T-cell immunity is important for recovery from COVID-19 and provides heightened immunity for re-infection. However, little is known about the SARS-CoV-2-specific T-cell immunity in virus-exposed individuals. Here we report virus-specific CD4+ and CD8+ T-cell memory in recovered COVID-19 patients and close contacts. We also demonstrate the size and quality of the memory T-cell pool of COVID-19 patients are larger and better than those of close contacts. However, the proliferation capacity, size and quality of T-cell responses in close contacts are readily distinguishable from healthy donors, suggesting close contacts are able to gain T-cell immunity against SARS-CoV-2 despite lacking a detectable infection. Additionally, asymptomatic and symptomatic COVID-19 patients contain similar levels of SARS-CoV-2-specific T-cell memory. Overall, this study demonstrates the versatility and potential of memory T cells from COVID-19 patients and close contacts, which may be important for host protection.

High-density carboxyl groups have been successfully grafted onto the pore surface of mesoporous nanocarriers which served to complex with platinum atoms in cisplatin, leading to much increased drug loading efficiency, distinctly prolonged and pH-responsive cisplatin release, and greatly enhanced growth inhibition effect against MCF-7 and HeLa cancer cell lines.

Phosphodiesterase 9A inhibitors have shown activity in preclinical models of cognition with potential application as novel therapies for treating Alzheimer's disease. Our clinical candidate, PF-04447943 (2), demonstrated acceptable CNS permeability in rats with modest asymmetry between central and peripheral compartments (free brain/free plasma = 0.32; CSF/free plasma = 0.19) yet had physicochemical properties outside the range associated with traditional CNS drugs. To address the potential risk of restricted CNS penetration with 2 in human clinical trials, we sought to identify a preclinical candidate with no asymmetry in rat brain penetration and that could advance into development. Merging the medicinal chemistry strategies of structure-based design with parallel chemistry, a novel series of PDE9A inhibitors was identified that showed improved selectivity over PDE1C. Optimization afforded preclinical candidate 19 that demonstrated free brain/free plasma ≥ 1 in rat and reduced microsomal clearance along with the ability to increase cyclic guanosine monophosphosphate levels in rat CSF.

Objective: To systematically evaluate the effectiveness and safety of the SARS‐CoV‐2 vaccines currently undergoing clinical trials. Methods: PubMed, EMBASE, and Cochrane Library databases were searched to collect open human COVID‐19 vaccines randomized controlled trials, without limiting the search time and language. The research papers collected in the above‐mentioned databases were initially screened according to the title and abstract content and merged, and the repeated ones were removed. After reading the full text of the remaining research, the studies that did not meet the inclusion criteria were excluded, and finally, nine studies were obtained. After extracting the statistical data of adverse events in the study, load them into Review Manager for heterogeneity analysis. Results: The incidence of adverse reactions of inactivated virus vaccines, RNA vaccines, and adenovirus vector vaccines was higher than that of placebo. Common adverse reactions included pain, swelling, and fever at the injection site. Conclusion: From the perspective of effectiveness, RNA vaccine > adenovirus vector vaccine > inactivated virus vaccine. From the perspective of safety, the incidence of adverse reactions of the three vaccines is higher than that of a placebo, and the incidence of adverse reactions of the adenovirus vector vaccine is higher.

A wide range of human diseases are associated with the aberrant activity of mammalian, viral, bacterial or parasitic proteases. These include members of all four classes of proteases, namely, serine, cysteine, aspartic and metallo- proteases. The involvement of proteases in disease states has provided the impetus behind studies related to the design of potent and selective inhibitors and their use as either therapeutic agents and/or pharmacological probes to gain a better understanding of the pathophysiology of a particular disease. This review focuses on recent developments related to the design of mechanism-based and alternate substrate inhibitors of serine proteases of mammalian and non-mammalian origin. Numerous examples are cited that illustrate the fundamental principles and subtleties associated with the design of covalent and non-covalent inhibitors of these enzymes. This is an exciting and promising area of investigation that will undoubtedly continue unabated in the future.

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Here, we report accessing small 3-fluoropyrrolidines and 3,3-difluoropyrrolidines through a 1,3-dipolar cycloaddition with a simple azomethine ylide and a variety of vinyl fluorides and vinyl difluorides. We demonstrate that vinyl fluorides within α,β-unsaturated, styrenyl and even enol ether systems can participate in the cycloaddition reaction. The vinyl fluorides are relatively easy to synthesize through a variety of methods, making the 3-fluoropyrrolidines very accessible.

This article documents the addition of 139 microsatellite marker loci and 90 pairs of singlenucleotide polymorphism sequencing primers to the Molecular Ecology Resources Database. Loci were developed for the following species: Aglaoctenus lagotis, Costus pulverulentus, Costus scaber, Culex pipiens, Dascyllus marginatus, Lupinus nanus Benth, Phloeomyzus passerini, Podarcis muralis, Rhododendron rubropilosum Hayata var. taiwanalpinum and Zoarces viviparus. These loci were cross-tested on the following species: Culex quinquefasciatus, Rhododendron pseudochrysanthum Hay. ssp. morii (Hay.) Yamazaki and R. pseudochrysanthum Hayata. This article also documents the addition of 48 sequencing primer pairs and 90 allele-specific primers for Engraulis encrasicolus. et al.