Showing papers by "Lei Zhang published in 2014"

Cabozantinib Suppresses Tumor Growth and Metastasis in Hepatocellular Carcinoma by a Dual Blockade of VEGFR2 and MET

Abstract: Purpose MET signaling has been suggested a potential role in hepatocellular carcinoma (HCC) and associated with prometastasis during antiangiogenesis therapy. We investigated the potential association between MET expression and therapeutic response to sorafenib in patients with HCC. Antitumor effects of cabozantinib, a dual inhibitor of MET and VEGFR2, were examined in cultured HCC cells as well as in vivo models. Experimental design Total MET and phosphorylated MET (p-MET) were measured in 29 resected HCC specimens, and correlated with response to sorafenib as postoperative adjuvant therapy. In the second set of experiments using cultured HCC cells, and mouse xenograft and metastatic models, effects of cabozantinib were examined. Results High level of p-MET in resected HCC specimens was associated with resistance to adjuvant sorafenib therapy. In cultured HCC cells that expressed p-MET, cabozantinib inhibited the activity of MET and its downstream effectors, leading to G1-phase arrest. Cabozantinib inhibited tumor growth in p-MET-positive and p-MET-negative HCC by decreasing angiogenesis, inhibiting proliferation, and promoting apoptosis, but it exhibited more profound efficacy in p-MET-positive HCC xenografts. Cabozantinib blocked the hepatocyte growth factor (HGF)-stimulated MET pathway and inhibited the migration and invasion of the HCC cells. Notably, cabozantinib reduced the number of metastatic lesions in the lung and liver in the experimental metastatic mouse model. Conclusions Patients with HCC with high level of p-MET are associated with resistance to adjuvant sorafenib treatment. The dual blockade of VEGFR2 and MET by cabozantinib has significant antitumor activities in HCC, and the activation of MET in HCC may be a promising efficacy-predicting biomarker. Clin Cancer Res; 20(11); 2959-70. ©2014 AACR.

Global burden of transmitted HIV drug resistance and HIV-exposure categories: a systematic review and meta-analysis.

Abstract: OBJECTIVES Our aim was to review the global disparities of transmitted HIV drug resistance (TDR) in antiretroviral-naive MSM, people who inject drugs (PWID) and heterosexual populations in both high-income and low/middle-income countries. DESIGN/METHODS We undertook a systematic review of the peer-reviewed English literature on TDR (1999-2013). Random-effects meta-analyses were performed to pool TDR prevalence and compare the odds of TDR across at-risk groups. RESULTS A total of 212 studies were included in this review. Areas with greatest TDR prevalence were North America (MSM: 13.7%, PWID: 9.1%, heterosexuals: 10.5%); followed by western Europe (MSM: 11.0%, PWID: 5.7%, heterosexuals: 6.9%) and South America (MSM: 8.3%, PWID: 13.5%, heterosexuals: 7.5%). Our data indicated disproportionately high TDR burdens in MSM in Oceania (Australia 15.5%), eastern Europe/central Asia (10.2%) and east Asia (7.8%). TDR epidemics have stabilized in high-income countries, with a higher prevalence (range 10.9-12.6%) in MSM than in PWID (5.2-8.3%) and heterosexuals (6.4-9.0%) over 1999-2013. In low/middle-income countries, TDR prevalence in all at-risk groups in 2009-2013 almost doubled than that in 2004-2008 (MSM: 7.8 vs. 4.2%, P = 0.011; heterosexuals: 4.1 vs. 2.6%, P < 0.001; PWID: 4.8 vs. 2.4%, P = 0.265, respectively). The risk of TDR infection was significantly greater in MSM than that in heterosexuals and PWID. We observed increasing trends of resistance to non-nucleoside reverse transcriptase and protease inhibitors among MSM. CONCLUSION TDR prevalence is stabilizing in high-income countries, but increasing in low/middle-income countries. This is likely due to the low, but increasing, coverage of antiretroviral therapy in these settings. Transmission of TDR is most prevalent among MSM worldwide.

HIV prevalence trends, risky behaviours, and governmental and community responses to the epidemic among men who have sex with men in China.

Abstract: Purpose of Review. Numerous studies reported the rapid spread of HIV/AIDS epidemic among men who have sex with men (MSM) in China. This paper aims to investigate the overall epidemic trend and associated high-risk behaviours among Chinese MSM and to explore the governmental and community responses to the epidemic. Recent Findings. HIV prevalence among Chinese MSM increased rapidly in all Chinese regions in the past decade and disproportionally affected the Southwest China. In addition to the high-risk homosexual behaviours, overlapping bisexual, commercial, and drug use behaviours are commonly observed among Chinese MSM. The Chinese government has significantly expanded the surveillance efforts among MSM over the past decade. Community responses against HIV have been substantially strengthened with the support of international aid. However, lack of enabling legal and financial environment undermines the role of community-based organisations (CBOs) in HIV surveillance and prevention. Conclusion. HIV continues to spread rapidly among MSM in China. The hidden nature of MSM and the overlapping homosexual, bisexual, and commercial behaviours remain a challenge for HIV prevention among MSM. Strong collaboration between the government and CBOs and innovative intervention approaches are essential for effective HIV surveillance and prevention among MSM in China.

Mir-184 post-transcriptionally regulates SOX7 expression and promotes cell proliferation in human hepatocellular carcinoma.

Abstract: Hepatocellular carcinoma (HCC) is one of the most common human malignancies and the third leading cause of cancer mortality worldwide. The development and progression of HCC is a complicated process, involving the deregulation of multiple genes that are essential to cell biological processes. Recently, microRNAs (miRNAs) have been suggested to be closely associated with tumorigenesis. Our study showed that miR-184 is upregulated in HCC cell lines and tissues. Overexpression of miR-184 in HCC cells increased cell proliferation, tumorigenicity, and cell cycle progression, whereas inhibition of miR-184 reduced cell proliferation, tumorigenicity, and cell cycle progression. Additionally, we identified SOX7 as a direct target of miR-184. Ectopic expression of miR-184 led to downregulation of the SOX7 protein, resulting in upregulation of c-Myc, Cyclin D1, and phosphorylation of Rb. Our findings suggested that miR-184 represents a potential onco-miR and plays an important role in HCC progression by suppressing SOX7 expression.

Rural-to-urban migrants are at high risk of sexually transmitted and viral hepatitis infections in China: a systematic review and meta-analysis.

Abstract: Rapid economic development in urban China has led to a mass migration of surplus rural residents into urban areas for better employment opportunities. This study aims to identify prevalence levels and risks of sexually transmitted infections (STIs) and hepatitis among the rural-to-urban migrant population in China. Chinese and English literature databases were searched for studies reporting prevalence of HIV, STIs and viral hepatitis among rural-to-urban migrants in China between 1990 and 2013. The estimates were summarised through a systematic review and meta-analysis. The risks of infection were compared between migrants and the general Chinese population. We identified a total of 411 eligible studies. The prevalence of HIV, syphilis, gonorrhea, genital warts and HCV among migrants were 0.23% (0.20-0.27%), 0.69% (0.57-0.84%), 2.18% (1.30-3.64%), 1.54% (0.70-3.36%) and 0.45% (0.31-3.65%), representing 4.0 (3.1-5.2), 1.9 (1.1-3.0), 13.6 (5.8-32.1), 38.5 (15.7-94.5) and 3.8 (1.9-7.3) higher odds of infection than among the general population. Construction workers, long-distance truck drivers and migrant women through marriage were migrant subgroups that were highly susceptible to STIs and hepatitis. HIV prevalence among migrant pregnant women (0.10%, 0.02-0.49%) was significantly higher than that of pregnant women in the general Chinese population (OR = 7.7, 3.4-17.4). However, no significant differences were observed in STIs and hepatitis between overall female sex workers (FSWs), men who have sex with men (MSM) and drug users (DUs), and the corresponding subgroups with a migratory background. Rural-to-urban migrants have a higher risk of STIs and hepatitis than the general Chinese population, but a migratory background does not increase the infection risks of STIs and hepatitis in FSWs, MSM and DUs.

Disparities and Risks of Sexually Transmissible Infections among Men Who Have Sex with Men in China: A Meta-Analysis and Data Synthesis

Abstract: Background Sexually transmitted infections (STIs), including Hepatitis B and C virus, are emerging public health risks in China, especially among men who have sex with men (MSM). This study aims to assess the magnitude and risks of STIs among Chinese MSM. Methods Chinese and English peer-reviewed articles were searched in five electronic databases from January 2000 to February 2013. Pooled prevalence estimates for each STI infection were calculated using meta-analysis. Infection risks of STIs in MSM, HIV-positive MSM and male sex workers (MSW) were obtained. This review followed the PRISMA guidelines and was registered in PROSPERO. Results Eighty-eight articles (11 in English and 77 in Chinese) investigating 35,203 MSM in 28 provinces were included in this review. The prevalence levels of STIs among MSM were 6.3% (95% CI: 3.5-11.0%) for chlamydia, 1.5% (0.7-2.9%) for genital wart, 1.9% (1.3-2.7%) for gonorrhoea, 8.9% (7.8-10.2%) for hepatitis B (HBV), 1.2% (1.0-1.6%) for hepatitis C (HCV), 66.3% (57.4-74.1%) for human papillomavirus (HPV), 10.6% (6.2-17.6%) for herpes simplex virus (HSV-2) and 4.3% (3.2-5.8%) for Ureaplasma urealyticum. HIV-positive MSM have consistently higher odds of all these infections than the broader MSM population. As a subgroup of MSM, MSW were 2.5 (1.4-4.7), 5.7 (2.7-12.3), and 2.2 (1.4-3.7) times more likely to be infected with chlamydia, gonorrhoea and HCV than the broader MSM population, respectively. Conclusion Prevalence levels of STIs among MSW were significantly higher than the broader MSM population. Co-infection of HIV and STIs were prevalent among Chinese MSM. Integration of HIV and STIs healthcare and surveillance systems is essential in providing effective HIV/STIs preventive measures and treatments. Trial registration PROSPERO NO: CRD42013003721.

Chrysin ameliorates diabetes-associated cognitive deficits in Wistar rats.

Abstract: Chrysin (CH) is an important natural plant flavonoid and possesses diverse pharmacological activities. Our present investigations aimed to assess the neuroprotection of CH against diabetes-associated cognitive decline (DACD) in a rat model of diabetes and exploring its potential mechanism. Diabetic model was induced by intraperitoneal injection of streptozotocin. Then, they were treated with vehicle or CH by doses of 30 and 100 mg/kg for 26 days. Learning and memory function was evaluated by Morris water maze test. The oxidative indicators [malondialdehyde (MDA), catalase (CAT), superoxide dismutase (SOD) and glutathione (GSH)], NF-κB p65 unit, TNF-α, IL-1β, IL-6 and caspase-3 were measured in cerebral cortex and hippocampus using corresponding commercial kits. The diabetic rats showed marked reductions in body weight, percentage of time spent in target quadrant and number of times of crossing platform, coupled with increases in plasma glucose levels, escape latency, mean path length and oxidative stress (increased MDA level and decreased CAT and SOD as well as reduced GSH), NF-κB p65 unit, TNF-α, IL-1β, IL-6 and caspase-3 in cerebral cortex and hippocampus. Moreover, CH supplement dramatically reversed the corresponding behavioral, biochemical and molecular alterations in diabetes. The alterations of swimming speed among different groups were not observed after CH adminstration. In conclusion, our current work discloses that CH remarkably alleviates DACD and suggests that oxidative stress, inflammation and apoptotic cascades are linked with diabetes-associated cognitive deficits. These findings point toward the therapeutic potential of CH in DACD.

Tribological Behavior of Cu Matrix Composites Containing Graphite and Tungsten Disulfide

Abstract: Copper matrix composites containing graphite and tungsten disulfide were prepared and tested under the loads of 1–5 N to investigate their friction and wear behaviors. The microstructure, worn surfaces, and cross section of worn subsurfaces were observed, and the lubricating films formed on the worn surfaces were analyzed. It is found that the Cu–24 vol% WS2 composite presents a higher mechanical performance and lower wear rate compared to the Cu–24 vol% graphite composite with same volume fraction of solid lubricant. This could be attributed to the high-strength chemical bonding of the interface between WS2 and the copper matrix. The high-strength interfacial bonding also helps prevent plastic deformation and the formation of cracks at the worn subsurfaces of the composites. The amount of lubricant on the outmost worn surfaces is significantly higher than that in the composite. The lubricating film of WS2 with relatively high thickness provides a low friction coefficient to the composites.

TLR9 and BAFF: Their expression in patients with IgA nephropathy

Abstract: Since it was first described in 1968, immunoglobulin (Ig)A nephropathy (IgAN) has become the most commonly diagnosed form of primary glomerular disease worldwide. A number of reports have shown that toll‑like receptor 9 (TLR9) and B‑cell activating factor (BAFF) may be associated with IgAN; however, sufficient evidence has not yet to be delivered. In the present study, serum levels of BAFF as well as TLR9 mRNA and protein levels in peripheral blood mononuclear cells (PBMCs) were assessed. Expression of TLR9 mRNA in PBMCs was examined by quantitative polymerase chain reaction and the TLR9 protein was determined by western blot analysis. The levels of serum BAFF and IgA1 were determined by specific ELISA. Serum levels of BAFF and IgA1 as well as levels of TLR9 mRNA and protein in PMBCs were significantly higher in patients with IgAN compared with patients with minimal glomerular abnormalities (P<0.05, P<0.01, P<0.01 and P<0.01, respectively) and normal controls (P<0.01, P<0.01, P<0.05 and P<0.01, respectively). A correlation and regression analysis was performed to determine the pathogenesis of IgAN. In patients with IgAN, serum levels of BAFF were positively correlated with IgA1 levels (rp, 0.515; P<0.01) and mesangial IgA deposition density (rp, 0.746; P<0.01). Expression levels of TLR9 protein in PBMCs of IgAN patients were positively correlated with levels of serum BAFF (rp, 0.444; P<0.05) and IgA1 (rp, 0.633; P<0.01). These results suggested that overexpression of TLR9 mRNA and protein in PBMCs and elevated levels of serum BAFF may be associated with overexpression of serum IgA1, and, furthermore, may have a role in the development of IgAN.

Neuromyelitis optica spectrum disorders without and with autoimmune diseases

Abstract: Neuromyelitis optica spectrum disorder (NMOSD) can coexist with non-organ-specific or organ-specific autoimmune diseases. The aim of this study was to investigate and compare the features between NMOSD without and with autoimmune diseases, and NMOSD with non-organ-specific and organ-specific autoimmune diseases. One hundred and fifty five NMOSD patients without autoimmune diseases (n = 115) and with autoimmune diseases (n = 40) were enrolled. NMOSD with autoimmune diseases were divided by organ-specific autoimmune diseases. The clinical, laboratory and magnetic resonance imaging features between two groups were assessed. Motor deficit was less frequent in NMOSD patients with non-organ-specific autoimmune diseases (p = 0.024). Cerebrospinal fluid white blood cell and protein, serum C-reactive protein and immunoglobulin G were lower in NMOSD patients without autoimmune diseases, while several autoantibodies seropositivity and thyroid indexes were significantly higher in NMOSD patients with autoimmune diseases (p 0.05). NMOSD patients with autoimmune diseases had higher brain abnormalities than NMOSD without autoimmune diseases (p < 0.001). The characteristics between NMOSD without and with autoimmune diseases were similar. NMOSD with autoimmune diseases have high frequency of brain abnormalities.

Comparative clinical characteristics of neuromyelitis optica spectrum disorders with and without medulla oblongata lesions

Abstract: Brainstem involvement, especially the medulla oblongata (MO), has been reported in neuromyelitis optica spectrum disorders (NMOSDs). The purpose of this study was to investigate retrospectively and compare clinical, laboratory, and imaging features of NMOSDs with and without MO lesions. A total of 170 patients with NMOSDs were enrolled, including 44 patients with MO lesions and 126 patients without MO lesions. Clinical features, laboratory tests, and magnetic resonance imaging findings among these patients were assessed. MO lesions were found in 25.9 % of the NMOSDs patients. The mean duration was 13 months. Patients with MO lesions had a higher Annualized relapse rate and Expanded Disability Status Score Scale. Headache, dizziness, nystagmus, dysarthria, intractable hiccup and nausea, choking cough or dysphagia, movement disorders, and neuropathic pain were more common in MO lesion patients. Patients with MO lesions were more frequently complicated with thyroid diseases. Multiple brain involvement, More importantly, Longitudinally extensive transverse myelitis were more frequently found in patients with MO lesions. MO lesions might be a symbol of more severe neurologic deficits and worse prognosis of NMOSDs.

Possible Targets for Nonimmunosuppressive Therapy of Graves' Orbitopathy

Abstract: Context: Graves' orbitopathy (GO) is caused by expansion of the orbital contents by excess adipogenesis and overproduction of hyaluronan (HA). Immunosuppressive and antiinflammatory treatments of GO are not always effective and can have side effects, whereas targeting GO-associated tissue remodeling might be a more logical therapeutic strategy. Previously we reported that signaling cascades through IGF1 receptor and thyrotropin receptor within orbital preadipocytes/fibroblasts drove adipogenesis and HA production. Our current study combined the stimulation of IGF1 receptor and thyrotropin receptor increase of HA accumulation, which we hypothesize is by activation of phosphatidylinositol 3-kinase (PI3K)-1A/PI3K1B, respectively. The central aim of this study was to investigate whether PI3K/mammalian target of rapamycin complex 1 (mTORC1) inhibitors affected adipogenesis and/or HA production within orbital preadipocyte/fibroblasts. Methods: Human orbital preadipocytes were treated with/without inhibitors, LY294002 (PI3K1A/mTORC1), AS-605240 (PI3K1B), or PI103 (PI3K1A/mTORC1) in serum-free medium for 24 hours or cultured in adipogenic medium for 15 days. Quantitative PCR was used to measure hyaluronan synthases (HAS2) transcripts and the terminal adipogenesis differentiation marker lipoprotein lipase. HA accumulation in the medium was measured by an ELISA. Results: Unlike AS-605240, both LY294002 (10 μM) and PI-103 (5 μM) significantly decreased HAS2 transcripts/HA accumulation and adipogenesis. Because PI-103 and LY294002 are dual PI3K/mTOR inhibitors, we investigated the inhibition of mTORC1 (rapamycin 100 nM), which significantly decreased adipogenesis but had no effect on HAS2 transcripts/HA, implicating PI3K-1A in the latter. Conclusions: The combined inhibition of PI3K1A and mTORC1 signaling in vitro decreased both HA accumulation and adipogenesis. Because PI3K and mTOR inhibitors are clinically used to treat other conditions, they have the potential to be repositioned to be used as an alternative nonimmunosuppressive therapy of GO.

Modeling of multi-band circular dichroism using metal/dielectric/metal achiral metamaterials

Abstract: We show that an elliptical nanohole array (ENA) penetrating through a metal/dielectric/metal (MDM) film produces multi-band circular dichroism (CD) in the near infrared (N-IR) region when the incident light is off-normal incidence. This extrinsic CD is a result of the elliptical symmetry of the nanohole, which gives rise to different polarization modes along its short and long axes. These two polarization modes introduce a net polar vector that forms a chiral triad with the off-normal incidence and the vector normal to the plane of the ENA. The proposed structure possesses four resonance peaks arising from the excitation of both internal- and external- surface plasmon polariton (SPP) modes with different diffraction orders to those wavelengths at which they couple to the incoming light. The formation of these resonance peaks is responsible for the multi-band CD.

Downregulation of microRNA-100 enhances the ICMT-Rac1 signaling and promotes metastasis of hepatocellular carcinoma cells

Abstract: Metastasis is responsible for rapid recurrence of hepatocellular carcinoma (HCC) and poor survival of HCC patients. Here we showed that miR-100 downregulation in HCC tissues was significantly associated with venous invasion, advanced TNM stage, tumor nodule without complete capsule, poorer cell differentiation, and shorter recurrence-free survival. Both gain- and loss-of-function studies showed that miR-100 dramatically suppressed the ability of HCC cells to migrate and to invade through Matrigel in vitro. Analyses using mouse orthotopic xenograft model further revealed that xenografts of miR-100-stable-expressing HCC cells displayed a significant reduction in pulmonary metastasis, compared with control group. Subsequent investigations revealed that miR-100 directly inhibited the expression of isoprenylcysteine carboxyl methyltransferase (ICMT) and ras-related C3 botulinum toxin substrate 1 (Rac1) by binding to their 3'-UTRs, and in turn suppressed lamellipodia formation and matrix metallopeptidase 2 (MMP2) activation. Furthermore, knockdown of ICMT and Rac1 phenocopied the anti-metastasis effect of miR-100, whereas overexpression of the constitutively active Rac1 (Q61L) antagonized the function of miR-100. Taken together, miR-100 represses metastasis of HCC cells by abrogating the ICMT-Rac1 signaling. Downregulation of miR-100 contributes to HCC metastasis and the restoration of miR-100 is a potential strategy for cancer therapy.

Comparison of deep gray matter lesions on magnetic resonance imaging among adults with acute disseminated encephalomyelitis, multiple sclerosis, and neuromyelitis optica

Abstract: Background:Deep gray matter lesions have been reported in patients with acute disseminated encephalomyelitis (ADEM), multiple sclerosis (MS), and neuromyelitis optica (NMO).Objectives:The purpose of this study was to compare the features of deep gray matter lesions on magnetic resonance imaging (MRI) among adult patients with ADEM, MS, and NMO.Methods:Ninety-five adult patients with ADEM (n=12), MS (n=60), and NMO (n=23) who had deep gray matter lesions on MRI were enrolled. Morphological features of deep gray matter lesions among these patients were assessed.Results:Putamen involvement was more common in patients with ADEM than in patients with MS and NMO. Differing from children, thalamus involvement might not be helpful in differentiating ADEM from MS in adults. Hypothalamus involvement was more common in patients with NMO than in patients with ADEM and MS. More importantly, bilateral hypothalamus involvement was more helpful in differentiating NMO from MS. The diameter of the thalamus lesions in patie...

Does thyroid peroxidase provide an antigenic link between thyroid autoimmunity and breast cancer

Abstract: Women with breast cancer (BC) and antithyroid peroxidase (TPO) autoantibodies (TPOAb) have a better prognosis than women lacking TPOAb. Sera from women with TPOAb displayed immunoreactivity to BC tissue by immunofluorescence that was not apparent in women without TPOAb. We hypothesize a BC/thyroid shared antigen that provides a target for humoral or cell-mediated immune activity; candidates include the sodium/iodide symporter (expressed in thyroid and BC), cross-reacting epitopes in TPO and lactoperoxidase (LPO) or TPO itself. As the association is with TPOAb, we investigated TPO expression in BC, breast peritumoral tissue (PT), other tissues (tumoral and not) and thyroid as positive control. Transcripts for known and novel TPO isoforms were detected in BC (n = 8) and PT (n = 8) but at approximately 104-fold lower than in thyroid while in non-BC tumors (n = 5) they were at the limit of detection. TPO was expressed also in adipose tissue (n = 17), 103-fold lower than in thyroid. Full length TPO (Mr 105–110 kDa) was detected in Western blots in the majority of examined tissues; preabsorption of the TPO antibody with recombinant TPO (but not LPO) reduced the signal, indicating specificity. The same occurred with some lower molecular weight bands, which could correspond to smaller TPO transcript isoforms, present in all samples. In conclusion, TPO is weakly expressed in BC and other tissues; this could partly explain the high frequency and protective role of TPOAb in BC patients. Further studies will investigate tissue specificity, function and immunogenicity of the novel TPO variants (some BC-specific) identified.

Urban, semi-urban and rural difference in the prevalence of metabolic syndrome in Shaanxi province, northwestern China: a population-based survey

Abstract: The ongoing rapid urbanization in China offers rural population opportunities not only for economic improvement but also for substantial health risks. Albeit some researches related to rural-urban difference of metabolic syndrome (MS), there lacks studies focusing on this point in undeveloped provinces in China. The survey, as part of China National Diabetes and Metabolic disorders Study, was conducted in Shaanxi province from June 2007 to May 2008. A total of 3,297 adults aged 20 years or older were included, of which 1,467 individuals were from urban areas, 839 from semi-urban areas, and 890 from rural areas. The MS was defined according to the 2009 Joint Interim Statement. The age-standardized prevalence of MS was significant higher in rural residents than in urban counterparts (29.0% vs. 25.9%, P = 0.017), in particular among females (30.2% vs. 24.4%, P = 0.003). After adjusted for the listed risk factors, rural residents had a 27.6% increased risk of having MS than urban residents. With respect to MS components, the crude prevalence of raised fasting glucose and raised blood pressure was significantly greater in rural than in urban participants. However, no significant difference in the prevalence of MS was observed between semi-urban and urban participants. Rural residents in Shaanxi province, northwest China, were at increased risk of MS, which could be partly explained by sociodemographic and lifestyle differences. In addition, the gap between urban and semi-urban areas seemed to be minimized in related to MS prevalence. Much more attention should be paid to and intervention strategies were needed to address the rural-urban disparities in China.

A novel wild-type Saccharomyces cerevisiae strain TSH1 in scaling-up of solid-state fermentation of ethanol from sweet sorghum stalks.

Abstract: The rising demand for bioethanol, the most common alternative to petroleum-derived fuel used worldwide, has encouraged a feedstock shift to non-food crops to reduce the competition for resources between food and energy production. Sweet sorghum has become one of the most promising non-food energy crops because of its high output and strong adaptive ability. However, the means by which sweet sorghum stalks can be cost-effectively utilized for ethanol fermentation in large-scale industrial production and commercialization remains unclear. In this study, we identified a novel Saccharomyces cerevisiae strain, TSH1, from the soil in which sweet sorghum stalks were stored. This strain exhibited excellent ethanol fermentative capacity and ability to withstand stressful solid-state fermentation conditions. Furthermore, we gradually scaled up from a 500-mL flask to a 127-m3 rotary-drum fermenter and eventually constructed a 550-m3 rotary-drum fermentation system to establish an efficient industrial fermentation platform based on TSH1. The batch fermentations were completed in less than 20 hours, with up to 96 tons of crushed sweet sorghum stalks in the 550-m3 fermenter reaching 88% of relative theoretical ethanol yield (RTEY). These results collectively demonstrate that ethanol solid-state fermentation technology can be a highly efficient and low-cost solution for utilizing sweet sorghum, providing a feasible and economical means of developing non-food bioethanol.

Comparison of clinical characteristics between neuromyelitis optica spectrum disorders with and without spinal cord atrophy

Abstract: Spinal cord lesions is one of the predominant characteristics in patients with neuromyelitis optica spectrum disorders (NMOSD). Interestingly, mounting evidence indicates that spinal cord atrophy (SCA) is one of common clinical features in multiple sclerosis (MS) patients, and correlates closely with the neurological disability. However, Clinical studies related to the SCA aspects of NMOSD are still scarce. We retrospectively analyzed 185 patients with NMOSD, including 23 patients with SCA and 162 patients without SCA. Data were collected regarding clinical characteristics, laboratory tests, and magnetic resonance imaging findings. 12.4% of patients had SCA in NMOSD. Patients with SCA had a longer disease duration and higher EDSS at clinical onset and last visit. More importantly, SCA patients were more prone to reach disability milestones (EDSS ≥ 6.0). Bowel or bladder dysfunction, movement disorders, and sensory disturbances symptoms were more common in patients with SCA. ESR and CRP were significantly higher in patients with SCA than those without SCA. Patients with SCA were more frequently complicated with cervical cord lesions. However, the ARR, progression index, seropositive rate of NMO-IgG and OCB were similar in the two groups. Futhermore, LETM did not differ significantly between patients with SCA and without SCA in NMOSD patients. Patients with SCA might have longer disease duration, more severe clinical disability, and more frequently complicated with cervical spinal cord lesions. SCA might be predictive of the more severe neurologic dysfunction and worse prognosis in NMOSD. Inflammation contributes to the development of SCA in NMOSD.

Determinants of virological failure after 1 year's antiretroviral therapy in Vietnamese people with HIV: findings from a retrospective cohort of 13 outpatient clinics in six provinces

Abstract: Objective This study examines the proportions and causes of virological failure after one year of antiretroviral therapy (ART) among people living with HIV (PLHIV) in Vietnam. It also evaluates the positive predictive value (PPV) of immunological criteria to detect treatment failure. Method A retrospective cohort of 3449 people with HIV who started ART between 1 January 2005 and 31 December 2009 in 13 outpatient clinics in Vietnam was studied. Multivariate logistic regression modeling was used to calculate crude and adjusted ORs and 95% CIs for associations between patient characteristics and virological failure. Results An estimated 6.5% (226/3449) of HIV patients in the participating clinics in Vietnam had confirmed virological failure one year after the start of ART. After adjusting for other factors, patients with a baseline CD4 count of 50–100 cells/mm 3 and 101–200 cells/mm 3 were statistically significantly less likely to have virological failure, compared to those with a baseline CD4 count lower than 50 cells/mm 3 (OR=0.61, 95% CI 0.23–0.89; and OR=0.43, 0.18–0.78, respectively). In contrast, patients with a history of injecting drug use were statistically significantly more likely to have viraemia than otherwise (OR=1.32, 1.16–1.67). The PPV of the WHO immunological criteria was 60.1% (57.1–69.3%). Conclusions Routine viral load tests should be conducted early to detect virological failure and prevent unnecessary changes to second-line treatments. To improve treatment outcomes, timely ART initiation and adherence to treatment among those with history of injecting drug use should be promoted.

Socio-cultural influences on the transmission of HIV among gay men in rural China

Abstract: Bisexual behaviours are relatively common among men who have sex with men in China. This pilot study aims to reveal the complex processes through which such men manage their sexuality, family responsibilities and sexual behaviours in a rural Chinese setting. A total of 15 men who have sex with men were recruited by purposive sampling. Face-to-face in-depth interviews were conducted to explore participants' views about their sexual experiences and practices. The Chinese traditional moral code, family values and gender roles that form the crucial components of Confucianism were reflected in the participants' efforts to maintain familial and social harmony through a compromised form of sexual partnership. Most study participants demonstrated a mixed experience of social stigma, sexual naivete and ignorance of HIV and sexually transmitted infections (STIs). Under cultural and family pressure, men who have sex with men entered heterosexual marriages with the intention of maintaining a balance between their collectivist (familial) obligations and their individualistic (same-sex sexual) desires. However, the opaque nature of their concurrent sexual relationships may endanger their personal health and accelerate HIV and STI transmission. Reducing the stigma and social prejudice associated with male same-sex sexual relations is essential for any culturally sensitive HIV-prevention programme to succeed in rural China.

Spending of HIV resources in Asia and Eastern Europe: systematic review reveals the need to shift funding allocations towards priority populations.

Abstract: Introduction : It is increasingly important to prioritize the most cost-effective HIV interventions. We sought to summarize the evidence on which types of interventions provide the best value for money in regions with concentrated HIV epidemics. Methods : We conducted a systematic review of peer-reviewed and grey literature reporting measurements of cost-effectiveness or cost-benefit for HIV/AIDS interventions in Asia and Eastern Europe. We also collated HIV/AIDS spending assessment data from case-study countries in the region. Results : We identified 91 studies for inclusion, 47 of which were from peer-reviewed journals. Generally, in concentrated settings, prevention of mother-to-child transmission programmes and prevention programmes targeting people who inject drugs and sex workers had lower incremental cost-effectiveness ratios than programmes aimed at the general population. The few studies evaluating programmes targeting men who have sex with men indicate moderate cost-effectiveness. Collation of prevention programme spending data from 12 countries in the region (none of which had generalized epidemics) indicated that resources for the general population/non-targeted was greater than 30% for eight countries and greater than 50% for five countries. Conclusions : There is a misalignment between national spending on HIV/AIDS responses and the most affected populations across the region. In concentrated epidemics, scarce funding should be directed more towards most-at-risk populations. Reaching consensus on general principles of cost-effectiveness of programmes by epidemic settings is difficult due to inconsistent evaluation approaches. Adopting a standard costing, impact evaluation, benefits calculation, analysis and reporting framework would enable cross comparisons and improve HIV resource prioritization and allocation. Keywords: HIV; cost-benefit analyses; programme evaluation; systematic review; concentrated epidemics; Asia; Eastern Europe; cost-effectiveness. To access the supplementary material to this article please see Supplementary Files in the column to the right (under Article Tools). (Published: 25 February 2014) Citation: Craig AP et al. Journal of the International AIDS Society 2014, 17 :18822 http://www.jiasociety.org/index.php/jias/article/view/18822 | http://dx.doi.org/10.7448/IAS.17.1.18822

Differentiation and morphogenesis of the ovary and expression of gonadal development‐related genes in the protogynous hermaphroditic ricefield eel Monopterus albus

Abstract: The ovarian differentiation, morphogenesis and expression of some putative gonadal development-related genes were analysed in the ricefield eel Monopterus albus, a protogynous hermaphroditic teleost with a single elongate ovary. At c. 1 day post-hatching (dph), the gonadal ridge was colonized with primordial germ cells (PGCs) at the periphery and transformed into the gonadal primordium, which appeared to contain two germinal epithelia. At c. 7 dph, four ovarian cavities appeared in the gonadal tissue with two in each germinal epithelial compartment, and the indifferent gonad might have begun to differentiate into the ovary. The oocytes at the leptotene stage in meiosis I appeared at c. 14 dph, and oocytes at the diplotene stage at c. 30 dph. As development proceeded, the connective tissue separating the two germinal epithelia disappeared, and two of the four ovarian cavities collapsed into one. At 60 dph, the gonad had already taken the shape as observed in the adults. One outer and two inner ovarian cavities could be easily recognized, with slightly basophilic primary growth oocytes usually residing close to the outer ovarian cavity. The expression of cyp19a1a and erb in the early gonad was detected at 6 dph. The abundant expression of foxl2 coincided with the up-regulation of cyp19a1a at 8 dph onwards. The expression of dmrt1 isoforms was not detectable until 8 dph for dmrt1a and dmrt1b and until 33 dph for dmrt1d. The earlier appearance of cyp19a1a compared to dmrt1 transcripts in the indifferent gonad may contribute to the initial differentiation of the gonad towards the ovary in M. albus.

Fast tuning of Fano resonance in metal/phase-change materials/metal metamaterials

Abstract: We propose fast tuning of a Fano resonance (FR) in a three dimensional metamaterial (MM). The MM consists of an elliptical nanohole array (ENA) embedded through a metal/ phase-change material (PCM)/metal multilayer. The results show that the interference between the electric and magnetic resonances can be significantly enhanced when the elliptical nanoholes occupy the sites of a rectangular lattice, thus providing a FR with a higher value quality factor (Q) compared to the ENA with a square lattice. By switching the PCM (Ge2Sb2Te5) between its amorphous and crystalline states, the FR peak can be red-shifted by up to 42%. The FR can be tuned with a ultra low energy mid-infrared laser pulse of 0.38 ns duration and an intensity of 3.2μW/μm2.

Optimization of ethanol production from NaOH-pretreated solid state fermented sweet sorghum bagasse.

Abstract: Ethanol production from NaOH-Pretreated solid state fermented sweet sorghum bagasse with an engineered strain of Z. mobilis TSH-ZM-01 was optimized. Results showed that: (1) residual solid removal during ethanol fermentation was unnecessary and 24 h fermentation duration was optimal for ethanol production; (2) ethanol yield of 179.20 g/kg of solid state fermented sweet sorghum bagasse achieved under the optimized process conditions of cellulase loading of 0.04 g/g-glucan, xylanase loading of 0.01 g/g-xylan, liquid to solid ratio of 9:1 and pre-hydrolysis duration for 72 h.