A nanocomposite hydrogel for co-delivery of multiple anti-biofilm therapeutics to enhance the treatment of bacterial biofilm-related infections.

The characteristics of biofilms have exacerbated the issue of clinical antibiotic resistance, rendering it a pressing challenge in need of resolution. The combination of biofilm-dispersing agents and antibiotics can eliminate biofilms and promote healing synergistically in infected wounds. In this study, we developed a novel nanocomposite hydrogel (NC gel) comprised of the poly(lactic acid)-hyperbranched polyglycerol (PLA-HPG) based bioadhesive nanoparticles (BNPs) and a hydrophilic carboxymethyl chitosan (CS) network. The NC gel was designed to co-deliver two biofilm-dispersing agents (an NO-donor SNO, and an α-amylase Am) and an antibiotic, cefepime (Cef), utilizing a synergistic anti-biofilm mechanism in which Am loosens the matrix structure and NO promotes the release of biofilm bacteria via quorum sensing, and Cef kills bacteria. The drug-loaded NC gel (SNO/BNP/CS@Am-Cef) demonstrated sustained drug release, minimal cytotoxicity, and increased drug-bacterial interactions at the site of infection. When applied to mice infected with methicillin-resistant Staphylococcus aureus (MRSA) biofilms in vivo, SNO/BNP/CS@Am-Cef enhanced biofilm elimination and promoted wound healing compared to traditional antibiotic treatments. Our work demonstrates the feasibility of the co-delivery of biofilm-dispersing agents and antibiotics using the NC gel and presents a promising approach for the polytherapy of bacterial biofilm-related infections.

Pangenome analysis of the genus Herbiconiux and proposal of four new species associated with Chinese medicinal plants.

Five Gram-stain-positive, aerobic, non-motile actinobacterial strains designated as CPCC 205763T, CPCC 203386T, CPCC 205716T, CPCC 203406T, and CPCC 203407 were obtained from different ecosystems associated with four kinds of Chinese traditional medicinal plants. The 16S rRNA gene sequences of these five strains showed closely related to members of the genus Herbiconiux of the family Microbacteriaceae, with the highest similarities of 97.4-99.7% to the four validly named species of Herbiconiux. In the phylogenetic trees based on 16S rRNA gene sequences and the core genome, these isolates clustered into the clade of the genus Herbiconiux within the lineage of the family Microbacteriaceae. The overall genome relatedness indexes (values of ANI and dDDH) and the phenotypic properties (morphological, physiological and chemotaxonomic characteristics) of these isolates, readily supported to affiliate them to the genus Herbiconiux, representing four novel species, with the isolates CPCC 203406T and CPCC 203407 being classified in the same species. For which the names Herbiconiux aconitum sp. nov. (type strain CPCC 205763T = I19A-01430T = CGMCC 1.60067T), Herbiconiux daphne sp. nov. (type strain CPCC 203386T = I10A-01569T = DSM 24546T = KCTC 19839T), Herbiconiux gentiana sp. nov. (type strain CPCC 205716T = I21A-01427T = CGMCC 1.60064T), and Herbiconiux oxytropis sp. nov. (type strain CPCC 203406T = I10A-02268T = DSM 24549T = KCTC 19840T) were proposed, respectively. In the genomes of these five strains, the putative encoding genes for amidase, endoglucanase, phosphatase, and superoxidative dismutase were retrieved, which were classified as biosynthetic genes/gene-clusters regarding plant growth-promotion (PGP) functions. The positive results from IAA-producing, cellulose-degrading and anti-oxidation experiments further approved their potential PGP bio-functions. Pangenome analysis of the genus Herbiconiux supported the polyphasic taxonomy results and confirmed their bio-function potential.

Dissolved Organic Phosphorus Removal in Secondary Effluent by Ferrate (VI): Performance and Mechanism.

Dissolved organic phosphorus (DOP), which is recalcitrant in municipal wastewater treatment, accounts for 26-81% of dissolved total phosphorus in the effluent. More importantly, the majority of DOP could be bioavailable, potentially threatening the aquatic environment through eutrophication. This study aimed to develop a ferrate (VI)-based advanced treatment to effectively destruct and remove DOP from secondary effluent and use deoxyribonucleic acid (DNA) and adenosine-5'-triphosphate (ATP) as DOP model compounds to explore the relevant mechanisms. The results showed that ferrate (VI) treatment could efficiently destruct and remove 75% of the DOP in secondary effluent from an activated sludge-adopted municipal wastewater treatment plant, under normal operating conditions. Moreover, the coexistence of nitrate, ammonia, and alkalinity barely affected the effectiveness, while the presence of phosphate significantly inhibited DOP removal. The mechanistic study revealed that ferrate (VI)-induced particle adsorption was the dominant way to achieve DOP reduction, rather than oxidating DOP to phosphate and forming precipitation afterward. Meanwhile, DOP molecules could be effectively decomposed into smaller ones by ferrate (VI) oxidation. This study clearly demonstrated that ferrate (VI) treatment could achieve a promising DOP removal from secondary effluent for mitigating the risk of eutrophication in receiving water bodies.

Corrigendum: Pangenome analysis of the genus Herbiconiux and proposal of four new species associated with Chinese medicinal plants.

[This corrects the article DOI: 10.3389/fmicb.2023.1119226.].

Rumex hanus by. Extract Protects Against Chronic Alcohol-Induced Liver Injury in Mice.

Alcoholic liver disease (ALD) has become a global health problem. The hepatoprotective effects of bioactive ingredients extracted from Rumex hanus by. on chronic alcoholic liver injury was investigated for the first time. The extract from R. hanus by. (ERHB) was obtained by 70% ethanol extraction, and the endotoxin antagonism rate of ERHB was 88.94 ± 1.24% in vitro. The animal experiments demonstrated that ERHB promoted hepatic function by significantly enhancing the activities of alcohol dehydrogenase and acetaldehyde dehydrogenase, and by reducing the activities of cytochrome P450 proteins, alkaline phosphatase, aspartate aminotransferase, and alanine aminotransferase. Furthermore, ERHB improved alcohol-induced dyslipidemia by regulating lipid metabolism. In addition, ERHB ameliorated the alcohol-induced liver injury by inhibiting endotoxin-caused inflammation. Seven compounds with antagonistic activity on endotoxin were identified in ERHB. These results demonstrated that ERHB had protective effects on ALD and if the results can be confirmed in humans, it might be useful as a functional food supplement for ALD treatment.

Characterization of three Stenotrophomonas strains isolated from different ecosystems and proposal of Stenotrophomonas mori sp. nov. and Stenotrophomonas lacuserhaii sp. nov.

Stenotrophomonas spp. have primarily been reported as non-pathogenic, plant-probiotic bacteria, despite the presence of some opportunistic human pathogens in the genus. Here, three Gram-stain negative, rod-shaped, non-spore-forming bacteria, designated as strains CPCC 101365T, CPCC 101269T, and CPCC 101426 were isolated from surface-sterilized medicinal plant roots of a mulberry plant in Chuxiong of the Yunnan Province, freshwater from Erhai Lake in the Yunnan Province, and sandy soils in the Badain Jaran desert in Inner Mongolia Autonomous Region, China, respectively. The 16S rRNA gene sequences analysis of these isolates in comparison with sequences from the GenBank database indicated that they belong to the genus Stenotrophomonas, with nucleotide similarities of 96.52-99.92% to identified Stenotrophomonas members. Phylogenetic analysis based on 16S rRNA gene and genome sequences confirmed that the isolates are members of the genus Stenotrophomonas. Values for genomic average nucleotide identity (ANI; <95%) and digital DNA-DNA hybridization (dDDH; < 70%) indicated that strains CPCC 101365T and CPCC 101269T were well-differentiated from validly described Stenotrophomonas species, while strain CPCC 101426 shared high ANI (97.7%) and dDDH (78.3%) identity with its closest phylogenetic neighbor, Stenotrophomonas koreensis JCM 13256T. The three genomes were approximately 3.1-4.0 Mbp in size and their G + C content ranged in 66.2-70.2%, with values slightly differing between CPCC 101365T (3.4 Mbp; 70.2%), CPCC 101269T (4.0 Mbp; 66.4%), and CPCC 101426 (3.1 Mbp; 66.2%). Genes encoding enzymes involved in the biosynthesis of indole-3-acetic acid (IAA) and siderophores were identified in the genomes of the three isolates, suggesting that these strains might serve roles as plant-growth promoting microorganisms. The polar lipid fractions of the three isolates primarily comprised diphosphatidylglycerol (DPG), phosphatidylglycerol (PG), and phosphatidylethanolamine (PE). The predominant cellular fatty acid was iso-C15: 0, with moderate amounts of antesio-C15: 0, iso-C11: 0, iso C17: 1 É·9c/C16: 0 10-methyl, iso-C14: 0, and C16: 1 É·7c/C16: 1 É·6c. These results indicated that polyphasic characteristics of strains CPCC 101365T and CPCC 101269T differed from other identified Stenotrophomonas species and that strain CPCC 101426 was affiliated with the species Stenotrophomonas koreensis. Accordingly, two novel species of the genus Stenotrophomonas were consequently proposed, corresponding to Stenotrophomonas mori sp. nov. (type strain CPCC 101365T = DY006T = KCTC 82900T) and Stenotrophomonas lacuserhaii sp. nov. (type strain CPCC 101269T = K32T = KCTC 82901T). Highlights: Members of the genus Stenotrophomonas, and particularly Stenotrophomonas maltophilia, are opportunistic human pathogens, but not enough research has evaluated the identification of environmental Stenotrophomonas spp. However, most Stenotrophomonas spp. serves as plant-probiotic bacteria.In this study, we obtained and characterized three Stenotrophomonas strains from different ecosystems. Based on phenotypic differences, chemotaxonomic properties, ANI and dDDH identity values, and phylogenetic analyses, two novel Stenotrophomonas species are proposed for the strains identified here. The encoding genes related to plant-growth promotion in the genomes of the newly recovered Stenotrophomonas spp. were retrieved. Follow-on experiments confirmed that these strains produced the important plant hormone IAA. Thus, these Stenotrophomonas spp. could considerably contribute to shaping and maintaining ecological stability in plant-associated environments, particularly while acting as plant-probiotic microorganisms.

Kaempferol-3-O-Glucuronide Ameliorates Non-Alcoholic Steatohepatitis in High-Cholesterol-Diet-Induced Larval Zebrafish and HepG2 Cell Models via Regulating Oxidation Stress.

NAFLD (non-alcoholic fatty liver disease) is one of the most prominent liver diseases in the world. As a metabolic-related disease, the development of NAFLD is closely associated with various degrees of lipid accumulation, oxidation, inflammation, and fibrosis. Ilex chinensis Sims is a form of traditional Chinese medicine which is used to treat bronchitis, burns, pneumonia, ulceration, and chilblains. Kaempferol-3-O-glucuronide (K3O) is a natural chemical present in Ilex chinensis Sims. This study was designed to investigate the antioxidative, fat metabolism-regulating, and anti-inflammatory potential of K3O. A high-cholesterol diet (HCD) was used to establish steatosis in larval zebrafish, whereby 1mM free fatty acid (FFA) was used to induce lipid accumulation in HepG2 cells, while H2O2 was used to induce oxidative stress in HepG2. The results of this experiment showed that K3O reduced lipid accumulation and the level of reactive oxygen species (ROS) both in vivo (K3O, 40 µM) and in vitro (K3O, 20 µM). Additionally, K3O (40 µM) reduced neutrophil aggregation in vivo. K3O (20 µM) also decreased the level of malondialdehyde (MDA) and significantly increased the level of glutathione peroxidase (GSH-px) in both the HCD-induced larval zebrafish model and H2O2-exposed HepG2 cells. In the mechanism study, keap1, nrf2, tnf-α, and il-6 mRNA were all significantly reversed by K3O (20 µM) in zebrafish. Changes in Keap1 and Nrf2 mRNA expression were also detected in H2O2-exposed HepG2 cells after they were treated with K3O (20 µM). In conclusion, K3O exhibited a reduction in oxidative stress and lipid peroxidation, and this may be related to the Nrf2/Keap1 pathway in the NAFLD larval zebrafish model.

Efficacy of traditional herbal medicine versus transcatheter arterial chemoembolization in postsurgical patients with hepatocellular carcinoma: A retrospective study.

BACKGROUND: Recurrence is a major obstacle to improve the prognosis of hepatocellular carcinoma (HCC) patients. Transcatheter arterial chemoembolization (TACE) has been routinely used as an adjuvant therapy in treating HCC, but efficacy of TACE in preventing the recurrence of HCC remains unsatisfactory. This study aimed to compare the efficacy of a traditional herbal medicine (THM) therapy and TACE in preventing tumor recurrence and improving survival in postsurgical patients with HCC. MATERIALS AND METHODS: A total of 1506 HCC patients were enrolled from January 2008 to June 2017, including 262 patients who received THM therapy and 1244 patients who were treated with TACE. All patients were followed up until the occurrence of outcome event or June 30th, 2019. The recurrence-free survival (RFS) and overall survival (OS) were calculated by the Kaplan-Meier method, and the differences of RFS and OS between THM group and TACE group were analyzed by the log-rank test. Factors affecting the RFS or OS among these patients were assessed by the Cox proportional hazard regression model. A nomogram was built with the factors based on the Cox regression analysis to predict the prognosis. RESULTS: The 1-, 3-, and 5-year RFS were 91.0%, 68.3%, and 49.7%, respectively, in the THM group and 79.4%, 38.6%, and 19.3%, respectively, in the TACE group. The RFS in the THM group was significantly higher than that of the TACE group (P = 6.2 × 10-11). The 1-, 3-, and 5-year OS were significantly improved in the THM group as compared to those in the TACE group (94.3%, 65.2%, and 41.4% vs. 82.7%, 46.0%, and 25.4%, P = 2.2 × 10-11). Multivariate analysis revealed that serum AFP level ≥400 ng/mL, HBV DNA load ≥500 copies/mL, TNM stage III-IV, tumor diameter ≥5 cm, presence of MVI, and multiple tumor nodules were independent risk factors for RFS, while complete tumor encapsulation and THM therapy were protective factors for RFS and OS. The nomogram demonstrated good accuracy in predicting RFS and OS, with the adjusted C-index of 0.748 and 0.796, respectively. CONCLUSION: The efficacy of THM therapy was superior to that of TACE in preventing recurrence and improving survival for HCC patients after hepatectomy.

Influence of hydrotherapy combined with breathing training on lung function and activity ability of patients with thoracolumbar spinal cord injury / 中国综合临床

Objective:To explore the effect of hydrotherapy combined with breathing training on lung function and mobility of patients with thoracolumbar spinal cord injury.Methods:A total of 80 patients with thoracolumbar spinal cord injury admitted to Beijing Rehabilitation Hospital Affiliated to Capital Medical University from April 2018 to March 2020 were selected as observation objects.A prospective cohort study was conducted and randomly divided into observation group and control group with 40 cases in each group.The control group was given routine rehabilitation therapy combined with respiratory training.On the basis of the control group, the observation group was treated with water therapy.The indexes of lung function, motor function, lower limb muscle tension, function evaluation and activities of daily living were compared between the two groups.Results:After intervention, the observation group′s forced vital capacity (FVC) was (3.86±0.82) L, the forced expiratory volume in the first second (FEV1) was (3.76±0.68) L, the maximum ventilation (MVV) was (102.34±10.38) L/min, the maximum suction pressure (MIP) is (50.36±4.62) cmH 2O; the control group FVC was (3.41±0.76) L, and FEV1 was ( 3.35±0.63) L, MVV was (90.67±11.68) L/min, MIP was (44.38±4.85) cmH 2O, the difference between the two groups is statistically significant ( t=2.546, 2.797, 4.723, 5.646, respectively, all P<0.05). After the intervention, the motor function score of the american spinal injury association (ASIA) of the observation group was (58.62±7.56) points, and the modified ashworth scale (MAS) score was (2.74±0.89) points; The ASIA motor function score of the control group was (42.24±6.40) points, and the MAS score was (3.36±0.94) points.The difference between the two groups was statistically significant ( t=10.459 and -3.029, respectively, all P<0.05). After intervention, the observation group′s spinal cord independence measure (SCIM III) score was (75.33±10.72) points, and the modified barthel index (MBI) was (66.64±6.34) points; the SCIM III score of the control group was (68.34±9.55) points, and the MBI score was (57.52±6.77) points, the difference between the two groups was statistically significant ( t=3.079 and 6.219, respectively, all P<0.05). Conclusion:Hydrotherapy combined with breathing training can significantly improve lung function and respiratory muscle strength in patients with thoracolumbar spinal cord injury, and improve motor function and ability of daily living.

Composition, physicochemical properties, and anti-fatigue activity of water-soluble okra (Abelmoschus esculentus) stem pectins.

Okra, Abelmoschus esculentus (L.) Moench, an annual herbaceous plant, is widely distributed in tropical and subtropical regions. Water-soluble pectic hydrocolloids from okra stems (HOS) were extracted and purified using polydivinylbenzene HP-20 resins. The sugar composition of the purified HOS with an weight-average molecular weight of 178.4 ± 2.1 kDa and a polydispersity index of 1.02 ± 0.02 contained galacturonic acid (34%), galactose (31%), rhamnose (21%), arabinose (4.2%), glucuronic acid (2.5%), xylose (1.2%), and other monosaccharides (6.1%) by weight. Its favorable rheological behaviors were evident on relatively higher concentrations (20, 25, and 30 mg/mL) and moderately lower pH levels (3 and 5) of HOS. The anti-fatigue experiments in vivo demonstrated that a high dose of HOS (450 mg/kg feed) prolonged the exhaustive swimming time of mice, significantly induced an increase in blood glucose and glycogen, and decreased lactic acid and serum urea nitrogen levels. HOS digestion in vivo was fairly conducive to the improvement of energy storage capacity and renal function for physically induced fatigue, compared with the conventional herbal supplement Panax quinquefolium. Accordingly, HOS exhibits potential for reutilization of okra stem waste.

Influence of fermentation on antioxidant and hypolipidemic properties of maifanite mineral water-cultured common buckwheat sprouts.

Buckwheat sprouts (BS) becomes popular due to its' health-promoting properties as food product. The effects of fermentation with Saccharomyces cerevisiae and Lactobacillus plantarum on antioxidant and hypolipidemic activities as well as functional composition in common BS cultivated in maifanite mineral water were investigated here. DPPH and ·OH results showed higher antioxidant potential in fermented BS compared to unfermented BS, due to the higher rutin, orientin, isoorientin, vitexin, isovitexin, and total phenolic and flavonoid contents. The S. cerevisiae-fermented BS also exhibited 113% and 110% higher DPPH and ·OH scavenging activities than the L. plantarum-fermented BS, respectively. In hyperlipidemic mice, blood lipid parameters were improved as dose-dependent manner when supplemented the food with S. cerevisiae-fermented BS. Fermented BS also restored liver antioxidant levels significantly. The fermented BS had greater effect on different parameters than those of unfermented BS. Therefore, fermentation is a valuable method to enhance the bioactive potential of BS.

Dihydromyricetin increases endothelial nitric oxide production and inhibits atherosclerosis through microRNA-21 in apolipoprotein E-deficient mice.

Natural products were extracted from traditional Chinese herbal emerging as potential therapeutic drugs for treating cardiovascular diseases. This study examines the role and underlying mechanism of dihydromyricetin (DMY), a natural compound extracted from Ampelopsis grossedentata, in atherosclerosis. DMY treatment significantly inhibits atherosclerotic lesion formation, proinflammatory gene expression and the influx of lesional macrophages and CD4-positive T cells in the vessel wall and hepatic inflammation, whereas increases nitric oxide (NO) production and improves lipid metabolism in apolipoprotein E-deficient (Apoe-/- ) mice. Yet, those protective effects are abrogated by using NOS inhibitor L-NAME in Apoe-/- mice received DMY. Mechanistically, DMY decreases microRNA-21 (miR-21) and increases its target gene dimethylarginine dimethylaminohydrolase-1 (DDAH1) expression, an effect that reduces asymmetric aimethlarginine (ADMA) levels, and increases endothelial NO synthase (eNOS) phosphorylation and NO production in cultured HUVECs, vascular endothelium of atherosclerotic lesions and liver. In contrast, systemic delivery of miR-21 in Apoe-/- mice or miR-21 overexpression in cultured HUVECs abrogates those DMY-mediated protective effects. These data demonstrate that endothelial miR-21-inhibited DDAH1-ADMA-eNOS-NO pathway promotes the pathogenesis of atherosclerosis which can be rescued by DMY. Thus, DMY may represent a potential therapeutic adjuvant in atherosclerosis management.

Effects of individual volatile fatty acids (VFAs) on phosphorus recovery by magnesium ammonium phosphate.

Volatile fatty acids (VFAs) are a major component of dissolved organic matter in alkaline fermentation supernatants. In this study, effects of different VFAs (acetate, propionate, and butyrate) on phosphorus recovery, as magnesium ammonium phosphate (MgNH4PO4·6H2O, or MAP), were studied. Results showed that optimal pH was 9.5 and MAP purity was ∼70% in VFA-free wastewater. With VFA addition, MAP purities of precipitates were higher, reaching 75%-85%. The crystalline characterization of precipitates suggested that VFAs had a weak complexation ability with Mg2+ and NH4+. Further, pH changes during the MAP crystallization process were monitored and results indicated VFAs only contributed to the alkalinity condition, which, in turn, improved the MAP crystallization process. These data provide for a better understanding of P recovery by MAP precipitates from VFA-rich fermented supernatants.

One-step Ferrate(VI) treatment as a core process for alternative drinking water treatment.

Traditional water treatment plants adopt multiple treatments to sequentially treat raw water for producing potable water. Besides complex treatment design and operation, they typically require a large space to accommodate different reactors. Furthermore, emerging issues (e.g. poor removal of persistent micro-pollutants) challenge the conventional treatment train. In this study, bench-scale tests were performed with real surface waters to evaluate ferrate(VI) treatment as a key alternative process for traditional water treatment. Of note, most earlier investigations on ferrate(VI) for water treatment utilized ferrate(VI) merely for pre- or post-treatment or simply as a disinfecting agent. Fundamentally different from the previous efforts, this study aimed to assess whether one-step ferrate(VI) addition, coupled with sedimentation, provided a comprehensive treatment, better than or equivalent to conventional surface water treatment. Results show that ferrate(VI) could simultaneously and effectively remove turbidity, degrade natural organic matter (NOM), and inactivate bacterial indicators in one single dose. The treatment performance relied heavily on ferrate(VI) dose and pH. Generally, higher ferrate(VI) dose improved the treatment results, except that it might re-suspend particles at a high dose at an alkaline condition. Lower pH favored coagulation due to reduction of zeta potentials on particle surface and promotion of their aggregation and enhanced the degradation of NOM because of higher Fe(VI) reactivity toward reductive moieties. In contrast, higher pH benefited the disinfection efficiency due to better stability and greater exposure of ferrate(VI). This study demonstrates that ferrate(VI) treatment can serve as a core treatment process in alternative water treatment designs for addressing various challenges.

Brewing Rutin-Enriched Lager Beer with Buckwheat Malt as Adjuncts.

Brewing with buckwheat as an ingredient has been proven to be successful in several previous studies. However, few studies have focused on the effects of buckwheat on the rutin content and antioxidant activity of beer. In order to develop a lager beer with high rutin content and desirable sensory characteristics, tartary buckwheat malt was used as a brewing adjunct. The results showed that the rutin-degrading enzyme was the key factor affecting the rutin content in the wort and beer. Compared to beer made using the common mashing method, the rutin content in the buckwheat beers produced using an improved mashing method was approximately 60 times higher. The total flavonoid contents in buckwheat beers also depended strongly on the mashing methods, ranging from 530.75 to 1,704.68 mg QE/l. The rutin-rich beers also showed better oxidative stability during forced-aging. Meanwhile, the buckwheat beers were found to be acceptable in terms of the main quality attributes, flavor, and taste.

Identification and analysis of components in Shen-Fu-Shu granule extract and in rat plasma after oral administration by UPLC-ESI/Q-TOF-MS.

BACKGROUND AND OBJECTIVES: Shen-Fu-Shu granule is traditional Chinese herb formula for acute and chronic renal failure. This work was aimed to identify the compounds in Shen-Fu-Shu granule extract and absorbed compounds in rat plasma following oral administration of Shen-Fu-Shu granule. METHODS: A high-resolution and high-sensitivity ultra-performance liquid chromatography with electrospray ionization quadrupole time-of-flight tandem mass spectrometry in positive and negative ion mode were established. The methodology of plasma pharmacochemistry was adopted to analyze the herbal components in vivo. A post-acquisition data processing software UNIFI could automatically, rapidly and accurately achieve the qualitative analysis of the chemical components in Shen-Fu-Shu granule extract and the absorbed components (and their metabolites) in rat plasma after oral administration of Shen-Fu-Shu granule. RESULTS: Combined with fragments and structure information of LC-Q-TOF-MS, a total of 264 compounds were detected and identified in Shen-Fu-Shu granule extract, while 66 absorbed components (including 38 prototype compounds and 28 metabolites) in plasma were discovered or tentatively characterized in rat plasma. CONCLUSIONS: This study offers a systematically applicable approach for rapid screening and identification of absorbed components derived from multi-herb prescription. It is helpful for understanding the material basis of its therapeutic effects and provides useful information for further study of mechanism of action of Shen-Fu-Shu granule.

A 0.2 V Micro-Electromechanical Switch Enabled by a Phase Transition.

Micro-electromechanical (MEM) switches, with advantages such as quasi-zero leakage current, emerge as attractive candidates for overcoming the physical limits of complementary metal-oxide semiconductor (CMOS) devices. To practically integrate MEM switches into CMOS circuits, two major challenges must be addressed: sub 1 V operating voltage to match the voltage levels in current circuit systems and being able to deliver at least millions of operating cycles. However, existing sub 1 V mechanical switches are mostly subject to significant body bias and/or limited lifetimes, thus failing to meet both limitations simultaneously. Here 0.2 V MEM switching devices with ≳106 safe operating cycles in ambient air are reported, which achieve the lowest operating voltage in mechanical switches without body bias reported to date. The ultralow operating voltage is mainly enabled by the abrupt phase transition of nanolayered vanadium dioxide (VO2 ) slightly above room temperature. The phase-transition MEM switches open possibilities for sub 1 V hybrid integrated devices/circuits/systems, as well as ultralow power consumption sensors for Internet of Things applications.

An LC-MS/MS method for determination of bioactive components of liquorice and Semen Strychni in rat plasma: Application to a pharmacokinetics study.

Semen Strychni is known for its treatment of rheumatic arthritis with a low therapeutic index. Liquorice contributes a lot in herb detoxification according to the traditional Chinese medicine theory. A simple, rapid, and sensitive liquid chromatography-mass spectrometric method (LC-MS) was developed and validated for simultaneous determination of main bioactive ingredients in liquorice and Semen Strychni in rat plasma. Using moclobemide and cyproterone acetate as the internal standards, the analytes were pretreated via protein precipitation with methanol. An Ultimate AQ-C18 column (3.0 µm, 3.0 × 100 mm) was employed for chromatographic separation, combining with gradient elution. The mobile phase consisted of 0.07% formic acid and 0.12% ammonium acetate in aqueous phase (A) and acetonitrile in organic phase (B). The elution program was as follows: 0-0.5 min, 20% B; 0.5-1 min, 20-60% B; 1-7 min, 60-85% B; and 7-7.5 min, returned to 20% B, then continued to 12 min. Selected reaction monitoring was performed in both positive and negative ESI. Positive mode was adopted for detection of strychnine, brucine, and moclobemide, while negative mode was used for glycyrrhizic acid, glycyrrhetinic acid, liquiritigenin, isoliquiritigenin, liquiritin, and cyproterone acetate. The method was validated for specificity, linearity, matrix effect, recovery, precision, accuracy, and stability. The results show that this method is sensitive, accurate and robust for biological matrix analysis. Moreover, the proposed method was applied to a pharmacokinetic study in Sprague-Dawley rats for investigating the mechanism of which liquorice detoxifies Semen Strychni.

The Ethanol Extract of Licorice (Glycyrrhiza uralensis) Protects against Triptolide-Induced Oxidative Stress through Activation of Nrf2.

To investigate the potential role of nuclear factor erythroid 2-related factor 2 (Nrf2) in licorice ethanol extract (LEE) against triptolide- (TP-) induced hepatotoxicity, HepG2 cells were exposed to LEE (30, 60, and 90 mg·L-1) for 12 h and then treated with TP (50 nM) for 24 h. Besides, an acute liver injury model was established in ICR mice by a single dose of TP (1.0 mg·kg-1, i.p.). Relevant oxidant and antioxidant mediators were analyzed. TP led to an obvious oxidative stress as evidenced by increasing levels of ROS and decreasing GSH contents in HepG2 cells. In vitro results were likely to hold true in in vivo experiments. LEE protected against TP-induced oxidative stress in both in vitro and in vivo conditions. Furthermore, the decreased level of Nrf2 in the TP-treated group was observed. The mRNA levels of downstream genes decreased as well in ICR mice liver, whereas they increased in HepG2 cells. In contrast, LEE pretreatment significantly increased the level of Nrf2 and its downstream genes. LEE protects against TP-induced oxidative stress partly via the activation of Nrf2 pathway.

[Study of polymorphisms of genes related to folic acid metabolism among women of child-bearing age from Shanxi].

OBJECTIVE: To analyze polymorphisms of genes related to folic acid metabolism among women of child-bearing age from Shanxi. METHODS: Buccal smears were collected from 1070 women of child bearing age with cotton swabs. Sequences of MTHFR C667T and A1298C, MTRR A66G, and SLC19A1 A80G were determined by DNA sequencing. The results were compared with data from other regions of China. RESULTS: For MTHFR C667T, the wild type homozygote, heterozygous mutants, and homozygous mutants have respectively accounted for 20.5%, 50.3%, and 29.2% of the study group, with the frequency of the mutant T allele being 54.4%. For MTHFR A1298C, these were 68.7%, 29.3%, and 2.0%, with the frequency of mutant C allele being 16.6%. For MTRR A66G, the above frequencies were 51.5%, 41.8%, and 6.7%, with the frequency of the mutant G allele being 27.6%. For SLC19A1 A80G, these were 29.2%, 48.0%, 22.8%, with the frequency of mutation G allele being 46.8%. Compared with other regions of China, women of child-bearing age from Shanxi has shown a significant difference in allelic distribution of MTRR A66G and SLC19A1 A80G (P<0.05). CONCLUSION: The polymorphisms of genes related to folic acid metabolism showed significant regional difference. Over half of women from Shanxi have carried high-risk alleles for folic acid insufficiency and should have individualized folic acid supplement.