Discovery of Novel Diphenyl Acrylonitrile Derivatives That Promote Adult Rats' Hippocampal Neurogenesis.

We previously discovered WS-6 as a new antidepressant in correlation to its function of stimulating neurogenesis. Herein, several different scaffolds (stilbene, 1,3-diphenyl 1-propene, 1,3-diphenyl 2-propene, 1,2-diphenyl acrylo-1-nitrile, 1,2-diphenyl acrylo-2-nitrile, 1,3-diphenyl trimethylamine), further varied through substitutions of twelve amide substituents plus the addition of a methylene unit and an inverted amide, were examined to elucidate the SARs for promoting adult rat neurogenesis. Most of the compounds could stimulate proliferation of progenitors, but just a few chemicals possessing a specific structural profile, exemplified by diphenyl acrylonitrile 29b, 32a, and 32b, showed better activity than the clinical drug NSI-189 in promoting newborn cells differentiation into mature neurons. The most potent diphenyl acrylonitrile 32b had an excellent brain AUC to plasma AUC ratio (B/P = 1.6), suggesting its potential for further development as a new lead.

In Situ Insight into the Availability and Desorption Kinetics of Per- and Polyfluoroalkyl Substances in Soils with Diffusive Gradients in Thin Films.

The physicochemical exchange dynamics between the solid and solution phases of per- and polyfluoroalkyl substances (PFAS) in soils needs to be better understood. This study employed an in situ tool, diffusive gradients in thin films (DGT), to understand the distribution and exchange kinetics of five typical PFAS in four soils. Results show a nonlinear relationship between the PFAS masses in DGT and time, implying that PFAS were partially supplied by the solid phase in all of the soils. A dynamic model DGT-induced fluxes in soils/sediments (DIFS) was used to interpret the results and derive the distribution coefficients for the labile fraction (Kdl), response time (tc), and adsorption/desorption rates (k1 and k-1). The larger labile pool size (indicated by Kdl) for the longer chain PFAS implies their higher potential availability. The shorter chain PFAS tend to have a larger tc and relatively smaller k-1, implying that the release of these PFAS in soils might be kinetically limited but not for more hydrophobic compounds, such as perfluorooctanesulfonic acid (PFOS), although soil properties might play an important role. Kdl ultimately controls the PFAS availability in soils, while the PFAS release from soils might be kinetically constrained (which may also hold for biota uptake), particularly for more hydrophilic PFAS.

Effect of nimodipine combined with atorvastatin calcium on microinflammation and oxidative stress levels in patients with cerebral vasospasm after subarachnoid hemorrhage.

Objective: To evaluate the effect of nimodipine combined with atorvastatin calcium on the micro inflammation and oxidative stress levels in patients with cerebral vasospasm (CVS) after subarachnoid hemorrhage (SAH) and its clinical implications. Methods: A total of 80 patients with CVS caused by SAH who had been admitted to Baoding First Central Hospital from August 2021 to August 2022 were selected and randomly divided into two groups. The control group underwent conventional symptomatic treatment, while the experimental group was administered nimodipine combined with atorvastatin calcium on the basis of conventional treatment. The changes in the micro inflammatory cytokines and oxidative stress factors in the two groups were compared, as well as the differences in clinical efficacy and incidence of adverse drug reactions. Result: After treatment, the levels of inflammatory cytokines in the experimental group decreased more significantly than those in the control group (p=0.00). After treatment, the serum levels of oxidative stress factors were obviously higher in the experimental group than in the control group (p=0.00). After treatment, the total efficacy was 77.5% in the experimental group and 55% in the control group, and the difference was statistically significant (p=0.04). Conclusions: Nimodipine combined with atorvastatin calcium could significantly improve the clinical symptoms in patients with CVS after SAH, which would be beneficial, safe, and effective for the patient's recovery.

Study on the Anti-demyelination Mechanism of Bu-Shen-Yi-Sui Capsule in the Central Nervous System Based on Network Pharmacology and Experimental Verification.

Methods: The potential active ingredients and corresponding potential targets of BSYS Capsule were obtained from the TCMSP, BATMAN-TCM, Swiss Target Prediction platform, and literature research. Disease targets of CNSD were explored through the GeneCards and the DisGeNET databases. The matching targets of BSYS in CNSD were identified from a Venn diagram. The protein-protein interaction (PPI) network was constructed using bioinformatics methods. Gene Ontology (GO) function and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment analyses were performed to predict the mechanisms of BSYS. Furthermore, the neuroprotective effects of BSYS were evaluated using a cell model of hydrogen peroxide- (H2O2-) induced cell death in OLN-93 cells. Results: A total of 59 potential bioactive components of BSYS Capsule and 227 intersection targets were obtained. Topological analysis showed that AKT had the highest connectivity degrees in the PPI network. Enrichment analysis revealed that the targets of BSYS in the treatment of CNSD were the PI3K-Akt and MAPK signaling pathway, among other pathways. GO analysis results showed that the targets were associated with various biological processes, including apoptosis, reactive oxygen species metabolic process, and response to oxidative stress, among others. The experimental results demonstrated that BSYS drug-containing serum alleviated the H2O2-induced increase in LDH, MDA, and ROS levels and reversed the decrease in SOD and mitochondrial membrane potential induced by H2O2. BSYS treatment also decreased the number of TUNEL (+) cells, downregulated Bcl-2 expression, and upregulated Bax and c-caspase-3 expression by promoting Akt phosphorylation. Conclusion: BSYS Capsule alleviated H2O2-induced OLN-93 cell injury by increasing Akt phosphorylation to suppress oxidative stress and cell apoptosis. Therefore, BSYS can be potentially used for CNSD treatment. However, the results of this study are only derived from in vitro experiments, lacking the validation of in vivo animal models, which is a limitation of our study. We will further verify the underlying mechanisms of BSYS in animal experiments in the future.

Functional Analysis of the GPI Transamidase Complex by Screening for Amino Acid Mutations in Each Subunit.

Glycosylphosphatidylinositol (GPI) anchor modification is a posttranslational modification of proteins that has been conserved in eukaryotes. The biosynthesis and transfer of GPI to proteins are carried out in the endoplasmic reticulum. Attachment of GPI to proteins is mediated by the GPI-transamidase (GPI-TA) complex, which recognizes and cleaves the C-terminal GPI attachment signal of precursor proteins. Then, GPI is transferred to the newly exposed C-terminus of the proteins. GPI-TA consists of five subunits: PIGK, GPAA1, PIGT, PIGS, and PIGU, and the absence of any subunit leads to the loss of activity. Here, we analyzed functionally important residues of the five subunits of GPI-TA by comparing conserved sequences among homologous proteins. In addition, we optimized the purification method for analyzing the structure of GPI-TA. Using purified GPI-TA, preliminary single particle images were obtained. Our results provide guidance for the structural and functional analysis of GPI-TA.

Naturally Occurring Flavonoids and Isoflavonoids and Their Microbial Transformation: A Review.

Flavonoids and isoflavonoids are polyphenolic secondary metabolites usually produced by plants adapting to changing ecological environments over a long period of time. Therefore, their biosynthesis pathways are considered as the most distinctive natural product pathway in plants. Seemingly, the flavonoids and isoflavones from fungi and actinomycetes have been relatively overlooked. In this review, we summarized and classified the isoflavones and flavonoids derived from fungi and actinomycetes and described their biological activities. Increasing attention has been paid to bioactive substances derived from microorganism whole-cell biotransformation. Additionally, we described the utilization of isoflavones and flavonoids as substrates by fungi and actinomycetes for biotransformation through hydroxylation, methylation, halogenation, glycosylation, dehydrogenation, cyclisation, and hydrogenation reactions to obtain rare and highly active biofunctional derivatives. Overall, among all microorganisms, actinomycetes are the main producers of flavonoids. In our review, we also summarized the functional genes involved in flavonoid biosynthesis.

Rapid preparation of auto-healing gels with actuating behaviour.

Gels with multiple stimuli-responsive actuating behaviour have shown great potential in many applications. Nevertheless, facile approaches to rapidly preparing gel actuators are still highly needed, and obtaining gels possessing both actuating and auto-healing capabilities remains a challenge. Herein, we report the rapid preparation of gel actuators with a self-healing ability. Dual-component gels, composed of poly(BA-co-VI-co-AM) (G-1) and poly(BA-co-AA-co-AM/ß-CD) (G-2) (BA = butyl acrylate, VI = N-vinyl imidazole, AM = acrylamide, AA = acrylic acid, ß-CD = ß-cyclodextrin), are prepared within 10 minutes (min) via biphase frontal polymerization (FP). Both G-1 and G-2 gels show excellent intrinsic self-healing properties based on hydrogen bonds, with healing efficiencies of 91% and 97%, respectively; self-healing between G-1 and G-2 also occurs due to hydrogen bonding and host-guest interactions. Moreover, dual-component gels, in terms of G-1 and G-2 bilayer gel flowers and strips, heterogeneous healed bilayer gel strips, and microfluidic-directed bilayer gel microsphere ensembles, all show actuating behaviour in acidic, alkaline and organic solutions, with actuation degrees up to 96% in 5 min. The actuation mechanism is also proposed. This work might provide new insights into fast synthesis of self-healing dual-component gels towards application in the actuator field.

iTRAQ and RNA-Seq Analyses Provide New Insights into Regulation Mechanism of Symbiotic Germination of Dendrobium officinale Seeds (Orchidaceae).

Mycorrhizal fungi colonize orchid seeds and induce germination. This so-called symbiotic germination is a critical developmental process in the lifecycle of all orchid species. However, the molecular changes that occur during orchid seed symbiotic germination remain largely unknown. To better understand the molecular mechanism of orchid seed germination, we performed a comparative transcriptomic and proteomic analysis of the Chinese traditional medicinal orchid Dendrobium officinale to explore the change in protein expression at the different developmental stages during asymbiotic and symbiotic germination and identify the key proteins that regulate the symbiotic germination of orchid seeds. Among 2256 identified plant proteins, 308 were differentially expressed across three developmental stages during asymbiotic and symbiotic germination, and 229 were differentially expressed during symbiotic germination compared to asymbiotic development. Of these, 32 proteins were coup-regulated at both the proteomic and transcriptomic levels during symbiotic germination compared to asymbiotic germination. Our results suggest that symbiotic germination of D. officinale seeds shares a common signaling pathway with asymbiotic germination during the early germination stage. However, compared to asymbiotic germination, fungal colonization of orchid seeds appears to induce higher and earlier expression of some key proteins involved in lipid and carbohydrate metabolism and thus improves the efficiency of utilization of stored substances present in the embryo. This study provides new insight into the molecular basis of orchid seed germination.

[Molecular cloning and characterization of a novel DoSWEET1 gene from Dendrobium officinale].

SWEET (sugars will be eventually exported transporters) constitute a large and conserved gene family of sugar transporters in eukaryotes, which are important in the cellular metabolisms, growth and development, and plant-microbe interaction in plants. In the present study, a full length cDNA of SWEET encoding gene, designed as DoSWEET1 (GenBank accession No. KT957550), was identified in Dendrobium officinale using RT-PCR and RACE approaches. DoSWEET1 was 1 150 bp in length and encoded a 262-aa protein with a molecular weight of 29.18 kD and an isoelectric point of 9.49. The deduced DoSWEET1 protein contained seven transmembrane regions and two conserved MtN3-slv domains (11-94, 130-212）. Multiple sequence alignment revealed that DoSWEET1 had high identities 45%-54.6%） with SWEET proteins from various plants. A neighbor joining phylogenetic analysis suggests that DoSWEET1 belonged to the class Ⅱ subgroup of the SWEET evolutionary tree, and was closely related to rice OsSWEET13, OsSWEET14, and OsSWEET15. qPCR analysis demonstrated that DoSWEET1 gene was differentially expressed in the three included organs of D. officinale, and the expression was most abundant in the roots at 9.88 fold over that of the stems, followed by that of the leaves with 2.85 fold higher. In the 3rd symbiotic germinating seeds infected by Tulasnella sp., the transcipts were dramatically induced by 1 359.06 fold over that in the ungerniamted control seeds, suggesting a vital role of the gene in the D. officinale symbiotic germination process. Molecular cloning and characterization of the novel DoSWEET1 gene provides a foundation for the functional study of the gene in sugar translocation during the D. officinale symbiotic germination process.

[Establishment of vulnerable plaque model by mast cell activation in adventitia and evaluation of effectiveness of intervention of Shenlian tablet].

This study was designed to investigate the activity of Shenlian tablet in stabilization of the atherosclerosis (As) plaque in apoE(-/-) mice and explore the mechanisms. Rat peritoneal mast cells were randomly allocated and treated with Shenlian tablet (100, 50, 25, 12.5 mg·L(-1)) or cromoglicate sodium (200 µg·L(-1)) for 2 h before exposure to substance P. Histamine, tryptase, IL-1ß and NF-κB were measured in the cell culture supernatant by ELISA assay. The plaque formation was induced by common carotid artery cannula method combined with high-fat diet in apoE(-/-) mice, and the plaque instability was induced by substance P through local mast cell degranulation. Mice were divided into eight groups that included the model 1 (M1, sham-operated group), M2 (carotid artery cannula combined with high-fat diet）, M3 (M2 combined with substance P 0.5 µg/mouse, Shenlian extract (95, 190 and 380 mg·kg(-1)·d(-1)), atorvastatin (2.6 mg·kg-1·d(-1)) and normal control group. Total cholesterol (TC), high-density lipoprotein (HDL-C), high-sensitivity C-reactive protein (hs CRP), matrix metalloproteinases 9 (MMP-9) and histamine were measured by ELISA. Thickness, plaque area, mast cell degranulation were observed by hematoxylin and eosin staining, toluidine blue staining. CD117 antigen expression were observed by confocal microscopy. Intracellular phosphorylation was detected using the Bio-Plex 6-plex phosphoprotein assay kit. The results show that the mast cell membrane was stabilized by Shenlian tablet. Histamine, tryptase, interleukin l-ß and NF-κB exhibited a significantly reduction in the Shenlian tablet-treated group (P < 0.05 or P < 0.01). Substance P significantly enhanced activation and degranulation of adventitial mast cells. In addition, it increased adventitia inflammatory cells infiltration and promoted intraplaque hemorrhages in apoE(-/-) mice model group. The proliferation, degranulation and inflammation of mast cell were significantly inhibited by Shenlian tablet. On the other hand, the same treatment decreased hs-CRP, MMP-9 and histamine in serum. IκB, p38 MAPK phosphorylation, intraplaque hemorrhage and collagen degradation were reduced in the presence of Shenlian tablet, which increased the stability of the As plaque. The results show that the vulnerable plaque model induced by mast cell activation in adventitia was established. Shenlian tablet exhibited a protective effect in this model. Shenlian tablet may increase the plaque stability via inhibition of mast cell-mediated inflammatory response.

Comparative Transcriptome Analysis of Genes Involved in GA-GID1-DELLA Regulatory Module in Symbiotic and Asymbiotic Seed Germination of Anoectochilus roxburghii (Wall.) Lindl. (Orchidaceae).

Anoectochilus roxburghii (Wall.) Lindl. (Orchidaceae) is an endangered medicinal plant in China, also called "King Medicine". Due to lacking of sufficient nutrients in dust-like seeds, orchid species depend on mycorrhizal fungi for seed germination in the wild. As part of a conservation plan for the species, research on seed germination is necessary. However, the molecular mechanism of seed germination and underlying orchid-fungus interactions during symbiotic germination are poorly understood. In this study, Illumina HiSeq 4000 transcriptome sequencing was performed to generate a substantial sequence dataset of germinating A. roxburghii seed. A mean of 44,214,845 clean reads were obtained from each sample. 173,781 unigenes with a mean length of 653 nt were obtained. A total of 51,514 (29.64%) sequences were annotated, among these, 49 unigenes encoding proteins involved in GA-GID1-DELLA regulatory module, including 31 unigenes involved in GA metabolism pathway, 5 unigenes encoding GID1, 11 unigenes for DELLA and 2 unigenes for GID2. A total of 11,881 genes showed significant differential expression in the symbiotic germinating seed sample compared with the asymbiotic germinating seed sample, of which six were involved in the GA-GID1-DELLA regulatory module, and suggested that they might be induced or suppressed by fungi. These results will help us understand better the molecular mechanism of orchid seed germination and orchid-fungus symbiosis.

Short-term mass loads of per- and polyfluoroalkyl substances in a wastewater treatment plant from South China.

Wastewater treatment plants (WWTPs) are one of the most important sources and sinks for per- and polyfluoroalkyl substances (PFAS). However, limited studies have evaluated short-term temporal variability of PFAS in WWTPs, particularly for their intra-day variations. For this purpose, a time-composite sampling campaign was carried out at a WWTP influent from South China for 1 week. Five out of ten PFAS were found in the influent, i.e., perfluoroheptanoic acid (PFHpA), perfluorooctanoic acid (PFOA), perfluorononanoic acid (PFNA), perfluorobutane sulfonic acid (PFBS), and perfluorooctanesulfonic acid (PFOS). PFOA was the most domain PFAS whereas PFOS was detected occasionally, which might be associated with the prohibition of PFOS use in China. For the first time, we observed significant intra-day fluctuations in mass fluxes for PFOS. Different from a morning peak of pharmaceuticals reported previously, PFOS mass loads fluctuated sharply at noon and night on the weekdays. Furthermore, the mass fluxes of PFOA on the weekend were significantly elevated. For the other PFAS detected, no significant diurnal variations in mass loads were identified. Correlation analysis indicated that domestic activities (e.g., home cleaning) are likely to be the major source of these perfluorocarboxylic acids especially PFOA. In addition, flow fluxes had little effects on these PFAS mass load. These results can aid in future sampling campaigns and optimizing removal strategies for PFAS in wastewater.

Discovery of a novel lead characterized by a stilbene-extended scaffold against sepsis as soluble epoxide hydrolase inhibitors.

Recently, some inhibitors of soluble epoxide hydrolase (sEH) showed limited potential in treating sepsis by increasing survival time, but they have unfortunately failed to improve survival rates. In this study, we initially identified a new hit 11D, belonging to a natural skeleton known as stilbene and having an IC50 of 644 nM on inhibiting murine sEH. Natural scaffold-based sEH inhibitors are paid less attention. A combination of structure-activity relationships (SARs)-guided structural optimization and computer-aided skeleton growth led to a highly effective lead compound 70P (IC50: 4.0 nM). The dose-response study indicated that 70P (at doses of 0.5-5 mg/kg, ip.) significantly increased survival rates and survival time by reducing the levels of the inflammatory factors TNF-α and IL-6 in the liver. Interestingly, 70P exhibited much higher accumulation in the liver than in plasma (AUC ratio: 175). In addition, 70P exhibits equal IC50 value (1.5 nM) on inhibiting human sEH as EC5026 (1.7 nM). In conclusion, the natural scaffold-extended sEH inhibitor 70P has the potential to become a new promising lead for addressing the unmet medical need in sepsis treatment, which highlighted the importance of natural skeleton in developing sEH inhibitors.

Effects of early intraoral acesulfame-K stimulation to mice on the adult's sweet preference and the expression of α-gustducin in fungiform papilla.

Exposure to artificial sweetener acesulfame-K (AK) at early development stages may influence the adult sweet preference and the periphery gustatory system. We observed that the intraoral AK stimulation to mice from postnatal day 4 (P4) to weaning decreased the preference thresholds for AK and sucrose solutions in adulthood, with the preference pattern unchanged. The preference scores were increased in the exposure group significantly when compared with the control group at a range of concentrations for AK or sucrose solution. Meanwhile, more α-Gustducin-labeled fungiform taste buds and cells in a single taste bud were induced from week 7 by the early intraoral AK stimulation. However, the growth in the number of α-Gustducin-positive taste bud or positive cell number per taste bud occurred only in the anterior region, the rostral 1-mm part, but not in the intermediate region, the caudal 4-mm part, of the anterior two-third of the tongue containing fungiform papillae. This work extends our previous observations and provides new information about the developmental and regional expression pattern of α-Gustducin in mouse fungiform taste bud under early AK-stimulated conditions.

Occurrence, fate and ecological risks of 90 typical emerging contaminants in full-scale textile wastewater treatment plants from a large industrial park in Guangxi, Southwest China.

Recent industrial relocation in China causes lots of environment concerns including risks of emerging contaminants (ECs). Herein, the occurrence, fate, removal and ecological risks of 34 per- and polyfluoroalkyl substances (PFAS), 17 endocrine disrupting chemicals (EDCs), 16 phthalate esters (PAEs), and 23 polycyclic aromatic hydrocarbons (PAHs) were investigated in two textile WWTPs (conventional and Fenton-modified) from a large textile industrial park in Southwest China. Totally 50 ECs were identified and the levels followed the order of PAEs > EDCs > PFAS ≈ PAHs. The EDCs predominated in textile washing and rinsing wastewater whereas the PAEs did in desizing wastewater. Biphasic correlations of log Kd and log P, molecular weight, and numbers of rings (r2 = 0.63-0.66, p < 0.01) were observed for PAHs, suggesting that hydrophobicity might not facilitate adsorption of super-hydrophobic PAHs onto activated sludge. 63-69% of detected ECs were effectively removed by two textile WWTPs with removal efficiencies ≥ 80%, which were much higher than previous reports. Fenton processing enhanced the removal efficiencies for long-chain PFAS rather than short-chain PFAS. The PAEs and EDCs posed a medium-to-high risk to aquatic organisms and were screened as the priority ECs. To date, such a comprehensive investigation for ECs has not been previously conducted in textile WWTPs and this study provides basic information about regional chemical emission inventory of ECs.

Insights into the release of triclosan from microplastics in aquatic environment assessed with diffusive gradient in thin-films.

Organic chemicals associated with microplastics (MPs) can be released and thus pose potential risks during weathering processes. However, the thermodynamics and kinetics of their release processes still need to be better understood. Herein, the adsorption and desorption kinetics of triclosan on polystyrene (PS) and polyvinyl chloride (PVC) were investigated by using both batch experiments and diffusive gradients in thin-films (DGT) technique. The pseudo-second-order model fitted the data best, implying that both intraparticle diffusion and external liquid film diffusion influence the adsorption and desorption processes. DGT continuously accumulated triclosan from MP suspensions but slower than theoretical values, indicating some restrictions to desorption. The DGT-induced fluxes in Soils/Sediment (DIFS) model, employed to interpret DGT data, gave distribution coefficients for labile species (Kdl) of 5000 mL g-1 (PS) and 1000 mL g-1 (PVC) and the corresponding response times (Tc) were 10 s and 1000 s, respectively. Higher Kdl but smaller Tc for PS than PVC showed that more triclosan adsorbed on PS could be rapidly released, while there were some kinetic limitations for triclosan on PVC. A novel finding was that pH and ionic strength individually and interactively affected the supply of triclosan to DGT. This is the first study to quantify interactions of organics with MPs by using DGT, aiding our understanding of MPs' adsorption/desorption behavior in the aquatic environment.

Mariculture affects antibiotic resistome and microbiome in the coastal environment.

Antibiotics are increasingly used and released into the marine environment due to the rapid development of mariculture, resulting in spread of antibiotic resistance. The pollution, distribution, and characteristics of antibiotics, antibiotic resistance genes (ARGs) and microbiomes have been investigated in this study. Results showed that 20 antibiotics were detected in Chinese coastal environment, with predominance of erythromycin-H2O, enrofloxacin and oxytetracycline. In coastal mariculture sites, antibiotic concentrations were significantly higher than in control sites, and more types of antibiotics were detected in the South than in the North of China. Residues of enrofloxacin, ciprofloxacin and sulfadiazine posed high resistance selection risks. ß-Lactam, multi-drug and tetracycline resistance genes were frequently detected with significantly higher abundance in the mariculture sites. Of the 262 detected ARGs, 10, 26, and 19 were ranked as high-risk, current-risk, future-risk, respectively. The main bacterial phyla were Proteobacteria and Bacteroidetes, of which 25 genera were zoonotic pathogens, with Arcobacter and Vibrio in particular ranking in the top10. Opportunistic pathogens were more widely distributed in the northern mariculture sites. Phyla of Proteobacteria and Bacteroidetes were the potential hosts of high-risk ARGs, while the conditional pathogens were associated with future-risk ARGs, indicating a potential threat to human health.

Green tea polyphenols alleviate di-(2-ethylhexyl) phthalate-induced liver injury in mice.

BACKGROUND: Di (2-ethylhexyl) phthalate (DEHP) is a common plasticizer known to cause liver injury. Green tea is reported to exert therapeutic effects on heavy metal exposure-induced organ damage. However, limited studies have examined the therapeutic effects of green tea polyphenols (GTPs) on DEHP-induced liver damage. AIM: To evaluate the molecular mechanism underlying the therapeutic effects of GTPs on DEHP-induced liver damage. METHODS: C57BL/6J mice were divided into the following five groups: Control, model [DEHP (1500 mg/kg bodyweight)], treatment [DEHP (1500 mg/kg bodyweight) + GTP (70 mg/kg bodyweight), oil, and GTP (70 mg/kg bodyweight)] groups. After 8 wk, the liver function, blood lipid profile, and liver histopathology were examined. Differentially expressed micro RNAs (miRNAs) and mRNAs in the liver tissues were examined using high-throughput sequencing. Additionally, functional enrichment analysis and immune infiltration prediction were performed. The miRNA-mRNA regulatory axis was elucidated using the starBase database. Protein expression was evaluated using immunohistochemistry. RESULTS: GTPs alleviated DHEP-induced liver dysfunction, blood lipid dysregulation, fatty liver disease, liver fibrosis, and mitochondrial and endoplasmic reticulum lesions in mice. The infiltration of macrophages, mast cells, and natural killer cells varied between the model and treatment groups. mmu-miR-141-3p (a differentially expressed miRNA), Zcchc24 (a differentially expressed mRNA), and Zcchc24 (a differentially expressed protein) constituted the miRNA-mRNA-protein regulatory axis involved in mediating the therapeutic effects of GTPs on DEHP-induced liver damage in mice. CONCLUSION: This study demonstrated that GTPs mitigate DEHP-induced liver dysfunction, blood lipid dysregulation, fatty liver disease, and partial liver fibrosis, and regulate immune cell infiltration. Additionally, an important miRNA-mRNA-protein molecular regulatory axis involved in mediating the therapeutic effects of GTPs on DEHP-induced liver damage was elucidated.

Antimicrobial secondary metabolites from an endophytic fungus Aspergillus polyporicola.

Two new nucleoside derivatives, kipukasins O (1) and P (2), one new cyclohexenone derivative, arthropsadiol D (5), and one new natural product, (+)-2,5-dimethyl-3(2H)-benzofuranone (6), together with eleven known compounds (3, 4, 7-15), were obtained from the culture broth of the endophytic fungus Aspergillus polyporicola R2 isolated from the roots of Synsepalum dulcificum. Among them, the absolute configuration of compound 5 was determined by quantum chemical calculations of NMR chemical shifts and ECD spectrum. The antimicrobial activities of these compounds were evaluated. Compound 11 exhibited obvious inhibitory activity against MRSA, Staphylococcus aureus, Salmonella typhimurium, Botrytis cinerea, and Fusarium graminearum with MIC values of 4, 4, 4, 32, and 16 µg/mL, respectively. Compound 12 exhibited antibacterial activity against S. typhimurium and MRSA with MIC values of 4 and 16 µg/mL. Compound 6 exhibited antifungal activity against F. graminearum with MIC value of 32 µg/mL.

Polyhydroxylated sesquiterpenes and ergostane glycosides produced by the endophytic fungus Xylaria sp. from Azadirachta indica.

The investigation of the metabolites from the endophytic fungus Xylaria sp. YM 311647 in solid fermentation resulted in the isolation of six undescribed compounds, namely xylarioxides A-F, respectively. These included one eremophilane sesquiterpene, three guaiane sesquiterpene glycosides, and two ergostane glycosides. The structures of the compounds were determined by extensive analyses of spectroscopic data, including 1D and 2D NMR, as well as HRESIMS data. The stereochemistry of xylarioxide A was confirmed by X-ray crystallographic analysis. All of the isolated compounds were assayed for their antifungal activities against seven phytopathogenic fungi and two human pathogenic fungi. Among them, xylarioxides A, E and F showed potent activities against the tested phytopathogens. Particularly, xylarioxide E exhibited the highest activity against Gibberella saubinetii, Curvularia lunata, and Colletotrichum gloeosporioides with MIC values of 4, 4, and 8 µg/mL, respectively, which were comparable to the positive control of nystatin. Interestingly, guaiane sesquiterpene glycosides have been rarely reported from fungal sources. Additionally, xylarioxide E represented an unusual naturally occurring 3,4-seco-steroidal glycoside with a seven-membered lactone in ring A.