Nanoflake‐Assembled Hierarchical Na3V2(PO4)3/C Microflowers: Superior Li Storage Performance and Insertion/Extraction Mechanism

Na₃V₂(PO₄)₃ (NVP) has excellent electrochemical stability and fast ion diffusion coefficient due to the 3D Na⁺ ion superionic conductor framework, which make it an attractive cathode material for lithium ion batteries (LIBs). However, the electrochemical performance of NVP needs to be further improved for applications in electric vehicles and hybrid electric vehicles. Here, nanoflake‐assembled hierarchical NVP/C microflowers are synthesized using a facile method. The structure of as‐synthesized materials enhances the electrochemical performance by improving the electron conductivity, increasing electrode–electrolyte contact area, and shortening the diffusion distance. The as‐synthesized material exhibits a high capacity (230 mAh g^?1), excellent cycling stability (83.6% of the initial capacity is retained after 5000 cycles), and remarkable rate performance (91 C) in hybrid LIBs. Meanwhile, the hybrid LIBs with the structure of NVP || 1 m LiPF₆/EC (ethylene carbonate) + DMC (dimethyl carbonate) || NVP and Li₄Ti₅O₁₂ || 1 m LiPF₆/EC + DMC || NVP are assembled and display capacities of 79 and 73 mAh g^?1, respectively. The insertion/extraction mechanism of NVP is systematically investigated, based on in situ X‐ray diffraction. The superior electrochemical performance, the design of hybrid LIBs, and the insertion/extraction mechanism investigation will have profound implications for developing safe and stable, high‐energy, and high‐power LIBs.     

解淀粉芽孢杆菌TF28抗菌蛋白TasA基因序列分析及蛋白质结构预测

本研究以解淀粉芽孢杆菌TF28为材料,采用PCR方法从基因组DNA中扩增出抗菌蛋白Tas A基因,利用生物信息学方法对Tas A基因序列及其编码的蛋白质结构进行分析和预测。结果表明Tas A基因全长786 bp,含有一个完整的开放阅读框和一个终止密码子,编码261个氨基酸,经Blast比对,该基因与其它解淀粉芽孢杆菌Tas A基因同源性为95%~99%,与B.amyloliquefaciens FZB42(CP 000560.1)Tas A基因序列同源性最高为99%,与B.amyloliquefaciens DSM7(FN597644.1)的同源性最低为95%。预测该基因编码蛋白质分子量为28 k D,等电点为6.35,是含有信号肽和跨膜结构的亲水蛋白,蛋白结构中含有糖基化和磷酸化位点,二级结构中以琢螺旋、茁折叠和无规则卷曲为主。     

Impaired M. tuberculosis Antigen-Specific IFN-γ Response without IL-17 Enhancement in Patients with Severe Cavitary Pulmonary Tuberculosis

BackgroundTh1 cells play an essential role in immune protection against tuberculosis. Th17 cells might be involved with immune pathology in active human tuberculosis (TB). The balance between Th1 and Th17 cells in patients with cavitary tuberculosis needs to be clarified which might help understanding the immunological basis of pathologic pathogenesis in TB.MethodInitially treated pulmonary TB (PTB) patients with or without cavities were recruited before chemotherapy. We isolated peripheral blood mononuclear cells, stimulated with phytohemagglutinin (PHA), PPD, or ESAT-6 antigens, and assayed supernatant IFN-γ and IL-17 by ELISA after 24 or 72 hours incubation, respectively. Cells were also stained with antibodies to CD3, CD4, CD8, IFN-γ or IL-17 and the proportion of stained cells was measured by flow cytometry.ResultsWe found wide variation of IFN-γ response in active PTB patients, but less subject-to-subject variation of IL-17 was observed as we previously reported. There were no significant differences in IFN-γ and IL-17 between cavitary and non-cavitary PTB; however, we found decreased IFN-γ secretion in severe cavitary PTB compared to mild lesion non-cavitary PTB (p < 0.05). We also found a decrease in the proportion of CD3+CD4+ T cells in the blood of severe cavitary PTB patients (p < 0.05).ConclusionsIL-17 seemed to have no association with the formation of cavities in active PTB from the study of PBMC. Impaired IFN-γ without IL-17 enhancement occurs in peripheral blood during severe cavitary PTB. Our results demonstrate that M. tuberculosis antigen-specific Th1 response is decreased when PTB lesions develop to severe cavities.     

Relationship between Body Mass Index and Percent Body Fat in Vietnamese: Implications for the Diagnosis of Obesity

BackgroundThe burden of obesity in Vietnam has not been well defined because there is a lack of reference data for percent body fat (PBF) in Asians. This study sought to define the relationship between PBF and body mass index (BMI) in the Vietnamese population.MethodsThe study was designed as a comparative cross-sectional investigation that involved 1217 individuals of Vietnamese background (862 women) aged 20 years and older (average age 47 yr) who were randomly selected from the general population in Ho Chi Minh City. Lean mass (LM) and fat mass (FM) were measured by DXA (Hologic QDR 4500). PBF was derived as FM over body weight.ResultsBased on BMI ≥30, the prevalence of obesity was 1.1% and 1.3% for men and women, respectively. The prevalence of overweight and obesity combined (BMI ≥25) was ~24% and ~19% in men and women, respectively. Based on the quadratic relationship between BMI and PBF, the approximate PBF corresponding to the BMI threshold of 30 (obese) was 30.5 in men and 41 in women. Using the criteria of PBF >30 in men and PBF >40 in women, approximately 15% of men and women were considered obese.ConclusionThese data suggest that body mass index underestimates the prevalence of obesity. We suggest that a PBF >30 in men or PBF >40 in women is used as criteria for the diagnosis of obesity in Vietnamese adults. Using these criteria, 15% of Vietnamese adults in Ho Chi Minh City was considered obese.     

SIRT5 regulation of ammonia-induced autophagy and mitophagy

In liver the mitochondrial sirtuin, SIRT5, controls ammonia detoxification by regulating CPS1, the first enzyme of the urea cycle. However, while SIRT5 is ubiquitously expressed, urea cycle and CPS1 are only present in the liver and, to a minor extent, in the kidney. To address the possibility that SIRT5 is involved in ammonia production also in nonliver cells, clones of human breast cancer cell lines MDA-MB-231 and mouse myoblast C2C12, overexpressing or silenced for SIRT5 were produced. Our results show that ammonia production increased in SIRT5-silenced and decreased in SIRT5-overexpressing cells. We also obtained the same ammonia increase when using a new specific inhibitor of SIRT5 called MC3482. SIRT5 regulates ammonia production by controlling glutamine metabolism. In fact, in the mitochondria, glutamine is transformed in glutamate by the enzyme glutaminase, a reaction producing ammonia. We found that SIRT5 and glutaminase coimmunoprecipitated and that SIRT5 inhibition resulted in an increased succinylation of glutaminase. We next determined that autophagy and mitophagy were increased by ammonia by measuring autophagic proteolysis of long-lived proteins, increase of autophagy markers MAP1LC3B, GABARAP, and GABARAPL2, mitophagy markers BNIP3 and the PINK1-PARK2 system as well as mitochondrial morphology and dynamics. We observed that autophagy and mitophagy increased in SIRT5-silenced cells and in WT cells treated with MC3482 and decreased in SIRT5-overexpressing cells. Moreover, glutaminase inhibition or glutamine withdrawal completely prevented autophagy. In conclusion we propose that the role of SIRT5 in nonliver cells is to regulate ammonia production and ammonia-induced autophagy by regulating glutamine metabolism.     

Presynaptic Plasticity as a Hallmark of Rat Stress Susceptibility and Antidepressant Response

Two main questions are important for understanding and treating affective disorders: why are certain individuals susceptible or resilient to stress, and what are the features of treatment response and resistance? To address these questions, we used a chronic mild stress (CMS) rat model of depression. When exposed to stress, a fraction of rats develops anhedonic-like behavior, a core symptom of major depression, while another subgroup of rats is resilient to CMS. Furthermore, the anhedonic-like state is reversed in about half the animals in response to chronic escitalopram treatment (responders), while the remaining animals are resistant (non-responder animals). Electrophysiology in hippocampal brain slices was used to identify a synaptic hallmark characterizing these groups of animals. Presynaptic properties were investigated at GABAergic synapses onto single dentate gyrus granule cells. Stress-susceptible rats displayed a reduced probability of GABA release judged by an altered paired-pulse ratio of evoked inhibitory postsynaptic currents (IPSCs) (1.48 ± 0.25) compared with control (0.81 ± 0.05) and stress-resilient rats (0.78 ± 0.03). Spontaneous IPSCs (sIPSCs) occurred less frequently in stress-susceptible rats compared with control and resilient rats. Finally, a subset of stress-susceptible rats responding to selective serotonin reuptake inhibitor (SSRI) treatment showed a normalization of the paired-pulse ratio (0.73 ± 0.06) whereas non-responder rats showed no normalization (1.2 ± 0.2). No changes in the number of parvalbumin-positive interneurons were observed. Thus, we provide evidence for a distinct GABAergic synaptopathy which associates closely with stress-susceptibility and treatment-resistance in an animal model of depression.     

Physical Activity in Vietnam: Estimates and Measurement Issues

IntroductionOur aims were to provide the first national estimates of physical activity (PA) for Vietnam, and to investigate issues affecting their accuracy.MethodsMeasurements were made using the Global Physical Activity Questionnaire (GPAQ) on a nationally-representative sample of 14706 participants (46.5% males, response 64.1%) aged 25−64 years selected by multi-stage stratified cluster sampling.ResultsApproximately 20% of Vietnamese people had no measureable PA during a typical week, but 72.9% (men) and 69.1% (women) met WHO recommendations for PA by adults for their age. On average, 52.0 (men) and 28.0 (women) Metabolic Equivalent Task (MET)-hours/week (largely from work activities) were reported. Work and total PA were higher in rural areas and varied by season. Less than 2% of respondents provided incomplete information, but an additional one-in-six provided unrealistically high values of PA. Those responsible for reporting errors included persons from rural areas and all those with unstable work patterns. Box-Cox transformation (with an appropriate constant added) was the most successful method of reducing the influence of large values, but energy-scaled values were most strongly associated with pathophysiological outcomes.ConclusionsAround seven-in-ten Vietnamese people aged 25–64 years met WHO recommendations for total PA, which was mainly from work activities and higher in rural areas. Nearly all respondents were able to report their activity using the GPAQ, but with some exaggerated values and seasonal variation in reporting. Data transformation provided plausible summary values, but energy-scaling fared best in association analyses.     

TALE nickase mediates high efficient targeted transgene integration at the human multi-copy ribosomal DNA locus

Although targeted gene addition could be stimulated strikingly by a DNA double strand break (DSB) created by either zinc finger nucleases (ZFNs) or TALE nucleases (TALENs), the DSBs are really mutagenic and toxic to human cells. As a compromised solution, DNA single-strand break (SSB) or nick has been reported to mediate high efficient gene addition but with marked reduction of random mutagenesis. We previously demonstrated effective targeted gene addition at the human multicopy ribosomal DNA (rDNA) locus, a genomic safe harbor for the transgene with therapeutic potential. To improve the transgene integration efficiency by using TALENs while lowering the cytotoxicity of DSBs, we created both TALENs and TALE nickases (TALENickases) targeting this multicopy locus. A targeting vector which could integrate a GFP cassette at the rDNA locus was constructed and co-transfected with TALENs or TALENickases. Although the fraction of GFP positive cells using TALENs was greater than that using TALENickases during the first few days after transfection, it reduced to a level less than that using TALENickases after continuous culture. Our findings showed that the TALENickases were more effective than their TALEN counterparts at the multi-copy rDNA locus, though earlier studies using ZFNs and ZFNickases targeting the single-copy loci showed the reverse. Besides, TALENickases mediated the targeted integration of a 5.4 kb fragment at a frequency of up to 0.62% in HT1080 cells after drug selection, suggesting their potential application in targeted gene modification not being limited at the rDNA locus.     

Ubiquitin ligase CHIP suppresses cancer stem cell properties in a population of breast cancer cells

Cancer stem cells (CSCs) have several distinctive characteristics, including high metastatic potential, tumor-initiating potential, and properties that resemble normal stem cells such as self-renewal, differentiation, and drug efflux. Because of these characteristics, CSC is regarded to be responsible for cancer progression and patient prognosis. In our previous study, we showed that a ubiquitin E3 ligase carboxyl terminus of Hsc70-interacting protein (CHIP) suppressed breast cancer malignancy. Moreover, a recent clinical study reported that CHIP expression levels were associated with favorable prognostic parameters of patients with breast cancer. Here we show that CHIP suppresses CSC properties in a population of breast cancer cells. CHIP depletion resulted in an increased proportion of CSCs among breast cancers when using several assays to assess CSC properties. From our results, we propose that inhibition of CSC properties may be one of the functions of CHIP as a suppressor of cancer progression.     

Androgen-independent proliferation of LNCaP prostate cancer cells infected by xenotropic murine leukemia virus-related virus

Xenotropic murine leukemia virus-related virus (XMRV) is a novel gammaretrovirus that was originally isolated from human prostate cancer. It is now believed that XMRV is not the etiologic agent of prostate cancer. An analysis of murine leukemia virus (MLV) infection in various human cell lines revealed that prostate cancer cell lines are preferentially infected by XMRV, and this suggested that XMRV infection may confer some sort of growth advantage to prostate cancer cell lines. To examine this hypothesis, androgen-dependent LNCaP cells were infected with XMRV and tested for changes in certain cell growth properties. We found that XMRV-infected LNCaP cells can proliferate in the absence of the androgen dihydrotestosterone. Moreover, androgen receptor expression is significantly reduced in XMRV-infected LNCaP cells. Such alterations were not observed in uninfected and amphotropic MLV-infected LNCaP cells. This finding explains why prostate cancer cell lines are preferentially infected with XMRV.