Regiodivergent C-H alkynylation of 2-arylthiazoles switched by RuII and PdII catalysis.

Two complementary regiodivergent C-H alkynylations of 2-arylthiazoles are reported. When RuII catalysis is employed, an aryl ortho-alkynylation process is favored. The alkynylated products are gained in good yields. With the use of PdII catalysis, a thiazole C5-alkynylation process is developed, allowing for the construction of C5-alkynylated products. This strategy not only expands the methods for the functionalization of 2-arylthiazoles, but also provides new opportunities for the rapid assembly of complex molecular structures, which may have great potential in organic synthesis, medicinal chemistry, and materials science.

Molecular action mechanisms of two novel and selective calcium release-activated calcium channel antagonists.

The prototypical calcium release-activated calcium (CRAC) channel, composed of STIM1 and Orai1, is a sought-after drug target for treating autoimmune disorders. Herein, we identified two novel and selective CRAC channel inhibitors, the indole-like compound C63368 and pyrazole core-containing compound C79413, potently and reversibly inhibiting the CRAC channel with low micromolar IC50s and sparing various off-target ion channels. These two compounds did not inhibit STIM1 activation or its coupling with Orai1, nor did they affect the channel's calcium-dependent fast inactivation. Instead, they directly acted on the Orai1 protein, with the channel's pore geometry profoundly affecting their potencies. In vitro, C63368 and C79413 effectively inhibited Jurkat cell proliferation and cytokines production in human T lymphocytes. Intragastric administration of C63368 and C79413 to mice yielded great therapeutic benefits in psoriasis and colitis animal models of autoimmune disorders, reducing serum cytokines production and significantly relieving pathological symptoms. It's worth noting, that this study provided the first insight into the characterization and mechanistic investigation of an indole-like CRAC channel antagonist. Altogether, the identification of these two highly selective CRAC channel antagonists, coupled with the elucidation of their action mechanisms, not only provides valuable template molecules but also offers profound insights for drug development targeting the CRAC channel.

The Molecular Composition of Peptide Toxins in the Venom of Spider Lycosa coelestis as Revealed by cDNA Library and Transcriptomic Sequencing.

In the so-called "struggle for existence" competition, the venomous animals developed a smart and effective strategy, envenomation, for predation and defense. Biochemical analysis revealed that animal venoms are chemical pools of proteinase, peptide toxins, and small organic molecules with various biological activities. Of them, peptide toxins are of great molecular diversity and possess the capacity to modulate the activity of ion channels, the second largest group of drug targets expressed on the cell membrane, which makes them a rich resource for developing peptide drug pioneers. The spider Lycosa coelestis (L. coelestis) commonly found in farmland in China is a dominant natural enemy of agricultural pests; however, its venom composition and activity were never explored. Herein, we conducted cDNA library and transcriptomic sequencing of the venom gland of L. coelestis, which identified 1131 high-quality expressed sequence tags (ESTs), grouped into three categories denoted as toxin-like ESTs (597, 52.79%), cellular component ESTs (357, 31.56%), and non-matched ESTs (177, 15.65%). These toxin-like ESTs encode 98 non-reductant toxins, which are artificially divided into 11 families based on their sequence homology and cysteine frameworks (2-14 cysteines forming 1-7 disulfide bonds to stabilize the toxin structure). Furthermore, RP-HPLC purification combined with off-line MALDI-TOF analysis have detected 147 different peptides physically existing in the venom of L. coelestis. Electrophysiology analysis confirmed that the venom preferably inhibits the voltage-gated calcium channels in rat dorsal root ganglion neurons. Altogether, the present study has added a great lot of new members to the spider toxin superfamily and built the foundation for characterizing novel active peptides in the L. coelestis venom.

A virucidal face mask based on the reverse-flow reactor concept for thermal inactivation of SARS-CoV-2.

While facial coverings reduce the spread of SARS-CoV-2 by viral filtration, masks capable of viral inactivation by heating can provide a complementary method to limit transmission. Inspired by reverse-flow chemical reactors, we introduce a new virucidal face mask concept driven by the oscillatory flow of human breath. The governing heat and mass transport equations are solved to evaluate virus and CO2 transport. Given limits imposed by the kinetics of SARS-CoV-2 thermal inactivation, human breath, safety, and comfort, heated masks may inactivate SARS-CoV-2 to medical-grade sterility. We detail one design, with a volume of 300 ml at 90°C that achieves a 3-log reduction in viral load with minimal impedance within the mask mesh, with partition coefficient around 2. This is the first quantitative analysis of virucidal thermal inactivation within a protective face mask, and addresses a pressing need for new approaches for personal protective equipment during a global pandemic.

Storage Management Strategy in Mobile Phones for Photo Crowdsensing.

In mobile crowdsensing, some users jointly finish a sensing task through the sensors equipped in their intelligent terminals. In particular, the photo crowdsensing based on Mobile Edge Computing (MEC) collects pictures for some specific targets or events and uploads them to nearby edge servers, which leads to richer data content and more efficient data storage compared with the common mobile crowdsensing; hence, it has attracted an important amount of attention recently. However, the mobile users prefer uploading the photos through Wifi APs (PoIs) rather than cellular networks. Therefore, photos stored in mobile phones are exchanged among users, in order to quickly upload them to the PoIs, which are actually the edge services. In this paper, we propose a utility-based Storage Management strategy in mobile phones for Photo Crowdsensing (SMPC), which makes a sending/deleting decision on a user's device for either maximizing photo delivery ratio (SMPC-R) or minimizing average delay (SMPC-D). The decision is made according to the photo's utility, which is calculated by measuring the impact of reproducing or deleting a photo on the above performance goals. We have done simulations based on the random-waypoint model and three real traces: roma/taxi, epfl, and geolife. The results show that, compared with other storage management strategies, SMPC-R gets the highest delivery ratio and SMPC-D achieves the lowest average delay.