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"Cheng, Ting"
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Identification of existing pharmaceuticals and herbal medicines as inhibitors of SARS-CoV-2 infection
The outbreak of COVID-19 caused by SARS-CoV-2 has resulted in more than 50 million confirmed cases and over 1 million deaths worldwide as of November 2020. Currently, there are no effective antivirals approved by the Food and Drug Administration to contain this pandemic except the antiviral agent remdesivir. In addition, the trimeric spike protein on the viral surface is highly glycosylated and almost 200,000 variants with mutations at more than 1,000 positions in its 1,273 amino acid sequence were reported, posing a major challenge in the development of antibodies and vaccines. It is therefore urgently needed to have alternative and timely treatments for the disease. In this study, we used a cell-based infection assay to screen more than 3,000 agents used in humans and animals, including 2,855 small molecules and 190 traditional herbal medicines, and identified 15 active small molecules in concentrations ranging from 0.1 nM to 50 μM. Two enzymatic assays, along with molecular modeling, were then developed to confirm those targeting the virus 3CL protease and the RNA-dependent RNA polymerase. Several water extracts of herbal medicines were active in the cell-based assay and could be further developed as plant-derived anti–SARS-CoV-2 agents. Some of the active compounds identified in the screen were further tested in vivo, and it was found that mefloquine, nelfinavir, and extracts of Ganoderma lucidum (RF3), Perilla frutescens, and Mentha haplocalyx were effective in a challenge study using hamsters as disease model.
Journal Article
الضمان الاجتماعي والحد من الفقر : التجربة الصينية
هذا الكتاب يلخص التجربة الصينية في الضمان الاجتماعي والحد من الفقر مستعرضا التحديات التي واجهتها الصين حتى صارت نموذجا للبلدان الساعية لتحقيق نتائج إيجابية في مكافحة الفقر والضمان الاجتماعي، إذ يفند التجربة الصينية من عدة جوانب، ويجذب الانتباه إلى المواضع التي تنتظر التحديث والتطوير. كما يناقش القضايا النظرية الأساسية في مجالات الرعاية والتأمين الاجتماعي والمساعدة الاجتماعية ويستعرض قضية التنسيق والتكامل بين الضمان الاجتماعي والحد من الفقر، كما يجري تحليلات وتوقعات للقضايا والتحديات والتطورات في المجالات ذات الصلة مستندا إلى البيانات والمعلومات الصادرة عن الجهات الرسمية الصينية.
Book
Modulators of microglia activation and polarization in ischemic stroke
Ischemic stroke is one of the leading causes of mortality and disability worldwide. However, there is a current lack of effective therapies available. As the resident macrophages of the brain, microglia can monitor the microenvironment and initiate immune responses. In response to various brain injuries, such as ischemic stroke, microglia are activated and polarized into the proinflammatory M1 phenotype or the anti-inflammatory M2 phenotype. The immunomodulatory molecules, such as cytokines and chemokines, generated by these microglia are closely associated with secondary brain damage or repair, respectively, following ischemic stroke. It has been shown that M1 microglia promote secondary brain damage, whilst M2 microglia facilitate recovery following stroke. In addition, autophagy is also reportedly involved in the pathology of ischemic stroke through regulating the activation and function of microglia. Therefore, this review aimed to provide a comprehensive overview of microglia activation, their functions and changes, and the modulators of these processes, including transcription factors, membrane receptors, ion channel proteins and genes, in ischemic stroke. The effects of autophagy on microglia polarization in ischemic stroke were also reviewed. Finally, future research areas of ischemic stroke and the implications of the current knowledge for the development of novel therapeutics for ischemic stroke were identified.
Journal Article
Low-voltage high-performance flexible digital and analog circuits based on ultrahigh-purity semiconducting carbon nanotubes
Carbon nanotube (CNT) thin-film transistor (TFT) is a promising candidate for flexible and wearable electronics. However, it usually suffers from low semiconducting tube purity, low device yield, and the mismatch between p- and n-type TFTs. Here, we report low-voltage and high-performance digital and analog CNT TFT circuits based on high-yield (19.9%) and ultrahigh purity (99.997%) polymer-sorted semiconducting CNTs. Using high-uniformity deposition and pseudo-CMOS design, we demonstrated CNT TFTs with good uniformity and high performance at low operation voltage of 3 V. We tested forty-four 2-µm channel 5-stage ring oscillators on the same flexible substrate (1,056 TFTs). All worked as expected with gate delays of 42.7 ± 13.1 ns. With these high-performance TFTs, we demonstrated 8-stage shift registers running at 50 kHz and the first tunable-gain amplifier with 1,000 gain at 20 kHz. These results show great potentials of using solution-processed CNT TFTs for large-scale flexible electronics.
Carbon nanotube thin-film transistor is promising for solution-processed, large-scale flexible electronics, but the device yields remain poor to date. Lei et al. show low-voltage flexible digital and analog circuits based on high-purity and high-yield separation of semiconducting carbon nanotubes.
Journal Article
Potent antibody-mediated neutralization limits bacteriophage treatment of a pulmonary Mycobacterium abscessus infection
post
An 81-year-old immunocompetent patient with bronchiectasis and refractory
Mycobacterium abscessus
lung disease was treated for 6 months with a three-phage cocktail active against the strain. In this case study of phage to lower infectious burden, intravenous administration was safe and reduced the
M. abscessus
sputum load tenfold within one month. However, after two months,
M. abscessus
counts increased as the patient mounted a robust IgM- and IgG-mediated neutralizing antibody response to the phages, which was associated with limited therapeutic efficacy.
Initial promise of a bacteriophage therapy for a persistent bacterial infection in an immunocompetent patient was curtailed in conjunction with a rise in phage-specific neutralizing antibodies.
Journal Article
Gene Mapping via Bulked Segregant RNA-Seq (BSR-Seq)
Bulked segregant analysis (BSA) is an efficient method to rapidly and efficiently map genes responsible for mutant phenotypes. BSA requires access to quantitative genetic markers that are polymorphic in the mapping population. We have developed a modification of BSA (BSR-Seq) that makes use of RNA-Seq reads to efficiently map genes even in populations for which no polymorphic markers have been previously identified. Because of the digital nature of next-generation sequencing (NGS) data, it is possible to conduct de novo SNP discovery and quantitatively genotype BSA samples by analyzing the same RNA-Seq data using an empirical Bayesian approach. In addition, analysis of the RNA-Seq data provides information on the effects of the mutant on global patterns of gene expression at no extra cost. In combination these results greatly simplify gene cloning experiments. To demonstrate the utility of this strategy BSR-Seq was used to clone the glossy3 (gl3) gene of maize. Mutants of the glossy loci exhibit altered accumulation of epicuticular waxes on juvenile leaves. By subjecting the reference allele of gl3 to BSR-Seq, we were able to map the gl3 locus to an ≈ 2 Mb interval. The single gene located in the ≈ 2 Mb mapping interval whose expression was down-regulated in the mutant pool was subsequently demonstrated to be the gl3 gene via the analysis of multiple independent transposon induced mutant alleles. The gl3 gene encodes a putative myb transcription factor, which directly or indirectly affects the expression of a number of genes involved in the biosynthesis of very-long-chain fatty acids.
Journal Article
Biocompatible and totally disintegrable semiconducting polymer for ultrathin and ultralightweight transient electronics
Increasing performance demands and shorter use lifetimes of consumer electronics have resulted in the rapid growth of electronic waste. Currently, consumer electronics are typically made with nondecomposable, nonbiocompatible, and sometimes even toxic materials, leading to serious ecological challenges worldwide. Here, we report an example of totally disintegrable and biocompatible semiconducting polymers for thin-film transistors. The polymer consists of reversible imine bonds and building blocks that can be easily decomposed under mild acidic conditions. In addition, an ultrathin (800-nm) biodegradable cellulose substrate with high chemical and thermal stability is developed. Coupled with iron electrodes, we have successfully fabricated fully disintegrable and biocompatible polymer transistors. Furthermore, disintegrable and biocompatible pseudo-complementary metal–oxide–semiconductor (CMOS) flexible circuits are demonstrated. These flexible circuits are ultrathin (<1 μm) and ultralightweight (∼2 g/m²) with low operating voltage (4 V), yielding potential applications of these disintegrable semiconducting polymers in low-cost, biocompatible, and ultralightweight transient electronics.
Journal Article
Optically Induced Ferroelectric Polarization Switching in a Molecular Ferroelectric with Reversible Photoisomerization
Ferroelectrics usually exhibit temperature‐triggered structural changes, which play crucial roles in controlling their physical properties. However, although light is very striking as a non‐contact, non‐destructive, and remotely controlled external stimuli, ferroelectric crystals with light‐triggered structural changes are very rare, which holds promise for optical control of ferroelectric properties. Here, an organic molecular ferroelectric, N‐salicylidene‐2,3,4,5,6‐pentafluoroaniline (SA‐PFA), which shows light‐triggered structural change of reversible photoisomerization between cis‐enol and trans‐keto configuration is reported. SA‐PFA presents clear ferroelectricity with the saturate polarization of 0.84 μC cm−2, larger than those of some typical organic ferroelectrics with thermodynamically structural changes. Benefit from the reversible photoisomerization, the dielectric real part of SA‐PFA can be reversibly switched by light. More strikingly, the photoisomerization enables SA‐PFA to show reversible optically induced ferroelectric polarization switching. Such intriguing behaviors make SPFA a potential candidate for application in next‐generation photo‐controlled ferroelectric devices. This work sheds light on further exploration of more excellent molecular ferroelectrics with light‐triggered structural changes for optical control of ferroelectric properties. Organic N‐salicylidene‐2,3,4,5,6‐pentafluoroaniline is a ferroelectric that experiences a light‐triggered structural change of reversible photoisomerization between cis‐enol and trans‐keto configuration, different from the general temperature‐triggered structural changes in other ferroelectrics. It has a saturate polarization of 0.84 μC cm−2. The photoisomerization makes it show reversible optically induced ferroelectric polarization switching.
Journal Article
A genetic tradeoff for tolerance to moderate and severe heat stress in US hybrid maize
Global climate change is increasing both average temperatures and the frequencies of extreme high temperatures. Past studies have documented a strong negative effect of exposures to temperatures >30°C on hybrid maize yields. However, these studies could not disentangle genetic adaptation via artificial selection from changes in agronomic practices. Because most of the earliest maize hybrids are no longer available, side-by-side comparisons with modern hybrids under current field conditions are generally impossible. Here, we report on the collection and curation of 81 years of public yield trial records covering 4,730 maize hybrids, which enabled us to model genetic variation for temperature responses among maize hybrids. We show that selection may have indirectly and inconsistently contributed to the genetic adaptation of maize to moderate heat stress over this time period while preserving genetic variance for continued adaptation. However, our results reveal the existence of a genetic tradeoff for tolerance to moderate and severe heat stress, leading to a decrease in tolerance to severe heat stress over the same time period. Both trends are particularly conspicuous since the mid-1970s. Such a tradeoff poses challenges to the continued adaptation of maize to warming climates due to a projected increase in the frequency of extreme heat events. Nevertheless, given recent advances in phenomics, enviromics, and physiological modeling, our results offer a degree of optimism for the capacity of plant breeders to adapt maize to warming climates, assuming appropriate levels of R&D investment.
Journal Article