O2-mediated MPO heme depletion was confirmed by HPLC analysis, and in-gel heme staining showing 60-70% less heme content compared to the control. A nonreducing denaturing SDS-PAGE showed no fragmentation or degradation of protein. Myeloperoxidase heme loss was completely prevented by preincubation of MPO with saturating amounts of Cl(-). Chloride binding to the active site of MPO constrains ONOO(-) binding by filling the space directly above the heme moiety or by causing a protein conformational change that constricts the distal heme pocket, thus preventing ONOO(-) from binding to MPO heme iron. Peroxynitrite interaction with MPO may serve as a novel mechanism for modulating MPO catalytic activity, influencing the regulation of local inflammatory and infectious events in vivo.

Aquifex aeolicus aspartate transcarbamoylase, an enzyme specialized for the efficient utilization of unstable carbamoyl phosphate at elevated temperature.

Aquifex aeolicus, an organism that flourishes at 95 degrees C, is one of the most thermophilic eubacteria thus far described. The A. aeolicus pyrB gene encoding aspartate transcarbamoylase (ATCase) was cloned, overexpressed in Escherichia coli, and purified by affinity chromatography to a homogeneous form that could be crystallized. Chemical cross-linking and size exclusion chromatography showed that the protein was a homotrimer of 34-kDa catalytic chains. The activity of A. aeolicus ATCase increased dramatically with increasing temperature due to an increase in kcat with little change in the Km for the substrates, carbamoyl phosphate and aspartate. The Km for both substrates was 30-40-fold lower than the corresponding values for the homologous E. coli ATCase catalytic subunit. Although rapidly degraded at high temperature, the carbamoyl phosphate generated in situ by A. aeolicus carbamoyl phosphate synthetase (CPSase) was channeled to ATCase. The transient time for carbamoyl aspartate formation was 26 s, compared with the much longer transient times observed when A. aeolicus CPSase was coupled to E. coli ATCase. Several other approaches provided strong evidence for channeling and transient complex formation between A. aeolicus ATCase and CPSase. The high affinity for substrates combined with channeling ensures the efficient transfer of carbamoyl phosphate from the active site of CPSase to that of ATCase, thus preserving it from degradation and preventing the formation of toxic cyanate.