Drug Repurposing for the Identification of Compounds with Anti-SARS-CoV-2 Capability via Multiple Targets.

Since 2019, severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has been rapidly spreading worldwide, causing hundreds of millions of infections. Despite the development of vaccines, insufficient protection remains a concern. Therefore, the screening of drugs for the treatment of coronavirus disease 2019 (COVID-19) is reasonable and necessary. This study utilized bioinformatics for the selection of compounds approved by the U.S. Food and Drug Administration with therapeutic potential in this setting. In addition, the inhibitory effect of these compounds on the enzyme activity of transmembrane protease serine 2 (TMPRSS2), papain-like protease (PLpro), and 3C-like protease (3CLpro) was evaluated. Furthermore, the capability of compounds to attach to the spike-receptor-binding domain (RBD) was considered an important factor in the present assessment. Finally, the antiviral potency of compounds was validated using a plaque reduction assay. Our funnel strategy revealed that tamoxifen possesses an anti-SARS-CoV-2 property owing to its inhibitory performance in multiple assays. The proposed time-saving and feasible strategy may accelerate drug screening for COVID-19 and other diseases.

Effect of electroacupuncture at "Weizhong" (BL40) on expression of collagen I and matrix meta-lloproteinases 2 in rats with lumbar multifidus muscle injury / 针刺研究

OBJECTIVE: To observe the effect of electroacupuncture (EA) at "Weizhong" (BL40) on histopathological changes and expression of extracellular matrix (ECM) component Collagen Ⅰ， matrix metalloproteinases 2 (MMP2), MyoD and Pax7 proteins of lumbar muscle tissues in rats with lumbar multifidus muscle injury (LMMI), so as to explore its underlying mechanisms in improving muscular injury. METHODS: A total of 24 male SD rats were equally randomized into blank control, model and EA groups. The LMMI model was established by injection of 0.5% Bupivacaine (100 µL/ point) into bilateral multifidus muscles of lumbar 4 and 5 (4 points). EA (2 Hz/100 Hz in frequency, 1－2 mA) was applied to BL40 for 20 min, once a day for 3 days. The morphological changes of the left lumbar multifidus muscle were observed under microscope after H．E. and Masson staining, and the expression of Collagen Ⅰ， MMP2, MyoD and Pax7 of the right lumbar multifidus muscle was determined by Western blot. RESULTS: H．E. staining showed large areas of degeneration and necrosis of muscle fibers, and vacuolar structure formed by degradation of muscle fibers in the model group, and newborn juvenile muscle fibers with different diameters in the EA group. Masson staining showed a large number of morphologically damaged muscle fibers and blue stained collagen fibers in the model group, and significantly reduced collagen fibers as well as new muscle fibers with uneven diameters in the EA group. The expression levels of Collagen Ⅰ， MMP2 and MyoD proteins were significantly up-regulated (P<0.01, P<0.05), and that of Pax7 was considerably down-regulated in the model group relative to the control group (P<0.01). After EA intervention, the expression levels of Collagen Ⅰ was significantly down-regulated (P<0.01), and those of MMP2, MyoD and Pax7 proteins were obviously or further obviously up-regulated in the EA group compared with the model group (P<0.01, P<0.05). CONCLUSION: EA at BL40 can reduce the degree of skeletal muscle fibrosis to promote the regeneration of the injured multifidus at the early phase, which may be related to its effect in regulating the expression of Collagen Ⅰ and MMP2 proteins.

A National Study of Survival Trends and Conditional Survival in Nasopharyngeal Carcinoma: Analysis of the National Population-Based Surveillance Epidemiology and End Results Registry / Journal of the Korean Cancer Association, 대한암학회지

PURPOSE: Conditional survival (CS) provides important information on survival for a period of time after diagnosis. Currently, information on CS patterns of patients with nasopharyngeal carcinoma (NPC) is lacking. We aimed to analyze survival rate over time and estimate CS for NPC patients using a national population-based registry. MATERIALS AND METHODS: Patients diagnosed with NPC between 1973 and 2007 with at least 5-year follow-up were identified from the Surveillance Epidemiology End Results registry. Traditional survival rates and crude CS estimateswere calculated using Kaplan-Meier analysis. Risk-adjusted survival curves were plotted from the proportional hazards model using the correct group prognosis method. RESULTS: For 7,713 patients analyzed, adjusted baseline 5-year overall survival improved significantly from 36.0% in patients diagnosed in 1973-1979, 41.7% in 1980-1989, 46.6% in 1990-1999, to 54.7% in 2000-2007 (p < 0.01). CS analysis demonstrated that for every additional year survived, adjusted probability of surviving the next 5 years increased from 66.7% (localized), 54.0% (regional), and 35.3% (distant) at the time of diagnosis, to 83.7% (localized), 75.0% (regional), and 62.2% (distant) for patients who had survived 5 years. Adjusted 5-year CS differed among age, sex, tumor histology, ethnicity, and stage subgroups initially, but converged with time. CONCLUSION: Treatment outcomes of NPC patients have greatly improved over the decades. Increases in CS become more prominent in patients with distant disease than in those with localized or regional disease as patients survive longer. CS provides more dynamic prognostic information for patients who have survived a period of time after diagnosis.

Low-Temperature Growth of Hydrogenated Amorphous Silicon Carbide Solar Cell by Inductively Coupled Plasma Deposition Toward High Conversion Efficiency in Indoor Lighting.

A p-a-SiC:H window layer was used in amorphous Si thin film solar cells to boost the conversion efficiency in an indoor lighting of 500 lx. The p-a-SiC:H window layer/p-a-Si:H buffer layer scheme moderates the abrupt band bending across the p/i interface for the enhancement of VOC, JSC and FF in the solar spectra of short wavelengths. The optimized thickness of i-a-Si:H absorber layer is 400 nm to achieve the conversion efficiency of ~9.58% in an AM1.5 G solar spectrum. However, the optimized thickness of the absorber layer can be changed from 400 to 600 nm in the indoor lighting of 500 lx, exhibiting the maximum output power of 25.56 µW/cm2. Furthermore, various durability tests with excellent performance were investigated, which are significantly beneficial to harvest the indoor lights for applications in the self-powered internet of thing (IoT).

Molecular cloning and functional characterization of the gene encoding hydroxy-2-methyl-2-(E)-butenyl 4-diphosphate reductase gene from Artemisia annua L / 药学学报

Artemisinin is the first choice for malaria treatment. The plastidial MEP pathway provides 5-carbon precursors (IPP and its isomer DMAPP) for the biosynthesis of isoprenoid (including artemisinin). Hydroxy-2-methyl-2-(E)-butenyl 4-diphosphate reductase (HDR) is the last enzyme involved in the MEP pathway, which catalyzes HMBPP to form IPP and DMAPP. In this study, we isolated the full-length cDNA of HDR from Artemisia annua L. (AaHDR2) and performed functional analysis. According to gene expression analysis of AaHDR2 (GenBank:KX058541) and AaHDR1 reported ever (GenBank:ADC84348.1) by qPCR, we found that AaHDR1 and AaHDR2 had much higher expression level in trichomes than that in roots, stems, leaves and flowers. AaHDR2 had much higher expression level in flowers than that in leaves. Further, the plant hormones such as MeJA and ABA respectively up-regulated the expression level of AaHDR1 and AaHDR2 significantly, but GA3 up-regulated the expression level of AaHDR2 only. The gene expression analysis of AaHDR1 and AaHDR2 showed that AaHDR2 had a greater contribution than AaHDR1 to isoprenoid biosynthesis (including artemisinin). We used AaHDR2 for the following experiments. Bioinformatic analysis indicated that AaHDR2 belonged to the HDR family and the functional complementation assay showed that AaHDR2 did have the enzymatic function of HDR, using E. coli mutant MG1655araHDR as host cell. The subcellular localization assay showed that AaHDR2 fused with GFP at its N-terminal specifically targeted in chloroplasts. Finally, AaHDR2 was overexpressed in Arabidopsis thaliana. The AaHDR2-overexpressing plants produced the isoprenoids including chlorophyll a, chlorophyll b and carotenoids at significantly higher levels than the wild-type Arabidopsis plants. In summary, AaHDR2 might be a candidate gene for genetic improvement of the isoprenoid biosynthesis.

Optical-power-dependent photodesorption kinetics of graphene studied by conductance response.

The photodesorption kinetics of graphene with various UV laser power is studied by conductance response. Analytical expressions of the power-dependent photodesorption kinetics of graphene in ambience are derived. The photodesorption time constant τd, steady current, and magnitude of modulation current, can be expressed as functions of the adsorption time constant τa, desorption cross section σ, and photon flux density. Under illumination the steady occupation ratio of adsorbed O2 on graphene is equal to τd/τa. It is suggested that the photodesorption of O2 on graphene is attributed the injection of photogenerated hot electrons and is restricted by the density of antibonding states of O2.

Realization of metal-insulator transition and oxidation in silver nanowire percolating networks by terahertz reflection spectroscopy.

Metal nanowires (NWs) enable versatile applications in printed electronics and optoelectronics by serving as thin and flexible transparent electrodes. The performance of metal NWs as thin electrodes is highly correlated to the connectivity of NW meshes. The percolation threshold of metal NW films corresponds to the minimum density of NWs to form the transparent, yet conductive metal NW networks. Here, we determine the percolation threshold of silver NW (AgNW) networks by using morphological analysis and terahertz (THz) reflection spectroscopy. From the divergent behavior of carrier scattering time and the increase of carrier backscattering factor, the critical NW density at which crossover from Drude to non-Drude behavior of THz conductivity occurs can be unambiguously determined for AgNW thin films. Furthermore, the natural oxidation of AgNWs which causes the gradual reduction of the connectivity of the AgNW network is also realized by the THz spectroscopy. The selective oxidation of NW-to-NW junctions weakens the ohmic contact, and for AgNWs near a critical density, it can even lead to metal-insulator transition. The presented results offer invaluable information to accelerate the deployment of metal nanowires for next-generation electronics and optoelectronics on flexible substrates.