Spatial transcriptomics reveals light-induced chlorenchyma cells involved in promoting shoot regeneration in tomato callus.

Callus is a reprogrammed cell mass involved in plant regeneration and gene transformation in crop engineering. Pluripotent callus cells develop into fertile shoots through shoot regeneration. The molecular basis of the shoot regeneration process in crop callus remains largely elusive. This study pioneers the exploration of the spatial transcriptome of tomato callus during shoot regeneration. The findings reveal the presence of highly heterogeneous cell populations within the callus, including epidermis, vascular tissue, shoot primordia, inner callus, and outgrowth shoots. By characterizing the spatially resolved molecular features of shoot primordia and surrounding cells, specific factors essential for shoot primordia formation are identified. Notably, chlorenchyma cells, enriched in photosynthesis-related processes, play a crucial role in promoting shoot primordia formation and subsequent shoot regeneration. Light is shown to promote shoot regeneration by inducing chlorenchyma cell development and coordinating sugar signaling. These findings significantly advance our understanding of the cellular and molecular aspects of shoot regeneration in tomato callus and demonstrate the immense potential of spatial transcriptomics in plant biology.

The protective effect and bioactive compounds of Astragalus membranaceus against neurodegenerative disorders via alleviating oxidative stress in Drosophila.

Oxidative stress is proposed as a regulatory element in various neurological disorders, which is involved in the progress of several neurodegenerative diseases such as Alzheimer's disease (AD) and Parkinson's disease (PD). Antioxidant drugs are widely used to alleviate neurodegenerative disorders. Astragalus membranaceus (Huangqi, AM) is a commonly used medicinal herb with a wide range of pharmacological effects. Here, the protective effect and mechanism of AM extract (AME) and its bioactive compounds against neurodegenerative disorders via alleviating oxidative stress were detected using adult Drosophila melanogaster. The drug safety was measured by development analysis; oxidative stress resistance ability was detected by survival rate under H2O2 environment; ROS level was detected by DHE staining and gstD1-GFP fluoresence assay; antioxidative abilitiy was represent by measuring antioxidant enzyme activity, antioxidative-related gene expression, and ATP and MFN2 levels. The neuroprotective effect was evaluated by lifespan and locomotion analysis in Aß42 transgenic and Pink1B9 mutants. AME dramatically increased the survival rates, improved the CAT activity, restored the decreased mRNA expressions of Sod1, Cat, and CncC under H2O2 stimulation, and ameliorated the neurobehavioral defects of the AD and PD. Thirteen small molecules in AM had antioxidant function, in which vanillic acid and daidzein had the most potent antioxidant effect. Vanillic acid and daidzein could increase the activities of SOD and CAT, GSH level, and the expressions of antioxidant genes. Vanillic acid could improve the levels of ATP and MFN2, and mRNA expressions of ND42 and SDHC to rescue mitochondrial dysfunction. Furthermore, vanillic acid ameliorated neurobehavioral defects of PD. Daidzein ameliorated neurobehavioral defect of Aß-induced AD mode. Taken together, AM plays a protective role in oxidative damage, thereby as a potential natural drug to treat neurodegenerative disorders.

Regulating Catalytic Oxidation Enantiomers Behavior by Imparting Chiral Microenvironment in Zr-Based Metal-Organic Frameworks.

Chiral inversions of enantiomers have significantly different biological activities, so it is important to develop simple and effective methods to efficiently identify optically pure compounds. Inspired by enzyme catalysis, the construction of chiral microenvironments resembling enzyme pockets in the pore space structure of metal-organic frameworks (MOFs) to achieve asymmetric enantioselective recognition and catalysis has become a new research hotspot. Here, a super-stable porphyrin-containing material PCN-224 is constructed by solvothermal method and a chiral microenvironment around the existing catalytic site of the material is created by post-synthesis modifications of the histidine (His) enantiomers. Experimental and theoretical calculations results show that the modulation of chiral ligands around Zr oxide clusters produces different spatial site resistances, which can greatly affect the adsorption and catalytic level of the enantiomeric molecules of tryptophan guests, resulting in a good enantioselective property of the material. It provides new ideas and possibilities for future chiral recognition and asymmetric catalysis.

Mechanisms of Alveolar Type 2 Epithelial Cell Death During Acute Lung Injury.

Diffuse alveolar epithelial cell (AEC) death occurs extensively during acute lung injury (ALI). Due to the limited proliferative capacity of alveolar type 1 epithelial (AT1) cells, the differentiation and regenerative capacity of alveolar type 2 epithelial (AT2) cells are required to restore the barrier function of AECs. However, during lung injury, AT1 cells are particularly susceptible to injury, and ATII cells die in the presence of severe or certain types of injury. This disruption ultimately results in a hindrance to the ability of AT2 cells to proliferate and differentiate into AT1 cells in time to repair the extensively damaged AECs. Therefore, understanding the mechanism of injury death of AT2 cells may be beneficial to reverse the above situation. This article reviews the main death modes of AT2 cells, including apoptosis, necrosis, necroptosis, pyroptosis, autophagic cell death, and ferroptosis. It compares the various forms of death, showing that various cell injury death modes have unique action mechanisms and partially overlapping pathways. Studying the mechanism of AT2 cell death is helpful in screening and analyzing the target pathway of AEC barrier function recovery. It opens up new ideas and strategies for preventing and treating ALI.

Boosting the Capacitor Performance of the Metal Organic Frameworks Derived V2O5 Nanoflower by Cu Doping.

Due to its ultrahigh theoretical capacitance, vanadium pentoxide (V2O5) is considered to be a valid candidate for advanced supercapacitors. However, because of the low electron/electrolyte transfer rate, the capacitive performance still remains to be improved. In this report, Cu doping is adopted to improve the capacitive performance by a two-steps strategy consisting of microwave-assisted solvothermal and postannealing treatments. The electrochemical results indicate that the Cu doping was beneficial for improving the specific capacitance, extending the potential window, and improving the rate ability and long-term stability of V2O5. Furthermore, the mechanism for the performance improvement is explained in detail by combining theoretical calculation and experiments. The results indicated that, compared with that of undoped V2O5, the larger interplanar spacing, better electrical conductivity, a larger proportion of V3+/V4+, and more abundant oxygen vacancies result in an improved capacitive performance. Our proposed Cu-doped V2O5 (Cu-V2O5) can be used as both a positive electrode and a negative electrode for the assembly of the symmetric supercapacitor, which can be used as an energy storage device for light emitting diode lamps.

Structure-Based Discovery of the SARS-CoV-2 Main Protease Noncovalent Inhibitors from Traditional Chinese Medicine.

Traditional Chinese medicine (TCM) has been extensively employed for the treatment of coronavirus disease 2019 (COVID-19) caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). However, there is demand for discovering more SARS-CoV-2 Mpro inhibitors with diverse scaffolds to optimize anti-SARS-CoV-2 lead compounds. In this study, comprehensive in silico and in vitro assays were utilized to determine the potential inhibitors from TCM compounds against SARS-CoV-2 Mpro, which is an important therapeutic target for SARS-CoV-2. The ensemble docking analysis of 18263 TCM compounds against 15 SARS-CoV-2 Mpro conformations identified 19 TCM compounds as promising candidates. Further in vitro testing validated three compounds as inhibitors of SARS-CoV-2 Mpro and showed IC50 values of 4.64 ± 0.11, 7.56 ± 0.78, and 11.16 ± 0.26 µM, with EC50 values of 12.25 ± 1.68, 15.58 ± 0.77, and 29.32 ± 1.25 µM, respectively. Molecular dynamics (MD) simulations indicated that the three complexes remained stable over the last 100 ns of production run. An analysis of the binding mode revealed that the active compounds occupy different subsites (S1, S2, S3, and S4) of the active site of SARS-CoV-2 Mpro via specific poses through noncovalent interactions with key amino acids (e.g., HIS 41, ASN 142, GLY 143, MET 165, GLU 166, or GLN 189). Overall, this study provides evidence indicating that the three natural products obtained from TCM could be further used for anti-COVID-19 research, justifying the investigation of Chinese herbal medicinal ingredients as bioactive constituents for therapeutic targets.

Effects of combined microplastic and cadmium pollution on sorghum growth, Cd accumulation, and rhizosphere microbial functions.

The interaction between microplastics (MPs) and cadmium (Cd) poses a threat to agricultural soil environments, and their effects on plant growth and rhizosphere microbial community functions are not yet clear. In this study, energy sorghum was used as a test plant to investigate the effects of two types of MPs, polystyrene (PS) and polyethylene (PE), at different particle sizes (13 µm, 550 µm) and concentrations (0.1%, 1% w/w), and Cd, as well as their interactions, on the growth of sorghum in a soil-cultivation pot experiment. The results showed that the combined effects of MP and Cd pollution on the dry weight and Cd accumulation rate in sorghum varied depending on the type, concentration, and particle size of the MPs, with an overall trend of increasing stress from combined pollution with increasing Cd content and accumulation. High-throughput sequencing analysis revealed that combined MP and Cd pollution increased bacterial diversity, and the most significant increase was observed in the abundance-based coverage estimator (ACE), Shannon, and Sobs indices in the 13 µm 1% PS+Cd treatment group. Metagenomic analysis based on the Kyoto Encyclopedia of Genes and Genomes (KEGG) metabolic pathways revealed that 19 groups of metabolic pathways, including microbial metabolism and methane metabolism, differed significantly under combined MP and Cd pollution. Hierarchical clustering results indicated that Cd treatment and combined MP and Cd treatment affected the abundances of sorghum rhizosphere soil nitrogen (N) and phosphorus (P) cycling genes and that the type of MP present was an important factor affecting N and P cycling genes. The results of this study provide a basis for exploring the toxic effects of combined MP and Cd pollution and for conducting soil environmental risk assessments.

Fabrication strategies for chiral self-assembly surface.

Chiral self-assembly is the spontaneous organization of individual building blocks from chiral (bio)molecules to macroscopic objects into ordered superstructures. Chiral self-assembly is ubiquitous in nature, such as DNA and proteins, which formed the foundation of biological structures. In addition to chiral (bio) molecules, chiral ordered superstructures constructed by self-assembly have also attracted much attention. Chiral self-assembly usually refers to the process of forming chiral aggregates in an ordered arrangement under various non-covalent bonding such as H-bond, π-π interactions, van der Waals forces (dipole-dipole, electrostatic effects, etc.), and hydrophobic interactions. Chiral assembly involves the spontaneous process, which followed the minimum energy rule. It is essentially an intermolecular interaction force. Self-assembled chiral materials based on chiral recognition in electrochemistry, chiral catalysis, optical sensing, chiral separation, etc. have a broad application potential with the research development of chiral materials in recent years.

Engineering photocatalytic ammonia synthesis.

Photocatalytic ammonia synthesis (PAS) is an emerging zero carbon emission technology, which is critical for mitigating energy crises and achieving carbon neutrality. Herein, we summarize the recent advances and challenges in PAS from an engineering perspective based on its whole chain process, i.e., materials engineering, structure engineering and reaction engineering. For materials engineering, we discuss the commonly used photocatalytic materials including metal oxides, bismuth oxyhalides and graphitic carbon nitride and emerging materials, such as organic frameworks, along with the analysis of their characteristics and regulation methods to enhance the PAS performance. For structure engineering, the design of photocatalysts is described in terms of morphology, vacancy and band, corresponding to the crystal, atom and electron scales, respectively. Moreover, the structure-performance relationship of photocatalysts has been deeply explored in this section. For reaction engineering, we identify three key processes from the chemical reaction and mass transfer, i.e., nitrogen activation, molecule transfer and electron transfer, to intensify and optimize the PAS reaction. Hopefully, this review will provide a novel paradigm for the design and preparation of high-efficiency ammonia synthesis photocatalysts and inspire the practical application of PAS.

Iron oxyhydroxide catalyzes production of artificial humic substances from waste biomass.

Production of artificial humic substances (AHS) from waste biomass will contribute to environmental protection and agricultural productivity. However, there is still a lack of a faster, more efficient and eco-friendly way for sustainable production. In this study, we proposed a method to accelerate the production of AHS from cotton stalks by mild pyrolysis and H2O2 oxidation in only 4 hours, and investigated the formation of AHS during biomass transformation. We found that the process increased the aromatic matrix and facilitated biomass transformation by enhancing the depolymerization of lignin into micromolecular phenolics (e.g., guaiacol, p-ethyl guaiacol, etc.). The optimum conditions of pyrolysis at 250 °C and oxidation with 6 mL H2O2 (5 wt%) yielded up to 19.28 ± 1.30 wt% artificial humic acid (AHA) from cotton stalks. In addition, we used iron oxyhydroxide (FeOOH) to catalyze biomass transformation and investigated the effect of FeOOH on the composition and properties of AHS. 1.5 wt% FeOOH promoted the increased content of artificial fulvic acid (AFA) in AHS from 10.1% to 26.5%, eventually improving the activity of AHS. FeOOH raised the content of oxygen-containing groups, such as carboxylic acids and aldehyde, and significantly increased polysaccharide (10.94%-18.95%) and protein (1.95%-2.18%) derivatives. Polymerization of amino acid analogs and many small-molecule carbohydrates (e.g., furans, aldehydes, ketones, and their derivatives) promoted AFA formation. Finally, carbon flow analysis and maize incubation tests confirmed that AHS were expected to achieve carbon emission reductions and reduce environmental pollution from fertilizers. This study provides a sustainable strategy for the accelerated production of AHS, which has important application value for waste biomass resource utilization.

The Antioxidant Action of Astragali radix: Its Active Components and Molecular Basis.

Astragali radix is a traditional medicinal herb with a long history and wide application. It is frequently used in prescriptions with other medicinal materials to replenish Qi. According to the classics of traditional Chinese medicine, Astragali radix is attributed with properties such as Qi replenishing and surface solidifying, sore healing and muscle generating, and inducing diuresis to reduce edema. Modern pharmacological studies have demonstrated that some extracts and active ingredients in Astragali radix function as antioxidants. The polysaccharides, saponins, and flavonoids in Astragali radix offer beneficial effects in preventing and controlling diseases caused by oxidative stress. However, there is still a lack of comprehensive research on the effective components and molecular mechanisms through which Astragali radix exerts antioxidant activity. In this paper, we review the active components with antioxidant effects in Astragali radix; summarize the content, bioavailability, and antioxidant mechanisms; and offer a reference for the clinical application of Astragalus and the future development of novel antioxidants.

Advances in understanding effects of miRNAs on apoptosis, autophagy, and pyroptosis in knee osteoarthritis.

MicroRNAs (miRNAs) are a class of endogenous small non-coding RNAs. MicroRNAs-mediated signaling pathways play a critical regulatory role in inducing apoptosis, autophagy, and pyroptosis in developing knee osteoarthritis (KOA). Given this, we searched databases, such as PubMed, using keywords including "miRNA," "knee osteoarthritis," "apoptosis," "autophagy," "pyroptosis", and their combinations. Through an extensive literature review, we conclude that miRNAs can be modulated through various signaling pathways, such as Wnt/ß-catenin, TGF-ß, PI3K/AKT/mTOR, and NLRP3/Caspase-1, to regulate apoptosis, autophagy, and pyroptosis in KOA. Furthermore, we note that P2X7R and HMGB1 may be crucial regulatory molecules involved in the interconnected regulation of apoptosis, autophagy, and pyroptosis in KOA. Additionally, we describe that miR-140-5p and miR-107 can modulate the advancement of KOA chondrocytes by targeting distinct molecules involved in apoptosis, autophagy, and pyroptosis, respectively. Therefore, we conclude that miRNAs may be potential biomarkers and therapeutic targets for the early prediction, diagnosis, and effective therapeutic approaches of KOA.

Benzo[b]fluoranthene induced oxidative stress and apoptosis in human airway epithelial cells via mitochondrial disruption.

Benzo[b]fluoranthene (BbF) is a common constituent of polycyclic aromatic hydrocarbons (PAHs). While numerous studies revealed adverse effects of PAHs on human health, the health effects of individual PAHs differ, and few investigations were performed on BbF. Therefore, the present study established cytotoxicity models of human lung epithelial cells (BEAS-2B cells) and bronchial epithelial cells (16HBE cells) exposed to BbF (10, 20, and 40 µM) for 24 h to reveal the mechanisms. Results from cytotoxicity and proliferation studies demonstrated that BbF inhibited cell growth in a dose-dependent manner. Flow cytometric analysis showed that BbF induced the appearance of a sub G1 peak, S-phased arrest, and apoptosis in both cells. Mechanistic investigations illustrated that BbF promoted reactive oxygen species (ROS) production, altered the expression of oxidative stress indicators, and decreased mitochondrial membrane potential. BbF also interfered with the expression of regulators associated with mitochondria disruption pathway. Taken together, these results strongly suggested that BbF inhibited cell growth and induced apoptosis in human airway epithelial cells via ROS-mediated mitochondria disruption.

Plant growth-promoting bacteria modulate gene expression and induce antioxidant tolerance to alleviate synergistic toxicity from combined microplastic and Cd pollution in sorghum.

Microplastics (MPs) can act as carriers for environmental pollutants; therefore, MPs combined with heavy metal pollution are attracting increasing attention from researchers. In this study, the potential of the plant growth-promoting bacterium Bacillus sp. SL-413 to mitigate the stress caused by exposure to both MPs and cadmium (Cd) in sorghum plants was investigated. The effects of inoculation on sorghum biomass were investigated using hydroponic experiments, and evaluation of Cd accumulation and enzyme activity changes and transcriptomics approaches were used to analyze its effect on sorghum gene expression. The results showed that combined polyethylene (PE) and Cd pollution reduced the length and the fresh and dry weights of sorghum plants and thus exerted a synergistic toxic effect. However, inoculation with the strains alleviated the stress caused by the combined pollution and significantly increased the biomass. Inoculation increased the dry weights of the aboveground and belowground parts by 11.5-44.6% and 14.9-38.4%, respectively. Plant physiological measurements indicated that inoculation reduced the reactive oxygen species (ROS) content of sorghum by 10.5-27.2% and thereby alleviated oxidative stress. Transcriptome sequencing showed that exposure to combined Cd+MP contamination induced downregulation of gene expression, particularly that of genes related to amino sugar and nucleotide sugar metabolism, starch and sucrose metabolism, and plant hormone signal transduction, in sorghum. However, inoculation with Bacillus sp. SL-413 resulted in an increase in the proportion of upregulated genes involved in signal transduction, antioxidant defense, cell wall biology, and other metabolic pathways, which included the phenylpropanoid biosynthesis, photosynthesis, flavonoid biosynthesis, and MAPK signaling pathways. The upregulation of these genes promoted the tolerance of sorghum under combined Cd+MP pollution stress and alleviated the stress induced by these conditions. This study provides the first demonstration that plant growth-promoting bacteria can alleviate the stress caused by combined pollution with MPs and Cd by regulating plant gene expression. These findings provide a reference for the combined plant-microbial remediation of MPs and Cd.

Antiviral therapy in hepatitis B virus-infected with immune-tolerant: A meta-analysis.

To access the efficacy of antiviral therapy in patients of HBV-infected with immune-tolerant. We conducted a meta-analysis search of the Cochrane Library, PubMed, ClinicalTrials.gov, Web of science, and EMBASE on through August 2021. We combined the data by means of a random-effect DrSimonian-Laird model and calculated risk ratios (RRs) for the outcomes of hepatitis B surface antigen (HBsAg) loss, hepatitis B e antigen (HBeAg) seroconversion, HBV deoxyribonucleic acid (DNA) negative conversion rate, and the risk for hepatocellular carcinoma (HCC) and cirrhosis. An extensive literature search identified 328 relevant publications, and five were included in the study. Antiviral therapy was in favor of HBsAg loss (RR=2.34, 95%CI 0.68-4.00, p=0.91, I2=0.00%), HBV DNA negative conversion (RR=2.08, 95%CI 0.10-4.05, p=0.07, I2=58.24%) and reduce the risk for HCC (HR=0.189, 95%CI 0.052-0.692, p=0.004) and cirrhosis (HR=0.347, 95%CI 0.095-1.270, p=0.036), but not beneficial to HBeAg seroconversion (RR=0.83, 95%CI -0.03 to 1.70, p=0.11, I2=46.99%). Subgroup-analyzed by the research type was similar results of HBsAg loss, HBV DNA negative conversion, and HBeAg seroconversion.Patients in HBV-infected with immune-tolerant responded well to antiviral therapy. The evidence from this meta-analysis supports antiviral therapy for patients with HBV in the immune tolerance stage. Well-designed, multi-center, larger sample sizes, and excellent quality prospective studies are needed to confirm our conclusion.

Zhongfeng Capsules protects against cerebral ischemia-reperfusion injury via mediating the phosphoinositide 3-kinase/Akt and toll-like receptor 4/nuclear factor kappa B signaling pathways by regulating neuronal apoptosis and inflammation.

Inflammatory reaction and neuronal apoptosis are the major pathophysiological mechanisms involved in cerebral ischemia-reperfusion injury (CI/RI). It has been reported that Zhongfeng Capsules (ZFCs), which contain Panax notoginseng, Hirudo, Red ginseng, Eupolyphaga sinensis, Pangolin scales, Rhubarb, and Radix Salvia miltiorrhizae, have a definite therapeutic effect on CI/RI. However, the specific molecular mechanisms of ZFCs are unclear. In this study, the effects of ZFCs on middle cerebral artery occlusion were investigated in rats. Our results showed that neurological impairment and neuronal apoptosis were alleviated in ZFC-treated rats. Additionally, infarct volume and cerebral edema decreased and there was an improvement in histopathological features. Furthermore, the expression levels of IL-1ß, IL-6, and TNF-α were downregulated in ZFC-treated rats. TLR 4, NF-κB, Bax, and Caspase-3 expression also tended to decrease, whereas the expression of Bcl-2, p-PI3K, p-Akt, and I-κBα increased. The results indicate that the ZFCs effectively protected the rats against CI/RI possibly via the TLR4/NF-κB signaling pathway. Additionally, the formulation regulated the transcriptional activity of NF-κB, secretion of downstream inflammatory factors, and the expression of Bcl-2-Bax proteins in the PI3K/Akt pathway. Our findings suggest that ZFCs suppress neuronal apoptosis and inflammatory reaction via the PI3K/Akt and TLR4/NF-κB signaling pathways, respectively. Moreover, activation of the PI3K/Akt pathway may result in the inhibition of proinflammatory cytokine secretion, which may be another mechanism by which ZFCs alleviate CI/RI.

Efficacy and safety of targeted drugs in advanced or metastatic gastric and gastroesophageal junction cancer: A network meta-analysis.

WHAT IS KNOWN AND OBJECTIVE: An increasing number of targeted drugs have been used to treat advanced or metastatic gastric cancer (GC) and gastroesophageal junction cancer (GEJC). However, the optimal treatment efficacy of these drugs is still controversial. The aims of this study are to systematically summarize the efficacy and safety of current targeted drugs for advanced or metastatic GC and GEJC. METHODS: PubMed, EmBase, Cochrane Library, Web of Science and ClinicalTrials were searched for double-blind randomized controlled trials (RCTs) on GC and GEJC up to December 2019. Additionally, we updated the literature search from Jan, 1, 2020 to September 30, 2021. Narrative and quantitative analysis were performed to analyse the efficacy and safety. STATA 15.1 was used to identify publication bias, and the SUCRA (surface under the cumulative ranking) curve was conducted to rank the treatments for each outcome. RESULTS: A total of 27 RCTs with 9295 GC and GEJC patients treated by 19 drugs were included. SUCRA showed that regorafenib was the most likely to improve patients' progression-free survival (96.4%), followed by apatinib (90.7%), nivolumab (82.4%), everolimus (76.5%) and pertuzumab (68.5%). Meanwhile, apatinib (92.4%) was most likely to improve overall survival, followed by nivolumab (87.9%), regorafenib (72.5%), olaparib (67.7%) and lapatinib (63.2%). Additionally, neutropenia, diarrhoea and fatigue were the most common adverse events caused by these drugs, followed by pain, nausea, decreased appetite, anaemia and vomiting. WHAT IS NEW AND CONCLUSION: Regorafenib and nivolumab have higher efficacy and tolerability and are the most advantageous for advanced GC and GEJC. Moreover, apatinib has higher efficacy but lower tolerability. Everolimus and pertuzumab combined with chemotherapy have best secondary higher efficacy for progression-free survival and good tolerability. Lapatinib and olaparib combined with chemotherapy have moderate efficacy for overall survival and good tolerability.

[Research progress on Astragali Radix and prediction of its quality markers (Q-markers)].

Astragali Radix, a medicinal herb for invigorating Qi, has anti-aging, anti-tumor, immunoregulatory, blood sugar-and lipid-lowering, anti-fibrosis, anti-radiation and other pharmacological effects. This article reviewed the studies about the chemical components and pharmacological effects of Astragali Radix. According to the theory of quality markers(Q-markers) of Chinese medicinal materials, we predicted the Q-markers of Astragali Radix from traditional efficacy, chemical component validity, measurability, plant phylogeny, and pharmacokinetis. The results showed that total polysaccharides, flavonoids(e.g., calycosin-7-O-ß-D-glucoside, formononetin, calycosin, quercetin, and ononin), and saponins(e.g., astragalosides Ⅱ, Ⅲ, and Ⅳ) can be taken as the main Q-markers. This review lays a foundation for regulating the quality research and standard establishment of Astragali Radix, and benefits the control and quality supervision of the production process of Astragali Radix and its related products.

[Material basis and molecular mechanism of Angelicae Sinensis Radix in activating blood:based on computer-aided drug design].

Angelicae Sinensis Radix excels in activating blood, but the scientific mechanism has not been systematically analyzed, thus limiting the development of the medicinal. This study employed the computer-aided drug design methods, such as structural similarity-based target reverse prediction, complex network analysis, molecular docking, binding free energy calculation, cluster analysis, and ADMET(absorption, distribution, metabolism, excretion, toxicity) calculation, and enzyme activity assay in vitro, to explore the components and mechanism of Angelicae Sinensis Radix in activating blood. Target reverse prediction and complex network analysis yielded 40 potential anticoagulant targets of the medicinal. Gene Ontology(GO) term enrichment and Kyoto Encyclopedia of Genes and Genomes(KEGG) pathway enrichment analysis indicated that the targets mainly acted on the complement and coagulation cascade signaling pathway to exert the anticoagulant function. Among them, the key enzymes thrombin(THR) and coagulation factor Xa(FXa) in coagulation cascade and thrombosis were the drug targets for thromboembolic diseases. At the same time, molecular docking and cluster analysis showed that the medicinal had high selectivity for FXa. According to binding free energy score, 8 potential active components were selected for enzyme activity assay in vitro. The results demonstrated that 8 components inhibited THR and FXa, and the inhibition was stronger on FXa than on THR. The pharmacophore model of 8 active compounds was constructed, which suggested that the components had the common pharmacophore AAHH. The ADMET calculation result indicated that they had good pharmacokinetic properties and were safe. Based on target reverse prediction, complex network analysis, molecular docking and binding free energy calculation, anticoagulant activity in vitro, spatial binding conformation of molecules and targets, pharmacophore model construction, and ADMET calculation, this study preliminarily clarified the material basis and molecular mechanism of Angelicae Sinensis Radix in activating blood from the perspective of big data, and calculated the pharmacology and toxicology parameters of the active components. Our study, for the first time, revealed that the medicinal had obvious selectivity and pertinence for different coagulation proteins, reflecting the unique effect of different Chinese medicinals and the biological basis. Therefore, this study can provide clues for precision application of Angelicae Sinensis Radix and the development of the blood-activating components with modern technology.

Systematic insight into the active constituents and mechanism of Guiqi Baizhu for the treatment of gastric cancer.

Traditional Chinese medicine treatment of diseases has been recognized, but the material basis and mechanisms are not clear. In this study, target prediction of the antigastric cancer (GC) effect of Guiqi Baizhu (GQBZP) and the analysis of potential key compounds, key targets, and key pathways for the therapeutic effects against GC were carried out based on the method of network analysis and Kyoto Encyclopedia of Genes and Genomes enrichment. There were 33 proteins shared between GQBZP and GC, and 131 compounds of GQBZP had a high correlation with these proteins, indicating that the PI3K-AKT signaling pathway might play a key role in GC. From these studies, we selected human epidermal growth factor receptor 2 (HER2) and programmed cell death 1-ligand 1 (PD-L1) for docking; the results showed that 385 and 189 compounds had high docking scores with HER2 and PD-L1, respectively. Six compounds were selected for microscale thermophoresis (MST). Daidzein/quercetin and isorhamnetin/formononetin had the highest binding affinity for HER2 and PD-L1, with Kd values of 3.7 µmol/L and 490, 667, and 355 nmol/L, respectively. Molecular dynamics simulation studies based on the docking complex structures as the initial conformation yielded the binding free energy between daidzein/quercetin with HER2 and isorhamnetin/formononetin with PD-L1, calculated by molecular mechanics Poisson-Boltzmann surface area, of -26.55, -14.18, -19.41, and -11.86 kcal/mol, respectively, and were consistent with the MST results. In vitro experiments showed that quercetin, daidzein, and isorhamnetin had potential antiproliferative effects in MKN-45 cells. Enzyme activity assays showed that quercetin could inhibit the activity of HER2 with an IC50 of 570.07 nmol/L. Our study provides a systematic investigation to explain the material basis and molecular mechanism of traditional Chinese medicine in treating diseases.