An outbreak of coronavirus disease 2019 (COVID‐19) occurred in Wuhan and it has rapidly spread to almost all parts of the world. For coronaviruses, RNA‐dependent RNA polymerase (RdRp) is an important ...protease that catalyzes the replication of RNA from RNA template and is an attractive therapeutic target. In this study, we screened these chemical structures from traditional Chinese medicinal compounds proven to show antiviral activity in severe acute respiratory syndrome coronavirus (SARS‐CoV) and the similar chemical structures through a molecular docking study to target RdRp of SARS‐CoV‐2, SARS‐CoV, and Middle East respiratory syndrome coronavirus (MERS‐CoV). We found that theaflavin has a lower idock score in the catalytic pocket of RdRp in SARS‐CoV‐2 (−9.11 kcal/mol), SARS‐CoV (−8.03 kcal/mol), and MERS‐CoV (−8.26 kcal/mol) from idock. To confirm the result, we discovered that theaflavin has lower binding energy of −8.8 kcal/mol when it docks in the catalytic pocket of SARS‐CoV‐2 RdRp by using the Blind Docking server. Regarding contact modes, hydrophobic interactions contribute significantly in binding and additional hydrogen bonds were found between theaflavin and RdRp. Moreover, one π‐cation interaction was formed between theaflavin and Arg553 from the Blind Docking server. Our results suggest that theaflavin could be a potential SARS‐CoV‐2 RdRp inhibitor for further study.
Highlights
Theaflavin has a lower idock score in the catalytic pocket of RdRp in SARS‐CoV‐2, SARS‐CoV and MERS‐CoV from idock.
Theaflavin has a lowest binding energy when it docks in the catalytic pocket of SARS‐CoV‐2 RdRp.
Theaflavin could be potential SARS‐CoV‐2 RdRp inhibitor.
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BFBNIB, FZAB, GIS, IJS, KILJ, NLZOH, NUK, OILJ, SBCE, SBMB, UL, UM, UPUK
To evaluate the performance of machine learning (ML) algorithms and to compare them with logistic regression for the prediction of risk of cardiovascular diseases (CVDs), chronic kidney disease ...(CKD), diabetes (DM), and hypertension (HTN) and in a prospective cohort study using simple clinical predictors.
We conducted analyses in a population-based cohort study in Asian adults (n = 6,762). Five different ML models were considered—single-hidden-layer neural network, support vector machine, random forest, gradient boosting machine, and k-nearest neighbor—and were compared with standard logistic regression.
The incidences at 6 years of CVD, CKD, DM, and HTN cases were 4.0%, 7.0%, 9.2%, and 34.6%, respectively. Logistic regression reached the highest area under the receiver operating characteristic curve for CKD (0.905 0.88, 0.93) and DM (0.768 0.73, 0.81) predictions. For CVD and HTN, the best models were neural network (0.753 0.70, 0.81) and support vector machine (0.780 0.747, 0.812), respectively. However, the differences with logistic regression were small (less than 1%) and nonsignificant. Logistic regression, gradient boosting machine, and neural network were systematically ranked among the best models.
Logistic regression yields as good performance as ML models to predict the risk of major chronic diseases with low incidence and simple clinical predictors.
•Low-dimensional settings include low number of events and predictors.•In such settings, logistic regression yields as good performance as ML models.•ML techniques may not be warranted in such cases.
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GEOZS, IJS, IMTLJ, KILJ, KISLJ, NLZOH, NUK, OILJ, PNG, SAZU, SBCE, SBJE, UILJ, UL, UM, UPCLJ, UPUK, ZAGLJ, ZRSKP
Accumulating evidence indicates that circular RNAs (circRNAs) are abundant in the human transcriptome. However, their involvement in biological processes, including pluripotency, remains mostly ...undescribed. We identified a subset of circRNAs that are enriched in undifferentiated human embryonic stem cells (hESCs) and demonstrated that two, circBIRC6 and circCORO1C, are functionally associated with the pluripotent state. Mechanistically, we found that circBIRC6 is enriched in the AGO2 complex and directly interacts with microRNAs, miR-34a, and miR-145, which are known to modulate target genes that maintain pluripotency. Correspondingly, circBIRC6 attenuates the downregulation of these target genes and suppresses hESC differentiation. We further identified hESC-enriched splicing factors (SFs) and demonstrated that circBIRC6 biogenesis in hESCs is promoted by the SF ESRP1, whose expression is controlled by the core pluripotency-associated factors, OCT4 and NANOG. Collectively, our data suggest that circRNA serves as a microRNA "sponge" to regulate the molecular circuitry, which modulates human pluripotency and differentiation.
Summary Background Numerous population-based studies of age-related macular degeneration have been reported around the world, with the results of some studies suggesting racial or ethnic differences ...in disease prevalence. Integrating these resources to provide summarised data to establish worldwide prevalence and to project the number of people with age-related macular degeneration from 2020 to 2040 would be a useful guide for global strategies. Methods We did a systematic literature review to identify all population-based studies of age-related macular degeneration published before May, 2013. Only studies using retinal photographs and standardised grading classifications (the Wisconsin age-related maculopathy grading system, the international classification for age-related macular degeneration, or the Rotterdam staging system) were included. Hierarchical Bayesian approaches were used to estimate the pooled prevalence, the 95% credible intervals (CrI), and to examine the difference in prevalence by ethnicity (European, African, Hispanic, Asian) and region (Africa, Asia, Europe, Latin America and the Caribbean, North America, and Oceania). UN World Population Prospects were used to project the number of people affected in 2014 and 2040. Bayes factor was calculated as a measure of statistical evidence, with a score above three indicating substantial evidence. Findings Analysis of 129 664 individuals (aged 30–97 years), with 12 727 cases from 39 studies, showed the pooled prevalence (mapped to an age range of 45–85 years) of early, late, and any age-related macular degeneration to be 8·01% (95% CrI 3·98–15·49), 0·37% (0·18–0·77), and 8·69% (4·26–17·40), respectively. We found a higher prevalence of early and any age-related macular degeneration in Europeans than in Asians (early: 11·2% vs 6·8%, Bayes factor 3·9; any: 12·3% vs 7·4%, Bayes factor 4·3), and early, late, and any age-related macular degeneration to be more prevalent in Europeans than in Africans (early: 11·2% vs 7·1%, Bayes factor 12·2; late: 0·5% vs 0·3%, 3·7; any: 12·3% vs 7·5%, 31·3). There was no difference in prevalence between Asians and Africans (all Bayes factors <1). Europeans had a higher prevalence of geographic atrophy subtype (1·11%, 95% CrI 0·53–2·08) than Africans (0·14%, 0·04–0·45), Asians (0·21%, 0·04–0·87), and Hispanics (0·16%, 0·05–0·46). Between geographical regions, cases of early and any age-related macular degeneration were less prevalent in Asia than in Europe and North America (early: 6·3% vs 14.3% and 12·8% Bayes factor 2·3 and 7·6; any: 6·9% vs 18·3% and 14·3% 3·0 and 3·8). No significant gender effect was noted in prevalence (Bayes factor <1·0). The projected number of people with age-related macular degeneration in 2020 is 196 million (95% CrI 140–261), increasing to 288 million in 2040 (205–399). Interpretation These estimates indicate the substantial global burden of age-related macular degeneration. Summarised data provide information for understanding the effect of the condition and provide data towards designing eye-care strategies and health services around the world. Funding National Medical Research Council, Singapore.
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GEOZS, IJS, IMTLJ, KILJ, KISLJ, NLZOH, NUK, OILJ, PNG, SAZU, SBCE, SBJE, UILJ, UL, UM, UPCLJ, UPUK, ZAGLJ, ZRSKP
Vacuum‐sublimed inorganic cesium lead halide perovskite thin films are prepared and integrated in all‐vacuum‐deposited solar cells. Special care is taken to determine the stoichiometric balance of ...the sublimation precursors, which has great influence on the device performance. The mixed halide devices exhibit exceptional stabilized power conversion efficiency (11.8%) and promising thermal and long‐term stabilities.
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BFBNIB, FZAB, GIS, IJS, KILJ, NLZOH, NUK, OILJ, SBCE, SBMB, UL, UM, UPUK
The novel growth of cesium lead halide perovskite thin films, which are prepared through thousand‐layer rapid alternative deposition, is performed by developing an active perovskite film consisting ...of a layer‐by‐layer structure. This method is considerably more difficult to be implemented from the solution process. The obtained thin film morphology and characteristics are distinguished from that of the traditional a few layers and two‐material codeposition. These alternative deposited perovskites are integrated with vacuum‐deposited carrier‐transporting layers and electrodes, and all vacuum‐sublimed perovskite solar cells exhibit an outstanding power conversion efficiency of 13.0%. The use of these devices for environmental light energy harvesting provides a power conversion efficiency of 33.9% under fluorescent light illumination of 1000 lux.
Rapid alternative deposition provides new approaches for Cs‐based perovskite fabrication. The thousand‐layer CsPbI2Br thin films obtained through this method exhibit a smooth surface and high crystallinity, and the solar cell devices deliver excellent performance under both 1‐sun solar and fluorescent light illumination.
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BFBNIB, FZAB, GIS, IJS, KILJ, NLZOH, NUK, OILJ, SBCE, SBMB, UL, UM, UPUK
Abstract The choroid is a highly vascular structure; therefore, a wide range of systemic conditions can affect it. Conversely, choroid health may also give us insight into systemic health. With the ...emergence of optical coherence tomography, there has been a surge in the research on choroidal thickness and factors affecting it. Studies regarding the effect of systemic health on the choroid have largely been in the form of cross-sectional, prospective, and case studies. We offer a summary of recent findings on the topic.
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GEOZS, IJS, IMTLJ, KILJ, KISLJ, NUK, OILJ, PNG, SAZU, SBCE, SBJE, UL, UM, UPCLJ, UPUK, ZRSKP
Abstract
Background
The crude extract of the fruit bearing plant,
Physalis peruviana
(golden berry), demonstrated anti-hepatoma and anti-inflammatory activities. However, the cellular mechanism ...involved in this process is still unknown.
Methods
Herein, we isolated the main pure compound, 4β-Hydroxywithanolide (4βHWE) derived from golden berries, and investigated its antiproliferative effect on a human lung cancer cell line (H1299) using survival, cell cycle, and apoptosis analyses. An alkaline comet-nuclear extract (NE) assay was used to evaluate the DNA damage due to the drug.
Results
It was shown that DNA damage was significantly induced by 1, 5, and 10 μg/mL 4βHWE for 2 h in a dose-dependent manner (
p
< 0.005). A trypan blue exclusion assay showed that the proliferation of cells was inhibited by 4βHWE in both dose- and time-dependent manners (
p
< 0.05 and 0.001 for 24 and 48 h, respectively). The half maximal inhibitory concentrations (IC
50
) of 4βHWE in H1299 cells for 24 and 48 h were 0.6 and 0.71 μg/mL, respectively, suggesting it could be a potential therapeutic agent against lung cancer. In a flow cytometric analysis, 4βHWE produced cell cycle perturbation in the form of sub-G
1
accumulation and slight arrest at the G
2
/M phase with 1 μg/mL for 12 and 24 h, respectively. Using flow cytometric and annexin V/propidium iodide immunofluorescence double-staining techniques, these phenomena were proven to be apoptosis and complete G
2
/M arrest for H1299 cells treated with 5 μg/mL for 24 h.
Conclusions
In this study, we demonstrated that golden berry-derived 4βHWE is a potential DNA-damaging and chemotherapeutic agent against lung cancer.
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DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK
Danshen (salvia miltiorrhiza Bunge) is widely used in traditional Chinese medicine. However, it is definite clinical effort and mechanism on breast cancer is unclear. In our study, we used the ...real-world database to investigate
in vivo
protective effort of danshen in the breast cancer patients through using population-based data from the Taiwan National Health Insurance Research Database (NHIRD).
In vitro
, human breast cancer cells (MCF-7 cells and MDA-MB-231 cells) were used to investigate the effect and the underlying mechanism through XTT assay, flow cytometry, glutathione peroxidase (GPX) activity assay, GSH (reduced glutathione)/GSSG (oxidized glutathione), malondialdehyde (MDA), and western blot analysis. The
in vivo
effect was investigated through a xenograft nude mouse model. We found that dihydroisotanshinone I (DT), a pure compound present in danshen, can inhibit the growth of breast carcinoma cells, including MCF-7 cells and MDA-MB-231 cells. Moreover, DT induced apoptosis and ferroptosis in these breast cancer cells. DT also repressed the protein expression of GPX4 (Glutathione peroxidase 4). For
in vivo
study, DT treatment also significantly inhibited the final tumor volume without adverse effects in a xenograft nude mouse model. In conclusion, danshen has protective efforts in breast cancer patients, which could be attributed to DT through inducing apoptosis and ferroptosis of breast cancer cells.
Every year cervical cancer affects more than 300,000 people, and on average one woman is diagnosed with cervical cancer every minute. Early diagnosis and classification of cervical lesions greatly ...boosts up the chance of successful treatments of patients, and automated diagnosis and classification of cervical lesions from Papanicolaou (Pap) smear images have become highly demanded. To the authors' best knowledge, this is the first study of fully automated cervical lesions analysis on whole slide images (WSIs) of conventional Pap smear samples. The presented deep learning-based cervical lesions diagnosis system is demonstrated to be able to detect high grade squamous intraepithelial lesions (HSILs) or higher (squamous cell carcinoma; SQCC), which usually immediately indicate patients must be referred to colposcopy, but also to rapidly process WSIs in seconds for practical clinical usage. We evaluate this framework at scale on a dataset of 143 whole slide images, and the proposed method achieves a high precision 0.93, recall 0.90, F-measure 0.88, and Jaccard index 0.84, showing that the proposed system is capable of segmenting HSILs or higher (SQCC) with high precision and reaches sensitivity comparable to the referenced standard produced by pathologists. Based on Fisher's Least Significant Difference (LSD) test (P < 0.0001), the proposed method performs significantly better than the two state-of-the-art benchmark methods (U-Net and SegNet) in precision, F-Measure, Jaccard index. For the run time analysis, the proposed method takes only 210 seconds to process a WSI and is 20 times faster than U-Net and 19 times faster than SegNet, respectively. In summary, the proposed method is demonstrated to be able to both detect HSILs or higher (SQCC), which indicate patients for further treatments, including colposcopy and surgery to remove the lesion, and rapidly processing WSIs in seconds for practical clinical usages.
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IZUM, KILJ, NUK, PILJ, PNG, SAZU, UL, UM, UPUK
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