Respiration monitoring is important for evaluating human health. Humidity sensing is a promising way to establish a relationship between human respiration and electrical signal. This work describes polymer humidity sensors with ultrafast response for respiration monitoring. The humidity-sensitive polyelectrolyte is in situ cross-linked on the substrate printed with interdigitated electrodes by a thiol–ene click reaction. The polyelectrolyte humidity sensor shows rapid water adsorption/desorption ability, excellent stability, and repeatability. The sensor with ultrafast response and recovery (0.29/0.47 s) when changing humidity between 33 and 95% shows good application prospects in breath monitoring and touchless sensing. Different respiration patterns can be distinguished, and the breath rate/depth of detection subjects can also be determined by the sensor. In addition, the obtained sensor can sense the skin evaporation in a noncontact way.

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Motivation Since December 2019, the newly identified coronavirus SARS-CoV-2 has caused a massive health crisis worldwide and resulted in over 70 000 COVID-19 infections so far. Clinical drugs targeting SARS-CoV-2 are urgently needed to decrease the high fatality rate of confirmed COVID-19 patients. Traditional de novo drug discovery needs more than 10 years, so drug repurposing seems the best option currently to find potential drugs for treating COVID-19. Results Compared with traditional non-covalent drugs, covalent drugs have attracted escalating attention recent years due to their advantages in potential specificity upon careful design, efficiency and patient burden. We recently developed a computational protocol named as SCAR (steric-clashes alleviating receptors) for discovering covalent drugs. In this work, we used the SCAR protocol to identify possible covalent drugs (approved or clinically tested) targeting the main protease (3CLpro) of SARS-CoV-2. We identified 11 potential hits, among which at least six hits were exclusively enriched by the SCAR protocol. Since the preclinical or clinical information of these identified drugs is already available, they might be ready for being clinically tested in the treatment of COVID-19. Contact senliu.ctgu@gmail.com

Hookworm glutathione S-transferases (GSTs) are critical for parasite blood feeding and survival and represent potential targets for vaccination. Three cDNAs, each encoding a full-length GST protein from the human hookworm Necator americanus (and designated Na-GST-1, Na-GST-2, and Na-GST-3, respectively) were isolated from cDNA based on their sequence similarity to Ac-GST-1, a GST from the dog hookworm Ancylostoma caninum. The open reading frames of the three N. americanus GSTs each contain 206 amino acids with 51% to 69% sequence identity between each other and Ac-GST-1. Sequence alignment with GSTs from other organisms shows that the three Na-GSTs belong to a nematode-specific nu-class GST family. All three Na-GSTs, when expressed in Pichia pastoris, exhibited low lipid peroxidase and glutathione-conjugating enzymatic activities but high heme-binding capacities, and they may be involved in the detoxification and/or transport of heme. In two separate vaccine trials, recombinant Na-GST-1 formulated with Alhydrogel elicited 32 and 39% reductions in adult hookworm burdens (P < 0.05) following N. americanus larval challenge relative to the results for a group immunized with Alhydrogel alone. In contrast, no protection was observed in vaccine trials with Na-GST-2 or Na-GST-3. On the basis of these and other preclinical data, Na-GST-1 is under possible consideration for further vaccine development.

Signaling pathways depend on regulatory protein-protein interactions; controlling these interactions in cells has important applications for reengineering biological functions. As many regulatory proteins are modular, considerable progress in engineering signaling circuits has been made by recombining commonly occurring domains. Our ability to predictably engineer cellular functions, however, is constrained by complex crosstalk observed in naturally occurring domains. Here we demonstrate a strategy for improving and simplifying protein network engineering: using computational design to create orthogonal (non-crossreacting) protein-protein interfaces. We validated the design of the interface between a key signaling protein, the GTPase Cdc42, and its activator, Intersectin, biochemically and by solving the crystal structure of the engineered complex. The designed GTPase (orthoCdc42) is activated exclusively by its engineered cognate partner (orthoIntersectin), but maintains the ability to interface with other GTPase signaling circuit components in vitro. In mammalian cells, orthoCdc42 activity can be regulated by orthoIntersectin, but not wild-type Intersectin, showing that the designed interaction can trigger complex processes. Computational design of protein interfaces thus promises to provide specific components that facilitate the predictable engineering of cellular functions.computational modeling and design | signal transduction | synthetic biology

Covalent ligands modulating protein activities/signals have attracted unprecedented attention in recent years, but the insufficient understanding of their advantages in the early days of drug discovery has hindered their rational discovery and development. This also left us inadequate knowledge on the rational design of covalent ligands, e.g., how to balance the contribution from the covalent group and the noncovalent group, respectively. In this work, we dissected the noncovalent docking from covalent docking by creating SCARs (steric-clashes alleviating receptors). We showed that the SCAR method outperformed those specifically developed but more complicated covalent docking protocols. We furthermore provided a "proof-of-principle" example by implementing this method in the first high-throughput screening and discovery of novel covalent inhibitors of S-adenosylmethionine decarboxylase. This work demonstrated that noncovalent groups play a predeterminate role in the design of covalent ligands, and would be of great value in accelerating the discovery and development of covalent ligands.

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Broadband photodetection (PD) covering the deep ultraviolet to near-infrared (200–1000 nm) range is significant and desirable for various optoelectronic designs. Herein, we employ ultraviolet (UV) luminescent concentrators (LC), iodine-based perovskite quantum dots (PQDs), and organic bulk heterojunction (BHJ) as the UV, visible, and near-infrared (NIR) photosensitive layers, respectively, to construct a broadband heterojunction PD. Firstly, experimental and theoretical results reveal that optoelectronic properties and stability of CsPbI3 PQDs are significantly improved through Er3+ doping, owing to the reduced defect density, improved charge mobility, increased formation energy, tolerance factor, etc. The narrow bandgap of CsPbI3:Er3+ PQDs serves as a visible photosensitive layer of PD. Secondly, considering the matchable energy bandgap, the BHJ (BTP-4Cl: PBDB-TF) is selected as to NIR absorption layer to fabricate the hybrid structure with CsPbI3:Er3+ PQDs. Thirdly, UV LC converts the UV light (200–400 nm) to visible light (400–700 nm), which is further absorbed by CsPbI3:Er3+ PQDs. In contrast with other perovskites PDs and commercial Si PDs, our PD presents a relatively wide response range and high detectivity especially in UV and NIR regions (two orders of magnitude increase that of commercial Si PDs). Furthermore, the PD also demonstrates significantly enhanced air- and UV- stability, and the photocurrent of the device maintains 81.5% of the original one after 5000 cycles. This work highlights a new attempt for designing broadband PDs, which has application potential in optoelectronic devices.