Highlights d SARS-CoV-2 genome sequencing and phylogenetic analyses identify 35 recurrent mutations d Association with 117 clinical phenotypes reveals potentially important mutations d D500-532 in Nsp1 coding region correlates with lower viral load and serum IFN-b d Viral isolates with D500-532 mutation induce lower IFN-I response in the infected cells

graphene in 2004, diverse layered transition metal dichalcogenides with tunable band gaps have been shown to exhibit extraordinary electrical and optical properties in logic circuits, photodetectors, light-emitting diodes, gas sensors, and energy storage devices. [7][8][9][10][11][12][13][14] However, owing to their low mobility ceiling of a few hundred cm 2 V −1 s −1 , 2D-based fieldeffect transistors (FETs) still encounter a bottleneck for their application in highfrequency electronic devices. In this regard, indium selenide (InSe), with ultrahigh mobility near 1000 cm 2 V −1 s −1 at room temperature, has successfully attracted attention as one of the burgeoning III-VI group layered metal chalcogenides. The van der Waals layered Se-In-In-Se stacked structure, with a smooth surface and narrow band gap (1.26 eV), exhibits a perfect photoresponse to the visible spectrum. [15][16][17][18] Recent studies, which have focused on gating engineering with graphene, a passivation layer with hexagonal boron nitride or a self-assembled monolayer, and contact engineering with low work-function electrodes, have demonstrated that layered InSe possesses an intrinsically excellent charge transport and optoelectronic performance that are comparable with majority of 2D materials. [19][20][21][22][23][24][25] For instance, Wang Tunability and stability in the electrical properties of 2D semiconductors pave the way for their practical applications in logic devices. A robust layered indium selenide (InSe) field-effect transistor (FET) with superior controlled stability is demonstrated by depositing an indium (In) doping layer. The optimized InSe FETs deliver an unprecedented high electron mobility up to 3700 cm 2 V −1 s −1 at room temperature, which can be retained with 60% after 1 month. Further insight into the evolution of the position of the Fermi level and the microscopic device structure with different In thicknesses demonstrates an enhanced electron-doping behavior at the In/InSe interface. Furthermore, the contact resistance is also improved through the In insertion between InSe and Au electrodes, which coincides with the analysis of the low-frequency noise. The carrier fluctuation is attributed to the dominance of the phonon scattering events, which agrees with the observation of the temperature-dependent mobility. Finally, the flexible functionalities of the logic-circuit applications, for instance, inverter and not-and (NAND)/not-or (NOR) gates, are determined with these surface-doping InSe FETs, which establish a paradigm for 2D-based materials to overcome the bottleneck in the development of electronic devices. InSe TransistorsBecause of the down scaling limit of silicon-based devices, 2D materials with prominent mechanical flexibility and carrier transport performance have provided significant potential for their use in the new generation atomic electronic devices. [1][2][3][4][5][6] Following in the footsteps of the discovery of monolayer

Heat stress (HS) influences the growth and development of organisms. Thus, a comprehensive understanding of how organisms sense HS and respond to it is required. Ganoderma lucidum, a higher basidiomycete with bioactive secondary metabolites, has become a potential model system due to the complete sequencing of its genome, transgenic systems, and reliable reverse genetic tools. In this study, we found that HS inhibited mycelium growth, reduced hyphal branching, and induced the accumulation of ganoderic acid biosynthesis and heat shock proteins (HSPs) in G. lucidum. Our data showed that HS induced a significant increase in cytosolic Ca 2؉ concentration. Further evidence showed that Ca 2؉ might be a factor in the HS-mediated regulation of hyphal branching, ganoderic acid (GA) biosynthesis, and the accumulation of HSPs. Our results further showed that the calcium-permeable channel gene (cch)-silenced and phosphoinositide-specific phospholipase gene (plc)-silenced strains reduced the HS-induced increase in HSP expression compared with that observed for the wild type (WT). This study demonstrates that cytosolic Ca 2؉ participates in heat shock signal transduction and regulates downstream events in filamentous fungi. IMPORTANCEGanoderma lucidum, a higher basidiomycete with bioactive secondary metabolites, has become a potential model system for evaluating how environmental factors regulate the development and secondary metabolism of basidiomycetes. Heat stress (HS) is an important environmental challenge. In this study, we found that HS inhibited mycelium growth, reduced hyphal branching, and induced HSP expression and ganoderic acid biosynthesis in G. lucidum. Further evidence showed that Ca 2؉ might be a factor in the HS-mediated regulation of hyphal branching, GA biosynthesis, and the accumulation of HSPs. This study demonstrates that cytosolic Ca 2؉ participates in heat shock signal transduction and regulates downstream events in filamentous fungi. Our research offers a new way to understand the mechanism underlying the physiological and metabolic responses to other environmental factors in G. lucidum. This research may also provide the basis for heat shock signal transduction studies of other fungi. Ganoderma lucidum, a traditional precious medicinal mushroom, has been commonly used throughout China and Southeast Asia for many centuries as a home remedy for treating minor disorders and promoting vitality and longevity (1). Modern pharmacological and clinical research has demonstrated that G. lucidum has significant antitumor, antiviral, antihypertensive, and immunomodulatory activities (2, 3). These pharmaceutical activities come from the bioactive compounds of G. lucidum. In recent years, many of these biologically useful compounds, including ganoderic acids (GAs) and polysaccharides, have been isolated and characterized in G. lucidum (4,5). Ganoderic acids, also called triterpenoids, are one of the major secondary metabolites with pharmacological activity and are also known to be an important medicinal i...

Ganoderma lucidum is one of the most important medicinal mushrooms; however, molecular genetics research on this species has been limited due to a lack of reliable reverse genetic tools. In this study, the endogenous orotidine 5′-monophosphate decarboxylase gene (URA3) was cloned as a silencing reporter, and four gene-silencing methods using hairpin, sense, antisense, and dual promoter constructs, were introduced into G. lucidum through a simple electroporation procedure. A comparison and evaluation of silencing efficiency demonstrated that all of the four methods differentially suppressed the expression of URA3. Our data unequivocally indicate that the dual promoter silencing vector yields the highest rate of URA3 silencing compared with other vectors (up to 81.9%). To highlight the advantages of the dual promoter system, we constructed a co-silencing system based on the dual promoter method and succeeded in co-silencing URA3 and laccase in G. lucidum. The reduction of the mRNA levels of the two genes were correlated. Thus, the screening efficiency for RNAi knockdown of multiple genes may be improved by the co-silencing of an endogenous reporter gene. The molecular tools developed in this study should facilitate the isolation of genes and the characterization of the functions of multiple genes in this pharmaceutically important species, and these tools should be highly useful for the study of other basidiomycetes.

2 0 2 1 2 2 All rights reserved. No reuse allowed without permission. ABSTRACT 2 5Background: COVID-19 has been spreading globally since emergence, but the 2 6 diagnostic resources are relatively insufficient. 7Results: In order to effectively relieve the resource deficiency of diagnosing 2 8 COVID-19, we developed a machine learning-based diagnosis model on basis of 2 9 laboratory examinations indicators from a total of 620 samples, and subsequently 3 0implemented it as a COVID-19 diagnosis aid APP to facilitate promotion. 1Conclusions: External validation showed satisfiable model prediction performance 3 2 (i.e., the positive predictive value and negative predictive value was 86.35% and 3 3 84.62%, respectively), which guarantees the promising use of this tool for extensive 3 4 screening.3 5