Ethyl cinnamate suppresses tumor growth through anti-angiogenesis by attenuating VEGFR2 signal pathway in colorectal cancer.

ETHNOPHARMACOLOGICAL RELEVANCE: Kaempferia galanga Linn. is an aromatic medicinal herb with extensively applied in India, China, Malaysia and other South Asia countries for thousands of years. It has been mentioned to treat abdominal tumors. Ethyl cinnamate (EC), one of the main chemical constituents of the rhizome of K. galanga, exhibited nematocidal, sedative and vasorelaxant activities. However, its anti-angiogenic activity, and anti-tumor effect have not been investigated. AIM OF THE STUDY: To investigate the anti-angiogenic mechanism of EC and its anti-tumor effect by suppressing angiogenesis. MATERIALS AND METHODS: The in vitro anti-angiogenic effect was evaluated using HUVECs model induced by VEGF and zebrafish model in vivo. The influence of the EC on phosphorylation of VEGFR2 and its downstream signaling pathways were evaluated by western blotting assay. Molecule docking technology was conducted to explore the interaction between EC and VEGFR2. SPR assay was used for detecting the binding affinity between EC and VEGFR2. To further investigate the molecular mechanism of EC on anti-angiogenesis, VEGFR2 knockdown in HUVECs and examined the influence of the EC. Anti-tumor activity of EC was evaluated using colony formation assay and apoptosis assay. The inhibitory effect of EC on tumor growth was explored using HT29 colon cancer xenograft model. RESULTS: EC obviously inhibited proliferation, migration, invasion and tube formation of VEGF-induced HUVECs. EC also induced apoptosis of HUVECs. Moreover, it inhibited the development of vessel formation in zebrafish. Further investigations demonstrated that EC could suppress the phosphorylation of VEGFR2, and its downstream signaling pathways were altered in VEGF-induced HUVECs. EC formed a hydrogen bond to bind with the ATP binding site of the VEGFR2, and EC-VEGFR2 interaction was shown in SPR assay. The suppressive effect of EC on angiogenesis was abrogated after VEGFR2 knockdown in HUVECs. EC inhibited the colon cancer cells colony formation and induced apoptosis. In addition, EC suppressed tumor growth in colon cancer xenograft model, and no detectable hepatotoxicity and nephrotoxicity. In addition, it inhibited the phosphorylation of VEGFR2, and its downstream signal pathways in tumor. CONCLUSIONS: EC could inhibit tumor growth in colon cancer by suppressing angiogenesis via VEGFR2 signaling pathway, and suggested EC as a promising candidate for colon cancer treatment.

Effective substances and molecular mechanisms guided by network pharmacology: An example study of Scrophulariae Radix treatment of hyperthyroidism and thyroid hormone-induced liver and kidney injuries.

ETHNOPHARMACOLOGICAL RELEVANCE: Scrophulariae Radix (Xuanshen [XS]) has been used for several years to treat hyperthyroidism. However, its effective substances and pharmacological mechanisms in the treatment of hyperthyroidism and thyroid hormone-induced liver and kidney injuries have not yet been elucidated. AIM OF THE STUDY: This study aimed to explore the pharmacological material basis and potential mechanism of XS therapy for hyperthyroidism and thyroid hormone-induced liver and kidney injuries based on network pharmacology prediction and experimental validation. MATERIALS AND METHODS: Based on 31 in vivo XS compounds identified using ultra-performance liquid chromatography tandem quadruple exactive orbitrap high-resolution accurate-mass spectrometry (UPLC-QE-HRMS), a network pharmacology approach was used for mechanism prediction. Systematic networks were constructed to identify the potential molecular targets, biological processes (BP), and signaling pathways. A component-target-pathway network was established. Mice were administered levothyroxine sodium through gavage for 30 d and then treated with different doses of XS extract with or without propylthiouracil (PTU) for 30 d. Blood, liver, and kidney samples were analyzed using an enzyme-linked immunosorbent assay (ELISA) and western blotting. RESULTS: A total of 31 prototypes, 60 Phase I metabolites, and 23 Phase II metabolites were tentatively identified in the plasma of rats following the oral administration of XS extract. Ninety-six potential common targets between the 31 in vivo compounds and the diseases were identified. Kyoto Encyclopedia of Genes and Genomes (KEGG) analysis revealed that Bcl-2, BAD, JNK, p38, and ERK1/2 were the top targets. XS extract with or without PTU had the following effects: inhibition of T3/T4/fT3/fT4 caused by levothyroxine; increase of TSH levels in serum; restoration of thyroid structure; improvement of liver and kidney structure and function by elevating the activities of anti-oxidant enzymes catalase (CAT),superoxide dismutase (SOD), and glutathione peroxidase (GSH-Px); activation anti-apoptotic proteins Bcl-2; inhibition the apoptotic protein p-BAD; downregulation inflammation-related proteins p-ERK1/2, p-JNK, and p-p38; and inhibition of the aggregation of pro-inflammatory cytokines TNF-α, IL-1ß, and IL-6, as well as immune cells in the liver. CONCLUSION: XS can be used to treat hyperthyroidism and liver and kidney injuries caused by thyroid hormones through its anti-oxidant, anti-inflammatory, and anti-apoptotic properties. In addition, serum pharmacochemical analysis revealed that five active compounds, namely 4-methylcatechol, sugiol, eugenol, acetovanillone, and oleic acid, have diverse metabolic pathways in vivo and exhibit potential as effective therapeutic agents.

Discovery of sinomenine/8-Bis(benzylthio)octanoic acid hybrids as potential anti-leukemia drug candidate via mitochondrial pathway.

Traditional Chinese medicine Qingfengteng primarily acquired from the dried canes of Sinomenium acutum (Thunb.) Rehd. et Wils. var. cinereum Rehd. et Wils. and S. acutum (Thunb.) Rehd. et Wils. For the therapeutic treatment of rheumatism, acute arthritis, and rheumatoid arthritis based on Qingfengteng, sinomenine hydrochloride was recently made the principal active ingredient in various dosage forms. 8-Bis(benzylthio)octanoic acid (CPI-613) was an orphan medicine that the FDA and EMA approved orphan for the treatment of certain resistant malignancies. Its unique mode of action and minimal toxicity toward normal tissues made for an apt pharmacophore. In order to expand the field of sinomenine anticancer structures, sinomenine/8-Bis(benzylthio)octanoic acid derivatives were designed and synthesized. Among them, target hybrids e4 stood out for having notable cytotoxic effects against cancer cell lines, especially for K562 cells, with IC50 values of 2.45 µM and high safety. In-depth investigations demonstrated that e4 caused apoptosis by stopping the cell cycle at G1 phase, and doing so by altering the morphology of the nucleus and causing membrane potential of the in mitochondria to collapse. These results indicated e4 exerted an antiproliferative effect through apoptosis induction via mitochondrial pathway.

Genetic diversity, plant growth promotion potential, and antimicrobial activity of culturable endophytic actinobacteria isolated from Aconitum carmichaelii Debeaux.

AIM: This study evaluated the phylogenetic diversity, plant growth promotion capacity, antifungal activity, and biocontrol potential of culturable actinobacterial endophytes isolated from the medicinal plant Aconitum carmichaelii Debeaux. METHODS AND RESULTS: Isolation of actinobacteria from healthy A. carmichaelii plants was carried out on six different media. Full-length 16S rRNA gene was amplified by PCR from the genomic DNA of each strain. Indole-3-acetic acid and siderophore production were quantitatively assessed by the Salkowski and Chrome Azurol S methods, respectively. Rice seeds germination and seedling growth were employed to evaluate plant growth promotion capacities of candidate strains. Dual-culture assay and pot experiments were performed to investigate the antifungal and biocontrol potential of isolates. We obtained 129 actinobacterial isolates from A. carmichaelii, and they belonged to 49 species in 7 genera. These strains exhibited diverse plant growth promotion ability, among which one strain significantly enhanced rice seeds germination, while 31 strains significantly facilitated rice seedling growth. SWUST-123 showed strong antifungal activity against four pathogens in vitro and was most compatible with Qingchuan cultivar. SWUST-123 reduced around 40% of southern blight disease occurrence compared to blank control treatment. . CONCLUSION: Aconitum carmichaelii harbored genetically diverse actinobacterial endophytes exhibiting diverse plant growth promotion and antifungal potential, some of which can be served as good candidates for biofertilizers and biocontrol agents.

Fuzhuan brick tea ameliorates hepatic steatosis and steatohepatitis through gut microbiota-derived aryl hydrocarbon receptor ligands in high-fat diet-induced obese mice.

High-fat diet (HFD) induced obesity and its associated conditions, such as hepatic steatosis and steatohepatitis, are major health concerns worldwide. Previous studies have reported the excellent efficiency of Fuzhuan brick tea (FBT) in attenuating HFD-induced obesity and metabolic disorders. In this study, we investigated the effects of FBT on hepatic steatosis and simple steatohepatitis in HFD-induced obese mice, as well as the metabolic function of the gut microbiome using metagenomics and metabolomics. The results showed that FBT ameliorated dyslipidemia, hepatic steatosis and steatohepatitis in HFD-induced obese mice by normalizing the gut microbiota structure and tryptophan metabolism. FBT increased the cecal abundance of aryl hydrocarbon receptor (AhR)-ligand producing bacteria such as Lactobacillus_reuteri and Lactobacillus_johnsonii, at the expense of AhR-ligand consuming bacteria, such as Faecalibaculum_rodentium and Escherichia_coli, and elevated the cecal contents of AhR-ligands such as IAA, IPA, and KYNA. Furthermore, FBT regulated the expressions of AhR and its targeted lipometabolic genes such as Pemt, Fasn, and SREBP-1c, as well as other inflammatory genes including TNF-α, IL-6, and IL-1ß in the liver of mice. Overall, these findings highlight the beneficial effects of FBT on obesity-related hepatic steatosis and steatohepatitis via microbiota-derived AhR signaling.

Culturable bacterial endophytes of Aconitum carmichaelii Debx. were diverse in phylogeny, plant growth promotion, and antifungal potential.

Medicinal plants harbor tremendously diverse bacterial endophytes that maintain plant growth and health. In the present study, a total of 124 culturable bacterial endophytes were isolated from healthy Aconitum carmichaelii Debx. plants. These strains were clustered into 10 genera based on full-length 16S rDNA sequences, among which Bacillus and Pseudomonas were the dominant genera. In addition, A. carmichaelii may capture 10 potential new bacterial species based on multi-locus sequence analysis of three housekeeping genes (gyrA, rpoB, and atpD). The majority of these bacterial endophytes exhibited plant growth-promoting ability through diverse actions including the production of either indole acetic acid and siderophore or hydrolytic enzymes (glucanase, cellulose, and protease) and solubilization of phosphate or potassium. A total of 20 strains inhibited hyphal growth of fungal pathogens Sclerotium rolfsii and Fusarium oxysporum in vitro on root slices of A. carmichaelii by the dual-culture method, among which Pseudomonas sp. SWUSTb-19 showed the best antagonistic activity. Field experiment confirmed that Pseudomonas sp. SWUSTb-19 significantly reduced the occurrence of southern blight and promoted plant biomass compared with non-inoculation treatment. The possible mode of actions for Pseudomonas sp. SWUSTb-19 to antagonize against S. rolfsii involved the production of glucanase, siderophore, lipopeptides, and antimicrobial volatile compounds. Altogether, this study revealed that A. carmichaelii harbored diverse plant growth-promoting bacterial endophytes, and Pseudomonas sp. SWUSTb-19 could be served as a potential biocontrol agent against southern blight.

To study the protective effect of Huangqi Baihe Granules on Radiation brain injury based on network pharmacology and experiment.

ETHNOPHARMACOLOGICAL RELEVANCE: Huangqi baihe Granules (HQBHG), which is a key Chinese medical prescription, has a remarkable efficacy in oxidative stress and inflammation. Nevertheless, the therapeutic effect on Radiation brain injury (RBI) has rarely been studied. AIM OF THE STUDY: The study aimed to verify the effect of HQBHG against RBI and explore its potential mechanism. METHODS: The potential targets and mechanisms of HQBHG against RBI were predicted by network pharmacology and verified by established rat model of RBI Firstly, the therapeutic effect of HQBHG in RBI was confirmed by water maze test, HE staining and Enzyme-linked immunosorbent assay (ELISA). Secondly, the potential critical anti-RBI pathway of HQBHG was further explored by water maze, HE staining, immunofluorescence assays, ELISA and western blot. RESULTS: A total of 43 HQBHG anti-RBI targets were obtained. Gene Ontology (Go) and Kyoto Encyclopedia of Genes and Genomes (KEGG) functional annotations showed that the treatment of HQBHG in RBI might be mainly related to oxidative stress, inflammation and PI3K/AKT pathway. Experimental studies have indicated that HQBHG can improve spatial learning and memory ability, alleviate pathological damage of brain tissue in RBI of rats. HQBHG also can down-regulate the levels of IL-1ß, TNF-α, ROS and MDA, meanwhile, GSH was significantly up-regulated. In addition, the HQBHG can increase the protein expression phosphorylations PI3K (p-PI3K), phosphorylations AKT(p-AKT) and Nrf2 in the brain tissue of RBI. CONCLUSION: HQBHG may alleviated RBI by regulated oxidative stress and inflammatory response through PI3K/AKT/Nrf2 pathway.

Microbial nitrogen and phosphorus co-limitation across permafrost region.

The status of plant and microbial nutrient limitation have profound impacts on ecosystem carbon cycle in permafrost areas, which store large amounts of carbon and experience pronounced climatic warming. Despite the long-term standing paradigm assumes that cold ecosystems primarily have nitrogen deficiency, large-scale empirical tests of microbial nutrient limitation are lacking. Here we assessed the potential microbial nutrient limitation across the Tibetan alpine permafrost region, using the combination of enzymatic and elemental stoichiometry, genes abundance and fertilization method. In contrast with the traditional view, the four independent approaches congruently detected widespread microbial nitrogen and phosphorus co-limitation in both the surface soil and deep permafrost deposits, with stronger limitation in the topsoil. Further analysis revealed that soil resources stoichiometry and microbial community composition were the two best predictors of the magnitude of microbial nutrient limitation. High ratio of available soil carbon to nutrient and low fungal/bacterial ratio corresponded to strong microbial nutrient limitation. These findings suggest that warming-induced enhancement in soil nutrient availability could stimulate microbial activity, and probably amplify soil carbon losses from permafrost areas.

Total steroidal saponins from black nightshade (Solanum nigrum L.) overcome tumor multidrug resistance by inducing autophagy-mediated cell death in vivo and in vitro.

Multiple drug resistance (MDR) often occurs after prolonged chemotherapy, leading to refractory tumors and cancer recurrence. In this study, we demonstrated that the total steroidal saponins from Solanum nigrum L. (SN) had broad-spectrum cytotoxic activity against various human leukemia cancer cell lines, especially in adriamycin (ADR)-sensitive and resistant K562 cell lines. Moreover, SN could effectively inhibit the expression of ABC transporter in K562/ADR cells in vivo and in vitro. In vivo, by establishing K562/ADR xenograft tumor model, we demonstrated that SN might overcome drug resistance and inhibit the proliferation of tumors by regulating autophagy. In vitro, the increased LC3 puncta, the expression of LC3-II and Beclin-1, and the decreased expression of p62/SQSTM1 in SN-treated K562/ADR and K562 cells demonstrated autophagy induced by SN. Moreover, using the autophagy inhibitors or transfecting the ATG5 shRNA, we confirmed that autophagy induced by SN was a key factor in overcoming MDR thereby promoting cell death in K562/ADR cells. More importantly, SN-induced autophagy through the mTOR signaling pathway to overcome drug resistance and ultimately induced autophagy-mediated cell death in K562/ADR cells. Taken together, our findings suggest that SN has the potential to treat multidrug-resistant leukemia.

Mitigation of Paeoniae Radix Alba extracts on H2O2-induced oxidative damage in HepG2 cells and hyperglycemia in zebrafish, and identification of phytochemical constituents.

Paeoniae Radix Alba (PRA), as a Traditional Chinese Medicine, is widely used in Chinese cuisine due to high health-benefits and nutrition, but the effect of different polarity of solvents on the extraction of antioxidant and hypoglycemic constituents, as well as the major active compounds remain unclear. In this research, 40, 70, and 95% ethanol were firstly applied to extract the polyphenols from PRA, the extraction yields, total phenolics, and total flavonoids content, free radical scavenging ability, α-glucosidase inhibition ability, and anti-glycation ability of extracts were evaluated spectroscopically. The oxidative damage protection, hypoglycemic activity, and alleviation on peripheral nerve damage were evaluated by H2O2-induced HepG2 cells and hyperglycemic zebrafish models. UPLC-QTOF-MS/MS was used to identify the major chemical constituents. The results showed that 40, 70, and 95% ethanol exhibited insignificant difference on the extraction of phenolics and flavonoids from PRA. All extracts showed promising DPPH⋅ and ABTS⋅+ scavenging ability, α-glucosidase inhibition and anti-glycation ability. In addition, PRA extracts could restore the survival rate of HepG2 cells induced by H2O2, and alleviate the oxidative stress by reducing the content of MDA and increasing the levels of SOD, CAT, and GSH-Px. The 70% ethanol extract could also mitigate the blood glucose level and peripheral motor nerve damage of hyperglycemic zebrafish. Thirty-five compounds were identified from 70% ethanol extract, gallotannins, gallic acid and its derivatives, and paeoniflorin and its derivatives were the dominant bioactive compounds. Above results could provide important information for the value-added application of PRA in functional food and medicinal industry.

An anoxic-aerobic system combined with integrated vertical-flow constructed wetland to highly enhance simultaneous organics and nutrients removal in rural China.

The biggest problem in the treatment of rural domestic sewage is that the existing treatment projects require the big investment and the high operation and maintenance costs. To overcome this problem, cost-effective, low-consuming, resource-recovering and easy-maintenance technologies are urgently demanded. To this end, a novel anoxic-aerobic system combined with integrated vertical-flow constructed wetland (IVFCW) with source separation was proposed for treating rural sewage in this study. The anoxic-aerobic system contained the anoxic filter (ANF), two-stage waterwheel driving rotating biological contactors (ts-WDRBCs). Key parameters of ts-WDRBCs were identified to be 0.6 m drop height and 4 r/min rotational speed found on oxygenated clean water experiments. Then, the optimal operating parameters were determined to be 200% reflux ratio and 3 h hydraulic retention time of ts-WDRBCs. During the 80-day operation, 91.58 ± 1.86% COD, 96.17 ± 0.92% NH4+-N, 82.71 ± 3.92% TN and 92.28 ± 2.78% TP were removed under the optimal operating parameters. Compared with other treatment technologies, this combined bio-ecological system could achieve the higher simultaneous organics and nutrients removal. The effluent NO3--N/NH4+-N concentration ratio of ts-WDRBCs was 2.15 ± 0.54, which was proved to be beneficial for plants growth. The microbial communities coexisted in each section ensured the desired removal performance of combined bio-ecological system. Summarily, high performance together with low investment costs and cheap operation costs are characteristics that make this system a promising and competitive alternative for rural sewage treatment.

Antioxidant and ammonia-sensitive films based on starch, κ-carrageenan and Oxalis triangularis extract as visual indicator of beef meat spoilage.

In this study, we first investigated the rheological property of sweet potato starch (SPS), κ-carrageenan (KC) and Oxalis triangularis extract (OTE) blends and found that the blends exhibited high apparent viscosity with an apparent shear thinning behavior. And then films based on SPS, KC and OTE were developed and their structural and functional properties were studied. The physico-chemical test results showed that OTE exhibited different colors in solutions with different pH values and the incorporation with OTE and KC could significantly increase the thickness, water vapor permeability, light barrier ability, tensile strength and elongation at break as well as the pH- and ammonia-sensitive properties of the SPS film. The structural property test results showed that some intermolecular interactions between OTE and SPS/KC occurred in SPS-KC-OTE films. Finally, the functional properties of SPS-KC-OTE films were examined and SPS-KC-OTE films showed significant DPPH radical scavenging activity as well as a visible color change in response to changes in beef meat freshness. Our results suggested that the SPS-KC-OTE films could be used as an active and intelligent food packaging material in food industry.

Potential of natural products in the treatment of irritable bowel syndrome.

BACKGROUND: Irritable bowel syndrome (IBS) is a kind of functional bowel disease that is characterized by bellyache, abdominal distension, and diarrhea. Although not life-threatening, IBS has a long course and recurrent attacks and seriously affects the life quality of patients. Current drugs for treating IBS possess remarkable limitations, such as limited efficacy and severe adverse reactions. Therefore, developing novel medications to treat IBS is quite essential, and natural products may be a substantial source. PURPOSE: This is the first systematic review elaborating the recent advancement of natural products as potential drugs for the therapy of IBS. METHODS: A comprehensive retrieval of studies was carried out in scientific databases including PubMed, Web of Science, Elsevier, and CNKI. By using ("irritable bowel syndrome" OR "IBS") AND ("natural product" OR "natural compound" OR "phytochemical") as keywords, the eligible studies were screened, and the relevant information about therapeutic action and mechanism of natural products treating IBS was extracted. RESULTS: Natural products against IBS consisted of four categories, namely, terpenoids, flavonoids, alkaloids, and phenols. Furthermore, the underlying mechanisms for natural products treating IBS were tightly associated with increased TJs and mucus protein expression, regulation of the brain-gut axis and gut microbiota structure, and inhibition of inflammatory response and intestinal mucosal damage. CONCLUSION: Natural products could be extremely prospective candidate drugs used to treat IBS, and further preclinical and clinical researches are needed to guarantee their efficacy and safety.

Effectiveness of red yeast rice on carotid atherosclerosis: A systematic review and meta-analysis.

While several studies have demonstrated the preventive and therapeutic effects of red yeast rice (RYR), a traditional Chinese medicine, on carotid atherosclerosis through the reduction of low-density lipoprotein cholesterol (LDL-C) level and other risk factors, the evidence remains inconsistent. This study aimed to further evaluate the effects of RYR in carotid atherosclerosis. Several databases were searched for original trials of RYR for the treatment of carotid atherosclerosis that reported plaque indicators. Carotid plaque area (AREA), carotid plaque score (SCORE), and intima-media thickness (IMT) were set as the primary outcomes, while lipid profile and safety indicators were set as the secondary outcomes. Meta-analyses were performed on the randomized controlled trials (RCTs) using Comprehensive Meta-analysis software. Heterogeneity was evaluated using the I 2 index and Q statistic. Subgroup, sensitivity, and dose-effect analyses were conducted. Twenty RCTs with 2217 patients were included. Compared to the control group, AREA (SMD = -0.855, 95%CI: -1.259 to -0.451, p < 0.001), IMT (SMD = -0.588, 95%CI: -0.792 to -0.384, p < 0.001), SCORE (SMD = -0.708, 95%CI: -1.135 to -0.282, p = 0.001), LDL-C (SMD = -0.938, 95%CI: -1.375 to -0.502, p < 0.001), triglyceride (SMD = -0.766, 95%CI: -0.980 to -0.551, p < 0.001), and total cholesterol (SMD = -0.858, 95%CI: -1.254 to -0.462, p < 0.001) were significantly decreased and HDL-C (SMD = 0.389, 95%CI: 0.044-0.733, p = 0.027) was significantly increased following RYR therapy. The indicators for safety were not significant and did not differ between the two groups (p > 0.050). Heterogeneities mainly existed for the treatment time or control group setting. Most results showed no changes in the sensitivity analysis. Dose-effect relationships were observed for all indicators except for TC and HDL-C. We concluded that RYR therapy showed considerable efficacy and an acceptable safety profile for the treatment of carotid atherosclerosis in the Chinese population.

Recent advances in erythrocyte membrane-camouflaged nanoparticles for the delivery of anti-cancer therapeutics.

INTRODUCTION: Red blood cell (or erythrocyte) membrane-camouflaged nanoparticles (RBC-NPs) not only have a superior circulation life and do not induce accelerated blood clearance but also possess special functions, which offers great potential in cancer therapy. AREAS COVERED: This review focuses on the recent advances of RBC-NPs for delivering various agents to treat cancers in light of their vital role in improving drug delivery. Meanwhile, the construction and in vivo behavior of RBC-NPs are discussed to provide an in-depth understanding of the basis of RBC-NPs for improved cancer drug delivery. EXPERT OPINION: Although RBC-NPs are quite prospective in delivering anti-cancer therapeutics, they are still in their infancy stage and many challenges need to be overcome for successful translation into the clinic. The preparation and modification of RBC membranes, the optimization of coating methods, the scale-up production and the quality control of RBC-NPs, and the drug loading and release should be carefully considered in the clinical translation of RBC-NPs for cancer therapy.

Three-dimensional mapping of carbon, nitrogen, and phosphorus in soil microbial biomass and their stoichiometry at the global scale.

Soil microbial biomass and microbial stoichiometric ratios are important for understanding carbon and nutrient cycling in terrestrial ecosystems. Here, we compiled data from 12245 observations of soil microbial biomass from 1626 published studies to map global patterns of microbial biomass carbon (MBC), microbial biomass nitrogen (MBN), microbial biomass phosphorus (MBP), and their stoichiometry using a random forest model. Concentrations of MBC, MBN, and MBP were most closely linked to soil organic carbon, while climatic factors were most important for stoichiometry in microbial biomass ratios. Modeled seasonal MBC concentrations peaked in summer in tundra and in boreal forests, but in autumn in subtropical and in tropical biomes. The global mean MBC/MBN, MBC/MBP, and MBN/MBP ratios were estimated to be 10, 48, and 6.7, respectively, at 0-30 cm soil depth. The highest concentrations, stocks, and microbial C/N/P ratios were found at high latitudes in tundra and boreal forests, probably due to the higher soil organic matter content, greater fungal abundance, and lower nutrient availability in colder than in warmer biomes. At 30-100 cm soil depth, concentrations of MBC, MBN, and MBP were highest in temperate forests. The MBC/MBP ratio showed greater flexibility at the global scale than did the MBC/MBN ratio, possibly reflecting physiological adaptations and microbial community shifts with latitude. The results of this study are important for understanding C, N, and P cycling at the global scale, as well as for developing soil C-cycling models including soil microbial C, N, and P as important parameters.

Effects of sulfur-fumigated ginseng on the global quality of Si-Jun-Zi decoction, a traditional ginseng-containing multi-herb prescription, evaluated by metabolomics and glycomics strategies.

Si-Jun-Zi decoction (SJZD) with ginseng as the principal medicinal herb is a traditional Chinese Medicine multi-herb prescription that commonly employed to treat colorectal cancer etc. Previous studies showed that nearly half of the commercial ginseng was sulfur-fumigated, one of the postharvest processing methods that commonly causes sulfur-dioxide (SO2) residue and chemical composition transformation in medical herbs. In this study, the effect of sulfur-fumigated ginseng on global quality of SJZD was evaluated by UPLC-QTOF-MS/MS based metabolomics and multiple chromatographic techniques based glycomics strategies. For non-saccharides components, sulfur-fumigated ginseng led to the emergence of sulfur-containing derivatives and alteration of saponins and flavonoids in SJZD. For saccharide components, sulfur-fumigated ginseng decreased the total contents and molecular weights of polysaccharides, changed the monosaccharide composition of polysaccharides, and increased the contents of oligosaccharides and free monosaccharides of SJZD. The alterations of SJZD were aggravated with the sulfur-fumigated content of ginseng. Those phenomena might be attributed to 1) sulfur-fumigation caused the generation of sulfur-containing derivatives in ginseng, which further transferred to SJZD, and 2) sulfur-fumigation caused the residue of SO2 in ginseng, which reduced the pH value and further changed the dissolution of saponins and flavonoids and accelerated the degradation of the polysaccharides to oligosaccharides and/or monosaccharides in SJZD. Furthermore, although storage reduced the SO2 residue in sulfur-fumigated ginseng, it couldn't recover the alterations of chemical profiles in SJZD. In conclusion, sulfur-fumigated ginseng altered the global quality of SJZD, which promoted that extra attention must be paid during the application of herbal formulas that containing sulfur-fumigated herbs.

Deciphering the Active Compounds and Mechanisms of HSBDF for Treating ALI via Integrating Chemical Bioinformatics Analysis.

The Huashi Baidu Formula (HSBDF), a key Chinese medical drug, has a remarkable clinical efficacy in treating acute lung injury (ALI), and it has been officially approved by the National Medical Products Administration of China for drug clinical trials. Nevertheless, the regulated mechanisms of HSBDF and its active compounds in plasma against ALI were rarely studied. Based on these considerations, the key anti-inflammatory compounds of HSBDF were screened by molecular docking and binding free energy. The key compounds were further identified in plasma by LC/MS. Network pharmacology was employed to identify the potential regulatory mechanism of the key compounds in plasma. Next, the network pharmacological prediction was validated by a series of experimental assays, including CCK-8, EdU staining, test of TNF-α, IL-6, MDA, and T-SOD, and flow cytometry, to identify active compounds. Molecular dynamic simulation and binding interaction patterns were used to evaluate the stability and affinity between active compounds and target. Finally, the active compounds were subjected to predict pharmacokinetic properties. Molecular docking revealed that HSBDF had potential effects of inhibiting inflammation by acting on IL-6R and TNF-α. Piceatannol, emodin, aloe-emodin, rhein, physcion, luteolin, and quercetin were key compounds that may ameliorate ALI, and among which, there were five compounds (emodin, aloe-emodin, rhein, luteolin, and quercetin) in plasma. Network pharmacology results suggested that five key compounds in plasma likely inhibited ALI by regulating inflammation and oxidative damage. Test performed in vitro suggested that HSBDF (0.03125 mg/ml), quercetin (1.5625 µM), emodin (3.125 µM), and rhein (1.5625 µM) have anti-inflammatory function against oxidative damage and decrease apoptosis in an inflammatory environment by LPS-stimulation. In addition, active compounds (quercetin, emodin, and rhein) had good development prospects, fine affinity, and stable conformations with the target protein. In summary, this study suggested that HSBDF and its key active components in plasma (quercetin, emodin, and rhein) can decrease levels of pro-inflammatory factors (IL-6 and TNF-α), decrease expression of MDA, increase expression of T-SOD, and decrease cell apoptosis in an inflammatory environment. These data suggest that HSBDF has significant effect on anti-inflammation and anti-oxidative stress and also can decrease cell apoptosis in treating ALI. These findings provided an important strategy for developing new agents and facilitated clinical use of HSBDF against ALI.

Integrated estrogenic effects and semi-volatile organic pollutants profile in secondary and tertiary wastewater treatment effluents in North China.

Endocrine-disrupting effects on aquatic organisms caused by wastewater discharging have raised extensive concerns. However, the efficiency of various wastewater treatment processes to remove estrogenic activity in effluents and the association with organic micropollutants was not well known. We evaluated the estrogenic activity using a well-characterized in vivo bioassay featuring the Chinese rare minnows (Gobiocypris rarus) and analyzed 886 semi-volatile organic compounds (SVOCs) in effluents from four secondary wastewater treatment plants (SWTP A-D) and a tertiary wastewater treatment plant (TTP E) that utilized various common treatment processes in northern China. The final effluents from SWTPs and TTP E all exhibited estrogenic effects, increasing male fish plasma vitellogenin (VTG) contents and estradiol/testosterone (E2/T) ratios. Key regulating genes in the male fish liver including vtg1, vtg3, era, erß, and cyp19a were upregulated. TTP E demonstrated high performance in reducing estrogenic activity in the effluents, with a reduction of 64% in integrative biomarkers of estrogenic response (IBR). UV disinfection at SWTPs removed IBR by 14%- 33%, while ozone disinfection at TTP E did not reduce IBR. Several SVOCs including alkanes, chlorobenzenes, and phthalates, detected at ng/L to µg/L level, significantly correlated with effluent estrogenic activity. Our findings suggest the necessity and the potential means to improve the efficiency of current wastewater treatment approaches to achieve better protection for aquatic organisms against the joint effects of mixtures of various categories of micropollutants in effluents.