Integrated phenotypic, transcriptomics and metabolomics: growth status and metabolite accumulation pattern of medicinal materials at different harvest periods of Astragalus Membranaceus Mongholicus.

BACKGROUND: Astragalus membranaceus var. mongholicus (Astragalus), acknowledged as a pivotal "One Root of Medicine and Food", boasts dual applications in both culinary and medicinal domains. The growth and metabolite accumulation of medicinal roots during the harvest period is intricately regulated by a transcriptional regulatory network. One key challenge is to accurately pinpoint the harvest date during the transition from conventional yield content of medicinal materials to high and to identify the core regulators governing such a critical transition. To solve this problem, we performed a correlation analysis of phenotypic, transcriptome, and metabolome dynamics during the harvesting of Astragalus roots. RESULTS: First, our analysis identified stage-specific expression patterns for a significant proportion of the Astragalus root genes and unraveled the chronology of events that happen at the early and later stages of root harvest. Then, the results showed that different root developmental stages can be depicted by co-expressed genes of Astragalus. Moreover, we identified the key components and transcriptional regulation processes that determine root development during harvest. Furthermore, through correlating phenotypes, transcriptomes, and metabolomes at different harvesting periods, period D (Nov.6) was identified as the critical period of yield and flavonoid content increase, which is consistent with morphological and metabolic changes. In particular, we identified a flavonoid biosynthesis metabolite, isoliquiritigenin, as a core regulator of the synthesis of associated secondary metabolites in Astragalus. Further analyses and experiments showed that HMGCR, 4CL, CHS, and SQLE, along with its associated differentially expressed genes, induced conversion of metabolism processes, including the biosynthesis of isoflavones and triterpenoid saponins substances, thus leading to the transition to higher medicinal materials yield and active ingredient content. CONCLUSIONS: The findings of this work will clarify the differences in the biosynthetic mechanism of astragaloside IV and calycosin 7-O-ß-D-glucopyranoside accumulation between the four harvesting periods, which will guide the harvesting and production of Astragalus.

Fermented natto powder alleviates obesity by regulating LXR pathway and gut microbiota in obesity rats.

AIM: This study aimed to investigate the positive effect of natto powder on obese rats fed with a high-fat diet (HFD). METHODS AND RESULTS: Sprague-Dawley rats were fed with a HFD for 8 weeks continuously and gavaged with natto powder, respectively, for 8 weeks starting from the ninth week. The results showed that natto powder significantly reduced the body weight of rats and maintained the balance of cholesterol metabolism in the body by inhibiting the activity of liver X receptors (LXR) target genes, increasing the active expression of cholesterol 7 alpha-hydroxylase, and reducing the active expression of sterol-regulatory element-binding protein and 3-hydroxy-3-methylglutaryl coenzyme A reductase (HMGCR). Furthermore, natto powder increased the relative abundance of potentially beneficial microbiota in gut and decreased the relative abundance of obesity-related harmful bacteria, and also increased the Bacteroidetes/Firmicutes ratio and improved the composition of gut microbiota. CONCLUSIONS: Natto powder maintains the balance of cholesterol metabolism by inhibiting the LXR pathway and regulating the gut microbiota.

Structural Characterization and Properties of Modified Soybean Meal Protein via Solid-State Fermentation by Bacillus subtilis.

Soybean meal (SBM) is a high-quality vegetable protein, whose application is greatly limited due to its high molecular weight and anti-nutritional properties. The aim of this study was to modify the protein of soybean meal via solid-state fermentation of Bacillus subtilis. The fermentation conditions were optimized as, finally, the best process parameters were obtained, namely fermentation temperature of 37 °C, inoculum amount of 12%, time of 47 h, and material-liquid ratio of 1:0.58, which improved the content of acid-soluble protein. To explore the utilization of modified SBM as a food ingredient, the protein structure and properties were investigated. Compared to SBM, the protein secondary structure of fermented soybean meal (FSBM) from the optimal process decreased by 8.3% for α-helix content, increased by 3.08% for ß-sheet, increased by 2.71% for ß-turn, and increased by 2.51% for random coil. SDS-PAGE patterns showed that its 25-250 KDa bands appeared to be significantly attenuated, with multiple newborn peptide bands smaller than 25 KDa. The analysis of particle size and zeta potential showed that fermentation reduced the average particle size and increased the absolute value of zeta potential. It was visualized by SEM and CLSM maps that the macromolecular proteins in FSBM were broken down into fragmented pieces with a folded and porous surface structure. Fermentation increased the solubility, decreased the hydrophobicity, increased the free sulfhydryl content, decreased the antigenicity, improved the protein properties of SBM, and promoted further processing and production of FSBM as a food ingredient.

Optimization of Mixed Fermentation Conditions of Dietary Fiber from Soybean Residue and the Effect on Structure, Properties and Potential Biological Activity of Dietary Fiber from Soybean Residue.

Soybean residue is a by-product of soybean product production that is wasted unreasonably at present. Accomplishing the efficient utilization of soybean residue can save resources. A composite microbial system was constructed using lactic acid bacteria (LAB) and Saccharomyces cerevisiae (SC), and modified soybean residue was prepared by solid fermentation. In order to explore the value of modified soybean residue as a food raw material, its physical and chemical properties, adsorption properties, and antioxidant properties were studied. The results showed that the soluble dietary fiber (SDF) yield of mixed fermentation (MF) increased significantly. Both groups of soybean residues had representative polysaccharide infrared absorption peaks, and MF showed a looser structure and lower crystallinity. In terms of the adsorption capacity index, MF also has a higher adsorption capacity for water molecules, oil molecules, and cholesterol molecules. In addition, the in vitro antioxidant capacity of MF was also significantly higher than that of unfermented soybean residue (UF). In conclusion, our study shows that mixed fermentation could increase SDF content and improve the functional properties of soybean residue. Modified soybean residue prepared by mixed fermentation is the ideal food raw material.

In Vivo 18 F-APN-1607 Tau Positron Emission Tomography Imaging in MAPT Mutations: Cross-Sectional and Longitudinal Findings.

BACKGROUND: Frontotemporal lobar degeneration with tauopathy caused by MAPT (microtubule-associated protein tau) mutations is a highly heterogenous disorder. The ability to visualize and longitudinally monitor tau deposits may be beneficial to understand disease pathophysiology and predict clinical trajectories. OBJECTIVE: The aim of this study was to investigate the cross-sectional and longitudinal 18 F-APN-1607 positron emission tomography/computed tomography (PET/CT) imaging findings in MAPT mutation carriers. METHODS: Seven carriers of MAPT mutations (six within exon 10 and one outside of exon 10) and 15 healthy control subjects were included. All participants underwent 18 F-APN-1607 PET/CT at baseline. Three carriers of exon 10 mutations received follow-up 18 F-APN-1607 PET/CT scans. Standardized uptake value ratio (SUVR) maps were obtained using the cerebellar gray matter as the reference region. SUVR values observed in MAPT mutation carriers were normalized to data from healthy control subjects. A regional SUVR z score ≥ 2 was used as the criterion to define positive 18 F-APN-1607 PET/CT findings. RESULTS: Although the seven study patients had heterogenous clinical phenotypes, all showed a significant 18 F-APN-1607 uptake characterized by high-contrast signals. However, the anatomical localization of tau deposits differed in patients with distinct clinical symptoms. Follow-up imaging data, which were available for three patients, demonstrated worsening trends in patterns of tau accumulation over time, which were paralleled by a significant clinical deterioration. CONCLUSIONS: Our data represent a promising step in understanding the usefulness of 18 F-APN-1607 PET/CT imaging for detecting tau accumulation in MAPT mutation carriers. Our preliminary follow-up data also suggest the potential value of 18 F-APN-1607 PET/CT for monitoring the longitudinal trajectories of frontotemporal lobar degeneration caused by MAPT mutations. © 2021 International Parkinson and Movement Disorder Society.

Idiomarina rhizosphaerae sp. nov. isolated from rhizosphere soil of Kalidium cuspidatum, and reclassification of Idiomarina andamanensis as Pseudidiomarina andamanensis comb. nov., and Idiomarina mangrovi as Pseudidiomarina mangrovi comb. nov.

A Gram-stain-negative, strictly aerobic, gliding motile, non-spore forming, rod-shaped indole-3-acetic acid producing bacterial strain, designated M1R2S28T, was isolated from the rhizosphere soil of Kalidium cuspidatum, in Tumd Right Banner, Inner Mongolia, China. Strain M1R2S28T grew at pH 5.0-10.0 (optimum 8.0), 10-45 °C (optimum 37 °C), in the presence of 0-20% (w/v) NaCl (optimum 5%). The phylogenetic trees based on the 16S rRNA gene sequences and the core-genome both revealed that strain M1R2S28T clustered tightly with Idiomarina loihiensis L2-TRT, and shared 99.3, 99.2, 98.7, and < 98.7% of the 16S rRNA gene sequence similarities with I. loihiensis L2-TRT, I. abyssalis KMM 227 T, I. ramblicola R22T, and all the other current type strains. The strain contained ubiquinone-8 (Q-8) as the sole respiratory quinone. Its major polar lipids were phosphatidylethanolamine, phosphatidylglycerol, diphosphatidylglycerol, an unidentified aminolipid, an unidentified phospholipid, and three unidentified lipids. Its major fatty acids were iso-C15:0, iso-C17:0, and iso-C17:1 ω9c. The genomic DNA G + C content was 46.8%. The average nucleotide identity based on BLAST (ANIb) and the digital DNA-DNA hybridization (dDDH) values of strain M1R2S28T to I. loihiensis L2-TRT, I. ramblicola R22T, and I. abyssalis KMM 227 T were 93.0, 82.9, and 81.8%, and 51.2, 26.0, and 25.0%, respectively. The phylogenetic and physiological results allowed the discrimination of strain M1R2S28T from its phylogenetic relatives. Idiomarina rhizosphaerae sp. nov. is, therefore, proposed with strain M1R2S28T (= CGMCC 1.19026 T = KCTC 92133 T) as the type strain. Additionally, based on the phylogenomic and genomic analysis results, Idiomarina andamanensis and Idiomarina mangrovi were transferred into genus Pseudidiomarina and be named Pseudidiomarina andamanensis comb. nov. and Pseudidiomarina mangrovi comb. nov., respectively.

Luteimonas saliphila sp. nov. and Luteimonas salinisoli sp. nov., two novel strains isolated from saline soils.

Two Gram-stain-negative, motile with single polar flagellum, rod-shaped bacterial strains, named SJ-9T and SJ-92T, were isolated from saline soils from Inner Mongolia, PR China. SJ-9T and SJ-92T grew at pH 6.5-10.0 and 7.0-11.0, 10-35 °C, and in the presence of 0-5 % and 0-8 % NaCl, respectively. Both strains were positive for oxidase, and negative for catalase. The results of phylogenetic analysis based on 16S rRNA gene sequences indicated that SJ-9T clustered with Luteimonas marina FR1330T (sharing 97.9 % 16S rRNA gene similarity), Luteimonas huabeiensis HB2T (96.5 %), 'Luteimonas wenzhouensis' YD-1 (96.6 %), and Luteimonas composti CC-YY255T (95.1 %), and shared low 16S rRNA gene similarities (<97.0 %) with all the other type strains; while SJ-92T clustered with Luteimonas aestuarii B9T (98.2 %), and shared low 16S rRNA gene similarities (<98.0 %) with all the other type strains. The two strains shared 97.4 % 16S rRNA gene similarity with each other. The major cellular fatty acids of both strains are iso-C15 : 0 and summed feature 9 (C16 : 0 10-methyl and/or iso-C17 : 1ω9c). The major polar lipids of both strains are diphosphatidylglycerol, phosphatidylglycerol and phosphatidylethanolamine. The only respiratory quinone for both strains is ubiquinone-8 (Q-8). The genomic DNA G+C contents are 69.3 and 70.4 mol%, respectively. The digital DNA-DNA hybridization (dDDH) and average nucleotide identity by blast (ANIb) values between the two strains were 22.6 and 77.5 %, while the values between SJ-9T and 'L. wenzhouensis' YD-1, L. marina FR1330T, and L. huabeiensis HB2T were 38.1, 39.2, and 21.9 %, and 82.5, 84.4, and 78.5 %, while those between SJ-92T and L. aestuarii B9T were 21.3 and 76.7 %. On the basis of the phenotypic, physiological and phylogenetic results, SJ-9T and SJ-92T represent two novel species of the genus Luteimonas, for which the names Luteimonas saliphila [type stain SJ-9T (=CGMCC 1.17377T=KCTC 82248T)] and Luteimonas salinisoli [type strain SJ-92T (=CGMCC 1.17695T=KCTC 82208T)] are proposed.

Clinical characteristics of sitosterolemic children with xanthomas as the first manifestation.

BACKGROUND: Sitosterolemia (STSL) is an extremely rare genetic disease. Xanthomas as the first symptom are frequently misinterpreted as familial hypercholesterolemia (FH) in children. Inappropriate treatment may deteriorate the condition of STSL. OBJECTIVES: To present the clinical and laboratory characteristics of xanthomatous children diagnosed with sitosterolemia in comparison with childhood FH with xanthomas. METHODS: We summarized and compared the clinical characteristics of STSL and FH patients with xanthomas as the first manifestations and investigated the different indicators between the STSL and FH groups, as well as their diagnostic values for STSL. RESULTS: Two tertiary pediatric endocrinology departments contributed ten STSL cases. Five of the STSL patients (50%) experienced mild anemia, whereas two (20%) had vascular complications. The xanthomas of the STSL group displayed morphologies comparable to those of the FH group. There were ten cases of homozygous FH (HoFH) with xanthomas as the predominant symptom of the control group who had no anemia. The serum cholesterol (Chol) levels of the STSL and FH groups were 12.57 (9.55 ~ 14.62) mmol/L and 17.45 (16.04 ~ 21.47) mmol/L, respectively (p value 0.002). The serum low-density lipoprotein cholesterol (LDL-c) levels of the STSL and FH groups were 9.26 ± 2.71 mmol/L and 14.58 ± 4.08 mmol/L, respectively (p value 0.003). Meanwhile, the mean platelet volume (MPV) levels of the STSL and FH groups were 11.00 (9.79 ~ 12.53) fl. and 8.95 (8.88 ~ 12.28) fl., respectively (p value 0.009). The anemia proportions of the STSL and FH groups were 50% and 0%, respectively (p value 0.033). The AUC values of Chol, LDL-c, MPV, hemoglobin (Hb) for the diagnosis of STSL were 0.910, 0.886, 0.869, 0.879, respectively. Chol ≤ 15.41 mmol/L, LDL-c ≤ 13.22 mmol/L, MPV ≥ 9.05 fl., or Hb≤120 g/L were the best thresholds for diagnosing STSL with childhood xanthomas. CONCLUSION: The xanthoma morphology of STSL patients resembles that of FH patients. Xanthomas as the initial symptom of a child with Chol ≤ 15.41 mmol/L, LDL-c≤13.22 mmol/L, MPV ≥ 9.05 fl., or Hb≤120 g/L, he was most likely to have STSL.

[Quality assessment of different forms of Cervi Cornu Pantotrichum based on content of free amino acids].

In this study, we analyzed the composition and content of 25 free amino acids in 32 batches of different forms of Cervi Cornu Pantotrichum(CCP; one-branched, two-branched, and three-branched) from 15 producing areas. The clustering analysis and orthogonal partial least squares discriminant analysis(OPLS-DA) were performed based on the content of 25 free amino acids. Potential differential metabolites were identified based on VIP value. The results showed that there were 25 free amino acids in CCP, and the average content of essential, non-essential, and total amino acids was 6.13, 32.99, and 39.12 mg·g~(-1), respectively. The clustering analysis and OPLS-DA demonstrated that 25 free amino acids had different content among the three forms of CCP, of which two-branched CCP samples were separately gathered into a group. Five differential components, including glutamic acid, tryptophan, ornithine, γ-aminobutyric acid, and hydroxylysine, were screened out as potential quality markers for the identification of different forms of CCP. This study provides a theoretical basis for the quality evaluation, processing, and utilization of different forms of CCP.

Protection by ginseng saponins against cyclophosphamide-induced liver injuries in rats by induction of cytochrome P450 expression and mediation of the l-arginine/nitric oxide pathway based on metabolomics.

Ginseng saponins (GS) are the main active compounds in Panax ginseng and have been proven to be highly effective in attenuating the side effects of chemotherapy. However, there have been no reports on the mechanism of action of GS. Treatment with GS has certain benefits, including decreasing the toxicity levels in the liver [alanine aminotransferase (ALT), albumin (ALB), alkaline phosphatase (ALP), aspartate transaminase (AST)], reducing oxidative stress [malondialdehyde (MDA), nitric oxide (NO)], diminishing inflammatory factors [interleukin-1ß (IL-1ß) and tumor necrosis factor-α (TNF-α) levels], and augmenting the levels of glutathione (GSH) and superoxide dismutase (SOD). The pharmacokinetics study showed that the area under the curve from 0 to 24 hr (AUC 0-24 hr) of 4-ketocyclophosphamide (4-KetoCTX) and carboxyphosphamide (CPM) was significantly increased after GS treatment. This study found that GS treatment can reduce chloroacetaldehyde (CAA) production by affecting CYP3A4, CYP2B6, and CYP2C9 protein expression in the liver. For the metabolomics study, GS attenuated the abnormalities of amino acid metabolic pathways in CP-induced liver injuries of rats and significantly enhanced the l-arginine level while reducing the serum nitric oxide (NO) level. This outcome was confirmed by the inhibition of the activities of NO synthase in the liver of rats.

Schisandrin B Attenuates Hepatic Stellate Cell Activation and Promotes Apoptosis to Protect against Liver Fibrosis.

The activation of hepatic stellate cells (HSC) plays a key role in the progression of hepatic fibrosis, it is essential to remove activated HSC through apoptosis to reverse hepatic fibrosis. Schisandrin B (Sch B) is the main chemical component of schisandrin lignan, and it has been reported to have good hepatoprotective effects. However, Schisandrin B on HSC apoptosis remains unclear. In our study, we stimulated the HSC-T6 and LX-2 cell lines with TGF-ß1 to induce cell activation, and the proliferation and apoptosis of the activated HSC-T6 and LX-2 cells were detected after treatment with different doses of Schisandrin B. Flow cytometry results showed that Sch B significantly reduced the activity of activated HSC-T6 and LX-2 cells and significantly induced apoptosis. In addition, the cleaved-Caspase-3 levels were increased, the Bax activity was increased, and the Bcl-2 expression was decreased in HSC-T6 and LX-2 cells treated with Sch B. Our study showed that Sch B inhibited the TGF-ß1-induced activity of hepatic stellate cells by promoting apoptosis.

[Key to Indigo Naturalis' oral effectiveness: in vivo and in vitro verification of bile action].

Indigo Naturalis( IN) is mainly composed of 10% organic matter and 90% inorganic matter,with a poor wettability and strong hydrophobicity. Indigo,indirubin and effective ingredients are almost insoluble in water. And how it exerts its effect after oral administration still needs to be revealed. For this reason,this study put forward the hypothesis that " Indigo Naturalis forms a slightly soluble calcium carbonate carrier in a strong acid environment of gastric fluid,and organic substances are solubilized in the bile environment of intestinal fluid",and then verified the hypothesis. First,the dissolution apparatus was used to simulate the change process of IN in different digestive fluid,and the effects of low-dose and normal bile on the dissolution of inorganic substances and the release of organic substances were compared. After the surface morphology and element changes of IN in different digestive fluid were observed,it was found that bile is the key to promoting the dissolution of organic and inorganic substances in IN. Furthermore,the rat fever model induced by 2,4-dinitrophenol was used to study the antipyretic effect of IN in normal rats and bile duct ligation rats. It was found that the antipyretic effect of IN on normal rats was better than that of bile duct ligation rats. The above results indicated that after oral administration of IN,the calcium carbonate carrier was transformed into a slightly soluble state in acidic gastric fluid,and a small amount of organic matter was released. When IN entered the intestinal fluid mixed with bile,the carrier dissolved in a large amount,and indigo and indirubin were dissolved in a large amount,so as to absorb the blood and exert the effect. This study has a certain significance for guiding clinical application of IN. For patients with insufficient bile secretion( such as bile duct resection),oral administration with IN may not be effective and shall be paid attention.

Ginsenoside Rk1 alleviates LPS-induced depression-like behavior in mice by promoting BDNF and suppressing the neuroinflammatory response.

Ginsenoside Rk1, a saponin component produced by heat-processed ginseng, possesses anti-inflammatory and antitumor activities. The aim of our study was to explore the effects of Rk1 on Lipopolysaccharide (LPS)-induced depression-like behavior in mice and to observe its effects on oxidative stress, the inflammatory response and brain-derived neurotrophic factor (BDNF) - tropomyosin-related kinase B (TrkB) signaling. After mice were pretreated with Rk1 (5, 10, and 20 mg/kg), the immobility time in both the forced swimming test (FST) and the tail suspension test (TST) was reduced, suggesting that Rk1 effectively improved depression-like symptoms. Rk1 (10 and 20 mg/kg) and Fluoxetine (Flu, 20 mg/kg) increased the activity of the antioxidant enzyme SOD in the brain and protected against lipid peroxidation. Different concentrations of Rk1 (10 and 20 mg/kg) and Flu significantly decreased the levels of tumor necrosis factor (TNF)-α and interleukin (IL)-1 in serum, while Rk1 (5, 10, and 20 mg/kg) and Flu reduced the concentrations of IL-6 in a dose-dependent manner. Western blot analysis showed that the administration of Rk1 (20 mg/kg) and Flu significantly downregulated the level of Sirt1 and that Rk1 (5, 10, and 20 mg/kg) and Flu inhibited the p-NF-κb/NF-κb and p-IκB-α/IκB-α ratios, which indicated that the neuroprotective effect of Rk1 may be related to the suppression of inflammation. In addition 5, 10 and 20 mg/kg Rk1 significantly attenuated the LPS-induced decreases in BDNF and TrkB. These results indicated that Rk1 acts as an antidepressant through its antioxidant activity, the inhibition of neuroinflammation, and the positive regulation of the BDNF-TrkB pathway. This study may help develop active ginsenoside-based compounds for neurodegenerative diseases.

Comparison of TIPS alone and combined with partial splenic embolization (PSE) for the management of variceal bleeding.

OBJECTIVES: Transjugular intrahepatic portosystemic shunt (TIPS) and partial splenic embolization (PSE) were two interventional radiological treatments for the complications of cirrhosis. This study aimed to investigate the effects of concomitant PSE on the long-term shunt patency and overall survival of TIPS-treated patients. METHODS: Forty-eight patients with TIPS insertion were enrolled and studied retrospectively. They were divided into TIPS+PSE (n = 16) and TIPS groups (n = 32), undergoing combined therapy using TIPS and PSE, and monotherapy using TIPS alone, respectively. RESULTS: The 5-year cumulative primary patency rate in the TIPS+PSE group was markedly higher than in the TIPS group (56.8% vs. 32.8%, p = 0.028), whereas the 5-year cumulative secondary patency rate (93.8% vs. 87.7%, p = 0.749) and overall survival rate (62.5% vs. 30.7%, p = 0.414) were not significantly different between the two groups. Cox-regression models revealed that group (hazard ratio [HR], 0.235; 95% CI, 0.084-0.665; p = 0.006), portal venous pressure decline (HR, 0.687; 95% CI, 0.563-0.838; p = 0.000), and baseline portal vein thrombosis (HR, 3.955; 95% CI, 1.634-9.573; p = 0.002) were significant predictors for shunt dysfunction, while only ascites (HR, 2.941; 95% CI, 1.250-6.920; p = 0.013) was a significant predictor for mortality. No severe adverse event was noted in the two groups except for the potential risk of splenic abscess development in the TIPS+PSE group. CONCLUSIONS: Concomitant PSE may help increase the long-term primary shunt patency rate, but not the overall survival of TIPS-treated patients. Further prospective studies are needed to validate these retrospective findings and to investigate the potential mechanisms. KEY POINTS: • Combined therapy using TIPS and PSE is associated with higher primary patency rates than TIPS alone. • Combined therapy using TIPS and PSE is associated with similar rates of secondary patency and overall survival of patients than TIPS alone. • Group (TIPS alone or TIPS+PSE), PVD, and baseline PVT are three independent predictors for shunt dysfunction, while ascites is the only independent predictor for mortality.

Tenofovir Versus Entecavir for the Treatment of Acute-on-Chronic Liver Failure due to Reactivation of Chronic Hepatitis B With Genotypes B and C.

BACKGROUND AND AIMS: Acute-on-chronic liver failure (ACLF) can be triggered by reactivation of chronic hepatitis B (CHB). Tenofovir disoproxil fumarate (TDF) and entecavir (ETV) are now the most potent antiviral agents for CHB. This study aimed to compare the short-term safety and efficacy of TDF with ETV in the treatment of ACLF due to reactivation of CHB [hepatitis B virus (HBV)-ACLF]. PATIENTS AND METHODS: In total, 67 consecutive patients with HBV-ACLF were divided into TDF group (n=32) receiving daily TDF (300 mg/d) and ETV group (n=35) receiving daily ETV (0.5 mg/d). They were prospectively followed-up and the primary endpoint was overall survival at 3 months. RESULTS: At 2 weeks, the TDF group had significantly higher HBV-DNA reduction (P=0.003), lower HBV-DNA level (P=0.001), higher rate of HBV-DNA undetectbility (P=0.007), lower Child-Turcotte-Pugh (CTP; P=0.003), and model for end-stage liver disease (P=0.002) scores than the ETV group. At 3 months, HBV-DNA was undetectable in all survived patients; CTP (P=0.970) and model for end-stage liver disease (P=0.192) scores were comparable between the 2 groups, but markedly lower than at baseline (P<0.01); the TDF group had significantly higher cumulative survival rate than the ETV group (P=0.025). The white blood cell count (hazard ratio, 2.726; 95% confidence interval, 2.691-7.897; P=0.000), and HBV-DNA reduction (hazard ratio, 0.266; 95% confidence interval, 0.033-0.629; P=0.013) at 2 weeks were independent predictors for mortality. Both drugs were well tolerated. CONCLUSIONS: The short-term efficacy of TDF was superior to ETV for the treatment of HBV-ACLF. The white blood cell count and HBV-DNA reduction at 2 weeks were independent predictors for mortality at 3 months.

Komagataeibacter cocois sp. nov., a novel cellulose-producing strain isolated from coconut milk.

Phylogenetic analysis was performed on a cellulose-producing strain, designated WE7T, isolated from contaminated coconut milk. The analysis utilized nearly complete 16S rRNA gene sequences, as well as concatenated partial sequences of the housekeeping genes dnaK, groEL and rpoB, and allowed identification of the strain as belonging to the genus Komagataeibacter. DNA-DNA correlation or average nucleotide identity analysis was performed between WE7T and its closest phylogenetic neighbours, and the resulting values were below the species level (<70 % and <95 %), suggesting that the strain represents a novel species in genus Komagataeibacter. Strain WE7T was coupled with Komagataeibacter species more tightly than with Gluconacetobacter species in a 16S rRNA gene sequence phylogenetic tree. Strain WE7T can be differentiated from closely related Komagataeibacter and Gluconacetobacter entanii species by the ability to grow on the carbon sources d-mannitol, sodium d-gluconate and glycerol, the ability to form acid by d-fructose, sucrose, d-mannitol, d-galactose and ethanol, and the ability to grow without acetic acid. The major fatty acid of WE7T is C18 : 1ω9c (52.3 %). The DNA G+C content of WE7T is 63.2 mol%. The name Komagataeibacter cocois sp. nov. is proposed, with the type strain WE7T (=CGMCC 1.15338T=JCM 31140T).

The antitumor effect of static and extremely low frequency magnetic fields against nephroblastoma and neuroblastoma.

Certain magnetic fields (MF) have potential therapeutic antitumor effect whereas the underlying mechanism remains undefined. In this study, a well-characterized MF was applied to two common childhood malignancies, nephroblastoma and neuroblastoma. This MF has a time-averaged total intensity of 5.1 militesla (mT), and was generated as a superimposition of a static and an extremely low frequency (ELF) MF in 50 Hertz (Hz). In nephroblastoma and neuroblastoma cell lines including G401, CHLA255, and N2a, after MF exposure of 2 h per day, the cell viability decreased significantly after 2 days. After 3 days, inhibition rates of 17-22% were achieved in these cell lines. Furthermore, the inhibition rate was positively associated with exposure time. On the other hand, when using static MF only while maintaining the same time-averaged intensity of 5.1 mT, the inhibition rate was decreased. Thus, both time and combination of ELF field were positively associated with the inhibitory effect of this MF. Exposure to the field decreased cell proliferation and induced apoptosis. Combinational use of MF together with chemotherapeutics cisplatin (DDP) was performed in both in vitro and in vivo experiments. In cell lines, combinational treatment further increased the inhibition rate compared with single use of either DDP or MF. In G401 nephroblastoma tumor model in nude mice, combination of MF and DDP resulted in significant decrease of tumor mass, and the side effect was limited in mild liver injury. MF exposure by itself did not hamper liver or kidney functions. In summary, the antitumor effect of an established MF against neuroblastoma and nephroblastoma is reported, and this field has the potential to be used in combination with DDP to achieve increased efficacy and reduce side effects in these two childhood malignancies. Bioelectromagnetics. 39:375-385, 2018. © 2018 Wiley Periodicals, Inc.

In Situ Bioorthogonal Metabolic Labeling for Fluorescence Imaging of Virus Infection In Vivo.

Optical fluorescence imaging is an important strategy to explore the mechanism of virus-host interaction. However, current fluorescent tag labeling strategies often dampen viral infectivity. The present study explores an in situ fluorescent labeling strategy in order to preserve viral infectivity and precisely monitor viral infection in vivo. In contrast to pre-labeling strategy, mice are first intranasally infected with azide-modified H5N1 pseudotype virus (N3 -H5N1p), followed by injection of dibenzocyclooctyl (DBCO)-functionalized fluorescence 6 h later. The results show that DBCO dye directly conjugated to N3 -H5N1p in lung tissues through in vivo bioorthogonal chemistry with high specificity and efficacy. More remarkably, in situ labeling rather than conventional prelabeling strategy effectively preserves viral infectivity and immunogenicity both in vitro and in vivo. Hence, in situ bioorthogonal viral labeling is a promising and reliable strategy for imaging and tracking viral infection in vivo.