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Background: The high mortality rate of cancer is endangering human health, and the research and development of new anticancer drugs have the attention of scientists worldwide. Sulfonamides have become the focus of anticancer drug research. 1,2,3-triazole compounds can inhibit the formation of a variety of tumor cells. Based on the excellent antitumor activity exhibited by the 1,2,3-triazole compound skeleton, the sulfonamide moiety in the sulfonamide structure can be introduced into the triazole compound skeleton to obtain highly active anticancer drugs. Methods: The Topomer CoMFA method was used to study the three-dimensional quantitative structureactivity relationship of 58 new 1,2,3-triazole compounds with sulfa groups, and a 3D-QSAR model was obtained. Results: The cross-validation coefficient q2 is 0.545, the non-cross-correlation coefficient r2 is 0. 754, r_pred2 is 0.930, the optimal number of principal components N is 4, and the standard estimation error SEE is 0.319. These results show that the model has good internal and external forecasting capabilities. By searching for the R group in the Topomer search module and combining with the more active groups in the existing molecules, 6 new compounds with theoretically higher anti-HL-60 (leukemia cell line) activity are obtained. Conclusion: The prediction result of the Topomer CoMFA model is good, and the statistical verification is effective. The prediction results of ADMET show that the 6 new compounds meet the drug requirements and are expected to become potential anti-HL-60 inhibitors, providing guidance for the synthesis of anti-tumor drugs.

Three new lanostane triterpenoids (1-3) along with two new amides fatty compounds (4-5) were isolated from the ethyl acetate extract of a culture of the endophytic fungus Alternaria sp. gx-2. Their structures were identified by 1D and 2D NMR spectral data and HRESIMS. Compounds 1-12 were evaluated for their anti-inflammatory and tyrosinase inhibition activities. The isolated compounds did not show inhibitory activities at a concentration of 100 μM against tyrosinase, while under the concentration of 10 μM, the release of lactate dehydrogenase (LDH) inhibition rate of compound 1 was 54.45%, indicating that compound 1 had moderate anti-inflammatory activity on the activation of NLRP3 inflammasome.

Flexible aquatic vegetation exists widely in nature and serves multiple hydro-environmental functions mainly through fluid–structure interactions. The waving motion of vegetation arrays, known as Monami, is predominantly governed by Kelvin–Helmholtz (KH) instability, and its characteristic scales, such as wave height and wavelength, are still being explored. In this paper, the interactions between a large array of flexible vegetations and a laminar boundary-layer flow are investigated using direct numerical simulation. The parameters used are the Reynolds number Re = 400, mass ratio β = 1.0, bending rigidity γ = 0.04–0.22, and gap distance d = 0.4–1.6. A low frequency in Monami is found to be related to the fluctuation frequency of the onset position of the KH instability, which leads to the identification of four different Monami modes: regular Monami, quasi-regular Monami A, quasi-regular Monami B, and irregular Monami. The influences of the bending rigidity and gap distance on the Monami modes, KH instability onset position, and Monami characteristic scales are discussed. It was found that the causes of spatial and temporal variations in the characteristic scales of Monami vary depending on the mode. In the regular Monami mode, these variations result from the evolution of the KH vortex. In the quasi-regular Monami A mode, they are strongly affected by the shifting of the onset position of the KH instability. In the other two modes, these variations are caused by a combination of the fluctuation in the KH instability onset position and the complex interaction between vortices.

Mastitis is usually caused by a variety of pathogenic bacteria that seriously impact the health and milk-production ability of dairy cows, with consequent, economically detrimental effects on the dairy industry. Forsythoside A (FTA), isolated from the fruit and leaves of Forsythia suspensa (Thunb.) Vahl (Oleaceae), has been reported to have significant antioxidant, anti-inflammatory, and antibacterial effects. However, it is not clear whether FTA exerts a protective effect against lipopolysaccharide (LPS)-induced bovine mastitis and its potential gene signature. In this study, high-throughput sequencing technology was performed to analyze the differences between the mRNA and enrichment pathway of bovine mammary epithelial cells of the control, LPS, and LPS + FTA groups. The results showed that there were 139 differentially expressed genes (DEGs) (p-value < 0.05, |log2FoldChange| > 1, FPKM > 1) in the LPS group compared with the control group, including 121 up-regulated genes and 18 down-regulated genes, which were mainly enriched in the cellular response to lipopolysaccharide, cytokine activity, protein binding, and IL-17 signaling pathway based on Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) analysis, respectively. Compared with the control group and LPS + FTA group, there were 349 DEGs, including 322 up-regulated genes and 27 down-regulated genes. They were mainly enriched in protein localization to organelles, centrosomes, binding, and the IL-17 signaling pathway, based on GO and KEGG analysis. Compared to the LPS group, the LPS + FTA group had 272 DEGs, including 259 up-regulated genes and 13 down-regulated genes, which were mainly enriched in RNA processing, IL-6 receptor binding, and the lysosome pathway, based on GO and KEGG analyses. It can be seen that LPS stimulation induced the expression of inflammation-related genes, IL-17 and IL-6, whereas FTA treatment promoted the expression of the spliceosome-, lysosome-, and oxidative stress-related genes HSP70, HSPA8, and PARP2. The study utilized RNA-sequencing analysis of FTA against LPS-challenged bovine mammary epithelial cells to explore key mRNA findings that may be strongly associated with inflammation and oxidative stress, and provides a theoretical reference for further elucidation of molecular mechanisms of bovine mastitis and therapeutic effects of FTA against bovine mastitis.

The dried flower buds of Magnolia biondii Pamp (herbal name, Xin-Yi) are a traditional Chinese medicine with a long history of clinical use in the treatment of allergic rhinitis and sinusitis. However, the constituents responsible for its antiallergic effects remain clearly unidentified. In the present study, totally 33 lignans were obtained from M. biondii. Among them, two novel furofuran lignans (1 and 2), two novel tetrahydrofuran lignans (3 and 4), and other 16 known lignans were isolated first time from M. biondii. The antiallergic effects of compounds 1-33 on mouse bone marrow-derived mast cells (BMMCs) degrunaliton were evaluated and results showed that compounds 7, 8, 13, 15 and 18 could significantly inhibited β-hex release on BMMCs. The results proved that furofuran and tetrahydrofuran lignans were the main constituents in M. biondii and their antiallergic effects were related with suppressing mast cell activation.

Initial coordinate and simulation input files used for MD simulations and PMF generationsandcorresponding coordinate filesof the final output

This paper proposes a method for modelling volatilities (conditional covariance matrices) of high dimensional dynamic data. We combine the ideas of approximate factor models for dimension reduction and multivariate GARCH models to establish a model to describe the dynamics of high dimensional volatilities. Sparsity condition and thresholding technique are applied to the estimation of the error covariance matrices, and quasi maximum likelihood estimation (QMLE) method is used to estimate the parameters of the common factor conditional covariance matrix. Asymptotic theories are developed for the proposed estimation. Monte Carlo simulation studies and real data examples are presented to support the methodology.

In view of the importance of the magmatic oxidation state and volatile composition (H2O-S-Cl) in porphyry Cu mineralization, identification of magmatic information has become the basis for the evaluation of the Cu-mineralization potential of porphyries. Apatite, as a common accessory mineral in porphyry, is recognized as an effective petrogenetic and metallogenic indicator. In this study, we analyze the in situ major and trace elements and Nd isotope content of apatite from four granitic plutons in the Yidun Terrane, SW China, in order to provide new insights into the identification of the magmatic features of Cu-mineralized plutons. The plutons investigated in this study are a Cu-mineralized pluton (Hongshan) and three non-mineralized plutons (Cilincuo, Rongyicuo, and Hagela). Chemical composition and textural analysis indicate that the apatites are all of magmatic origin and have not been altered. Our results show that apatite δCe values rather than δEu and Ga values are more valid indicators of the magma oxidation state of the four plutons. Based on apatite δCe values and zircon compositions, the parental magma of the Hongshan pluton is identified as having been more oxidized than those of the other three plutons. Moreover, the higher Cl content (0.06–0.23 wt%) in the Hongshan apatite compared to that in apatite from the other three plutons (0.01–0.09 wt%), indicates that the parental magma of the former pluton was more enriched in Cl. Apatite from the Hongshan pluton contains more SO3 (average 0.05 wt%) than that from the other three plutons (SO3 content mostly lower than the detection limit of electron probe micro-analysis), which may be related to higher magmatic oxygen fugacity of the Hongshan pluton. In addition, the Nd isotopic composition of apatite [εNd(t): −13.6−5.9] demonstrates that the Cu-mineralized and non-mineralized plutons were derived from the melting of ancient lower crust. Furthermore, based on the geochemical signature of adakite revealed by apatite Sr/Y and δEu values, the Hongshan pluton can be considered to have been produced as the result of partial melting of the thickened lower crust. Finally, an index system consisting of apatite δCe, Sr/Y, and F/Cl values is established to distinguish between the Cu-mineralized and non-mineralized plutons.

Early antiviral treatments, including intravenous remdesivir (RDV), reduce hospitalization and severe disease caused by COVID-19. An orally bioavailable RDV analog may facilitate earlier treatment of non-hospitalized COVID-19 patients. Here we describe the synthesis and evaluation of alkyl glyceryl ether phosphodiesters of GS-441524 (RVn), lysophospholipid analogs which allow for oral bioavailability and stability in plasma. Oral treatment of SARS-CoV-2-infected BALB/c mice with 1-O-octadecyl-2-O-benzyl-sn-glyceryl-3-phospho-RVn (60 mg/kg orally, once daily for 5 days starting 12h after infection) reduced lung viral load by 1.5log10 units versus vehicle at day 2 and to below the limit of detection at day 5. Structure/activity evaluation of additional analogs that have hydrophobic ethers at the sn-2 of glycerol revealed improved in vitro antiviral activity by introduction of a 3-fluoro-4-methoxy-substituted benzyl or a 3- or 4-cyano-substituted benzyl. Collectively, our data support the development of RVn phospholipid prodrugs as oral antiviral agents for prevention and treatment of SARS-CoV-2 infections.

ObjectiveThe aim of this study was to evaluate the prevalence of burnout, clinical anxiety, depression, and insomnia and to estimate the associations of adverse emotional status, coping style, and level of self-efficacy with burnout of healthcare workers in the Shenzhen Longgang District Frontline District Headquarters of COVID-19 epidemic control, China.MethodsIn this cross-sectional study, 173 staff completed the anonymous questionnaires of the Maslach Burnout Inventory, Patient Health Questionnaire-9 (PHQ-9), Generalized Anxiety Disorder 7-item Scale (GAD-7), Insomnia Severity Index (ISI), General Self-efficacy Scale, and Simplified Coping Style Questionnaire electronically (https://www.wjx.cn/) in June 2022. Hierarchical logistic regression was used to explore the associated factors of burnout in this study.ResultsThe prevalence of burnout in our participants (defined as high emotional exhaustion or high depersonalization) was 47.40%, and reduced personal accomplishment was 92.49%. The prevalence of clinically significant depression (the cutoff score of ≥15), anxiety (the cutoff score of ≥10), and insomnia (the cutoff score of ≥15) was 11.56, 19.08, and 19.08%, respectively. There was a degree of overlap between burnout and other measures of adverse mental status, most notably for anxiety (odds ratio, 27.049; 95% CI, 6.125–117.732; p < 0.001). Hierarchical logistic regression demonstrated that burnout was strongly associated with anxiety (OR = 23.889; 95% CI, 5.216–109.414; p < 0.001) and negative coping style (OR = 1.869; 95% CI, 1.278–2.921; p < 0.01) independently.ConclusionMedical staff involved in COVID-19 epidemic control in the post-epidemic era were at high risk of burnout, and most of them were in low personal accomplishment. Reducing anxiety and improving coping style by medical management institutions from the system level may be effective in alleviating burnout in healthcare workers.

Mutation testing has been deemed an effective way to ensure Deep Learning (DL) software quality. Due to the requirements of generating and executing mass mutants, mutation testing suffers low-efficiency problems. In regard to traditional software, mutation operators that are hard to cause program logic changes can be reduced. Thus, the number of the mutants, as well as their executions, can be effectively decreased. However, DL software relies on model logic to make a decision. Decision boundaries characterize its logic. In this paper, we propose a DL software mutation operator reduction technique. Specifically, for each group of DL operators, we propose and use DocEntropy to measure the model’s decision boundary changes among mutants generated and the original model. Then, we select the operator group with the highest entropy value and use the involved operators for further mutation testing. An empirical study on two DL models verified that the proposed approach could lead to cost-effective DL software mutation testing (i.e., 33.61% mutants and their executions decreased on average) and archive more accuracy mutation scores (i.e., 9.45% accuracy increased on average). &nbsp

Background: In recent years, the number of people infected with the hepatitis C virus (HCV) is increasing rapidly. This has become a major threat to global health, therefore, new anti- HCV drugs are urgently needed. HCV NS5B polymerase is an RNA-dependent RNA polymerase (RdRp), which plays an important role in virus replication, and can effectively prevent the replication of HCV sub-genomic RNA in daughter cells. It is considered a very promising HCV therapeutic target for the design of anti-HCV drugs. Methods: In order to explore the relationship between the structure of benzimidazole derivative and its inhibitory activity on NS5B polymerase, holographic quantitative structure-activity relationship (HQSAR) and Topomer comparative molecular field analysis (CoMFA) were used to establish benzimidazole QSAR model of derivative inhibitors. Results: The results show that for the Topomer CoMFA model, the cross-validation coefficient q2 value is 0.883, and the non-cross-validation coefficient r2 value is 0.975. The model is reasonable, reliable, and has a good predictive ability. For the HQSAR model, the cross-validated q2 value is 0.922, and the uncross-validated r2 value is 0.971, indicating that the model data fit well and has a high predictive ability. Through the analysis of the contour map and color code diagram, 40 new benzimidazole inhibitor molecules were designed, and all of them have higher activity than template molecules, and the new molecules have significant interaction sites with protein 3SKE. Conclusion: The 3D-QSAR model established by Topomer CoMFA and HQSAR has good prediction results and the statistical verification is valid. The newly designed molecules and docking results provide theoretical guidance for the synthesis of new NS5B polymerase inhibitors and for the identification of key residues that the inhibitors bind to NS5B, which helps to better understand their inhibitory mechanism. These findings are helpful for the development of new anti-HCV drugs.

Since the 1990s, the climate in the Amur River Basin (ARB) has changed, and large-scale wetlands in the region have been reclaimed for paddy fields. The study of the influence of climate change and agricultural expansion on groundwater storage is of great significance to the evaluation of regional water resource balance and the promotion of ecological protection and agricultural development. In this work, the groundwater storage anomaly (GWSA) in the ARB and its drivers were analyzed for the period 2003–2016 using Gravity Recovery and Climate Experiment (GRACE) satellite data, a Global Land Data Assimilation System model, and in situ observations of groundwater levels. Results indicated that 1) the GWSA in the ARB increased at a rate of 2.0–2.4 mm/yr from 2003 to 2016; the GWSA in the upper reaches of the ARB increased, whereas the GWSA in the middle and lower reaches decreased during the study period. 2) The GWSA in the middle and lower reaches of the ARB was greatly influenced by temperature (Tmp) and evapotranspiration (ET). Tmp was positively correlated with GWSA, whereas ET was negatively correlated with GWSA (p < 0.05). 3) Extreme rainfall had a delayed effect on groundwater recharge. Wetland degradation and agricultural development were the main factors causing the decrease of the GWSA in the middle and lower reaches of the ARB. In summary, temperature and evapotranspiration affect groundwater storage by regulating the water–heat balance, wetland reclamation reduces the regional storage capacity, and the irrigation required for reclaimed farmland is the main source of groundwater loss.

Additional file 2.

Fermionic reduced density matrices summarize the key observables in fermionic systems. In electronic systems, the two-particle reduced density matrix (2-RDM) is sufficient to determine the energy and most physical observables of interest. Here, we consider the possibility of using matrix completion to reconstruct the two-particle reduced density matrix to chemical accuracy from partial information. We consider the case of noiseless matrix completion, where the partial information corresponds to a subset of the 2-RDM elements, as well as noisy completion, where the partial information corresponds to both a subset of elements, as well as statistical noise in their values. Through experiments on a set of 24 molecular systems, we find that the 2-RDM can be efficiently reconstructed from a reduced amount of information. In the case of noisy completion, this results in multiple orders of magnitude reduction in the number of measurements needed to determine the 2-RDM to chemical accuracy. These techniques can be readily applied to both classical and quantum algorithms for quantum simulations.

We present a general computational framework to investigate ground state properties of quantum spin models on infinite two-dimensional lattices using automatic differentiation-based gradient optimization of infinite projected entangled-pair states. The approach exploits the variational uniform matrix product states to contract infinite tensor networks with unit-cell structure and incorporates automatic differentiation to optimize the local tensors. We applied this framework to the Kitaev-type model, which involves complex interactions and competing ground states. To evaluate the accuracy of this method, we compared the results with exact solutions for the Kitaev model and found that it has a better agreement for various observables compared to previous tensor network calculations based on imaginary-time projection. Additionally, by finding out the ground state with lower variational energy compared to previous studies, we provided convincing evidence for the existence of nematic paramagnetic phases and 18-site configuration in the phase diagram of the $K$-$\Gamma$ model. Furthermore, in the case of the realistic $K$-$J$-$\Gamma$-$\Gamma'$ model for the Kitaev material $\alpha$-RuCl$_3$, we discovered a non-colinear zigzag ground state. Lastly, we also find that the strength of the critical out-of-plane magnetic field that suppresses such a zigzag state has a lower transition field value than the previous finite-cylinder calculations. The framework is versatile and will be useful for a quick scan of phase diagrams for a broad class of quantum spin models.

Removing degradation from document images not only improves their visual quality and readability, but also enhances the performance of numerous automated document analysis and recognition tasks. However, existing regression-based methods optimized for pixel-level distortion reduction tend to suffer from significant loss of high-frequency information, leading to distorted and blurred text edges. To compensate for this major deficiency, we propose DocDiff, the first diffusion-based framework specifically designed for diverse challenging document enhancement problems, including document deblurring, denoising, and removal of watermarks and seals. DocDiff consists of two modules: the Coarse Predictor (CP), which is responsible for recovering the primary low-frequency content, and the High-Frequency Residual Refinement (HRR) module, which adopts the diffusion models to predict the residual (high-frequency information, including text edges), between the ground-truth and the CP-predicted image. DocDiff is a compact and computationally efficient model that benefits from a well-designed network architecture, an optimized training loss objective, and a deterministic sampling process with short time steps. Extensive experiments demonstrate that DocDiff achieves state-of-the-art (SOTA) performance on multiple benchmark datasets, and can significantly enhance the readability and recognizability of degraded document images. Furthermore, our proposed HRR module in pre-trained DocDiff is plug-and-play and ready-to-use, with only 4.17M parameters. It greatly sharpens the text edges generated by SOTA deblurring methods without additional joint training. Available codes: https://github.com/Royalvice/DocDiff

Additional file 1.

Using a systematic ab initio quantum many-body approach that goes beyond low-energy models, we directly compute the superconducting pairing order of several doped cuprate materials and structures. We find that we can correctly capture two well-known trends: the pressure effect, where pairing order increases with intra-layer pressure, and the layer effect, where the pairing order varies with the number of copper-oxygen layers. From these calculations, we observe that the strength of superexchange and the covalency at optimal doping are the best descriptors of the maximal pairing order. Our microscopic analysis further identifies short-range copper spin fluctuations, together with multi-orbital charge fluctuations, as central to the pairing trends. Our work illustrates the possibility of a quantitative computational understanding of unconventional high-temperature superconducting materials., Comment: 10 pages, 5 figures, with supplementary materials

Cancer metastasis is responsible for the vast majority of cancer‐related deaths worldwide. In contrast to numerous discoveries that reveal the detailed mechanisms leading to the formation of the primary tumor, the biological underpinnings of the metastatic disease remain poorly understood. Cancer metastasis is a complex process in which cancer cells escape from the primary tumor, settle, and grow at other parts of the body. Epithelial‐mesenchymal transition and anoikis resistance of tumor cells are the main forces to promote metastasis, and multiple components in the tumor microenvironment and their complicated crosstalk with cancer cells are closely involved in distant metastasis. In addition to the three cornerstones of tumor treatment, surgery, chemotherapy, and radiotherapy, novel treatment approaches including targeted therapy and immunotherapy have been established in patients with metastatic cancer. Although the cancer survival rate has been greatly improved over the years, it is still far from satisfactory. In this review, we provided an overview of the metastasis process, summarized the cellular and molecular mechanisms involved in the dissemination and distant metastasis of cancer cells, and reviewed the important advances in interventions for cancer metastasis., Cancer metastasis is a complex process in which cancer cells escape from the primary tumor, settle and grow at other parts of the body. A variety of stromal cells, immune cells and other molecular components surrounding the tumor provide signals that enhance the metastatic potential of cancer cells. With the deepening understanding of mechanisms of tumorigenesis and metastasis in recent years, a plethora of treatment approaches have been established in patients with metastatic cancer.

In the study, we exogenously manipulate the chatbot’s ability to conduct the chit-chat, and investigate how the chit-chat influences human trust towards the recommendation made by the chatbot.

Once a majority of earthquakes occur without prediction, it is very likely to have a huge impact on human society. To solve the worldwide challenging problem of earthquake prediction, our laboratory has developed a set of sensory systems to monitor the abnormal activity of geological signals before an earthquake happens in China. At present, more than 300 stations have been deployed, and the observation time has exceeded 4 years. Based on the various geological activities collected, a local correlation tracking method is used to capture signal anomalies before an earthquake, and then the ROC curve is used for the evaluation of the predictive accuracy. The method is applied in the Sichuan-Yunnan area weekly, verifying the forecast within a 91-week time frame and a 30-week time frame. The method proposed in this article has earthquake prediction ability with a rate of over 70%. It promotes and contributes to helping people avoid the fear of unpredictable earthquakes.

This study aimed to investigate the application potential of Portulaca oleracea extract (POE) in active packaging for the preservation of chilled meat. First, the antioxidant capacity and active ingredients of POE were systematically studied. The results demonstrated that POE has excellent antioxidant capacity and contains abundant antioxidant compounds. Subsequently, antioxidant-active packaging films based on chitosan and starch containing different concentrations of POE (CS/POE films) were successfully developed. The main physicochemical and mechanical properties of the CS/POE films were characterized and evaluated. The CS/POE films exhibited remarkable antioxidant activity and can significantly reduce lipid oxidation in meat. Compared with polyethylene film, the CS/POE films-treated meats had better preservation effects and longer shelf-life. These findings suggested that CS/POE film has the potential to become a good alternative to conventional plastics in food packaging. In conclusion, Portulaca oleracea extract is an excellent natural antioxidant with great potential in active packaging for chilled meat preservation.

Carbon species incorporation and carbon deposits are common in the manufacture process and application of yttria-stabilized zirconia (YSZ) ceramics, while the potential corrosion induced by the resultant carburization is unclear. The 3YSZ hollow fiber membranes were prepared by wet spinning method. A sintering procedure at 1300–1450 °C under 0.02 MPa oxygen partial pressure, and thereafter an oxidation treatment at 800 °C were applied to investigate the carbothermal reaction and carburization corrosion mechanism. It was found that the trace carbon species of 1.0–2.2 mol% derived from polymeric precursors triggered the carburizing strengthening of porous YSZ membranes without sacrificing porosity and deformability. However, the carburization corrosion also occurred at the mild oxidation treatment, resulting in deterioration in bending strength and integrated structure converting into fine grains. Raman spectra, XPS bands and HR-TEM images confirmed that the in-situ synthesized ZrCxOy oxidized into monoclinic ZrO2, and micro-cracking formed along grain boundaries, which led to substantial mechanical strength loss.

The compression strength and breakage mechanism of a hierarchical porous sphere in hundred-micron size were investigated in the present work. 3 mol% yttria-stabilized zirconia (YSZ) microspheres were prepared by electro-spraying associated with phase inversion (ES-PI) technique. The characteristic compression strengths of the ES-PI microspheres were measured by quasi-static uniaxial compression test, which increased from 19 MPa to 155 MPa as the sintering temperature increased from 1100 °C to 1400 °C. With the similar porosity, the compression strength of the hierarchical structure microsphere was almost three times higher than that of the hollow microsphere. Further, the breakage mechanism of the ES-PI microspheres was proposed by the honeycomb model of cellular materials, which suggested that the breakage of the ES-PI microsphere initiated from the elastic instability of the walls around the finger-like pores. These findings can help the mechanical performance optimization for ceramic microspheres with lightweight structure.

The thermal cycling lifetime of thermal barrier coatings was doubled when deposited by electro-sprayed (ESP) microspheres instead of by commercial hollow spherical powders. It was believed that partial-molten nodules with featured microstructures inherited from the feedstock microspheres were the main contributor for prolonged thermal cycling durability due to improved fracture toughness and strain tolerance. The maximum lifetime was observed on samples with 20−30 vol.% of partial-molten microspheres. The hierarchy pores may both slow down the crack propagation by triggering multi-deflecting and promote cracking by reducing the tendency of interfacial deflection, the net effect depends on situation. The ESP coatings exhibited bimodal Weibull moduli upon indentation, which was regarded as originated from the hierarchy porous structure. Finally, the criterion was verified by micro-indentation and residual stain-stress evaluation by Raman spectroscopy.

A systematic review and meta-analysis on the relationship between social support and mental health symptoms during COVID-19 pandemic.

Meta-analysis and questionnaire studies were used to explore mental health issues in the context of epidemics.

The RAM system is the reactor control rod drive mechanism power supply system, which is the only power supply designed for the control rod drive mechanism. The RAM (control rod Power System) system of the Nuclear Power Plant only has two synchronous generators (RAM001/002AP) operating in parallel. On November 14, 2019,when one unit has an excitation system failure, due to the unreasonable setting of the protection value of the two units, the over-current protection of the unfailed unit precedes the loss of field protection action of the field lost unit, resulting the two generators in the RAM system tripping one after the other, therefore causing CRDM losing all power supply, resulting in the control rod dropping off and finally causing the automatic shutdown of the reactor, bringing serious consequences to the reactor and power grid. Therefore, the setting of synchronous generator protection in the RAM system is very important for the safe and stable operation of nuclear power plant. This report carries out the digital modeling and simulation of the RAM system of the Nuclear Power Plants, simulates various faults of RAM system synchronous generator RAM001/002AP and provides the important basis for verifying the settings of over-current protection and loss of excitation protection.

Adult brainstem gliomas are rare central nervous system tumors that represent a heterogeneous group of tumors. Somatic IDH mutations are uncommon in adult brainstem gliomas and there are few relevant clinical studies. Here, we reported five patients with IDH1 mutations associated with brainstem gliomas, including four cases of IDH1 R132H mutations and one case of R132G mutation. All patients were treated with focal intensity-modulated radiation therapy (IMRT) with concurrent temozolomide (TMZ). One patient died, one relapsed, and three survived to date. All these cases carried a pathogenic variant of TP53, among whom 1 harbored ATRX mutation and 1 had H3K27M mutation. Moreover, we also found some genes related to a worse prognosis, such as CDK4/6 amplification. These findings demonstrate that the specific characteristics of IDH-mutant brainstem gliomas should be considered in diagnostic workflows to make therapeutic regimens and improve the prognosis.

Although single-particle cryogenic electron microscopy (cryo-EM) has been applied extensively for elucidating many crucial biological mechanisms at the molecular level, this technique still faces critical challenges, the major one of which is to prepare the high-quality cryo-EM specimen. Aiming to achieve a more reproducible and efficient cryo-EM specimen preparation, novel supporting films including graphene-based two-dimensional materials have been explored in recent years. Here we report a robust and simple method to fabricate EM grids coated with single- or few-layer reduced graphene oxide (RGO) membrane in large batch for high-resolution cryo-EM structural determination. The RGO membrane has decreased interlayer space and enhanced electrical conductivity in comparison to regular graphene oxide (GO) membrane. Moreover, we found that the RGO supporting film exhibited nice particle-absorption ability, thus avoiding the air–water interface problem. More importantly, we found that the RGO supporting film is particularly useful in cryo-EM reconstruction of sub-100-kDa biomolecules at near-atomic resolution, as exemplified by the study of RBD-ACE2 complex and other small protein molecules. We envision that the RGO membranes can be used as a robust graphene-based supporting film in cryo-EM specimen preparation.

BackgroundRelatively little is known about the effect of traditional Chinese medicine (TCM) on prognosis of non-small cell lung cancer (NSCLC).MethodsIn this nationwide, multicenter, prospective, cohort study, eligible patients aged 18-75 years with radical resection, and histologically confirmed stage II-IIIA NSCLC were enrolled. All patients received 4 cycles of standard adjuvant chemotherapy. Patients who received Chinese herbal decoction and (or) oral Chinese patent medicine for a cumulative period of not less than 6 months were defined as TCM group, otherwise they were considered as control group. The primary endpoint was DFS calculated using the Kaplan–Meier method. A time-dependent Cox proportional hazards model was used to correct immortal time bias. The secondary endpoints included DFS in patients of different characteristics, and safety analyses. This study was registered with the Chinese Clinical Trial Registry (ChiCTR1800015776).ResultsA total of 507 patients were included (230 patients in the TCM group; 277 patients in the control group). The median follow-up was 32.1 months. 101 (44%) in the TCM group and 186 (67%) in the control group had disease relapse. The median DFS was not reached in the TCM group and was 19.4 months (95% CI, 14.2 to 24.6) in the control group. The adjusted time-dependent HR was 0.61 (95% CI, 0.47 to 0.78), equalling to a 39% reduction in the risk of disease recurrence with TCM. the number needed to treat to prevent one patient from relapsing was 4.29 (95% CI, 3.15 to 6.73) at 5 years. Similar results were observed in most of subgroups. Patients had a significant improvement in white blood cell decrease, nausea, decreased appetite, diarrhea, pain, and fatigue in the TCM group.ConclusionTCM may improves DFS and has a better tolerability profile in patients with stage II-IIIA NSCLC receiving standard chemotherapy after complete resection compared with those receiving standard chemotherapy alone. Further studies are warranted.

Inspired by bioinspired layered materials with excellent mechanical and chemical property due to their interface cohesive force, a nanocellulose-graphene layered structure with covalent linkaged (C-C bond) is constructed. The mechanical properties are systematically studied by molecular dynamics (MD) simulations in terms of the effects of temperature, strain rate and the covalent bond contents. The elastic modulus and tensile strength of layered nanocomposites are sensitive to temperature and much higher than these of the pristine nanocellulose at the same temperatures. They also increase significantly with the increase of strain rate and covalent bond coverage. The results showed significant improvements in the mechanical properties by addition of grapheme layers due to the covalent bonding interactions and Van der Waals force interactions at the interfaces. These findings can be useful in further modelling of other graphene-based polymers at the atomistic scales, which are critical for their potential applications as functional materials.

Generally, regulation of cyclic electron flow (CEF) and chloroplast ATP synthase play key roles in photoprotection for photosystems I and II (PSI and PSII) in C3 and C4 plants, especially when CO

Intersubband (intraband) transitions allow absorption of photons in the infrared spectral regime, which is essential for IR-photodetector and optical communication applications. Among various technologies, nanodisks embedded in nanowires offer a unique opportunity to be utilized in intraband devices due to the ease of tuning the fundamental parameters such as strain distribution, band energy, and confinement of the active region. Here, we show the transverse electric polarized intraband absorption using InGaN/GaN nanodisks cladded by AlGaN. Fourier transform infrared reflection (FTIR) measurement confirms absorption of normal incident in-plane transverse electric polarized photons in the mid-IR regime (wavelength of ~ 15 μm) at room temperature. The momentum matrix of the nanodisk energy states indicates electron transition from the ground state s into the px or py orbital-like excited states. Furthermore, the absorption characteristics depending on the indium composition and nanowire diameter exhibits tunability of the intraband absorption spectra within the nanodisks. We believe nanodisks embedded nanowires is a promising technology for achieving tunable detection of photons in the IR spectrum.