Chemical-free Extraxtion of Cotton Stalk Bark Fibers by Steam Flash Explosion

Cotton stalk bark fibers (CSBF) were extracted by steam flash explosion, completed within 0.09 s, and the extracted fibers were compared with those obtained by conventional alkaline treatment. Results indicate that the optimum steam pressure was 2.5 MP a when steaming time was set to 2 min for extracting CSBF. Under the optimized conditions, the obtained CBSF had a cellulose content of 72%, length of 48 mm, fineness of 45 dtex, crystallinity index of 68, moisture regain of 8%, water rention of 98%, and tensile strength of 2.4 cN/dtex, which were similar to results obtained by conventional alkaline treatment. Compared with bark of cotton stalks, CSBF had lower moisture regain and water retention, and higher onset decomposition temperature. The results sow that moderate steam flash explosion is a chemical-free, quick, and effective method for exploring the industrial applications of bark of cotton stalks as natural cellulose fibers

Notch1 is required for hypoxia-induced proliferation, invasion and chemoresistance of T-cell acute lymphoblastic leukemia cells

Background Notch1 is a potent regulator known to play an oncogenic role in many malignancies including T-cell acute lymphoblastic leukemia (T-ALL). Tumor hypoxia and increased hypoxia-inducible factor-1α (HIF-1α) activity can act as major stimuli for tumor aggressiveness and progression. Although hypoxia-mediated activation of the Notch1 pathway plays an important role in tumor cell survival and invasiveness, the interaction between HIF-1α and Notch1 has not yet been identified in T-ALL. This study was designed to investigate whether hypoxia activates Notch1 signalling through HIF-1α stabilization and to determine the contribution of hypoxia and HIF-1α to proliferation, invasion and chemoresistance in T-ALL. Methods T-ALL cell lines (Jurkat, Sup-T1) transfected with HIF-1α or Notch1 small interference RNA (siRNA) were incubated in normoxic or hypoxic conditions. Their potential for proliferation and invasion was measured by WST-8 and transwell assays. Flow cytometry was used to detect apoptosis and assess cell cycle regulation. Expression and regulation of components of the HIF-1α and Notch1 pathways and of genes related to proliferation, invasion and apoptosis were assessed by quantitative real-time PCR or Western blot. Results Hypoxia potentiated Notch1 signalling via stabilization and activation of the transcription factor HIF-1α. Hypoxia/HIF-1α-activated Notch1 signalling altered expression of cell cycle regulatory proteins and accelerated cell proliferation. Hypoxia-induced Notch1 activation increased the expression of matrix metalloproteinase-2 (MMP2) and MMP9, which increased invasiveness. Of greater clinical significance, knockdown of Notch1 prevented the protective effect of hypoxia/HIF-1α against dexamethasone-induced apoptosis. This sensitization correlated with losing the effect of hypoxia/HIF-1α on Bcl-2 and Bcl-xL expression. Conclusions Notch1 signalling is required for hypoxia/HIF-1α-induced proliferation, invasion and chemoresistance in T-ALL. Pharmacological inhibitors of HIF-1α or Notch1 signalling may be attractive interventions for T-ALL treatment

Valproic acid inhibits Aβ production, neuritic plaque formation, and behavioral deficits in Alzheimer's disease mouse models

Neuritic plaques in the brains are one of the pathological hallmarks of Alzheimer's disease (AD). Amyloid β-protein (Aβ), the central component of neuritic plaques, is derived from β-amyloid precursor protein (APP) after β- and γ-secretase cleavage. The molecular mechanism underlying the pathogenesis of AD is not yet well defined, and there has been no effective treatment for AD. Valproic acid (VPA) is one of the most widely used anticonvulsant and mood-stabilizing agents for treating epilepsy and bipolar disorder. We found that VPA decreased Aβ production by inhibiting GSK-3β–mediated γ-secretase cleavage of APP both in vitro and in vivo. VPA treatment significantly reduced neuritic plaque formation and improved memory deficits in transgenic AD model mice. We also found that early application of VPA was important for alleviating memory deficits of AD model mice. Our study suggests that VPA may be beneficial in the prevention and treatment of AD

History and Current Status of Development and Use of Viral Insecticides in China

The use of insect viruses as biological control agents started in the early 1960s in China. To date, more than 32 viruses have been used to control insect pests in agriculture, forestry, pastures, and domestic gardens in China. In 2014, 57 products from 11 viruses were authorized as commercial viral insecticides by the Ministry of Agriculture of China. Approximately 1600 tons of viral insecticidal formulations have been produced annually in recent years, accounting for about 0.2% of the total insecticide output of China. The development and use of Helicoverpa armigera nucleopolyhedrovirus, Mamestra brassicae nucleopolyhedrovirus, Spodoptera litura nucleopolyhedrovirus, and Periplaneta fuliginosa densovirus are discussed as case studies. Additionally, some baculoviruses have been genetically modified to improve their killing rate, infectivity, and ultraviolet resistance. In this context, the biosafety assessment of a genetically modified Helicoverpa armigera nucleopolyhedrovirus is discussed

Molecular mechanism of Alzheimer's disease pathogenesis in Down syndrome

Alzheimer's disease (AD) is the most common neurodegenerative disease leading to dementia. Neuritic plaques and neurofibrillary tangles are the two hallmarks of AD neuropathology. The molecular mechanism underlying AD pathogenesis remains unknown. It is believed that deposition of amyloid β (Aβ) protein in the brain plays a pivotal role in AD pathogenesis. Aβ, the central component of neuritic plaques, is derived from β-amyloid precursor protein (APP) by sequential cleavages by β- and γ-secretase. Nearly all individuals with Down Syndrome (DS) show characteristic AD pathological changes after their 30s. The molecular mechanism by which AD pathogenesis develops in DS patients is poorly defined. BACE1 is the major β-secretase in vivo. BACE2 is the homolog of BACE1 and located on chromosome 21. In this study, we cloned and functionally characterized BACE2 gene promoter. Our studies show that the BACE2 gene promoter has a higher activity in non-neuronal cells while BACE1 promoter has a higher activity in neuronal cells. Although both can be activated by SP1, the transcription of BACE1 and BACE2 are distinctly regulated. Even though they are homologous in amino acid sequence, BACE1 and BACE2 cleave APP at distinct sites, leading to their opposing functions in AP production. N-terminal sequencing of BACE2 cleavage product shows that the cleavage site of BACE2 in APP is located between the 19th and 20th amino acid of Aβ. Thus, BACE2 is identified as a novel θ-secretase. Overexpression of BACE2 drastically decreases AP production in cells, whereas overexpression of BACE1 greatly increases Aβ production. We and others have shown that Aβ is elevated in brains of DS patients. Our study further shows that β-secretase activity is abnormally increased. Further study reveals that BACE1 protein levels are markedly increased in DS fetal brain tissues. Time-lapse live imaging, cell fractionation, and pulse-chase experiments show that BACE1 accumulates abnormally in the Golgi of DS cells. These data demonstrate that abnormal BACE1 accumulation leads to elevated β-secretase activity and subsequent Aβ deposition in DS patients. Our results provide a novel molecular mechanism by which AD develops in DS and suggest that inhibiting BACE1 or potentiating BACE2 would benefit AD patients.Medicine, Faculty ofGraduat

Comparing lethal dose ratios using probit regression with arbitrary slopes

Abstract Background Evaluating the toxicity or effectiveness of two or more toxicants in a specific population often requires specialized statistical software to calculate and compare median lethal doses (LD50s). Tests for equality of LD50s using probit regression with parallel slopes have been implemented in many software packages, while tests for cases of arbitrary slopes are not generally available. Methods In this study, we established probit-log(dose) regression models and solved them by the maximum likelihood method using Microsoft Excel. The z- and χ 2-tests were used to assess significance and goodness of fit to the probit regression models, respectively. We calculated the lethal doses (LDs) of the toxicants at different significance levels and their 95% confidence limits (CLs) based on an accurate estimation of log(LD) variances. We further calculated lethal dose ratios and their 95% CLs for two examples without assuming parallel slopes following the method described by Robertson, et al., 2017. Results We selected representative toxicology datasets from the literature as case studies. For datasets without natural responses in the control group, the slopes, intercepts, χ 2 statistics and LDs calculated using our method were identical to those calculated using Polo-Plus and SPSS software, and the 95% CLs of the lethal dose ratios between toxicants were close to those calculated using Polo-Plus. For datasets that included natural responses in the control group, our results were also close to those calculated using Polo-Plus and SPSS. Conclusion This procedure yielded accurate estimates of lethal doses and 95% CLs at different significance levels as well as the lethal dose ratios and 95% CLs between two examples. The procedure could be used to assess differences in the toxicities of two examples without the assumption of parallelism between probit-log(dose) regression lines

Chemical-free Extraxtion of Cotton Stalk Bark Fibers by Steam Flash Explosion

Cotton stalk bark fibers (CSBF) were extracted by steam flash explosion, completed within 0.09 s, and the extracted fibers were compared with those obtained by conventional alkaline treatment. Results indicate that the optimum steam pressure was 2.5 MP a when steaming time was set to 2 min for extracting CSBF. Under the optimized conditions, the obtained CBSF had a cellulose content of 72%, length of 48 mm, fineness of 45 dtex, crystallinity index of 68, moisture regain of 8%, water rention of 98%, and tensile strength of 2.4 cN/dtex, which were similar to results obtained by conventional alkaline treatment. Compared with bark of cotton stalks, CSBF had lower moisture regain and water retention, and higher onset decomposition temperature. The results sow that moderate steam flash explosion is a chemical-free, quick, and effective method for exploring the industrial applications of bark of cotton stalks as natural cellulose fibers

RCAN1 overexpression exacerbates calcium overloading-induced neuronal apoptosis.

Down Syndrome (DS) patients develop characteristic Alzheimer's Disease (AD) neuropathology after their middle age. Prominent neuronal loss has been observed in the cortical regions of AD brains. However, the underlying mechanism leading to this neuronal loss in both DS and AD remains to be elucidated. Calcium overloading and oxidative stress have been implicated in AD pathogenesis. Two major isoforms of regulator of calcineurin 1 (RCAN1), RCAN1.1 and RCAN1.4, are detected in human brains. In this report we defined the transcriptional regulation of RCAN1.1 and RCAN1.4 by two alternative promoters. Calcium overloading upregulated RCAN1.4 expression by activating RCAN1.4 promoter through calcineurin-NFAT signaling pathway, thus forming a negative feedback loop in isoform 4 regulation. Furthermore, RCAN1.4 overexpression exacerbated calcium overloading-induced neuronal apoptosis, which was mediated by caspase-3 apoptotic pathway. Our results suggest that downregulating RCAN1.4 expression in neurons could be beneficial to AD patients

MTase Domain of Dendrolimus punctatus cypovirus VP3 Mediates Virion Attachment and Interacts with Host ALP Protein

Dendrolimus punctatus cypovirus (DpCPV) is an important pathogen of D. punctatus, but little is known about the mechanisms of DpCPV infection. Here, we investigated the effects of VP3, VP4 and VP5 structural proteins on the viral invasion. Both the C-terminal of VP3 (methyltransferase (MTase) domain) and VP4 (A-spike) bound to Spodoptera exigua midgut brush border membrane vesicles (BBMVs) in a dose-dependent manner, and the binding was inhibited by purified DpCPV virions. Importantly, anti-MTase and anti-VP4 antibodies inhibited viral binding to S. exigua BBMVs. Using far-Western blots, a 65 kDa protein in Bombyx mori BBMVs, identified as alkaline phosphatase protein (BmALP) by mass spectrometry, specifically interacted with DpCPV MTase. The interaction between MTase and BmALP was verified by co-immunoprecipitation in vitro. Pretreatment of B. mori BBMVs with an anti-ALP antibody or incubation of DpCPV virions with prokaryotically expressed BmALP reduced viral attachment. Additionally, BmALP inhibited DpCPV infection in S. exigua larvae. Our data provide evidence that the MTase domain and A-spike function as viral attachment proteins during the DpCPV infection process, and ALP is the ligand that interacts with DpCPV via the MTase domain. These results augment our understanding of the mechanisms used by cypoviruses to enter their hosts