Continuous Production of Lipase-Catalyzed Biodiesel in a Packed-Bed Reactor: Optimization and Enzyme Reuse Study

An optimal continuous production of biodiesel by methanolysis of soybean oil in a packed-bed reactor was developed using immobilized lipase (Novozym 435) as a catalyst in a tert-butanol solvent system. Response surface methodology (RSM) and Box-Behnken design were employed to evaluate the effects of reaction temperature, flow rate, and substrate molar ratio on the molar conversion of biodiesel. The results showed that flow rate and temperature have significant effects on the percentage of molar conversion. On the basis of ridge max analysis, the optimum conditions were as follows: flow rate 0.1 mL/min, temperature 52.1°C, and substrate molar ratio 1 : 4. The predicted and experimental values of molar conversion were 83.31 ± 2.07% and 82.81 ± .98%, respectively. Furthermore, the continuous process over 30 days showed no appreciable decrease in the molar conversion. The paper demonstrates the applicability of using immobilized lipase and a packed-bed reactor for continuous biodiesel synthesis

Inhibition of Mitochondria- and Endoplasmic Reticulum Stress-Mediated Autophagy Augments Temozolomide-Induced Apoptosis in Glioma Cells

Autophagy is a crucial process for cells to maintain homeostasis and survival through degradation of cellular proteins and organelles, including mitochondria and endoplasmic reticula (ER). We previously demonstrated that temozolomide (TMZ), an alkylating agent for brain tumor chemotherapy, induced reactive oxygen species (ROS)/extracellular signal-regulated kinase (ERK)-mediated autophagy to protect glioma cells from apoptosis. In this study, we investigated the role of mitochondrial damage and ER stress in TMZ-induced cytotoxicity. Mitochondrial depolarization and mitochondrial permeability transition pore (MPTP) opening were observed as a prelude to TMZ-induced autophagy, and these were followed by the loss of mitochondrial mass. Electron transport chain (ETC) inhibitors, such as rotenone (a complex I inhibitor), sodium azide (a complex IV inhibitor), and oligomycin (a complex V inhibitor), or the MPTP inhibitor, cyclosporine A, decreased mitochondrial damage-mediated autophagy, and therefore increased TMZ-induced apoptosis. TMZ treatment triggered ER stress with increased expression of GADD153 and GRP78 proteins, and deceased pro-caspase 12 protein. ER stress consequently induced autophagy through c-Jun N-terminal kinases (JNK) and Ca2+ signaling pathways. Combination of TMZ with 4-phenylbutyrate (4-PBA), an ER stress inhibitor, augmented TMZ-induced cytotoxicity by inhibiting autophagy. Taken together, our data indicate that TMZ induced autophagy through mitochondrial damage- and ER stress-dependent mechanisms to protect glioma cells. This study provides evidence that agents targeting mitochondria or ER may be potential anticancer strategies

Invasive fungal sinusitis in patients with hematological malignancy: 15 years experience in a single university hospital in Taiwan

<p>Abstract</p> <p>Background</p> <p>Risk factors and outcomes in hematological patients who acquire invasive fungal sinusitis (IFS) are infrequently reported in the modern medical era.</p> <p>Method</p> <p>A retrospective study of hospitalized patients with hematological disease was conducted at National Taiwan University Hospital between January 1995 and December 2009.</p> <p>Results</p> <p>Clinical characteristics and outcomes with their associated radiographic and microbiological findings were analyzed. Forty-six patients with IFS and 64 patients with chronic non-invasive sinusitis were enrolled as comparsion. IFS developed more commonly in patients with acute myeloid leukemia (AML) and with prolonged neutropenia (absolute neutrophil count less than 500/mm³for more than 10 days) (<it>p </it>< 0.001). <it>Aspergillus flavus </it>was the most common pathogen isolated (44%). Serum <it>Aspergillus </it>galactomannan antigen was elevated in seven of eleven patients (64%) with IFS caused by aspergillosis but negative for all three patients with mucormycosis. Bony erosion and extra-sinus infiltration was found in 15 of 46 (33%) patients on imaging. Overall, 19 of 46 patients (41.3%) died within 6 weeks. Patients with disease subtype of AML (p = 0.044; Odds Ratio [OR], 5.84; 95% confidence interval [95% CI], 1.02-30.56) and refractory leukemia status (p = 0.05; OR, 4.27; 95% CI, 1.003-18.15) had worse prognosis. Multivariate analysis identified surgical debridement as an independent good prognostic factor (p = 0.047) in patients with IFS.</p> <p>Conclusions</p> <p>Patients of AML with prolonged neutropenia (> 10 days) had significantly higher risk of IFS. Early introduction of anti-fungal agent and aggressive surgical debridement potentially decrease morbidity and mortality in high risk patients with IFS.</p

Identification of the NLS and NES motifs of VP2 from chicken anemia virus and the interaction of VP2 with mini-chromosome maintenance protein 3

<p>Abstract</p> <p>Background</p> <p>VP2 of chicken anemia virus (CAV) is a dual-specificity phosphatase required for virus infection, assembly and replication. The functions of the nuclear localization signal (NLS) and nuclear export signal (NES) of VP2 in the cell, however, are poorly understood. Our study identified the presence of a NLS in VP2 and showed that the protein interacted significantly with mini-chromosome maintenance protein 3 (MCM3) in the cell.</p> <p>Results</p> <p>An arginine-lysine rich NLS could be predicted by software and spanned from amino acids 133 to 138 of VP2. The critical amino acids residues between positions 136 and 138, and either residue 133 or 134 are important for nuclear import in mammalian cells based on systematic mutagenesis. A NES is also predicted in VP2; however the results suggest that no functional NES is present and that this protein is CRM1 independent. It was also shown that VP2 is a chromatin binding protein and, notably, using a co-immunoprecipitation assay, it was found that VP2 association with MCM3 and that this interaction does not require DSP activity.</p> <p>Conclusions</p> <p>VP2 contains a NLS that span from amino acids 133 to 138. VP2 is a CRM1 independent protein during nuclear export and associates with MCM3 in cells.</p

Clinical characteristics and outcomes of Mycobacterium tuberculosis disease in adult patients with hematological malignancies

BACKGROUND: Diseases caused by Mycobacterium tuberculosis (TB) among adult patients with hematological malignancies have rarely been investigated. METHODS: Adult patients with hematological malignancies at National Taiwan University Hospital between 1996 and 2009 were retrospectively reviewed. Patients with positive serology for HIV were excluded. TB disease is diagnosed by positive culture(s) in the presence of compatible symptoms and signs. The demographics, laboratory and, microbiological features, were analyzed in the context of clinical outcomes. RESULTS: Fifty-three of 2984 patients (1.78%) were diagnosed with TB disease. The estimated incidence was 120 per 100,000 adult patients with hematological malignancies. Patients with acute myeloid leukemia had a significantly higher incidence of TB disease than other subtypes of hematological malignancies (2.87% vs. 1.21%, p = 0.002, odds ratio, 2.40; 95% confidence interval, 1.39-4.41). Thirty-eight patients (72%) with non-disseminated pulmonary TB disease presented typically with mediastinal lymphadenopathy (53%), pleural effusion (47%) and fibrocalcific lesions (43%) on chest imaging. The 15 (28%) patients with extra-pulmonary disease had lower rates of defervescence within 72 h of empirical antimicrobial therapy (13% vs 45%, p = 0.03) and a higher 30-day in-hospital mortality (20% vs. 0%, p = 0.004) compared to those with disease confined to the lungs. CONCLUSIONS: TB disease is not uncommon among patients with hematological malignancies in Taiwan. Patients who received a diagnosis of extra-pulmonary TB suffered higher mortality than those with pulmonary TB alone. Clinicians should consider TB in the differential diagnoses of prolonged fever in patients with hematological malignancies, particularly in regions of high endemicity

Microbiologic Characteristics, Serologic Responses, and Clinical Manifestations in Severe Acute Respiratory Syndrome, Taiwan1

The genome of one Taiwanese severe acute respiratory syndrome-associated coronavirus (SARS-CoV) strain (TW1) was 29,729 nt in length. Viral RNA may persist for some time in patients who seroconvert, and some patients may lack an antibody response (immunoglobulin G) to SARS-CoV >21 days after illness onset. An upsurge of antibody response was associated with the aggravation of respiratory failure

Identified single-nucleotide polymorphisms and haplotypes at 16q22.1 increase diabetic nephropathy risk in Han Chinese population

Abstract Background Diabetic nephropathy (DN) has become one of the most common causes of end-stage renal disease (ESRD) in many countries, such as 44.5% in Taiwan. Previous studies have shown that there is a genetic component to ESRD. Studies attempting to determine which genetic variants are related to DN in Han Chinese are limited. A case–control study was conducted to identify DN susceptibility variants in Han Chinese patients with type 2 diabetes. Results We included 574 unrelated type 2 diabetes patients (217 DN cases and 357 controls), who were genotyped using Illumina HumanHap550-Duo BeadChip. In single-SNP association tests, the SNPs rs11647932, rs11645214, and rs6499323 located at 16q22.1 under the additive-effect disease model were significantly associated with an approximately 2-fold increased risk of DN. In haplotype association tests, identified haplotypes located in the chromosome 16q22.1 region (containing ST3GAL2, COG4, SF3B3, and IL34 genes) raised DN risk. The strongest association was found with haplotype rs2288491-rs4985534-rs11645214 (C-C-G) (adjusted odds ratio [AOR] 1.93, 95% confidence interval [CI] 1.83-2.03, p = 6.25 × 10−7), followed by haplotype rs8052125-rs2288491-rs4985534-rs11645214 (G-C-C-G) (AOR 1.92, 95% CI 1.82-2.02, p = 6.56 × 10−7), and haplotype rs2303792-rs8052125-rs2288491-rs4985534-rs11645214 (A-G-C-C-G) (AOR 1.91, 95% CI 1.81-2.01, p = 1.15 × 10−6). Conclusions Our results demonstrate that the novel SNPs and haplotypes located at the 16q22.1 region may involve in the biological pathways of DN in Han Chinese patients with type 2 diabetes. This study can provide new insights into the etiology of DN.http://deepblue.lib.umich.edu/bitstream/2027.42/109508/1/12863_2014_Article_113.pd

Seroprevalence and Severity of 2009 Pandemic Influenza A H1N1 in Taiwan

BACKGROUND: This study is to determine the seroprevalence of the pandemic influenza A H1N1 virus (pH1N1) in Taiwan before and after the 2009 pandemic, and to estimate the relative severity of pH1N1 infections among different age groups. METHODOLOGY/PRINCIPAL FINDINGS: A total of 1544 and 1558 random serum samples were collected from the general population in Taiwan in 2007 and 2010, respectively. Seropositivity was defined by a hemagglutination inhibition titer to pH1N1 (A/Taiwan/126/09) ≥1:40. The seropositivity rate of pH1N1 among the unvaccinated subjects and national surveillance data were used to compare the proportion of infections that led to severe diseases and fatalities among different age groups. The overall seroprevalence of pH1N1 was 0.91% (95% confidence interval [CI] 0.43-1.38) in 2007 and significantly increased to 29.9% (95% CI 27.6-32.2) in 2010 (p<0.0001), with the peak attack rate (55.4%) in 10-17 year-old adolescents, the lowest in elderly ≥65 years (14.1%). The overall attack rates were 20.6% (188/912) in unvaccinated subjects. Among the unvaccinated but infected populations, the estimated attack rates of severe cases per 100,000 infections were significantly higher in children aged 0-5 years (54.9 cases, odds ratio [OR] 4.23, 95% CI 3.04-5.90) and elderly ≥ 65 years (22.4 cases, OR 2.76, 95% CI 1.99-3.83) compared to adolescents aged 10-17 years (13.0 cases). The overall case-fatality rate was 0.98 per 100,000 infections without a significant difference in different age groups. CONCLUSIONS/SIGNIFICANCE: Pre-existing immunity against pH1N1 was rarely identified in Taiwanese at any age in 2007. Young children and elderly--the two most lower seroprotection groups showed the greatest vulnerability to clinical severity after the pH1N1 infections. These results imply that both age groups should have higher priority for immunization in the coming flu season