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.
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.
Spinal sarcopenia is a complex and multifactorial disorder associated with a loss of strength, increased frailty, and increased risks of fractures and falls. In addition, spinal sarcopenia has been ...associated with lumbar spine disorders and osteoporosis, which renders making decisions on treatment modalities difficult. Patients with spinal sarcopenia typically exhibit lower cumulative survival, a higher risk of in-hospital complications, prolonged hospital stays, higher postoperative costs, and higher rates of blood transfusion after thoracolumbar spine surgery. Several studies have focused on the relationships between spinal sarcopenia, appendicular muscle mass, and bone-related problems-such as osteoporotic fractures and low bone mineral density-and malnutrition and vitamin D deficiency. Although several techniques are available for measuring sarcopenia, each of them has its advantages and shortcomings. For treating spinal sarcopenia, nutrition, physical therapy, and medication have been proven to be effective; regenerative therapeutic options seem to be promising owing to their repair and regeneration potential. Therefore, in this narrative review, we summarize the characteristics, detection methodologies, and treatment options for spinal sarcopenia, as well as its role in spinal disorders.
To investigate the risk of poor prognosis regarding schizophrenic disorders, psychotic disorders, suicide, self-inflicted injury, and mortality after adult violence from 2000 to 2015 in Taiwan.
This ...study used data from National Health Insurance Research Database (NHIRD) on outpatient, emergency, and inpatient visits for two million people enrolled in the National Health Insurance (NHI) from 2000 to 2015. The case study defined ICD-9 diagnosis code N code 995.8 (abused adult) or E code E960-E969 (homicide and intentional injury of another). It analyzed first-time violence in adults aged 18-64 years (study group). 1:4 ratio was matched with injury and non-violent patients (control group). The paired variables were sex, age (± 1 year), pre-exposure to the Charlson comorbidity index, and year of medical treatment. Statistical analysis was conducted using SAS 9.4 and Cox regression for data analysis.
In total, 8,726 individuals experienced violence (case group) while34,904 did not experienced violence (control group) over 15 years. The prevalence of poor prognosis among victims of violence was 25.4/10
, 31.3/10
, 10.5/10,
and 104.6/10
for schizophrenic disorders, psychotic disorders, suicide or self-inflicted injury and mortality, respectively. Among adults, the risks of suicide or self-inflicted injury, schizophrenic disorders, psychotic disorders, and mortality after exposure to violence (average 9 years) were 6.87-, 5.63-, 4.10-, and 2.50-times (p < 0.01), respectively, compared with those without violence. Among males, the risks were 5.66-, 3.85-, 3.59- and 2.51-times higher, respectively, than those without violence (p < 0.01), and they were 21.93-, 5.57-, 4.60- and 2.46-times higher than those without violence (p < 0.01) among females.
The risk of poor prognosis regarding schizophrenic disorders, psychotic disorders, suicide, or self-inflicted injury and mortality after adult violence was higher than in those who have not experienced a violent injury. Adults at the highest risk for violent suicide or self-inflicted injuries due to exposure to violent injuries -males were at risk for schizophrenia and females were at risk for suicide or self-inflicted injuries. Therefore, it is necessary for social workers and medical personnel to pay attention to the psychological status of victims of violence.
Celotno besedilo
Dostopno za:
DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, SIK, UILJ, UKNU, 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.
Cell expansion of human pluripotent stem cells (hPSCs) commonly depends on Matrigel as a coating matrix on two-dimensional (2D) culture plates and 3D microcarriers. However, the xenogenic Matrigel ...requires sophisticated quality-assurance processes to meet clinical requirements. In this study, we develop an innovative coating-free medium for expanding hPSCs. The xenofree medium supports the weekend-free culture and competitive growth of hPSCs on several cell culture plastics without an additional pre-coating process. The pluripotent stemness of the expanded cells is stably sustained for more than 10 passages, featured with high pluripotent marker expressions, normal karyotyping, and differentiating capacity for three germ layers. The expression levels of some integrins are reduced, compared with those of the hPSCs on Matrigel. This medium also successfully supports the clonal expansion and induced pluripotent stem cell establishment from mitochondrial-defective MELAS (mitochondrial encephalomyopathy, lactic acidosis, and stroke-like episodes) patient’s peripheral blood mononuclear cells. This innovative hPSC medium provides a straightforward scale-up process for producing clinical-orientated hPSCs by excluding the conventional coating procedure.
Constituting approximately 10% of flowering plant species, orchids (Orchidaceae) display unique flower morphologies, possess an extraordinary diversity in lifestyle, and have successfully colonized ...almost every habitat on Earth. Here we report the draft genome sequence of Apostasia shenzhenica, a representative of one of two genera that form a sister lineage to the rest of the Orchidaceae, providing a reference for inferring the genome content and structure of the most recent common ancestor of all extant orchids and improving our understanding of their origins and evolution. In addition, we present transcriptome data for representatives of Vanilloideae, Cypripedioideae and Orchidoideae, and novel third-generation genome data for two species of Epidendroideae, covering all five orchid subfamilies. A. shenzhenica shows clear evidence of a whole-genome duplication, which is shared by all orchids and occurred shortly before their divergence. Comparisons between A. shenzhenica and other orchids and angiosperms also permitted the reconstruction of an ancestral orchid gene toolkit. We identify new gene families, gene family expansions and contractions, and changes within MADS-box gene classes, which control a diverse suite of developmental processes, during orchid evolution. This study sheds new light on the genetic mechanisms underpinning key orchid innovations, including the development of the labellum and gynostemium, pollinia, and seeds without endosperm, as well as the evolution of epiphytism; reveals relationships between the Orchidaceae subfamilies; and helps clarify the evolutionary history of orchids within the angiosperms.
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.
Autophagy, a cellular self-eating mechanism, is important for maintaining cell survival and tissue homeostasis in various stressed conditions. Although the molecular mechanism of autophagy induction ...has been well studied, how cells terminate autophagy process remains elusive. Here, we show that ULK1, a serine/threonine kinase critical for autophagy initiation, is a substrate of the Cul3-KLHL20 ubiquitin ligase. Upon autophagy induction, ULK1 autophosphorylation facilitates its recruitment to KLHL20 for ubiquitination and proteolysis. This autophagy-stimulated, KLHL20-dependent ULK1 degradation restrains the amplitude and duration of autophagy. Additionally, KLHL20 governs the degradation of ATG13, VPS34, Beclin-1, and ATG14 in prolonged starvation through a direct or indirect mechanism. Impairment of KLHL20-mediated regulation of autophagy dynamics potentiates starvation-induced cell death and aggravates diabetes-associated muscle atrophy. Our study identifies a key role of KLHL20 in autophagy termination by controlling autophagy-dependent turnover of ULK1 and VPS34 complex subunits and reveals the pathophysiological functions of this autophagy termination mechanism.
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•ULK1 autophosphorylation promotes its recruitment to KLHL20 for ubiquitination•KLHL20 promotes ubiquitination of phagophore-residing VPS34 and Beclin-1•KLHL20 mediates autophagy termination by degrading ULK1 and VPS34 complex subunits•Impairment of autophagy termination causes cell death and muscle atrophy
Liu et al. report a function of the Cul3-KLHL20 ubiquitin ligase in a feedback regulation, leading to autophagy termination through the degradation of multiple subunits of ULK1 and VPS34 complexes. This mechanism is important for cell survival and muscle homeostasis.
Increasing evidence suggests that tumor development requires not only oncogene/tumor suppressor mutations to drive the growth, survival, and metastasis but also metabolic adaptations to meet the ...increasing energy demand for rapid cellular expansion and to cope with the often nutritional and oxygen-deprived microenvironment. One well-recognized strategy is to shift the metabolic flow from oxidative phosphorylation (OXPHOS) or respiration in mitochondria to glycolysis or fermentation in cytosol, known as Warburg effects. However, not all cancer cells follow this paradigm. In the development of prostate cancer, OXPHOS actually increases as compared to normal prostate tissue. This is because normal prostate epithelial cells divert citrate in mitochondria for the TCA cycle to the cytosol for secretion into seminal fluid. The sustained level of OXPHOS in primary tumors persists in progression to an advanced stage. As such, targeting OXPHOS and mitochondrial activities in general present therapeutic opportunities. In this review, we summarize the recent findings of the key regulators of the OXPHOS pathway in prostate cancer, ranging from transcriptional regulation, metabolic regulation to genetic regulation. Moreover, we provided a comprehensive update of the current status of OXPHOS inhibitors for prostate cancer therapy. A challenge of developing OXPHOS inhibitors is to selectively target cancer mitochondria and spare normal counterparts, which is also discussed.
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