Design and Experimental Study of an Improved Pressure Core Sampler for Marine Gas Hydrates.

A pressure core sampler (PCS) is considered an effective tool to retrieve marine gas hydrate cores from hydrate-bearing sediments. However, according to the sampling application statistics, the success rate of pressure coring changed from 30% to 85% in different drilling wells. Such severe fluctuation will cause huge uncertainty in the practical application of technology and economic benefits. Herein, we present a new PCS designed to improve pressure-retaining reliability. The work principle, design and calculations, and structure composition were described. Through the laboratory tests and drilling experiments, the maximum holding pressure in the pressure chamber was 32.1 MPa, and the pressure loss rates of holding pressure after 2 h changed from 1.96% to 2.46%. The maximum temperature-rising value in the pressure chamber was 0.96 °C under a temperature of 23.5 °C in 2 h. Furthermore, the success rate of the pressure core reached 87.5% and the core recovery was not less than 80%, which were verified by 8 pressure core runs in three different offshore wells. Therefore, we conclude that this new and improved PCS has great application value in gas hydrate exploration that seeks to recover more accurate cores in situ, especially in the silt and sand layers.

Widely targeted metabolomics reveals differences in metabolites of Paeonia lactiflora cultivars.

INTRODUCTION: Paeonia lactiflora contains diverse active constituents and exhibits various pharmacological activities. However, only partial identification of biologically active substances from P. lactiflora has been achieved using low-throughput techniques. Here, the roots of P. lactiflora, namely, Fenyunu (CK), Dafugui (DFG), and Red Charm (HSML), were studied. The primary and secondary metabolites were investigated using ultrahigh-performance liquid chromatography-electrospray ionization-tandem mass spectrometry (UPLC-ESIMS/MS). METHODS: The chemical compounds and categories were detected using broadly targeted UPLC-MS/MS. Principal component analysis (PCA), orthogonal partial least-squares discriminant analysis (OPLS-DA), and hierarchical clustering analysis (HCA) were carried out for metabolites of different varieties of P. lactiflora. RESULTS: A total of 1237 compounds were detected and classified into 11 categories. HCA, PCA, and OPLS-DA of these metabolites indicated that each variety of P. lactiflora was clearly separated from the other groups. Differential accumulated metabolite analysis revealed that the three P. lactiflora varieties contained 116 differentially activated metabolites (DAMs) involved in flavonoid, flavone, and flavonol metabolism. KEGG pathway analysis revealed that, in 65 pathways, 336 differentially abundant metabolites (DMs) were enriched in the CK and DFG groups; moreover, the type and content of terpenoids were greater in the CK group than in the DFG group. The CK and HSML groups contained 457 DMs enriched in 61 pathways; the type and amount of flavonoids, terpenoids, and tannins were greater in the CK group than in the HSML group. The DFG and HSML groups contained 497 DMs enriched in 65 pathways; terpenoids and alkaloids were more abundant in the HSML variety than in the DFG variety. CONCLUSIONS: A total of 1237 compounds were detected, and the results revealed significant differences among the three P. lactiflora varieties. Among the three P. lactiflora varieties, phenolic acids and flavonoids composed the largest and most diverse category of metabolites, and their contents varied greatly. Therefore, CK is suitable for medicinal plant varieties, and DFG and HSML are suitable for ornamental plant varieties. Twelve proanthocyanidin metabolites likely determined the differences in color among the three varieties.

[Research on mechanism of hypolipidemic effect of Massa Medicata Fermentata based on metabolomics].

This paper aims to study the therapeutic effect of Massa Medicata Fermentata on hyperlipidemia model rats and investigate its mechanism of hypolipidemic effect with the help of non-targeted metabolomics. The mixed hyperlipidemia model rats were constructed by giving high-fat chow. After successful modeling, the rats were divided into the model group, pravastatin sodium group(4.4 mg·kg~(-1)), lipotropic group(0.1 g·kg~(-1)), high-dose group(2.4 g·kg~(-1)), medium-dose group(1.2 g·kg~(-1)), and low-dose group(0.6 g·kg~(-1)) of Massa Medicata Fermentata, and they were administered for four weeks once daily. An equal volume of ultrapure water was given to the blank group and model group. Serum lipid level and liver hematoxylin-eosin(HE) staining were used as indicators to estimate the intervention effect of Massa Medicata Fermentata on mixed hyperlipidemia, and the changes in metabolites in plasma of mixed hyperlipidemia model rats were analyzed by non-targeted metabolomics. The mechanism of the hypolipidemic effect of Massa Medicata Fermentata was analyzed through metabolite pathway enrichment. The results showed that compared with the model group, the Massa Medicata Fermentata administration group, especially the high-dose group, could significantly reduce the content of total cholesterol(TC), triglyceride(TG), and low-density lipoprotein cholesterol(LDL-c)(P<0.05 or P<0.01), and liver HE staining revealed that the number of adipocytes in the high-dose group was reduced to some extent. The potential biomarkers obtained by non-targeted metabolomics screening included glycerol 3-phosphate, sphingomyelin, sphingosine 1-phosphate, and deoxyuridine, which were mainly involved in the sphingolipid metabolism process, glycerophospholipid metabolism process, glycerol ester metabolism pathway, and pyrimidine metabolism pathway, totaling four possible metabolic pathways related to lipid metabolism. This study provides a reference for an in-depth investigation of the hypolipidemic mechanism of Massa Medicata Fermentata, which is of great significance for further promoting the clinical application of Massa Medicata Fermentata and increasing the indications.

Decorating Pd-Au Nanodots Around Porous In2 O3 Nanocubes for Tolerant H2 Sensing Against Switching Response and H2 S Poisoning.

With the recently-booming hydrogen (H2 ) economy by green H2 as the energy carriers and the newly-emerged exhaled diagnosis by human organ-metabolized H2 as a biomarker, H2 sensing is simultaneously required with fast response, low detection limit, and tolerant stability against humidity, switching, and poisoning. Here, reliable H2 sensing has been developed by utilizing indium oxide nanocubes decorated with palladium and gold nanodots (Pd-Au NDs/In2 O3 NCBs), which have been synthesized by combined hydrothermal reaction, annealing, and chemical bath deposition. As-prepared Pd-Au NDs/In2 O3 NCBs are observed with surface-enriched NDs and nanopores. Beneficially, Pd-Au NDs/In2 O3 NCBs show 300 ppb-low detection limit, 5 s-fast response to 500 ppm H2 , 75%RH-high humidity tolerance, and 56 days-long stability at 280 °C. Further, Pd-Au NDs/In2 O3 NCBs show excellent stability against switching sensing response, and are tolerant to H2 S poisoning even being exposed to 10 ppm H2 S at 280 °C. Such excellent H2 sensing may be attributed to the synergistic effect of the boosted Pd-Au NDs' spillover effect and interfacial electron transfer, increased adsorption sites over the porous NCBs' surface, and utilized Pd NDs' affinity with H2 and H2 S. Practically, Pd-Au NDs/In2 O3 NCBs are integrated into the H2 sensing device, which can reliably communicate with a smartphone.

Interfering with the AKT/mTOR/STAT3/ID1 signaling axis with usenamine A restrains the proliferative and invasive potential of human hepatocellular carcinoma cells.

BACKGROUND: Usenamine A, a novel natural compound initially isolated from the lichen Usnea longissima, has exhibited promising efficacy against hepatoma in prior investigation. Nevertheless, the underlying mechanisms responsible for its antihepatoma effects remain unclear. Furthermore, the role of the AKT/mechanistic target of the rapamycin (mTOR)/signal transducer and activator of transcription 3 (STAT3)/inhibitor of differentiation/DNA binding 1 (ID1) signaling axis in hepatocellular carcinoma (HCC), and the potential anti-HCC effects of drugs targeting this pathway are not well understood. METHODS: CCK-8 assay was used to investigate the effects of usenamine A on the proliferation of human HCC cells. Moreover, the effects of usenamine A on the invasion ability of human HCC cells were evaluated by transwell assay. In addition, expression profiling analysis, quantitative real-time PCR, immunoblotting, immunohistochemistry (IHC) analysis, RNAi, immunoprecipitation, and chromatin immunoprecipitation (ChIP) assay were used to explore the effects of usenamine A on the newly identified AKT/mTOR/STAT3/ID1 signaling axis in human HCC cells. RESULTS: Usenamine A inhibited the proliferation and invasion of human HCC cell lines (HepG2 and SK-HEP-1). Through the analysis of gene expression profiling, we identified that usenamine A suppressed the expression of ID1 in human HCC cells. Furthermore, immunoprecipitation experiments revealed that usenamine A facilitated the degradation of the ID1 protein via the ubiquitin-proteasome pathway. Moreover, usenamine A inhibited the activity of STAT3 in human HCC cells. ChIP analysis demonstrated that STAT3 positively regulated ID1 expression at the transcriptional level in human HCC cells. The STAT3/ID1 axis played a role in mediating the anti-proliferative and anti-invasive impacts of usenamine A on human HCC cells. Additionally, usenamine A suppressed the STAT3/ID1 axis through AKT/mTOR signaling in human HCC cells. CONCLUSION: Usenamine A displayed robust anti-HCC potential, partly attributed to its capacity to downregulate the AKT/mTOR/STAT3/ID1 signaling pathway and promote ubiquitin-proteasome-mediated ID1 degradation. Usenamine A has the potential to be developed as a therapeutic agent for HCC cases characterized by abnormal AKT/mTOR/STAT3/ID1 signaling, and targeting the AKT/mTOR/STAT3 signaling pathway may be a viable option for treating patients with HCC exhibiting elevated ID1 expression.

Novel peptides from sea cucumber intestines hydrolyzed by neutral protease alleviate exercise-induced fatigue via upregulating the glutaminemediated Ca2+ /Calcineurin signaling pathway in mice.

Sea cucumber intestines are considered a valuable resource in the sea cucumber processing industry due to their balanced amino acid composition. Studies have reported that peptides rich in glutamate and branched-chain amino acids have anti-fatigue properties. However, the function of the sea cucumber intestine in reducing exercise-induced fatigue remains unclear. In this study, we enzymatically hydrolyzed low molecular weight peptides from sea cucumber intestines (SCIP) and administered SCIP orally to mice to examine its effects on exercise-induced fatigue using swimming and pole-climbing exhaustion experiments. The results revealed that supplementation with SCIP significantly prolonged the exhaustion time of swimming in mice, decreased blood lactate and urea nitrogen levels, and increased liver and muscle glycogen levels following a weight-loaded swimming test. Immunofluorescence analysis indicated a notable increase the proportion of slow-twitch muscle fiber and a significant decrease the proportion of fast-twitch muscle fiber following SCIP supplementation. Furthermore, SCIP upregulated mRNA expression levels of Ca2+ /Calcineurin upstream and downstream regulators, thereby contributing to the promotion of skeletal muscle fiber type conversion. This study presents the initial evidence establishing SCIP as a potential enhancer of skeletal muscle fatigue resistance, consequently providing a theoretical foundation for the valuable utilization of sea cucumber intestines.

Intrathecal injection of methotrexate and dexamethasone for vasculitis granuloma of the fourth ventricle: a case report and literature review.

Granulomatosis with polyangiitis (GPA) is a pauci-immune small vessel vasculitis characterised by neutrophil-mediated vasculitis and granuloma. The presence of intracranial parenchymal space-occupying lesions is rarely seen in GPA patients. In this manuscript, we report a case of GPA with granuloma of the fourth ventricle accompanied by obstructive hydrocephalus. Treatment with glucocorticoids (GCs) and multiple immunosuppressants cyclophosphamide (CYC), mycophenolate mofetil (MMF), and rituximab (RTX) showed poor efficacy in this case. After removal of the granuloma by craniotomy, GPA relapsed within 3 months. Under the premise of GC and MMF treatment combined with intrathecal injection of dexamethasone (DXM) and methotrexate (MTX), the intracranial granuloma gradually shrank, and the patient's general condition was alleviated, showing that this is an effective treatment method. Key Points • To date, there are few reports of granulomatous vasculitis combined with granuloma of the fourth ventricle, and our case is the second. • In this case, multiple immunosuppressants and rituximab were ineffective treatments, and the intracranial granuloma was effectively controlled by intrathecal injection of dexamethasone (DXM) and methotrexate (MTX). • Based on this report, it can be suggested that intrathecal injection is effective in treating patients with GPA and central nervous system involvement, but large-scale sample studies are needed.

BMSCs alleviate liver cirrhosis by regulating Fstl1/Wnt/ß-Catenin signaling pathway.

Researchers have shown that bone mesenchymal stem cells (BMSCs) can alleviate the progression of liver cirrhosis; however, it is unclear how exactly BMSCs function to cure liver disease. In this study, we used bioinformatics methods to assess differentially expressed genes (DEGs) in liver cirrhosis and found a significantly upregulated gene, Fstl1, in liver cirrhosis. In vivo and in vitro experiments showed that compared with those in the disease model group, the mRNA, and protein expression levels of Fstl1 were significantly reduced after BMSCs treatment, and the ß-Catenin protein level was also significantly reduced after BMSCs treatment. Subsequently, we downregulated Fstl1 in activated hepatic stellate cells (HSCs) and found that Wnt and ß-Catenin protein expression levels also decreased. Finally, we found that in BMSCs-treated activated HSCs, overexpression of Fstl1 reversed the inhibitory effect of BMSCs on the Wnt/ß-Catenin signaling pathway to a certain extent. In summary, our results show that BMSCs can inhibit Wnt/ß-Catenin signaling pathway activation by downregulating the protein expression level of Fstl1, thus alleviating cirrhosis. Therefore, targeted regulation of Fstl1 may provide a new therapeutic strategy for the progression of liver cirrhosis.

[Morin induces autophagy and apoptosis in hepatocellular carcinoma cells through Akt/mTOR/STAT3 pathway].

This study investigated the effect and mechanism of morin in inducing autophagy and apoptosis in hepatocellular carcinoma cells through the protein kinase B(Akt)/mammalian target of rapamycin(mTOR)/signal transducer and activator of transcription protein 3(STAT3) pathway. Human hepatocellular carcinoma SK-HEP-1 cells were stimulated with different concentrations of morin(0, 50, 100, 125, 200, and 250 µmol·L~(-1)). The effect of morin on the viability of SK-HEP-1 cells was detected by Cell Counting Kit-8(CCK-8). The effect of morin on the proliferation and apoptosis of SK-HEP-1 cells was investigated using colony formation assay, flow cytometry, and BeyoClick~(TM) EdU-488 with different concentrations of morin(0, 125, and 250 µmol·L~(-1)). The changes in the autophagy level of cells treated with morin were examined by transmission electron microscopy and autophagy inhibitors. The impact of morin on the expression levels of proteins related to the Akt/mTOR/STAT3 pathway was verified by Western blot. Compared with the control group, the morin groups showed decreased viability of SK-HEP-1 cells in a time-and concentration-dependent manner, increased number of apoptotic cells, up-regulated expression level of apoptosis marker PARP, up-regulated phosphorylation level of apoptosis-regulating protein H2AX, decreased number of positive cells and the colony formation rate, an upward trend of expression levels of autophagy-related proteins LC3-Ⅱ, Atg5, and Atg7, and decreased phosphorylation levels of Akt, mTOR, and STAT3. These results suggest that morin can promote apoptosis, inhibit proliferation, and induce autophagy in hepatocellular carcinoma cells, and its mechanism of action may be related to the Akt/mTOR/STAT3 pathway.

Xianglian Zhixie Tablet Antagonizes Dextran Sulfate Sodium-Induced Ulcerative Colitis by Attenuating Systemic Inflammation and Modulating Gut Microbiota.

Purpose: Xianglian Zhixie Tablet (XLZXT), a classical traditional Chinese medicine formulation, is commonly used to treat Ulcerative Colitis (UC) in China. However, the therapeutic mechanisms of XLZXT for UC have yet to be fully understood. This study aimed to investigate the curative benefits of XLZXT and its associated mechanisms for healing UC in mice. Methods: In the present study, the 1% dextran sulfate sodium (DSS) solution was used to establish the UC model in C57BL/6N mice. To investigate the therapeutic effects of XLZXT on DSS-induced UC mice, several parameters were measured, including DAI score, colon length, spleen index, pathological changes in colon tissue, and levels of inflammatory factors in plasma and colon tissue. By investigating the gut microbiota, assessing the levels of intestinal mucosal protein expression, and looking at the proteins involved in the TLR4/MyD88/NF-B p65 signaling pathway, the mechanisms of XLZXT impact on UC were investigated. Mouse feces were examined for patterns of gut microbiota expression using high-throughput sequencing of 16S rRNA. Results: XLZXT effectively alleviated UC symptoms and colon pathological damage in DSS-induced UC mice. It improved body weight loss, stool consistency, and hematochezia, while also repairing colon damage. Moreover, it down-regulated pro-inflammatory cytokines (such as TNF-α, IL-1ß, and IL-6), and up-regulated anti-inflammatory cytokines (such as IL-10). XLZXT also increased the expression of MUC-2, Occludin and ZO-1, while decreasing the expression of NF-κB, MyD88 and TLR4. Additionally, it regulated gut microbiota disorder by increasing the abundance of beneficial bacteria and reducing the adhesion of intestinal harmful bacteria. Conclusion: XLZXT demonstrated therapeutic effects on DSS-induced UC mice. The mechanisms may be associated with repairing the intestinal mucosal barrier, regulating the TLR4/MyD88/NF-κB p65 signaling pathway, and restoring the balance of gut microbiota.

[Inhibitory effect and molecular mechanism of sinomenine on human hepatocellular carcinoma HepG2 and SK-HEP-1 cells].

This study aimed to investigate the effect and molecular mechanism of sinomenine on proliferation, apoptosis, metastasis, and combination with inhibitors in human hepatocellular carcinoma HepG2 cells and SK-HEP-1 cells. The effect of sinomenine on the growth ability of HepG2 and SK-HEP-1 cells were investigated by CCK-8 assay, colony formation assay, and BeyoClick~(TM) EdU-488 staining. The effect of sinomenine on DNA damage was detected by immunofluorescence assay, and the effect of sinomenine on apoptosis of human hepatocellular carcinoma cells was clarified by Hoechst 33258 staining and CellEvent~(TM) Cystein-3/7Green ReadyProbes~(TM) reagent assay. Cell invasion assay and 3D tumor cell spheroid invasion assay were performed to investigate the effect of sinomenine on the invasion ability of human hepatocellular carcinoma cells in vitro. The effect of sinomenine on the regulation of protein expression related to the protein kinase B(Akt)/mammalian target of rapamycin(mTOR)/signal transducer and activator of transcription 3(STAT3) signaling pathway in HepG2 and SK-HEP-1 cells was examined by Western blot. Molecular docking was used to evaluate the strength of affinity of sinomenine to the target cysteinyl aspartate specific proteinase-3(caspase-3) and STAT3, and combined with CCK-8 assay to detect the changes in cell viability after combination with STAT3 inhibitor JSI-124 in combination with CCK-8 assay. The results showed that sinomenine could significantly reduce the cell viability of human hepatocellular carcinoma cells in a concentration-and time-dependent manner, significantly inhibit the clonogenic ability of human hepatocellular carcinoma cells, and weaken the invasive ability of human hepatocellular carcinoma cells in vitro. In addition, sinomenine could up-regulate the cleaved level of poly ADP-ribose polymerase(PARP), a marker of apoptosis, and down-regulate the protein levels of p-Akt, p-mTOR, and p-STAT3 in human hepatocellular carcinoma cells. Molecular docking results showed that sinomenine had good affinity with the targets caspase-3 and STAT3, and the sensitivity of sinomenine to hepatocellular carcinoma cells was diminished after STAT3 was inhibited. Therefore, sinomenine can inhibit the proliferation and invasion of human hepatocellular carcinoma cells and induce apoptosis, and the mechanism may be attributed to the activation of caspase-3 signaling and inhibition of the Akt/mTOR/STAT3 pathway. This study can provide a new reference for the in-depth research and clinical application of sinomenine and is of great significance to further promote the scientific development and utilization of sinomenine.

Multifunctional Ti3C2Tx MXene/Silver Nanowire Membranes with Excellent Catalytic, Antifouling, and Antibacterial Properties for Nitrophenol-Containing Water Purification.

The uncontrolled release of nitrophenol and dye pollutants into water systems is an increasingly serious worldwide concern, and thus efficient wastewater treatment technologies are urgently needed. Herein we report a novel two-dimensional (2D) transition metal carbides and/or nitrides (Ti3C2Tx MXene) membrane modified with silver nanowires (AgNWs) by vacuum assisted filtration technology for the ultrafast nitrophenol catalysis and water purification applications. Regular and controllable membrane transport channels were constructed by stacking Ti3C2Tx MXene nanosheets. Furthermore, the intercalation of AgNWs into the Ti3C2Tx MXene interlayer greatly enlarged the interlayer spacing, resulting in more gaps for fast and selective molecular transport. The optimized Ti3C2Tx MXene@AgNWs (M@A) membrane exhibited a water flux up to ∼191.9 L/(m2 h) while maintaining a high bovine serum albumin (BSA) rejection of ∼95.4%. We emphatically used M@A membranes as efficient catalysts for the reduction of 4-nitrophenol (4-NP), and the results indicated that M@A-12% membrane exhibited the greatest catalytic reduction ability, and recycling utilization. M@A-12% membrane also had an antibacterial rate of more than 99% against Escherichia coli (E. coli) and Staphylococcus aureus (S. aureus). This work provides a possibility to expand the application of 2D multifunctional M@A membranes in wastewater treatment and pollutant catalytic degradation.

Clinical antitumor application and pharmacological mechanisms of Dahuang Zhechong Pill.

Cancer still has elevated morbidity and mortality, which undoubtedly impacts the life quality of affected individuals. Remarkable advances have been made in cancer therapy, although the toxicities of traditional therapies remain an obvious challenge. Dahuang Zhechong Pill (DHZCP), developed by Zhongjing Zhang in the Synopsis of the Golden Chamber, represents an effective anticancer traditional Chinese medicine (TCM). In this review, it was found that DHZCP is therapeutically utilized in liver, lung, gastric, pancreatic and other cancers in clinic. Pharmacological evidence showed that its anti-tumor mechanisms mainly involve induced cell cycle arrest, apoptosis and autophagy, as well as suppressed tumor cell proliferation, obstructed angiogenesis and metastasis, enhanced immunity, and reversal of multidrug resistance. The present review provides a solid basis for the clinical application of DHZCP and may promote the wide use of TCM in clinical antitumor application.

Anti-Diabetic Activity of a Novel Exopolysaccharide Produced by the Mangrove Endophytic Fungus Penicillium janthinellum N29.

Marine microorganisms often produce exopolysaccharides with novel structures and diverse biological activities due to their specific marine environment. The novel active exopolysaccharides from marine microorganisms have become an important research area in new drug discovery, and show enormous development prospects. In the present study, a homogeneous exopolysaccharide from the fermented broth of the mangrove endophytic fungus Penicillium janthinellum N29, designated as PJ1-1, was obtained. The results of chemical and spectroscopic analyses showed that PJ1-1 was a novel galactomannan with a molecular weight of about 10.24 kDa. The backbone of PJ1-1 was composed of →2)-α-d-Manp-(1→, →4)-α-d-Manp-(1→, →3)-ß-d-Galf-(1→ and →2)-ß-d-Galf-(1→ units with partial glycosylation at C-3 of →2)-ß-d-Galf-(1→ unit. PJ1-1 had a strong hypoglycemic activity in vitro, evaluated using the assay of α-glucosidase inhibition. The anti-diabetic effect of PJ1-1 in vivo was further investigated using mice with type 2 diabetes mellitus induced by a high-fat diet and streptozotocin. The results indicated that PJ1-1 markedly reduced blood glucose level and improved glucose tolerance. Notably, PJ1-1 increased insulin sensitivity and ameliorated insulin resistance. Moreover, PJ1-1 significantly decreased the levels of serum total cholesterol, triglyceride and low-density lipoprotein cholesterol, enhanced the level of serum high-density lipoprotein cholesterol and alleviated dyslipidemia. These results revealed that PJ1-1 could be a potential source of anti-diabetic agent.

Peptides from Antarctic krill (Euphausia superba) ameliorate acute liver injury in mice induced by carbon tetrachloride via activating the Nrf2/HO-1 pathway.

This study aimed to evaluate the hepatoprotective effects of peptides from Antarctic krill (AKP) on carbon tetrachloride (CCl4)-induced acute liver injury (ALI) in mice and the underlying molecular mechanisms. ICR mice were pretreated with AKP (500 mg kg-1, i.g.) and silybin (30 mg kg-1, i.g.) for 15 days before CCl4 (0.25 mL per kg BW, i.p.) injection. To assess hepatocellular damage and molecular indices, the serum and liver tissue were evaluated at harvest. The results showed that AKP pretreatment remarkably attenuated CCl4-induced liver injury, which was identified by the decrease in serum alanine aminotransferase (ALT) and aspartate aminotransferase (AST), alleviation of hepatocyte necrosis, and inhibition of the levels of the pro-inflammatory factors TNF-α and IL-1ß compared to those for silymarin. AKP pretreatment also enhanced the redox balance by reducing the concentrations of MDA and 8-iso-PG and increasing the activities of SOD, GSH and GSH-PX in the liver of mice. In addition, AKP upregulated oxidative stress-related mRNA expressions of Nrf2, Keap1, HO-1, and NQO1 and further activated the protein expression on the Nrf2/HO-1 singling pathway. In summary, AKP might be a promising hepatoprotective nutraceutical against ALI and its underlying mechanisms are associated with activation of the Nrf2/HO-1 pathway.

Evaluation of safety and efficacy of rapamycin-eluting balloon in patients with intracranial atherosclerotic stenosis: a cohort study.

OBJECTIVE: The safety and efficacy of drug-eluting balloon on the treatment of intracranial atherosclerotic stenosis (ICAS) remain unclear. Here, we present our observation in a cohort study on the safety and efficacy of rapamycin-eluting balloon for patients with ICAS. METHODS: A total of 80 ICAS patients with stenosis degree of 70-99% were included. All patients were treated with rapamycin-eluting balloon and were followed up for 12 months after operation. RESULTS: All patients were successfully treated, where the mean stenosis severity reduced from 85.1 ± 7.6 to 6 ± 4.9%. 8 patients experienced immediate post-operational complications. Two patients passed away during the first month of the follow-up period. Recurrent ischemic syndrome and angiographic restenosis only appeared 7 days after operation. During later follow-up period, none of the patients had clinical angiographic restenosis or needed target vessel revascularization. CONCLUSION: Our data suggest that intracranial stenting with rapamycin-eluting balloon seems to be safe and effective, although more clinical data are needed to support this notion.

Two-dimensional Aluminum Oxide Nanosheets Decorated with Palladium Oxide Nanodots for Highly Stable and Selective Hydrogen Sensing.

Hydrogen (H2 ) sensing materials such as semiconductor metal oxides may suffer from poor long-term stability against humidity and unsatisfactory selectivity against other interfering gases. To address the above issues, highly stable and selective H2 sensing built with palladium oxide nanodots decorating aluminum oxide nanosheets (PdO NDs//Al2 O3 NSs) has been achieved via combined template synthesis, photochemical deposition, and oxidation. Typically, the PdO NDs//Al2 O3 NSs are observed with thin NSs (≈17 nm thick) decorated with nanodots (≈3.3 nm in diameter). Beneficially, the sensor prototypes built with PdO NDs//Al2 O3 NSs show excellent long-term stability for 278 days, high selectivity against interfering gases, and outstanding stability against humidity at 300 °C. Remarkably, the sensor prototypes enable detection of a wide-range of 20 ppm - 6 V/V% H2 , and the response and recovery times are ≈5 and 16 s to 1 V/V% H2 , respectively. Theoretically, the heterojunctions of PdO NDs-Al2 O3 NSs with a large specific surface ratio and Al2 O3 NSs as the support exhibit excellent stability and selective H2 sensing. Practically, a sensing device integrated with the PdO NDs//Al2 O3 NSs sensor prototype is simulated for detecting H2 with reliable sensing response.

DHMMF, a natural flavonoid from Resina Draconis, inhibits hepatocellular carcinoma progression via inducing apoptosis and G2/M phase arrest mediated by DNA damage-driven upregulation of p21.

Hepatocellular carcinoma (HCC) is one of the most common cancers worldwide and is extremely malignant in nature. It is an important way to discover anti-cancer drugs from natural products at present. (R)-7,3'-dihydroxy-4'-methoxy-8-methylflavane (DHMMF), a natural flavonoid, was isolated from Resina Draconis which is the red resin from Dracaena cochinchinensis (Lour.) S. C. Chen. However, the anti-hepatoma effect and underlying mechanisms of DHMMF remain unclear. Herein, we demonstrated that DHMMF treatment significantly inhibited the proliferation of human hepatoma HepG2 and SK-HEP-1 cells. The IC50 value of DHMMF for HepG2 and SK-HEP-1 cells were 0.67 µM and 0.66 µM, respectively, while the IC50 value of DHMMF for human normal liver LO2 cells was 120.60 µM. DHMMF induced DNA damage, apoptosis, and G2/M phase arrest in HepG2 and SK-HEP-1 cells. Furthermore, the anti-proliferative and pro-apoptotic effects of DHMMF in human hepatoma cells were mediated by the upregulation of p21. Importantly, DHMMF exhibited potent anti-HCC efficacy in a xenograft mice model and an orthotopic mice model of liver cancer. Additionally, the combined administration of DHMMF and polo-like kinase 1 (PLK1) inhibitor BI 6727 showed a synergistic anti-HCC efficacy. Collectively, we demonstrated that DHMMF treatment induced apoptosis and G2/M phase arrest via DNA damage-driven upregulation of p21 expression in human hepatoma cells. DHMMF may serve as a promising drug candidate for HCC treatment, especially for patients of HCC with low p21 expression. Our results also suggested that DHMMF treatment in combination with PLK1 inhibitor may serve as a potential treatment strategy for patients with HCC.

Network pharmacology and experimental verification to explore the anti-migraine mechanism of Yufeng Ningxin Tablet.

ETHNOPHARMACOLOGICAL RELEVANCE: Yufeng Ningxin Tablet (YNT) is a traditional Chinese medicine formula, that has been used clinically to treat migraine for many years. It is composed of one herb Pueraria lobata var. lobata (Willd.) Ohwi (Relevant Chinese name: Gegen). Previously, it has been recorded by traditional Chinese doctor that Gegen could be used as medicine to treat migraine. However, the underlying mechanism of action remains to be investigated. AIM OF THE STUDY: It was to explore the effect and mechanism of YNT on migraine based on network pharmacology and experimental verification. MATERIALS AND METHODS: First, with the network pharmacology, the effective chemical components and target genes of YNT were filtrated, the YNT-compound-migraine-targets network was constructed. The protein-protein interaction network (PPI) and literature reports were combined to identify potential targets of YNT in the treatment of migraine. Then, the representative compounds of YNT were characterized by LC-MS/MS and the major effect components were identified. Finally, the prediction results of network pharmacology were verified by animal and cell experiments. RESULTS: 7 bioactive components of YNT could act on 97 migraine potential targets. The 5 bioactive components could be characterized comprehensively of YNT. The key therapeutic targets and pathways were collected including 5-HT, CGRP, inflammation and nociceptive factors, and NF-κB signaling pathway. Animal experiments showed that YNT could increase the expression level of 5-HT and reduce the expression of CGRP, NF-κB, c-fos and IL-1ß. YNT could inhibit LPS-induced neuroinflammation by NF-κB in BV2 cells in vitro. Western blotting analysis results showed YNT inhibited the NF-κB and phospho-NF-κB levels. CONCLUSIONS: It is the first time to verify the consistency between the metabolic components of YNT by LC-MS/MS and the active components predicted by network pharmacology. Meanwhile, the potential mechanism of YNT in the treatment of migraine was studied by combining network pharmacology and in vitro and in vivo experiments.