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.
Critical patients with the coronavirus disease 2019 (COVID-19), even those whose nucleic acid test results had turned negative and those receiving maximal medical support, have been noted to progress ...to irreversible fatal respiratory failure. Lung transplantation (LT) as the sole therapy for end-stage pulmonary fibrosis related to acute respiratory distress syndrome has been considered as the ultimate rescue therapy for these patients.
From February 10 to March 10, 2020, three male patients were urgently assessed and listed for transplantation. After conducting a full ethical review and after obtaining assent from the family of the patients, we performed three LT procedures for COVID-19 patients with illness durations of more than one month and extremely high sequential organ failure assessment scores.
Two of the three recipients survived post-LT and started participating in a rehabilitation program. Pearls of the LT team collaboration and perioperative logistics were summarized and continually improved. The pathological results of the explanted lungs were concordant with the critical clinical manifestation, and provided insight towards better understanding of the disease. Government health affair systems, virology detection tools, and modern communication technology all play key roles towards the survival of the patients and their rehabilitation.
LT can be performed in end-stage patients with respiratory failure due to COVID-19-related pulmonary fibrosis. If confirmed positive-turned-negative virology status without organ dysfunction that could contraindicate LT, LT provided the final option for these patients to avoid certain death, with proper protection of transplant surgeons and medical staffs. By ensuring instant seamless care for both patients and medical teams, the goal of reducing the mortality rate and salvaging the lives of patients with COVID-19 can be attained.
The demand for large antennas in future space missions has increasingly stimulated the development of deployable membrane antenna structures owing to their light weight and small stowage volume. ...However, there is little literature providing a comprehensive review and comparison of different membrane antenna structures. Space-borne membrane antenna structures are mainly classified as either parabolic or planar membrane antenna structures. For parabolic membrane antenna structures, there are five deploying and forming methods, including inflation, inflation-rigidization, elastic ribs driven, Shape Memory Polymer （SMP）-inflation, and electrostatic form- ing. The development and detailed comparison of these five methods are presented. Then, properties of membrane materials （including polyester film and polyimide film） for parabolic membrane antennas are compared. Additionally, for planar membrane antenna structures, frame shapes have changed from circular to rectangular, and different ten- sioning systems have emerged successively, including single Miura-Natori, double, and multi-layer tensioning systems. Recent advances in structural configurations, tensioning system design, and dynamic analysis for planar membrane antenna structures are investigated. Finally, future trends for large space membrane antenna structures are pointed out and technical problems are proposed, including design and analysis of membrane structures,materials and processes, membrane packing, surface accuracy stability, and test and verification technology. Through a review of large deployable membrane antenna structures, guidance for space membrane-antenna research and applications is provided.
There is an increasingly urgent need of lightweight components in aerospace industry, among which aluminum (Al) alloys have been the optimal materials of choice for aircraft structural parts since ...being used in the Junkers F.13 aircraft in the 1920s. Compared to other metal materials, Al alloys have a lower density, and the use of Al alloys reduces the total weight of the aircraft and improves fuel efficiency and load capacity. Meanwhile, the strength and hardness of Al alloys with alloying and heat treatment can be significantly enhanced for uses in high loads and vibration environments. Furthermore, in the harsh aerospace environment, aircraft may receive various climatic conditions and chemical corrosion. Due to good corrosion and fatigue resistance, Al alloys demonstrate excellent performance under these conditions, ensuring the long–term service life of aircraft. In addition, Al alloys have good recyclability, and they can be recycled to reduce resource consumption and environmental load, in line with the principle of sustainable development. In recent years, although composites have been widely used in aerospace, high–strength Al alloys are still in an indispensable position. Therefore, this article reviews the progress and applications of Al alloys commonly used in aerospace. The common strengthening methods and advanced manufacturing and processing technologies of Al alloy are also discussed, which can provide references for the development of advanced high–performance aviation Al alloys in the future.
Immune checkpoint blockade (ICB) therapy shows excellent efficacy against malignancies; however, insufficient tumor immunogenicity and the immunosuppressive tumor microenvironment (TME) are ...considered as the two major stumbling blocks to a broad ICB response. Here, a combinational therapeutic strategy is reported, wherein TME‐reactive oxygen species/pH dual‐responsive signal transducers and activators of transcription 3 inhibitor nanoprodrugs MPNPs are combined with oncolytic herpes simplex virus 1 virotherapy to synergistically ignite pyroptosis for enhancing immunotherapy. MPNPs exhibit a certain level of tumor accumulation, reduce tumor cell stemness, and enhance antitumor immune responses. Furthermore, the simultaneous application of oncolytic viruses (OVs) confers MPNPs with higher tumor penetration capacity and remarkable gasdermin‐E‐mediated pyroptosis, thereby reshaping the TME and transforming “cold” tumors into “hot” ones. This “fire of immunity” strategy successfully activates robust T‐cell‐dependent antitumor responses, potentiating ICB effects against local recurrence and pulmonary metastasis in preclinical “cold” murine triple‐negative breast cancer and syngeneic oral cancer models. Collectively, this work may pave a new way and offer an unprecedented opportunity for the combination of OVs with nanomedicine for cancer immunotherapy.
Combination therapy with oHSV + MPNPs boosts the effects of immune checkpoint therapy by inducing gasdermin‐E‐based tumor pyroptosis, reversing the immunosuppressive microenvironment, and inducing effective immune memory, thus potentiating anti‐PD‐1 effects against local recurrence and pulmonary metastasis and consequently elongating the survival period. The nanoprodrugs + oncolytic viruses strategy represents a promising way to overcome immune checkpoint blockade resistance.
Nitrotyrosine is one of the post-translational modifications (PTMs) in proteins that occurs when their tyrosine residue is nitrated. Compared with healthy people, a remarkably increased level of ...nitrotyrosine is detected in those suffering from rheumatoid arthritis, septic shock, and coeliac disease. Given an uncharacterized protein sequence that contains many tyrosine residues, which one of them can be nitrated and which one cannot? This is a challenging problem, not only directly related to in-depth understanding the PTM's mechanism but also to the nitrotyrosine-based drug development. Particularly, with the avalanche of protein sequences generated in the postgenomic age, it is highly desired to develop a high throughput tool in this regard. Here, a new predictor called "iNitro-Tyr" was developed by incorporating the position-specific dipeptide propensity into the general pseudo amino acid composition for discriminating the nitrotyrosine sites from non-nitrotyrosine sites in proteins. It was demonstrated via the rigorous jackknife tests that the new predictor not only can yield higher success rate but also is much more stable and less noisy. A web-server for iNitro-Tyr is accessible to the public at http://app.aporc.org/iNitro-Tyr/. For the convenience of most experimental scientists, we have further provided a protocol of step-by-step guide, by which users can easily get their desired results without the need to follow the complicated mathematics that were presented in this paper just for the integrity of its development process. It has not escaped our notice that the approach presented here can be also used to deal with the other PTM sites in proteins.
Previous studies have revealed the involvement of coffee and tea in the development of stroke and dementia. However, little is known about the association between the combination of coffee and tea ...and the risk of stroke, dementia, and poststroke dementia. Therefore, we aimed to investigate the associations of coffee and tea separately and in combination with the risk of developing stroke and dementia.
This prospective cohort study included 365,682 participants (50 to 74 years old) from the UK Biobank. Participants joined the study from 2006 to 2010 and were followed up until 2020. We used Cox proportional hazards models to estimate the associations between coffee/tea consumption and incident stroke and dementia, adjusting for sex, age, ethnicity, qualification, income, body mass index (BMI), physical activity, alcohol status, smoking status, diet pattern, consumption of sugar-sweetened beverages, high-density lipoprotein (HDL), low-density lipoprotein (LDL), history of cancer, history of diabetes, history of cardiovascular arterial disease (CAD), and hypertension. Coffee and tea consumption was assessed at baseline. During a median follow-up of 11.4 years for new onset disease, 5,079 participants developed dementia, and 10,053 participants developed stroke. The associations of coffee and tea with stroke and dementia were nonlinear (P for nonlinear <0.01), and coffee intake of 2 to 3 cups/d or tea intake of 3 to 5 cups/d or their combination intake of 4 to 6 cups/d were linked with the lowest hazard ratio (HR) of incident stroke and dementia. Compared with those who did not drink tea and coffee, drinking 2 to 3 cups of coffee and 2 to 3 cups of tea per day was associated with a 32% (HR 0.68, 95% CI, 0.59 to 0.79; P < 0.001) lower risk of stroke and a 28% (HR, 0.72, 95% CI, 0.59 to 0.89; P = 0.002) lower risk of dementia. Moreover, the combination of coffee and tea consumption was associated with lower risk of ischemic stroke and vascular dementia. Additionally, the combination of tea and coffee was associated with a lower risk of poststroke dementia, with the lowest risk of incident poststroke dementia at a daily consumption level of 3 to 6 cups of coffee and tea (HR, 0.52, 95% CI, 0.32 to 0.83; P = 0.007). The main limitations were that coffee and tea intake was self-reported at baseline and may not reflect long-term consumption patterns, unmeasured confounders in observational studies may result in biased effect estimates, and UK Biobank participants are not representative of the whole United Kingdom population.
We found that drinking coffee and tea separately or in combination were associated with lower risk of stroke and dementia. Intake of coffee alone or in combination with tea was associated with lower risk of poststroke dementia.
Covering: up to July 2020Naturally occurring chalcones carrying up to three modified or unmodified C
-, C
-, and C
-prenyl moieties on both rings A and B as well as at the α- and β-carbons are widely ...distributed in plants of the families of Fabaceae, Moraceae, Zingiberaceae and Cannabaceae. Xanthohumol and isobavachalcone being the most investigated representatives, exhibit diverse and remarkable biological and pharmacological activities. The present review deals with their structural characters, biological activities and occurrence in the plant kingdom. Biosynthesis of prenylated chalcones and metabolism of xanthohumol are also discussed.
A big challenge for nonlinear optical (NLO) materials is the application in high power lasers, which needs the simultaneous occurrence of large second harmonic generation (SHG) and high laser induced ...damage threshold (LIDT). Herein we report the preparation of a new Ga2Se3 phase, which shows the SHG intensities of around 2.3 times and the LIDT of around 16.7 times those of AgGaS2 (AGS), respectively. In addition, its IR transparent window ca. 0.59–25 μm is also significantly wider than that of AGS (ca. 0.48–≈11.4 μm). The occurrence of the strong SHG responses and good phase‐matching indicate that the structure of the new Ga2Se3 phase can only be non‐centrosymmetric and have a lower symmetry than the cubic γ‐phase. The observed excellent SHG and phase‐matching properties are consistent with our diffraction experiments and can be well explained by using the orthorhombic models obtained through our high throughput simulations.
A simple but perfect case: A new phase of gallium selenides (δ‐Ga2Se3) has been obtained via solid‐state reactions. δ‐Ga2Se3 is phase‐matchable with large second harmonic generation (SHG) responses, high laser‐induced damage thresholds (LIDTs), and wide transparent range of 0.59–25 μm. These properties are all required for the application of NLO materials with high‐power lasers.
Tailoring enzymes are important modification biocatalysts in natural product biosynthesis. We report herein six orthologous two‐gene clusters for mycocyclosin and guatyromycine biosynthesis. ...Expression of the cyclodipeptide synthase genes gymA1–gymA6 in Escherichia coli resulted in the formation of cyclo‐l‐Tyr‐l‐Tyr as the major product. Reconstruction of the biosynthetic pathways in Streptomyces albus and biochemical investigation proved that the cytochrome P450 enzymes GymB1–GymB6 act as both intramolecular oxidases and intermolecular nucleobase transferases. They catalyze not only the oxidative C−C coupling within cyclo‐l‐Tyr‐l‐Tyr, leading to mycocyclosin, but also its connection with guanine and hypoxanthine, and are thus responsible for the formation of tyrosine‐containing guatyromycines, instead of the reported tryptophan‐nucleobase adducts. Phylogenetic data suggest the presence of at least 47 GymB orthologues, indicating the occurrence of a widely distributed enzyme class.
Bioinformatic analysis unveiled a widely distributed two‐gene locus (gym) in actinobacteria. Reconstruction of the biosynthetic pathways and biochemical investigation led to the characterization of the cytochrome P450s GymBs as dual‐functional oxidases, which catalyze both intra‐ and intermolecular coupling reactions at different positions of cyclo‐l‐Tyr‐l‐Tyr to generate novel tyrosine‐based alkaloids.
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