Differentiating impacts of non‐pharmaceutical interventions on non‐coronavirus disease‐2019 respiratory viral infections: Hospital‐based retrospective observational study in Taiwan

Background Physical distancing and facemask use are worldwide recognized as effective non-pharmaceutical interventions (NPIs) against the coronavirus disease-2019 (COVID-19). Since January 2020, Taiwan has introduced both NPIs but their effectiveness on non-COVID-19 respiratory viruses (NCRVs) remain underexplored. Methods This retrospective observational study examined electronic records at a tertiary hospital in northern Taiwan from pre-COVID (January–December 2019) to post-COVID period (January–May 2020). Patients with respiratory syndromes were tested for both enveloped (eg, influenza virus and seasonal coronavirus) and non-enveloped RVs (eg, enterovirus and rhinovirus) using multiplex reverse transcription polymerase chain reaction assays. Monthly positivity rates of NCRVs among adult and pediatric patients were analyzed with comparison between pre- and post-COVID periods. Results A total of 9693 patients underwent 12 127 multiplex RT-PCR tests. The average positivity rate of NCRVs reduced by 11.2% (25.6% to 14.4%) after nationwide PHIs. Despite the COVID-19 pandemic, the most commonly identified enveloped and non-enveloped viruses were influenza virus and enterovirus/rhinovirus, respectively. Observed reduction in NCRV incidence was predominantly contributed by enveloped NCRVs including influenza viruses. We did not observe epidemiological impacts of NPIs on non-enveloped viruses but an increasing trend in enterovirus/rhinovirus test positivity rate among pediatric patients. Our data were validated using Taiwan's national notification database. Conclusions Our frontline investigation suggests that the current NPIs in Taiwan might not effectively control the transmission of non-enveloped respiratory viruses, despite their protective effects against influenza and seasonal coronavirus. Health authorities may consider using hydrogen peroxide or chloride-based disinfectants as additional preventative strategies against non-enveloped respiratory viruses in the post-COVID-19 era

Establishment of a Transgenic Zebrafish Line for Superficial Skin Ablation and Functional Validation of Apoptosis Modulators In Vivo

BACKGROUND: Zebrafish skin is composed of enveloping and basal layers which form a first-line defense system against pathogens. Zebrafish epidermis contains ionocytes and mucous cells that aid secretion of acid/ions or mucous through skin. Previous studies demonstrated that fish skin is extremely sensitive to external stimuli. However, little is known about the molecular mechanisms that modulate skin cell apoptosis in zebrafish. METHODOLOGY/PRINCIPAL FINDINGS: This study aimed to create a platform to conduct conditional skin ablation and determine if it is possible to attenuate apoptotic stimuli by overexpressing potential apoptosis modulating genes in the skin of live animals. A transgenic zebrafish line of Tg(krt4:NTR-hKikGR)(cy17) (killer line), which can conditionally trigger apoptosis in superficial skin cells, was first established. When the killer line was incubated with the prodrug metrodinazole, the superficial skin displayed extensive apoptosis as judged by detection of massive TUNEL- and active caspase 3-positive signals. Great reductions in NTR-hKikGR(+) fluorescent signals accompanied epidermal cell apoptosis. This indicated that NTR-hKikGR(+) signal fluorescence can be utilized to evaluate apoptotic events in vivo. After removal of metrodinazole, the skin integrity progressively recovered and NTR-hKikGR(+) fluorescent signals gradually restored. In contrast, either crossing the killer line with testing lines or transiently injecting the killer line with testing vectors that expressed human constitutive active Akt1, mouse constitutive active Stat3, or HPV16 E6 element displayed apoptosis-resistant phenotypes to cytotoxic metrodinazole as judged by the loss of reduction in NTR-hKikGR(+) fluorescent signaling. CONCLUSION/SIGNIFICANCE: The killer/testing line binary system established in the current study demonstrates a nitroreductase/metrodinazole system that can be utilized to conditionally perform skin ablation in a real-time manner, and provides a valuable tool to visualize and quantify the anti-apoptotic potential of interesting target genes in vivo. The current work identifies a potential use for transgenic zebrafish as a high-throughput platform to validate potential apoptosis modulators in vivo

AI is a viable alternative to high throughput screening: a 318-target study

: High throughput screening (HTS) is routinely used to identify bioactive small molecules. This requires physical compounds, which limits coverage of accessible chemical space. Computational approaches combined with vast on-demand chemical libraries can access far greater chemical space, provided that the predictive accuracy is sufficient to identify useful molecules. Through the largest and most diverse virtual HTS campaign reported to date, comprising 318 individual projects, we demonstrate that our AtomNet® convolutional neural network successfully finds novel hits across every major therapeutic area and protein class. We address historical limitations of computational screening by demonstrating success for target proteins without known binders, high-quality X-ray crystal structures, or manual cherry-picking of compounds. We show that the molecules selected by the AtomNet® model are novel drug-like scaffolds rather than minor modifications to known bioactive compounds. Our empirical results suggest that computational methods can substantially replace HTS as the first step of small-molecule drug discovery

Robust estimation of bacterial cell count from optical density

Optical density (OD) is widely used to estimate the density of cells in liquid culture, but cannot be compared between instruments without a standardized calibration protocol and is challenging to relate to actual cell count. We address this with an interlaboratory study comparing three simple, low-cost, and highly accessible OD calibration protocols across 244 laboratories, applied to eight strains of constitutive GFP-expressing E. coli. Based on our results, we recommend calibrating OD to estimated cell count using serial dilution of silica microspheres, which produces highly precise calibration (95.5% of residuals <1.2-fold), is easily assessed for quality control, also assesses instrument effective linear range, and can be combined with fluorescence calibration to obtain units of Molecules of Equivalent Fluorescein (MEFL) per cell, allowing direct comparison and data fusion with flow cytometry measurements: in our study, fluorescence per cell measurements showed only a 1.07-fold mean difference between plate reader and flow cytometry data

Expansion of Single Chains Released from a Spherical Cavity

A two-stage model is developed to explain the phenomena of chain expansion, released from a confining cavity. In the first stage, the chain is assumed to expand as a sphere, while in the second stage it expands like a coil. The kinetic equations for the variation of chain size are derived in the two stages by balancing the rate of the free energy change with the rate of the energy dissipation. Langevin dynamics simulations are then performed to examine the theory. We find that the expansion process is dominated by the second stage and the evolution of chain size follows, mainly, the predicted curve for coil expansion, which depends on the chain length and is not sensitive to the confining volume fraction. It permits to define the expansion time for the process. Further study reveals that the chain does undergo a spherical expansion in the first stage with the characteristic time much shorter than the one for the second stage. As a consequence, the first-stage variation of chain size can be regarded as an add-on to the principal curve of expansion designated by the second stage. The scaling behaviors and the associated scaling exponents are analyzed in details. The simulation results well support the theory

Study on the Correlation between Continuity of Care and Quality of Life for Patients with Coronary Heart Disease

Background: As coronary heart disease (CHD) is a highly complex disease, complex continuity of care (CoC) service should be provided for the patients, and the quality of life (QoL) needs to be regarded as an important measuring indicator for the health-care outcome. Purpose: To understand the general situation of CHD QoL and important predictors. Method: A cross-sectional study design was adopted from August 2019 to July 2020 by structured questionnaires. A total of 163 patients were enrolled, and data were statistically analyzed using SPSS 25.0. Result: The average score of the QoL questionnaire is 56.56/80, and the CoC is 4.32. The overall regression model can explain 58.7% of the variance regarding QoL. Patients’ instrumental activities of daily living (IADLs) (26.1%), age (18.1%), living situation (7%), information transfer (4.8%), main source of income (1.8%), and risk of disability are significantly different from their overall QoL in depression (0.9%). Conclusions: In order to improve the QoL of patients, it is suggested that medical teams should assess the needs of patients immediately upon hospitalization, provide patients with individual CoC, encourage them to participate in community health promotion activities, and strengthen the function of IADL to improve the QoL of patients

Factors Affecting the Amount of Cadmium Accumulated in Culinary-Medicinal Royal Sun Agaricus, Agaricus brasiliensis S. Wasser et al. (Agaricomycetideae), During Cultivation

This study was conducted to investigate accumulation of heavy metals in Agaricus brasiliensis at commercial farms in Taiwan. Among 14 samples of fruiting bodies of A. brasiliensis examined, five heavy metals, Cr, As, Cd, Hg, and Pb, were detected and only the content of cadmium (Cd) exceeded the level of 2 ppm (μg/g) specified by the Department of Health, Republic of China. The rates of Cd in fruiting bodies varied with samples ranging from 1.10 μg/g to 20.07 μg/g. Accumulation of Cd in fruiting bodies varied with strains of A. brasiliensis. Among the four strains studied, the strain A5 had the lowest rate of Cd absorption (4.57 μg/g) and the highest production of fruiting bodies (4592.4 g/24 bags), making it an ideal strain for commercial production. Among six cultivation adjuvants tested, the oyster shell powder contained the highest level of cadmium. The average cadmium level in the plastic bag was 0.077 μg/g, whereas the cadmium content in oyster shell powder was 0.363 μg/g. This study indicates that the oyster shell powder in the growth substrate may be one of the main sources for the accumulation of cadmium in the fruiting body of A. brasiliensis

Licochalcone A suppresses migration and invasion of human hepatocellular carcinoma cells through downregulation of MKK4/JNK via NF-κB mediated urokinase plasminogen activator expression.

Hepatocellular cell carcinoma (HCC) is one of the most commonly diagnosed cancers worldwide and in Taiwan. Chemoprevention of cancer with dietary bioactive compounds could potentially reverse, suppress, or prevent cancer progression. Licochalcone A (LicA) is a characteristic chalcone of licorice, which is the root of Glycyrrhiza inflate. It had been reported that LicA has anti-inflammatory, anti-microbial, and anti-tumor properties. However, the effects of LicA on the migration and invasion of human HCC cells have not yet been reported. In the present study, it was found that LicA inhibits the migratory and invasion ability of SK-Hep-1 and HA22T/VGH cells in a dose-dependent manner, as assessed by the cell migration and Matrigel cell invasion assay. Using casein zymography, Western blotting, reverse transcriptase polymerase chain reaction, and an immunofluorescence assay, it was found that LicA induces a dose-dependent inhibition of uPA activity and expression, as well as reduces mRNA levels in SK-Hep-1 and HA22T/VGH cells. LicA was also found to inhibit the expression of phosphor-JNK and phosphor-MKK4 in SK-Hep-1 cells. Furthermore, LicA significantly decreased uPA levels in SP600125-treated or si-MKK4-transfected cells alongside a marked reduction in cell migration and invasion, which supports the notion that an inhibition of MKK4/JNK results in anti-metastatic effects. Moreover, LicA inhibited the expression of nuclear NF-κB, as well as the binding ability of NF-κB to the uPA promoter. These findings further our understanding of the role of LicA in suppressing tumor metastasis and its underlying molecular mechanisms, as well as suggest that LicA may be a promising anti-metastatic agent