Various countries successively notice major disasters and climate anomaly resulted from the counterattack of nature that they have to emphasize the timing of environmental protection, energy saving & ...carbon reduction, and sustainable development issues. It continuously ferments sustainability-related green issues. In face of international environmental regulations and consumers’ environmental awareness, enterprises therefore encounter larger challenge and impact. In this study, a total of 360 questionnaires were distributed to supervisors and employees of Taiwan's high-tech industry, and 283 valid questionnaires were returned, with the retrieval rate of 79%. According to the results to propose conclusions, it is expected to help enterprises immediately adopt effective and flexible strategies & actions in the sustainable development process to ensure the competitiveness.
The MHC is recognized for its importance in human health and disease. However, many disease-associated variants throughout the region remain of unknown significance, residing predominantly within ...non-coding regions of the MHC. The characterization of non-coding RNA transcripts throughout the MHC is thus central to understanding the genetic contribution of these variants. Therefore, we characterize novel miRNA transcripts throughout the MHC by performing deep RNA sequencing of two B lymphoblastoid cell lines with completely characterized MHC haplotypes. Our analysis identifies 89 novel miRNA transcripts, 48 of which undergo Dicer-dependent biogenesis and are loaded onto the Argonaute silencing complex. Several of the identified mature miRNA and pre-miRNA transcripts are unique to specific MHC haplotypes and overlap common SNPs. Furthermore, 43 of the 89 identified novel miRNA transcripts lie within linkage disequilibrium blocks that contain a disease-associated SNP. These disease associated SNPs are associated with 65 unique disease phenotypes, suggesting that these transcripts may play a role in the etiology of numerous diseases associated with the MHC. Additional in silico analysis reveals the potential for thousands of putative pre-miRNA encoding loci within the MHC that may be expressed by different cell types and at different developmental stages.
The mechanistic target of rapamycin (mTOR) is a serine/threonine kinase whose activity contributes to leukemia proliferation and survival. Compounds targeting the mTOR active site inhibit ...rapamycin-resistant functions and have enhanced anticancer activity in mouse models. MLN0128 (formerly known as INK128) is a novel, orally active mTOR kinase inhibitor currently in clinical development. Here, we evaluated MLN0128 in preclinical models of B-cell acute lymphoblastic leukemia (B-ALL). MLN0128 suppressed proliferation of B-ALL cell lines in vitro and reduced colony formation by primary human leukemia cells from adult and pediatric B-ALL patients. MLN0128 also boosted the efficacy of dasatinib (DA) in Philadelphia Chromosome-positive (Ph+) specimens. In a syngeneic mouse model of lymphoid BCR-ABL+ disease, daily oral dosing of MLN0128 rapidly cleared leukemic outgrowth. In primary xenografts of Ph+ B-ALL specimens, MLN0128 significantly enhanced the efficacy of DA. In non-Ph B-ALL xenografts, single agent MLN0128 had a cytostatic effect that was most pronounced in mice with low disease burden. In all in vivo models, MLN0128 was well tolerated and did not suppress endogenous bone marrow proliferation. These findings support the rationale for clinical testing of MLN0128 in both adult and pediatric B-ALL and provide insight towards optimizing therapeutic efficacy of mTOR kinase inhibitors.
Various form features affect consumer preference regarding product design. It is, therefore, important that designers identify these critical form features to aid them in developing appealing ...products. However, the problems inherent in choosing product form features have not yet been intensively investigated. In this paper, an approach based on multiclass support vector machine recursive feature elimination (SVM-RFE) is proposed to streamline the selection of optimum product form features. First, a one-versus-one (OVO) multiclass fuzzy support vector machines (multiclass fuzzy SVM) model using a Gaussian kernel was constructed based on product samples from mobile phones. Second, an optimal training model parameter set was determined using two-step cross-validation. Finally, a multiclass SVM-RFE process was applied to select critical form features by either using overall ranking or class-specific ranking. The weight distribution of each iterative step can be used to analyze the relative importance of each of the form features. The results of our experiment show that the multiclass SVM-RFE process is not only very useful for identifying critical form features with minimum generalization errors but also can be used to select the smallest feature subset for building a prediction model with a given discrimination capability.
Since its introduction over 40 years ago, 5-fluorouracil (5-FU) has remained the only effective chemotherapy option available for the treatment of colorectal cancer (CRC). However, this cytotoxic ...anticancer drug often causes severe side effects because it does not act selectively on the tumor. It has been reported that the 5-FU showed considerable toxicity when administered by intravenous injections or via alimentary tract. Although, many materials have been developed for carrying 5-FU, there has been no clinically acceptable carrier for 5-FU till now. Montmorillonite, one of the clay minerals, consists of hydrated aluminum silicates with fine grains and large spaces between the layers. Isomorphous substitution of cations is common. In the study, we attempt to intercalate 5-FU into interlayers of montmorillonite through ion exchange.
Montmorillonite was purified from crude clays of bentonite in Tai-dong, Taiwan by filtration and sedimentation. Solutions of 5-FU with different concentrations were prepared by dissolving various amounts of 5-FU into 10
ml NaOH solution. Purified montmorillonite powder was soaked in 5-FU solution for a period of time with different pH values and temperatures. In this study, we try to intercalate 5-FU into interlayers of montmorillonite to find out optimum conditions, such as soaking time, temperature, pH value, initial 5-FU concentration, etc., to prepare composites of 5-FU and montmorillonite (5-FU/mont). UV, SDT, FTIR, XRD are used to characterize the 5-FU/mont composite.
From the results, 5-FU was successfully intercalated into the interlayer of montmorillonite both by free surface absorption and OH replacement. The optimum condition for 5-FU/mont preparations is 1.185
wt% of 5-FU as initial concentration under a pH value of 11.6 at a temperature of 80°C and a soaking time of 2
h. The total amount of 5-FU in montmorillonite is about 87.5
mg for each gram of montmorillonite, which can be proved by thermal gravimetric analysis. The composite of 5-FU/mont is expected to achieve in situ release for colorectal cancer therapy in future applications.
The presence and degree of neuronal degeneration already existing in patients at their initial presentation with a clinically isolated syndrome suggestive of multiple sclerosis (CIS) is unclear, and ...whole brain or whole normalised grey matter analyses have not demonstrated significant atrophy in CIS cohorts at clinical presentation. Voxel-based analyses allow detection of regional atrophy throughout the brain and, therefore, may be sensitive to regional atrophy in CIS patients, and these changes may correspond with clinical disability.
This study used a modified voxel-based morphometry (VBM) method to correct for lesion effects to analyse regional atrophy and perform voxel-wise correlations between volume and clinical metrics in 41 untreated CIS patients at presentation compared with 49 healthy controls.
The results confirmed that there was no significant difference in whole normalised grey matter volume between CIS and controls, whereas VBM showed significant areas of bilateral thalamic, hypothalamic, putamen and caudate atrophy. Voxel-wise correlations with clinical measures showed that cerebellar volumes correlated with clinical cerebellar function, nine-hole peg test scores and the Multiple Sclerosis Functional Composite (MSFC) score, and that the MSFC score was also correlated with putamen volume. Lastly, T1 lesion volumes were found to correlate with thalamic and hippocampal atrophy, suggesting a link between white matter lesions and grey matter degeneration at the earliest stages of multiple sclerosis.
Atrophy is present in CIS patients at presentations, particularly in the thalamus, and other deep grey matter structures. Furthermore, the correlations with clinical metrics suggest the importance of this atrophy to clinical status and the correlation with T1 lesion load suggests a possible role of Wallerian degeneration.
Abstract Since lung cancer is the most malignant cancer today, a specific drug-delivery system has been developed for superior outcome. In this study, gelatin nanoparticles (GPs) employed as native ...carriers were grafted with NeutrAvidinFITC on the particle's surface (GP–Av). Next, the biotinylated epithelial growth factor (EGF) molecules were conjugated with NeutrAvidinFITC , forming a core-shell-like structure (GP–Av–bEGF) to achieve the enhancement of targeting efficiency. These nanoparticles were applied as an EGF receptor (EGFR)-seeking agent to detect lung adenocarcinoma. The results showed that the modification process had no significant influence on particle size (220 nm) and zeta potential (−9.3 mV). By the in vitro cell culture test, GP–Av–bEGF resulted in higher entrance efficiency on adenocarcinoma cells (A549) than that on normal lung cells (HFL1) because A549 possessed greater amounts of EGFR. We also found that uptake of GP–Av–bEGF by A549 cells was time and dose dependent. Confocal microscopy confirmed the cellular internalization of GP–Av–bEGF, and more fluorescent spots of GP–Av–bEGF nanoparticles were obviously observed as well as lysosomal entrapment in A549. Finally, the delivery was demonstrated by in vivo aerosol administration to cancerous lung of the SCID mice model, and specific accumulation in cancerous lung was confirmed by image quantification. The targeting ability of GP–Av–bEGF was proved in vitro and in vivo , which holds promise for further anti-cancer drug applications.
Abstract Chlorin-core star-shaped block copolymer (CSBC) may self-assemble to form micelles, which act as nanosized photosensitizing agents for photodynamic therapy (PDT) and further encapsulate ...hydrophobic drugs. This functionalized micellar delivery system is a potential dual carrier for the synergistic combination of photodynamic therapy and chemotherapy for the treatment of cancer. In this study, SN-38 encapsulated CSBC micelles were successfully prepared using a lyophilization–hydration method. Our results show that the prolonged plasma residence time of SN-38/CSBC micelles as compared with free CPT-11 permit increased tumor accumulation and consequently, improved antitumor activity. The combined effects of SN-38/CSBC micelles with PDT were evaluated in an HT-29 human colon cancer xenograft model. Interesting, SN-38/CSBC-mediated PDT synergistically inhibited tumor growth, resulting in up to 60% complete regression of well-established tumors after 3 treatments. These treatments also decreased the microvessel density (MVD) and cell proliferation within the subcutaneous tumors. Therefore, this SN-38/CBSC delivery system has the potential to offer dual therapies for the synergistic combination of PDT and chemotherapy for the treatment of cancer.
The present study investigates the efficacy of polyethylenimine (PEI)-DNA complex that expressed human telomerase reverse transcriptase (hTERT) to transfect hair follicle stem cells and produce ...sufficient hTERT to stimulate hair growth. Transfection with pLC-hTERT-DNA-PEI complex (D+P group) in vitro induced expression of proliferating cell nuclear antigen in 35.8% of the purified stem cell population, suggesting enhanced cell proliferation. In vivo transfection efficiency of rat dorsal skin was determined by staining for β-gal activity. Cells positive for β-gal were located in the bulge region and dermal sheath of hair follicles. The follicles in the hTERT-transfected region entered anagenon day 15 after transfection, whereas non-transfected (Neg) controls remained in telogen. The similar effect was observed in 50-day-old rat dorsal skin. D+P group displayed a specific expression of hTERT and sufficient to initiate a transition to the anagen phase and promote new hair synthesis 18 days after the transfection. hTERT promoted follicle neogenesis following wounding. In all, 60 days after wounding, tissues of the D+P group showed more newly regenerating hair follicles (83±52 regenerated follicles per rat) in contrast to control group tissues (15±15 regenerated follicles per rat). These studies provide a potential approach for gene therapy of skin disease.
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