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This work demonstrates a distinctive almost HF-free route of etching Ti3AlC2 MAX phase by metal displacement reaction at room temperature. The Ti3AlC2 particles are directly etched by CuCl2 solutions in different concentrations instead of HF. The etchant is reduced to nano CuCl particles, adhering to the surface of Ti3C2 layers to form the Ti3C2@CuCl composite which is evaluated as working electrodes for supercapacitors. Due to the synergistic effect between CuCl and Ti3C2 matrix, the appropriate amount of CuCl enhances the specific capacitance to 508.7 F·g−1 at 1A·g−1 in 6 M KOH electrolyte solution, which is much higher than pure Ti3C2 electrode. This work shows the possibility of synthesis of various Mxene-based frameworks by other metallic cations with lower metal activity.

As a heavy metal, lead is a common toxic agent. Its accumulation in the body is harmful to physical health, particularly in children and adolescents. Studies have reported that folate may play a protective role in lead exposure. An association between serum folate concentrations (SFC) and blood lead levels (BLL) has been documented in adults, but studies in adolescents are limited. This study investigated the relationship between SFC and BLL in American adolescents. This cross-sectional study collected relevant data on both SFC and BLL of 5,195 adolescents in the NHANES database from 2007 to 2018. Multivariable linear regressions and smooth curve fittings were adopted to evaluate the correlation between BLL and SFC. After adjusting potential confounders, we found negative relationships between BLL and SFC [β = −0.0041 (−0.0063, −0.0019)], and the associations were significant in non-Hispanic Whites, Mexican Americans, and other races but not significant in non-Hispanic blacks (P = 0.139). Furthermore, the negative trends were significant in adolescents aged 16–19 years and females aged 12–15 years but insignificant in males aged 12–15 years (P = 0.172). Therefore, these findings provide a basis for future research on the mechanism of folate in regulating blood lead levels.

Objective: To identify the potential mechanism of Huzhang Tongfeng Granules (HTG) for the treatment of acute gouty arthritis (AGA). Methods: First of all, we used network pharmacology to build a network of components-targets of HTG. Secondly, the ClusterONE algorithm was applied to construct a modular network as well as discover hub genes and kernel pathways. Lastly, the MSU crystals-induced AGA mice model was used to verify the hub genes and kernel pathways of HTG. Results: HTG down-regulated the expressions of ADRB3, PIK3CA, FYN, PIK3R1, CASR, PLCG1, SYK, EGFR, and up-regulated MC1R, MC5R. Moreover, according to the kernel clusters enrichment analysis, HTG down-regulated NF-κB and P13K-Akt signaling pathways to ameliorate the AGA mice model. Conclusion: In summary, the potential targets and kernel pathways were proved in this study, supporting the clinical application of HTG for the treatment of AGA.

The paper aims to study a discrete boundary value problem of the Kirchhoff type based on the critical point theory and the strong maximum principle. Compared to the existing literature, the existence and multiplicity of positive solutions to the problem are considered according to the behavior of the nonlinear term f in some points between the zero and positive infinity, which is a new attempt. Under different assumptions of the nonlinear term f, we obtain the determined open intervals of the parameter λ, such that the problem has at least three positive solutions or at least two positive solutions in different intervals. In the end, two concrete examples are used to illustrate our main conclusions.

In recent years, high-fidelity three-dimensional (3D) oracle bone models (3D-OBMs) have received extensive attention from oracle bone experts due to their unparalleled reducibility to real oracle bone. In the research process of 3D-OBMs, the first procedure is to extract oracle bone inscriptions (OBIs) from the model to form individual oracle bone characters (OBCs). However, the manual extraction of OBIs is a time-consuming and labor-intensive task that relies heavily on oracle bone knowledge. To address these problems, we propose a texture-mapping-based OBI extractor (tm-OBIE), which leverages the symmetrical characteristics of the texture mapping process and is able to extract 3D-OBIs from 3D-OBMs saved as a wavefront file. The OBIs in the texture file were first located using a trained 2D object detector. After that, the 3D mesh area, where the OBIs are located, was obtained using an inverse texture mapping method. Thirdly, a specific 2D plane was fitted using the centroid of triangular faces in the flat regions of the mesh via a singular value decomposition (SVD) method. Finally, by measuring the distances between the triangle meshes and the fitted plane, the meshes of the 3D-OBIs were obtained. This paper verifies the feasibility of this method via experiments and analyzes the possibility of using the algorithm framework for extracting other ancient characters from their corresponding 3D models.

The high-quality development of new agricultural business entities (NABEs) is an important driving force for realizing rural revitalization and accelerating the modernization of agriculture and rural areas. The main purpose of the study is to investigate the spatial distribution pattern, aggregation scales, development mechanism, and internal differences of various types of NABEs in different regions. It provides targeted ideas for alleviating regional differences in the development of NABEs in different agricultural regions. Kernel density estimation, nearest neighbor distance analysis, Tyson’s polygon coefficient of variation, and Ripley’s K function are used to study the spatial and temporal evolution, spatial aggregation, and scale divergence of various types of NABEs, and Pearson correlation analysis is incorporated to explore the specific factors affecting the development of various types of NABEs. The study results: First, family farms are the most widely distributed, and agricultural enterprises are the most sparsely distributed, being distributed “more in the southeast and less in the northwest” in all three categories. Second, the strongest aggregation scales of different NABEs are increasing, and the strongest aggregation scales of agricultural enterprises are larger than those of family farms and cooperatives in all agricultural areas. Third, the development of specialized farmers’ cooperatives (abbreviated as ‘cooperatives’) is more constrained by traditional agricultural inputs and is a kind of agricultural input-oriented development. Family farms are more constrained by the living standards of rural residents in the region and are a kind of rural economy-oriented development. Agricultural enterprises are more subject to the economic level of the region, which is a kind of market economy-oriented development. Finally, in the process of developing NABEs, regional differences should be emphasized, and a small number of agriculturally leading enterprises and model cooperatives should drive a large number of small-scale family farms and smallholder farmers in order to become a characteristic path for China’s agricultural development.

ObjectiveTo analyze the correlation between personality characteristics and family environment of undergraduate medical students taking psychology course.MethodsIn June 2017， a cross-sectional survey was conducted among 67 undergraduate medical students taking psychology course， and all the selected individuals were assessed using Minnesota Multiphasic Personality Inventory （MMPI） and Family Environment Scale-Chinese Version （FES-CV）. Then Pearson correlation analysis was performed between the original scores of MMPI subscales and the scores of FES-CV subscales.ResultsThe scores of hypochondriasis， depression， hysteria， psychopathic deviate， masculine-femininity， paranoia， psychasthenia and schizophrenia in MMPI of undergraduates were all higher than those of the national norm， with statistical differences （t=2.070~8.350， P

Abstract Background Adult hippocampal neurogenesis (AHN) is restricted under the pathological conditions of neurodegenerative diseases, especially in Alzheimer’s disease (AD). The drop of AHN reduces neural circuit plasticity, resulting in the decrease of the generation of newborn neurons in dentate gyrus (DG), which makes it difficult to recover from learning/memory dysfunction in AD, therefore, it is imperative to find a therapeutic strategy to promote neurogenesis and clarify its underlying mechanism involved. Methods Amyloid precursor protein/presenilin 1 (APP/PS1) mice were treated with photobiomodulation therapy (PBMT) for 0.1 mW/mm2 per day in the dark for 1 month (10 min for each day). The neural stem cells (NSCs) were isolated from hippocampus of APP/PS1 transgenic mice at E14, and the cells were treated with PBMT for 0.667 mW/mm2 in the dark (5 min for each time). Results In this study, photobiomodulation therapy (PBMT) is found to promote AHN in APP/PS1 mice. The latent transforming growth factor-β1 (LTGFβ1) was activated in vitro and in vivo during PBMT-induced AHN, which promoted the differentiation of hippocampal APP/PS1 NSCs into newborn neurons. In particular, behavioral experiments showed that PBMT enhanced the spatial learning/memory ability of APP/PS1 mice. Mechanistically, PBMT-stimulated reactive oxygen species (ROS) activates TGFβ/Smad signaling pathway to increase the interaction of the transcription factors Smad2/3 with Smad4 and competitively reduce the association of Smad1/5/9 with Smad4, thereby significantly upregulating the expression of doublecortin (Dcx)/neuronal class-III β-tubulin (Tuj1) and downregulating the expression of glial fibrillary acidic protein (GFAP). These in vitro effects were abrogated when eliminating ROS. Furthermore, specific inhibition of TGFβ receptor I (TGFβR I) attenuates the DNA-binding efficiency of Smad2/3 to the Dcx promotor triggered by PBMT. Conclusion Our study demonstrates that PBMT, as a viable therapeutic strategy, directs the adult hippocampal APP/PS1 NSCs differentiate towards neurons, which has great potential value for ameliorating the drop of AHN in Alzheimer’s disease mice.

Alpha-fetoprotein producing gastric carcinomas (AFPGC) are rare and aggressive. Here, the authors profile AFPGC tumours using whole exome sequencing, and find amplifications in CCNE1 and ERBB2 that are associated with poor outcomes but are potential therapeutic targets, as shown in patient-derived xenografts.

The Qiangtang Mesozoic sedimentary basin is a new field of hydrocarbon exploration, in which the Buqu Formation dolostone reservoirs have attracted increasing attention in recent years. To determine the origin of these reservoirs, petrographic study, fluid inclusion thermometry dating, and C-O and Sr isotopic dating were performed. The results revealed the genesis and evolution of different types of dolomite matrix and cement, as follows: 1) The dolomite texture in the study area is closely related to its formation environment and process and can be categorized as primary fabric well-preserved dolomite (Rd1), primary fabric poorly-preserved dolomite, and dolomite filling. The primary fabric-poorly-preserved dolomite includes fine-grained euhedral dolomite (Rd2), fine-grained planar subhedral dolomite (Rd3), and medium-to coarse-grained anhedral dolomite (Rd4). The dolomite filling includes fine-grained planar subhedral cave-filling dolomite (Cd1) and medium-to coarse-grained anhedral, saddle dolomite (Cd2). 2) Rd1 has δ13C‰PDB of 3.42‰–4.23‰, δ18O‰PDB from −4.22‰ to −3.37‰, and 87Sr/86Sr of 0.707654–0.708176 and was formed in the contemporaneous or penecontemporaneous stage at low temperatures by mimic replacement related to seawater evaporation. Abundant supersaturated dolomitization fluids favored the preservation of its primary dolomite texture. 3) Rd2 has δ13C‰PDB of 3.18‰–4.11‰, δ18O‰PDB from −4.56‰ to −4.23‰, and 87Sr/86Sr (0.707525–0.708037), while Rd3 has δ13C‰PDB of 2.72‰–4.42‰, δ18O‰PDB from −6.57‰ to −5.56‰, and 87Sr/86Sr of 0.707432–0.707990. Both were formed at low temperatures in the shallow-burial stage, when the dolomitization fluid was mainly derived from seawater. Excessive dolomitization during the late shallow-burial stage caused the destruction of the dolomite crystals from euhedral to subhedral. 4) Rd4 has δ13C‰PDB of 3.24‰–4.14‰, δ18O‰PDB from −8.22‰ to −6.37‰, and 87Sr/86Sr of 0.707234–0.707884 and resulted from dolomitization or recrystallization at high temperatures in the medium-to deep-burial stage. The crystal curvature was caused by high environmental temperatures. 5) Cd1 has δ13C‰PDB of 3.02‰, δ18O‰PDB of −5.13‰, and 87Sr/86Sr of 0.708147 and was formed during cavern filling before the shallow-burial stage. Cd2 has δ13C‰PDB of −0.09‰−3.38‰, δ18O‰PDB from −10.41‰ to −8.56‰, and 87Sr/86Sr of 0.708180–0.708876 and was related to the collisional orogeny between the Lhasa termite and the Qiangtang Basin in the late Early Cretaceous. Fluids in the overlying and underlying clastic strata of the Buqu Formation were driven by the thermal hot spot during compressional tectonic setting. These fluids caused negative shifts in the oxygen isotope compositions of the earlier dolomite.

ObjectiveTo report the clinical features of the first child with infective endocarditis (IE) caused by Abiotrophia defectiva in mainland China and to raise awareness of the disease.MethodsThe clinical data of a child with IE caused by A. defectiva admitted to Xi’an Children’s Hospital in July 2021 were collected, and the relevant literature was reviewed.ResultsThe child was a female, 8 years old, admitted with fever for 4 days and right-sided limb weakness for 3 days. The illness started with suppurative tonsillitis, followed by headache, fatigue, right-sided mouth, slurred speech, right limb weakness, and unstable holding. Transthoracic echocardiography showed that the mitral valve vegetation was formed and vegetation could also be seen at the entrance of the pulmonary vein at the posterior wall of the left atrium. Cranial contrast-enhanced MRI + magnetic resonance angiography showed multiple intracranial pseudoaneurysm formation and pontine infarction. After A. defectiva was detected by metagenomic next-generation sequencing (mNGS) in cerebrospinal fluid and blood detected, the infection was controlled by anti-infective treatment with meropenem and vancomycin. On the 36th day after admission, due to severe headache and slurred speech, the head CT showed hemorrhage of right parietal pseudoaneurysm and cerebral sickle hernia, and right temporo-occipital hematoma evacuation, cerebrovascular malformation resection, and cranial decompression were performed immediately. After the surgery, her speech ability gradually recovered, the muscle strength of her left upper limb was about grade III, while the muscle strength of the rest of the limbs was normal. After a total of 60 days of hospitalization, her family requested to be discharged.ConclusionThis pediatric patient is the first case of childhood IE caused by A. defectiva in mainland China, and the first time in the world that A. defectiva was detected by mNGS in patients with IE.

Despite the advent of effective antiretroviral therapy (ART), human immunodeficiency virus (HIV) continues to pose major challenges, with extensive pathogenesis during acute and chronic infection prior to ART initiation and continued persistence in a reservoir of infected CD4 T cells during long-term ART. CD101 has recently been characterized to play an important role in CD4 Treg potency. Using the simian immunodeficiency virus (SIV) model of HIV infection in rhesus macaques, we characterized the role and kinetics of CD101+ CD4 T cells in longitudinal SIV infection. Phenotypic analyses and single-cell RNAseq profiling revealed that CD101 marked CD4 Tregs with high immunosuppressive potential, distinct from CD101- Tregs, and these cells also were ideal target cells for HIV/SIV infection, with higher expression of CCR5 and α4β7 in the gut mucosa. Notably, during acute SIV infection, CD101+ CD4 T cells were preferentially depleted across all CD4 subsets when compared with their CD101- counterpart, with a pronounced reduction within the Treg compartment, as well as significant depletion in mucosal tissue. Depletion of CD101+ CD4 was associated with increased viral burden in plasma and gut and elevated levels of inflammatory cytokines. While restored during long-term ART, the reconstituted CD101+ CD4 T cells display a phenotypic profile with high expression of inhibitory receptors (including PD-1 and CTLA-4), immunsuppressive cytokine production, and high levels of Ki-67, consistent with potential for homeostatic proliferation. Both the depletion of CD101+ cells and phenotypic profile of these cells found in the SIV model were confirmed in people with HIV on ART. Overall, these data suggest an important role for CD101-expressing CD4 T cells at all stages of HIV/SIV infection and a potential rationale for targeting CD101 to limit HIV pathogenesis and persistence, particularly at mucosal sites.

Background and aims: Pelvic inflammatory disease (PID) is infection-induced inflammation of the female upper reproductive tract that results in high fever, ectopic pregnancy, infertility, and varying degrees of chronic pelvic pain. Recent clinical studies have shown that Kangfuxiaoyanshuan (KFXYS), a Traditional Chinese Medicine (TCM) formulation, may short the course of the disease and reduce the occurrence of PID sequelae, but its pharmacological action and potential mechanism have not been fully elucidated. Here, we aimed to investigate the therapeutic effects and mechanism of KFXYS in rats with PID.Materials and Methods: A PID rat model was constructed through endometrial mechanical injury and pathogen infection. The rectal temperature was measured during the 14-days course of treatment, and the white blood cell (WBC) count in the blood and the levels of cytokines (IFN-γ, IL-1β, IL-4, TNF-α) in the serum were evaluated by ELISA. Hematoxylin and eosin (HE) staining was performed to analyze pathological changes, and transmission electron microscopy (TEM) was used to observe ultrastructural changes. The p-p65/p65 protein expression was evaluated by western blotting and the levels of MMP-2 and TGF-β in adhesion tissues were assessed by immunohistochemistry.Results: KFXYS lowered the rectal temperature and the WBC counts in the blood in the acute stage of PID and alleviated inflammatory cell infiltration of the uterus, especially when combined with levofloxacin. KFXYS significantly decreased the levels of proinflammatory cytokines (IFN-γ, IL-1β, IL-4) and adhesion-related factors (TNF-α) and protected the ultrastructure of endometrial epithelial cells. Mechanistically, KFXYS inhibited the NF-κB activation by decreasing phosphorylation of p65, thus the alleviation of inflammation further reduced the expression of TGF-β and MMP-2, and inhibited the occurrence of uterine adhesions.Conclusion: These results revealed that KFXYS alleviated pelvic inflammation and effectively inhibits inflammation-associated adhesion, which indicated the potential role of KFXYS for treatment of PID and the prevention of PID sequelae.

BackgroundRecurrent hypoglycemia (RH) is well known to impair awareness of hypoglycemia and increase the risk of severe hypoglycemia; the underlying mechanism requires further understanding. We aimed to investigate the metabolic characteristic profile for RH in type 2 diabetes mellitus (T2DM) patients and explore the potential metabolic mechanism and prevention strategies.MethodsWe screened 553 community-based T2DM patients. T2DM with RH (DH group, n=40) and T2DM without hypoglycemia (DC group, n=40) were assigned in the case-control study, matched by propensity score matching. Non-targeted, global metabolite profiling was conducted using ultra-high performance liquid chromatography-mass spectrometry. Principal component analysis and supervised projections to latent structures-discriminant analysis were constructed to evaluate the potential biomarkers. Metabolites with a fold change of >2.0 or 1 were identified as significantly differential metabolites. MetaboAnalyst was performed to analyze the related metabolic pathways.ResultsWe identified 12 significantly distinct metabolites as potential biomarkers of RH, which were enriched in five pathways; the caffeine metabolic pathway was the most dominant related one. Caffeine and its main downstream metabolites (theophylline and paraxanthine, all q

Abstract This paper derives several sufficient conditions for the existence of three solutions to the Dirichlet problem for a second-order self-adjoint difference equation involving p-Laplacian through the critical point theory. Furthermore, by using the strong maximum principle, we prove that the three solutions are positive under appropriate assumptions on the nonlinearity. Finally, we present three examples to confirm our results.

Abstract By employing critical point theory, we investigate the existence of solutions to a boundary value problem for a p-Laplacian partial difference equation depending on a real parameter. To be specific, we give precise estimates of the parameter to guarantee that the considered problem possesses at least three solutions. Furthermore, based on a strong maximum principle, we show that two of the obtained solutions are positive under some suitable assumptions of the nonlinearity.

Abstract Background High-risk human papilloma virus (hrHPV) is the main causal factor of cervical precancer and cancer when persistent infection is left untreated. Previous studies have confirmed the vaginal microbiota is associated with HPV infection and the development of cervical lesions. The microbiota at different parts of the female genital tract is closely related but different from each other. To analyze the distinction between the vaginal and cervical microbiota of hrHPV(+) women in China, one hundred subjects were recruited, including 10 patients with HPV16/18(+) and cervical carcinoma, 38 patients with HPV16/18(+) but no cervical carcinoma, 32 patients with other hrHPV(+) and 20 healthy controls with HPV(−). Vaginal and cervical microbiota were separately tested through next-generation sequencing (NGS) targeting the variable region (V3-V4) of the bacterial ribosome 16S rRNA gene. Results HrHPV(+) subjects had higher percentages of vaginal douching history (P = 0.001), showed more frequent usage of sanitary pads (P = 0.007), had more sex partners (P = 0.047), were more sexually active (P = 0.025) and more diversed in ways of contraception (P = 0.001). The alpha diversity of the cervical microbiota was higher than that of the vagina. The cervical microbiota consisted of a lower percentage of Firmicutes and a higher percentage of Proteobacteria than the vagina at the phylum level. Sphingomonas, belonging to α-Proteobacteria, was almost below the detection limit in the vagina but accounted for five to 10 % of the bacteria in the hrHPV(−) cervix (P

As the world’s largest developing country, China first proposed the construction of a Beautiful China initiative in 2012, with the aim of exploring Chinese solutions for sustainable regional development. The construction of a beautiful China is based on the guiding ideology of the Five-sphere Integrated Plan in China, that is, the overall plan for building socialism with Chinese characteristics, including economic construction, political construction, cultural construction, social construction and ecological civilization construction. This paper aims to understand the coupling relationship, as well as the spatial and temporal changes, between China’s sustainable development under the Beautiful China initiative and tourism. Using data from the China Statistical Yearbook database, we constructed an evaluation index system to measure both the construction of beautiful China and tourism development using a literature review, statistical analysis, the entropy method and GIS-based spatial analysis methods. Furthermore, using the 31 Chinese provinces as the research subject, we further analyzed the state of Beautiful China construction and tourism development, as well as their coupling relationships of the two systems. Our results show that firstly, the economic “hard power” plays the most prominent role in the process of building a beautiful China under the sustainable development regime, while the status of cultural “soft power” has also been well reflected. Secondly, the weight ranking of tourism evaluation indicators and the spatial distribution of tourism development levels both reflect the central and fundamental role of tourism market demand in tourism development. Third, the weight ranking of tourism evaluation indicators ranks the highest in the mean value of the coupling coordination degree of society, ecology and tourism in the Beautiful China subsystem, which reflects the harmony between society and ecology and the significant livelihood function of tourism as a happiness industry in the new era. Fourth, the spatial and temporal relationship between the coupled and coordinated development of the Beautiful China and tourism systems varies, indicating that there is a regional imbalance in China’s sustainable development. This further indicates the need to adapt to local conditions, and to build on strengths and avoid weaknesses to achieve regional sustainable development. The study highlights China’s contribution to global sustainable development. It also provides theoretical and practical guidance for the promotion of the coordinated development of both Beautiful China and tourism.

Long-life pavement construction is an important research direction for sustainable road development. Fatigue cracking of aging asphalt pavement is one of the main reasons that affects its service life, and improving the fatigue resistance of aging asphalt pavement has become a key factor in promoting the development of long-life pavement. In order to enhance the fatigue resistance of aging asphalt pavement, hydrated lime and basalt fiber were selected to prepare a modified asphalt mixture. The resistance to fatigue is evaluated by the four-point bending fatigue test and self-healing compensation test, based on the energy method, the phenomenon-based approach, and other methods. The results of each method of evaluation were also compared and analyzed. The results indicate that the incorporation of hydrated lime can improve the adhesion of the asphalt binder, while the incorporation of basalt fiber can stabilize the internal structure. When incorporated alone, basalt fiber has no noticeable effect, while hydrated lime significantly improves the fatigue performance of the mixture after thermal aging. Mixing both ingredients produced the best improvement effect under various conditions, with a fatigue life improvement of 53%. In the multi-scale evaluation of fatigue performance, it was found that the initial stiffness modulus was unsuitable as a direct evaluation index of fatigue performance. Using the fatigue damage rate or the stable value of dissipated energy change rate as an evaluation index can clearly characterize the fatigue performance of the mixture before and after aging. The self-healing rate and self-healing decay index clearly reflected the fatigue damage healing process under repeated loading and could be used as relevant indices for evaluating the new-scale fatigue performance of asphalt mixtures.

The loss rate is an important index to evaluate the harvesting performance of white radish. To reduce the loss rate, it is necessary to analyze the pulling dynamic characteristics of white radish and then optimize the structure and operating parameters of the harvesting device. In this paper, according to the growth characteristics of white radish in the field, the discrete element method (DEM) was used to simulate the pulling process. The pulling force was calculated using the Edinburgh elasto-plastic adhesion model (EEPA), and the effects of soil bed compactness, pulling speed and angle on the pulling force were analyzed. The tests on pulling mechanics were carried out in the laboratory to verify the accuracy of DEM simulation results. The results showed that in the soft soil bed with compactness less than 2.8 MPa, the pulling force of radish is generally smaller than the leaf breaking force, and it is feasible to pull the radish out directly. While in a soil bed with high compactness, it is necessary to install a loosening shovel to reduce the pulling force thus reducing the loss rate due to leaf breakage. The structure and operating parameters of the harvesting device were designed according to the pulling dynamic characteristics, and the white radish harvesting tests were carried out in different fields. Statistical results show that when the soil compaction was increased from 1.47 MPa to 2.21 MPa, the average loss rate increased from 0.68% to 1.75%, and the average damage rate increased from 2.41% to 2.70%. Similarly, when the forward speed was increased from 0.18 to 0.47 m/s, the average loss rate increased from 1.08% to 1.30%, and the average damage rate increased from 2.34% to 2.74%. Overall, the maximum loss rate and the maximum damage rate could be controlled below 2.0% and 3.0%, respectively. In the hard soil bed, the loss rate can be effectively reduced from 15% to 2.5% by installing a loosening shovel.

An airborne anemometer, which monitors wind on the basis of Meteorological Multi-rotor UAVs (Unmanned Aerial Vehicles), is important for the prevention of catastrophe. However, its performance will be affected by the self-excited air turbulence generated by UAV rotors. In this paper, for the purpose of the correction of an error, we developed a method for the elimination of the influence of air turbulence on wind speed measurement. The corresponding correction model is obtained according to the CFD (Computational Fluid Dynamics) simulation of a six-rotor UAV which is carried out with the sliding grid method and the S-A turbulence model. Then, the model is applied to the developed prototype by adding the angle of attack compensation model of the airborne anemometer. It is shown by the actual application that the airborne anemometer can maintain the original measurement accuracy at different ascent speeds.

Osteoarthritis (OA) is the most common degenerative bone and joint disease that can lead to disability and severely affect the quality of life of patients. However, its etiology and pathogenesis remain unclear. It is currently believed that articular cartilage lesions are an important marker of the onset and development of osteoarthritis. Long noncoding RNAs (lncRNAs) are a class of multifunctional regulatory RNAs that are involved in various physiological functions. There are many differentially expressed lncRNAs between osteoarthritic and normal cartilage tissues that play multiple roles in the pathogenesis of OA. Here, we reviewed lncRNAs that have been reported to play regulatory roles in the pathological changes associated with osteoarthritic cartilage and their potential as biomarkers and a therapeutic target in OA to further elucidate the pathogenesis of OA and provide insights for the diagnosis and treatment of OA.

The causes of sore throat are complex. It can be caused by diseases of the pharynx, adjacent organs of the pharynx, or even systemic diseases. Therefore, a lack of medical knowledge and experience may cause misdiagnoses or missed diagnoses in sore throat diagnoses, especially for general practitioners in primary hospitals. This study aims to develop a computer-aided diagnostic system to assist clinicians in the differential diagnoses of sore throat. The computer-aided system is developed based on the Dynamic Uncertain Causality Graph (DUCG) theory. We cooperated with medical specialists to establish a sore throat DUCG model as the diagnostic knowledge base. The construction of the model integrates epidemiological data, knowledge, and clinical experience of medical specialists. The chain reasoning algorithm of the DUCG is used for the differential diagnoses of sore throat. The system can diagnose 27 sore throat-related diseases. The model builder initially tests it with 81 cases, and all cases are correctly diagnosed. Then the system is verified by the third-party hospital, and the diagnostic accuracy is 98%. Now, the system has been applied in hundreds of primary hospitals in Jiaozhou City, China, and the degree of recognition for doctors to the diagnostic results of the system is more than 99.9%. It is feasible to use DUCG for the differential diagnoses of sore throat, which can assist primary doctors in clinical diagnoses and the diagnostic results are acceptable to clinicians.

In this paper, a patch antenna is proposed with reconfigurable patterns in the azimuth plane. The basic structure of the antenna is a circular patch upon which a vertical slot is etched. In addition, a row of shorting posts along the horizontal direction is placed underneath the patch. With the aid of characteristic mode analysis (CMA), reconfigurable patterns are achieved by synthesizing the currents of different modes. By switching over different sets of feeding ports, four steerable beams capable of covering the entire azimuth plane are obtained. One unique feature is that when the beam is switched to the direction orthogonal to it, the shape of the pattern will be switched accordingly. The antenna was fabricated and measured. The measured F/B ratio is close to 10 dB at 2.08 GHz, and the 3-dB beamwidth in the elevation (azimuth) plane is switchable from 82° (181°) to 190° (91°).

To solve some problems of high spatial resolution remote sensing images caused by land coverage, building coverage and shading of trees, such as difficult road extraction and low precision, a road extraction method based on multi-task key point constraints is put forward in this article based on Linknet. At the preprocessing stage, an auxiliary constraint task is designed to solve the connectivity problem caused by shading during road extraction from remote sensing images. At the encoding & decoding stage, first, a position attention (PA) mechanism module and channel attention (CA) mechanism module are applied to realize the effective fusion of semantic information in the context during road extraction. Second, a multi-branch cascade dilated spatial pyramid (CDSP) is established with dilated convolution, by which the problem of loss of partial information during information extraction from remote sensing road image is solved and the detection accuracy is further improved. The method put forward in this article is verified through the experiment with public datasets and private datasets, revealing that the proposed method provides better performance than several state of the art techniques in terms of detection accuracy, recall, precision, and F1-score.

TSNAD is a one-stop software solution for predicting neoantigens from the whole genome/exome sequencing data of tumor-normal pairs. Here we present TSNAD v2.0 which provides several new features such as the function of RNA-Seq analysis including gene expression and gene fusion analysis, the support of different versions of the reference genome. Most importantly, we replace the NetMHCpan with DeepHLApan we developed previously, which considers both the binding between peptide and major histocompatibility complex (MHC) and the immunogenicity of the presented peptide-MHC complex (pMHC). TSNAD v2.0 achieves good performamce on a standard dataset. For better usage, we provide the Docker version and the web service of TSNAD v2.0. The source code of TSNAD v2.0 is freely available at https://github.com/jiujiezz/tsnad. And the web service of TSNAD v2.0 is available at http://biopharm.zju.edu.cn/tsnad/.

Ratooning was a practical approach to increase the grain yield of rice. In this research, main and ratoon crop rice were compared in quality attributes, including composition, starch morphology, starch crystalline structure, protein components, pasting property, texture, and sensory attributes of cooked rice. As compared to main crop rice, ratoon crop rice showed an increase in amylose content and a decrease in protein content. Both main and ratoon crop rice starches exhibited similar polyhedral shape and A-type crystalline structure, but the ratoon crop rice had a lower relative crystallinity. Globulin content of ratoon crop rice protein was higher than that of main crop rice protein. As compared to main crop rice flour, ratoon crop rice flour showed a decrease in pasting temperature, peak viscosity, and breakdown viscosity but an increase in final viscosity and setback viscosity. After cooking, ratoon crop rice had higher hardness, cohesiveness, gumminess, and resilience than main crop rice. In sensory evaluation conducted with trained panelists, ratoon crop rice scored higher than main crop rice in overall acceptance.

The temperature-dependent layer-resolved structure of 3 to 44 unit cell thick SrRuO3 (SRO) films grown on Nb-doped SrTiO3 substrates is investigated using a combination of high-resolution synchrotron x-ray diffraction and high-resolution electron microscopy to understand the role that structural distortions play in suppressing ferromagnetism in ultra-thin SRO films. The oxygen octahedral tilts and rotations and Sr displacements characteristic of the bulk orthorhombic phase are found to be strongly dependent on temperature, the film thickness, and the distance away from the film–substrate interface. For thicknesses, t, above the critical thickness for ferromagnetism (t > 3 uc), the orthorhombic distortions decrease with increasing temperature above TC. Below TC, the structure of the films remains constant due to the magneto-structural coupling observed in bulk SRO. The orthorhombic distortions are found to be suppressed in the 2–3 interfacial layers due to structural coupling with the SrTiO3 substrate and correlate with the critical thickness for ferromagnetism in uncapped SRO films.

BackgroundPrevious reports on the treatment of neuropathic arthropathy of the wrist were generally conservative, with few case reports of treatment with osteoarticular surgery.Case PresentationA 25-year-old right-handed male complained of unpainful swelling of the dorsal aspect of his right wrist for 3 years. He was at that time diagnosed with synovitis and radiocarpal arthritis. The patient underwent a partial Four-Corner Arthrodesis and Synoviectomy to preserve motor function. Over the next 2 months, his right wrist also developed painful redness, with progressive swelling and stiffness. Rheumatoid arthritis, tuberculosis arthritis, and infectious diseases were ruled out in this case. Magnetic resonance imaging (MRI) indicated that he had Chiari II syringomyelia so the patient was eventually diagnosed with destructive neuropathic arthropathy (syringomyelia). After 2 months of conservative treatment, the patient’s right wrist spontaneously and completely fused and the pain disappeared.ConclusionNeuropathic arthropathy of the wrist is a rare but clinically significant disease due to its effect on the function of the active limb. Surgeons should rule out a diagnosis of it when treating patients with wrist swelling and osteoarticular abnormalities, otherwise, limited intercarpal arthrodesis should not be taken as a treatment option. Inappropriate partial surgery is likely to lead to rapid total fusion of neuropathic arthropathy of the wrist.

IntroductionTobacco smoking is associated with the onset and severity of psoriasis, and understanding the prevalence of tobacco smoking among patients with psoriasis is critical due to its high physical and mental influence and heavy disease burden. However, evidence on the association between tobacco smoking and psoriasis severity is still limited in China.ObjectivesThe objective of this study was to examine the prevalence of tobacco smoking and explore the association between tobacco smoking and diseases severity among patients with psoriasis.MethodsA total of 4,529 patients with psoriasis in 200 selected hospitals were recruited in China between January 2020 and September 2021. Detailed information covering demographic feature, tobacco smoking, and psoriasis history were collected through an electronic questionnaire, and clinical data were extracted from the health information system (HIS). SAS 9.4 was used for data analysis, and a p-value of 13, when compared with patients with PASI score < 3.0. Similarly, the OR of current tobacco smoking prevalence was 1.8 [95% CI: (1.5–2.2)] for PASI score (3.0–7.0), 1.9 for PASI score (7.1–13.0), and 3.1 for PASI score >13, when compared with patients with PASI score

Neuropathic pain is usually caused by injury or dysfunction of the somatosensory system, and medicine is a common way of treatment. Currently, there are still no satisfactory drugs, like opioids and lidocaine, which carry a high risk of addiction. Protein tyrosine phosphatase receptor type D (PTPRD) is a known therapeutic target in addiction pathways and small molecule inhibitors targeting it, such as 7-butoxy illudalic acid analog (7-BIA), have recently been developed to tackle addition. PTPRD is also upregulated in the dorsal root ganglion (DRG) in a rat model of neuropathic pain, but is not yet clear whether PTPRD contributes to the development of neuropathic pain. Here, we established a chronic constriction injury (CCI) and evaluated PTPRD expression and its association with neuropathic pain. PTPRD expression was found to gradually increase after CCI in DRGs, and its expression was concomitant with the progressive development of hypersensitivity as assessed by both mechanical and thermal stimuli. Both PTPRD knockdown and administration of PTPRD inhibitor 7-BIA alleviated CCI-induced neuropathic pain while upregulating STING and IFN-α in the DRG. Treatment with H-151, a STING inhibitor, abolished the analgesic effects of PTPRD knockdown. Taken together, our study suggests that increased levels of PTPRD in the DRG following CCI are involved in the development of neuropathic pain via the STING-IFN-I pathway. 7-BIA, a small molecule inhibitor of PTPRD with anti-addiction effects, may represent a novel and safe therapeutic strategy for the clinical management of neuropathic pain without the risk of addiction.

The persistent coronavirus disease 2019 (COVID-19), characterized by severe respiratory syndrome, is caused by coronavirus 2 (SARS-CoV-2), and it poses a major threat to public health all over the world. Currently, optimal COVID-19 management involves effective vaccination. Vaccination is known to greatly enhance immune response against viral infections and reduce public transmission of COVID-19. However, although current vaccines offer some benefits, viral variations and other factors demand the continuous development of vaccines to eliminate this virus from host. Hence, vaccine research and development is crucial and urgent to the elimination of this pandemic. Herein, we summarized the structural and replicatory features of SARS-CoV-2, and focused on vaccine-mediated disease prevention strategies like vaccine antigen selection, vaccine research, and vaccine application. We also evaluated the latest literature on COVID-19 and extensively reviewed action mechanisms, clinical trial (CT) progresses, advantages, as well as disadvantages of various vaccine candidates against SARS-CoV-2. Lastly, we discussed the current viral treatment, prevention trends, and future prospects.

This study utilizes the Weather Research and Forecasting model with a higher resolution (36 km × 36 km) to dynamically downscale the Community Earth System Model results forced by the three representative concentration pathways (RCP) scenarios (RCP4.5, RCP6.0, and RCP8.5) over China. The goal was to compare meteorological fields during the present (2006–2015) and future (2046–2055) climatological periods. An appropriate air stagnation judgment index was selected to explore the effect of climate change on air quality-related meteorological conditions. The results show that the occurrence of wintertime air stagnation over China in the middle of this century (2046–2055) will reduce slightly, with the largest reduction projected under the RCP8.5 scenario (−4 times). However, long-lasting air stagnation events (ASE) are projected to increase in the future, and this increasing trend is more obvious under the RCP8.5 scenario. The projected increase in the long-lasting ASE in different regions of China ranges from 3 to 11 times. Among these, Central China has the largest increase, followed by East and Northeast China, while South China has the lowest increase in ASE. Our results indicate that more attention should be dedicated to extreme pollution events that may potentially be caused by long-lasting air stagnation events in the future.

Atherosclerotic disease has become the major cause of death worldwide. Smoking, as a widespread independent risk factor, further strengthens the health burden of atherosclerosis. Irisin is a cytokine that increases after physical activity and shows an atheroprotective effect, while its specific mechanism in the process of atherosclerosis is little known. The reversal effect of irisin on intimal thickening induced by smoking-mediated atherosclerosis was identified in Apoe–/– mice through the integrin αVβ5 receptor. Endothelial cells treated with nicotine and irisin were further subjected to RNA-seq for further illustrating the potential mechanism of irisin in atherosclerosis, as well as the wound healing assays, CCK-8 assays, β-gal staining and cell cycle determination to confirm phenotypic alterations. Endothelial differential expressed gene enrichment showed focal adhesion for migration and proliferation, as well as the P53 signaling pathway for cell senescence and cell cycle control. Irisin exerts antagonistic effects on nicotine-mediated migration and proliferation via the integrin αVβ5/PI3K pathway. In addition, irisin inhibits nicotine-mediated endothelial senescence and cell cycle arrest in G0/G1 phase via P53/P21 pathway. This study further illustrates the molecular mechanism of irisin in atherosclerosis and stresses its potential as an anti-atherosclerotic therapy.

Since aspirin and clopidogrel are the widely and conventionally used drugs to treat acute myocardial infarction after percutaneous coronary intervention (PCI), it is important to explore potential risk factors of their resistance. The platelet aggregation rate with arachidonic acid (AA, PAg-AA%) and adenosine diphosphate (ADP, PAg-ADP%) of 219 PCI patients were measured after standard treatment for 24 h. The disease history and laboratory data (before PCI) were obtained. We found 101 (46.12%) patients to be aspirin-resistant, and PAg-ADP% was the most prominent risk factor of aspirin resistance. Clopidogrel resistance was present in 157 of 219 patients. Patients in the clopidogrel-resistant group carried more CYP2C19*3 or *2, which was associated with higher clopidogrel resistance in this group (69.11%, 47/68) than in the control group (64.29%, 36/56). Platelet count (10 9 /L) and hemoglobin (g/L) were the prominent risk factors of clopidogrel resistance. Among the 219 patients, 98 showed dual antiplatelet drug resistance, for which platelet count (10 9 /L) and monocyte count (g/L) were the risk factors. Aspirin resistance was found to usually accompany clopidogrel resistance.

Rheumatoid arthritis (RA) occurs in about 5 per 1,000 people and can lead to severe joint damage and disability. However, the knowledge of pathogenesis and treatment for RA remains limited. Here, we found that histone demethylase inhibitor GSK-J4 relieved collagen induced arthritis (CIA) symptom in experimental mice model, and the underlying mechanism is related to epigenetic transcriptional regulation in macrophages. The role of epigenetic regulation has been introduced in the process of macrophage polarization and the pathogenesis of inflammatory diseases. As a repressive epigenetic marker, tri-methylation of lysine 27 on histone H3 (H3K27me3) was shown to be important for transcriptional gene expression regulation. Here, we comprehensively analyzed H3K27me3 binding promoter and corresponding genes function by RNA sequencing in two differentially polarized macrophage populations. The results revealed that H3K27me3 binds on the promoter regions of multiple critical cytokine genes and suppressed their transcription, such as IL6, specifically in M-CSF derived macrophages but not GM-CSF derived counterparts. Our results may provide a new approach for the treatment of inflammatory and autoimmune disorders.

The importance of human wellbeing is documented in the literature of development economics because of its intensifying impacts on economic growth and productivity of labor in the long-run. To the best of the authors' knowledge, no empirical study has examined the symmetric association between China's financial institutional development, education, and health outcomes. Thus, our study aims to fill this vacuum by employing an autoregressive distributed lag (ARDL) approach to explore the impact of financial institutional development and education on life expectancy and infant mortality rate from 1990 to 2020. The empirical analysis reveals that financial institutional development and education report a significant increase in life expectancy and meaningful reduction in mortality rate in the long-run. Based on these findings, the study may deliver intuitive policy implications regarding improvement in health conditions that are imperative for promoting economic growth in the long-run.

The internet has influenced human wellbeing through social networking, time-saving, diffusion of knowledge, and access to health information. Health is a key component of human quality of life. This study examines the nexus between education, the internet, and quality of life using data from China spanning the period from 1991 to 2020. The study used ARDL to examine the short and long-term, exploring education and the impact of the internet on quality of life. Education status plays a significant role in promoting quality of life in the short and long term. The empirical findings show the significant positive impact of the internet and ICT on quality of life in the short and long-run. Financial development and FDI improve the quality of life in the long-term in China. Based on these results, policymakers in China should develop the ICT infrastructure and human capital to support increased quality of life.

Cu–Cr–Co combinatorial multilayer thin-films were prepared by a high-throughput ion beam sputtering system. Based on the thickness ratio among the individual nanoscale monolayers (Cu, Cr, Co), the resulting stoichiometry covered the entire phase diagram. The chemical composition and structure of Cu–Cr–Co combinatorial chip upon solid-state reaction were studied by lab-based micro-X-ray fluorescence (μ-XRF) and high-throughput synchrotron X-ray diffraction (XRD), respectively. A composition-structure map for Cu–Cr–Co combinatorial chip was developed through automated data analysis employing hierarchical clustering techniques. The structural evolution of Cu–Cr–Co combinatorial chip as a function of heat-treatment temperature, time, and modulation period were studied systematically. Furthermore, the effect of the elemental distribution in-depth direction was investigated to gain more insights regarding phase transformation. This work provides an efficient method and new perspectives for the design and optimization of the composition and structure of high-performance thin-films.

Bi2S3 has attracted wide attention due to its application in photoelectric converter, but its preparation conditions are relatively complicated. The Bi2S3 microflowers, which are self-assembled from nanowires and have high photoelectric responsiveness, were synthesized by using polyvinylpyrrolidone (PVP) as structure guide under ethylene glycol solvent heat condition. The effects of different types of surfactants and different reaction time on the morphology of the products were also studied. In addition, a prototype device with photoconductive structure of visible light detection was assembled by using Bi2S3 microflowers and gold fork finger electrode as substrate. The photoresponse properties show that the photocurrent under simulated sunlight is about two orders of magnitude higher than the dark current, and the response time and decay time are 142 ms and 151 ms, respectively, indicating the photodetector has excellent photoelectric responsiveness; the light current is not attenuated by the periodic opening and closing of the photodetector, indicating that the photodetector has good stability.

Limited clinical application of antibody-drug conjugates (ADCs) targeting tumor associated antigens (TAAs) is usually caused by on-target off-tumor side effect. Tumor-specific mutant antigens (TSMAs) only expressed in tumor cells which are ideal targets for ADCs. In addition, intracellular somatic mutant proteins can be presented on the cell surface by human leukocyte antigen class I (HLA I)molecules forming tumor-specific peptide/HLA I complexes. KRAS G12V mutation frequently occurred in varied cancer and was verified as a promising target for cancer therapy. In this study, we generated two TCR-mimic antibody-drug conjugates (TCRm-ADCs), 2E8-MMAE and 2A5-MMAE, targeting KRAS G12V/HLA-A*0201 complex, which mediated specific antitumor activity in vitro and in vivo without obvious toxicity. Our findings are the first time validate the strategy of TCRm-ADCs targeting intracellular TSMAs, which improves the safety of antibody-based drugs and provides novel strategy for precision medicine in cancer therapy.

Portrait matting is of vital importance for many applications such as portrait editing, background replacement, ecommerce demonstration, and augmented reality. The portrait matt can be accessed by predicting the α value of the original picture. Previous deep matting methods usually adopt a segmentation network to tackle portrait matting tasks. However, these traditional methods will introduce unpleasant blemishes in the matting results sometimes. The authors find that the key factor behind this phenomenon is how they model the matting problem. On the one hand, α value predicting can be modelled as a regression task. On the other hand, it can be viewed as a classification task of predicting background or foreground. To solve this problem, they explore different methods to model the nature of the α matting problem and propose a novel quantisation‐based adaption. Their method comes up with an α quantisation loss to achieve multi‐threshold filtering. Furthermore, they apply an α merging block to improve conventional regression methods. With their method, the gradient loss is reduced by 7.53% relatively, with mean square error and sum of absolute difference decreased by 14.7% relatively, leading to a more visually pleasant α matt in several segmentation backbones.

Abstract A new kind of smart antenna capable of automatically switching its main beam to track a moving target is presented. The antenna, which is suitable for mobile communication in long straight spaces, such as railways or highways, integrates a sensing element, signal processing element, and radiating element. The sensing element works based on a frequency-modulated continuous wave and delivers a beat frequency signal containing environmental information to the signal processing element, which is used to control the excitation of the radiating element. To verify the efficiency of the proposed antenna, a prototype is fabricated and implemented in a real corridor scenario. Furthermore, the error vector magnitude (EVM) along the test path is investigated to evaluate the system performance when using the proposed antenna. The results show that this kind of smart antenna is capable of improving mobile communication quality and decreasing energy consumption. Therefore, it is a promising candidate for mobile communication.

Abstract Background Schwann cells (SCs) play a crucial role in Wallerian degeneration after peripheral nerve injury. The expression of genes in SCs undergo a series of changes, which greatly affect the proliferation and apoptosis of SCs as well as the fate of peripheral nerve regeneration. However, how do these genes regulate the proliferation and apoptosis of SCs remains unclear. Results SPP1 and PKCα were found upregulated after human median peripheral nerve injury, which promoted SCs proliferation and survival. The promoted proliferation and inhibited apoptosis by SPP1 were blocked after the treatment of PKCα antagonist Gö6976. Whereas, the inhibited proliferation and enhanced apoptosis induced by silence of SPP1 could be rescued by the activation of PKCα, which suggested that SPP1 functioned through PKCα. Moreover, both CD44 and αvβ3 were found expressed in SCs and increased after peripheral nerve injury. Silence of CD44 or β3 alleviated the increased proliferation and inhibited apoptosis induced by recombinant osteopontin, suggesting the function of SPP1 on SCs were dependent on CD44 and β3. Conclusion These results suggested that SPP1 promoted proliferation and inhibited apoptosis of SCs through PKCα signaling pathway by binding with CD44 and αvβ3. This study provides a potential therapeutic target for improving peripheral nerve recovery.

The behavior of potassium chloride (KCl) as a main mud shale inhibitor remains poorly defined in the interlayer of montmorillonite (Mt). In this paper, a new analysis method of transmission electron microscopy-energy dispersive X-ray spectroscopy (TEM-EDS) was established. The distribution of K+ in the interlayer of Mt and the processes surrounding d-spacing shifts in Mt were investigated through X-ray diffraction and TEM-EDS. The experimental results revealed shoulder peaks in the diffraction patterns at KCl concentrations between 11% and 19%. The distribution of K+ varied in the inner and outer layers of Mt with different KCl concentrations. It could be concluded that the distribution of K+ and the changes in d-spacing of Na are determined by two factors: negative charge sites and concentration difference. When the KCl concentration was below 8%, both factors cause the outer layer of Mt to adsorb more K+ than the inner layer, with all layers exhibiting d-spacings within the 1.50 nm state. At an 8% KCl concentration, all negative charge sites were occupied by K+. As the KCl concentration rose above 8%, the outer layer of Mt adsorbed more K+ than the inner layer due to the concentration difference. With a further increase in the KCl concentration, the d-spacing shifted linearly to 1.30 nm from the outer to the inner layer of Mt. All layers of Mt exhibited a d-spacing of 1.30 nm at KCl concentrations of up to 23%. These results demonstrate the benefits and capabilities of the proposed method in investigating the intercalating mechanisms of Mt.

Brain ischemia has been associated with deficits in neural oscillations. Here in an animal model, the authors show that modulation of low-gamma oscillations using a light flicker can restore low gamma oscillations and protect ischemic neurons.

Abstract Objectives To assess the safety and therapeutic effects of allogeneic human dental pulp stem cells (DPSCs) in treating severe pneumonia caused by COVID-19. Trial design This is a single centre, two arm ratio 1:1, triple blinded, randomized, placebo-controlled, parallel group, clinical trial. Participants Twenty serious COVID-19 cases will be enrolled in the trial from April 6th to December 31st 2020. Inclusion Criteria: hospitalised patients at Renmin Hospital of Wuhan University satisfy all criteria as below: 1) Adults aged 18-65 years; 2) Voluntarily participate in this clinical trial and sign the “informed consent form” or have consent from a legal representative. 3) Diagnosed with severe pneumonia of COVID-19: nucleic acid test SARS-CoV-2 positive; respiratory distress (respiratory rate > 30 times / min); hypoxia (resting oxygen saturation < 93% or arterial partial pressure of oxygen / oxygen concentration < 300 mmHg). 4) COVID-19 featured lung lesions in chest X-ray image. Exclusion Criteria: Patients will be excluded from the study if they meet any of the following criteria. 1. Patients have received other experimental treatment for COVID-19 within the last 30 days; 2. Patients have severe liver condition (e.g., Child Pugh score >=C or AST> 5 times of the upper limit); 3. Patients with severe renal insufficiency (estimated glomerular filtration rate