ABSTRACT
Fluorinated ethers have become promising electrolyte solvent candidates for lithium metal batteries (LMBs) because they are endowed with high oxidative stability and high Coulombic efficiencies of lithium metal stripping/plating. Up to now, most reported fluorinated ether electrolytes are -CF3-based, and the influence of ion solvation in modifying degree of fluorination has not been well-elucidated. In this work, we synthesize a hexacyclic coordinated ether (1-methoxy-3-ethoxypropane, EMP) and its fluorinated ether counterparts with -CH2F (F1EMP), -CHF2 (F2EMP), or -CF3 (F3EMP) as terminal group. With lithium bis(fluorosulfonyl)imide as single salt, the solvation structure, Li-ion transport behavior, lithium deposition kinetics, and high-voltage stability of the electrolytes were systematically studied. Theoretical calculations and spectra reveal the gradually reduced solvating power from nonfluorinated EMP to fully fluorinated F3EMP, which leads to decreased ionic conductivity. In contrast, the weakly solvating fluorinated ethers possess higher Li+ transference number and exchange current density. Overall, partially fluorinated -CHF2 is demonstrated as the desired group. Further full cell testing using high-voltage (4.4 V) and high-loading (3.885 mAh cm-2) LiNi0.8Co0.1Mn0.1O2 cathode demonstrates that F2EMP electrolyte enables 80% capacity retention after 168 cycles under limited Li (50 µm) and lean electrolyte (5 mL Ah-1) conditions and 129 cycles under extremely lean electrolyte (1.8 mL Ah-1) and the anode-free conditions. This work deepens the fundamental understanding on the ion transport and interphase dynamics under various degrees of fluorination and provides a feasible approach toward the design of fluorinated ether electrolytes for practical high-voltage LMBs.
ABSTRACT
Background: West Nile virus is a severe zoonotic pathogen that can cause severe central nervous system symptoms in humans and horses, and is fatal for birds, chickens and other poultry. With no specific drugs or vaccines available, antibody-based therapy is a promising treatment. This study aims to develop neutralizing antibodies against West Nile virus and assess their cross-protective potential against Japanese encephalitis virus. Methods: Monoclonal antibodies against WNV and JEV were isolated by hybridoma technology. The therapeutic efficacy of these antibodies was evaluated using a mouse model, and a humanized version of the monoclonal antibody was generated for potential human application. Results: In this study, we generated eight monoclonal antibodies that exhibit neutralizing activity against WNV. Their therapeutic effects against WNV were validated both in vivo and in vitro. Among these antibodies, C9-G11-F3 also exhibited cross-protective activity against JEV. We also humanized the antibody to ensure that it could be used for WNV infection treatment in humans. Conclusion: This study highlights the importance of neutralizing antibodies as a promising approach for protection against West Nile virus infection and suggests their potential utility in the development of therapeutic interventions.
ABSTRACT
BACKGROUND: The efficacy of entecavir (ETV) add-on peg-interferon therapy compared with ETV monotherapy in treatment-naïve hepatitis B virus (HBV) patients remains controversial. We investigated whether adding peg-interferon to ongoing ETV treatment leads to a better curative effect or not. METHODS: All patients have been recruited between August 2013 and January 2015 from the Shanghai Public Health Clinical Center and Zhongshan Hospital (China). Eligible HBV patients (n = 144) were randomly divided (1:1) to receive either ETV monotherapy (nâ=â70) or peg-interferon add-on therapy from week 26 to 52 (nâ=â74). Patients were followed-up for at least 2 years. Indexes including hepatitis B surface antigen (HBsAg) and hepatitis B e antigen (HBeAg) seroconversion rate, sustained virologic response, transient elastography value, and histological scores were evaluated every 3 months until the end of the study. The rate of patients with HBsAg loss was defined as the primary endpoint criteria. RESULTS: At week 26, no patient achieved HBsAg seroconversion in either group. At week 52, one patient in the monotherapy group was HBsAg-negative but there was none in the combination therapy group. The monotherapy group showed significantly better liver function recovery results than the combination therapy group. At week 78, one patient in the combination group had HBsAg seroconverted. At week 104, only three patients in the combination therapy group were HBsAg-negative compared with one patient in monotherapy. The mean alanine aminotransferase and aspartate aminotransferase levels and transient elastography values decreased significantly compared with baseline. Both groups showed a favorable decrease in alpha-fetoprotein (monotherapy: 4.5 [2.8, 7.1] vs. 2.2 [1.8, 3.1] ng/mL, Pâ<â0.001; combination therapy: 5.7 [3.0, 18.8] vs. 3.2 [2.0, 4.3] ng/mL, Pâ<â0.001) and an improved result of liver biopsy examination scores. The combination group showed a better improvement in histology compared with the monotherapy group (mean transient elastography value 6.6 [4.9, 9.8] vs. 7.8 [5.4, 11.1] kPa, Pâ=â0.028). But there was no significant difference in HBsAg conversion rate (1.8% [1/56] vs. 4.1% [3/73], Pâ=â0.809) and HBeAg conversion rate (12.5% [7/56] vs. 11.0% [8/73], Pâ=â0.787), as well as HBV-DNA, sustained virologic response (93.2% vs. 98.5%, Pâ=â0.150) between the two groups. CONCLUSIONS: Both therapies supported liver function recovery and histology improvement. Combination therapy did not show better anti-viral efficacy in HBsAg or HBeAg seroconversion compared with monotherapy. However, combination therapy played a more positive role in reversing hepatic fibrosis compared with monotherapy. TRIAL REGISTRATION: ClinicalTrials.gov: NCT02849132; https://clinicaltrials.gov/ct2/show/NCT02849132.
Subject(s)
Hepatitis B, Chronic , Antiviral Agents/therapeutic use , China , DNA, Viral , Drug Therapy, Combination , Guanine/analogs & derivatives , Hepatitis B e Antigens , Hepatitis B virus , Hepatitis B, Chronic/drug therapy , Humans , Interferon-alpha/therapeutic use , Liver Cirrhosis/drug therapy , Polyethylene Glycols/therapeutic use , Prospective Studies , Treatment OutcomeABSTRACT
A drinking water plant was surveyed to determine the bacterial composition of different drinking water treatment processes (DWTP). Water samples were collected from different processing steps in the plant (i.e., coagulation, sedimentation, sand filtration, and chloramine disinfection) and from distantly piped water. The samples were pyrosequensed using sample-specific oligonucleotide barcodes. The taxonomic composition of the microbial communities of different DWTP and piped water was dominated by the phylum Proteobacteria. Additionally, a large proportion of the sequences were assigned to the phyla Actinobacteria and Bacteroidetes. The piped water exhibited increasing taxonomic diversity, including human pathogens such as the Mycobacterium, which revealed a threat to the safety of drinking water. Surprisingly, we also found that a sister group of SAR11 (LD12) persisted throughout the DWTP, which was always detected in freshwater aquatic systems. Moreover, Polynucleobacter, Rhodoferax, and a group of Actinobacteria, hgcI clade, were relatively consistent throughout the processes. It is concluded that smaller-size microorganisms tended to survive against the present treatment procedure. More improvement should be made to ensure the long-distance transmission drinking water.
Subject(s)
Bacteria/classification , DNA, Bacterial/analysis , DNA, Bacterial/genetics , Drinking Water/microbiology , Water Purification/methods , Actinobacteria/classification , Actinobacteria/genetics , Bacteria/genetics , Bacteroidetes/classification , Bacteroidetes/genetics , Biodiversity , DNA Primers , Ecosystem , Filtration , Humans , Mycobacterium/classification , Mycobacterium/genetics , Phylogeny , Proteobacteria/classification , Proteobacteria/genetics , RNA, Ribosomal, 16S/genetics , Sequence Analysis, DNA , Water MicrobiologyABSTRACT
A Gram-negative, rod-shaped and non-spore-forming bacterial strain, JM27(T), was isolated from a tidal flat of Dongtan Wetland, Chongming Island, China. The strain formed smooth yellow colonies on R2A plates. Growth occurred at 10-37 °C (optimum, 30-37 °C), at pH 6.0-10.0 (optimum, pH 7.0-9.0) and in the presence of 0-1â% NaCl (optimum, 0â%). Catalase test was positive and oxidase test was negative. Ubiquinone 10 (Q10) was the major respiratory quinone. C18:0ω7c and C17:1ω6c were the most abundant fatty acids. Diphosphatidylglycerol, phosphatidylethanolamine and phosphatidylglycerol were the major polar lipids. The DNA G+C content of strain JM27(T) was 66.4 mol%. The 16S rRNA gene sequence of the isolate showed highest similarity to that of Altererythrobacter marinus H32(T) (96.4â%). Phylogenetic analysis based on 16S rRNA gene sequences indicated that the strain belonged to the genus Altererythrobacter of the family Erythrobacteraceae of the class Alphaproteobacteria. On the basis of phylogenetic analysis, whole-cell fatty acids, polar lipid compositions, and biochemical and physiological characteristics, strain JM27(T) is proposed to represent a novel species of the genus Altererythrobacter for which the name Altererythrobacter dongtanensis sp. nov. is proposed. The type strain is JM27(T) (â=âKCTC 22672(T) â=âCCTCC AB 209199(T)).