COVID-19疫情停課後中小學之復課策略 盧玉玫(Yu-Mei Lu); 馮嘉玉(Jia-Yuh Ferng); 陳凱倫(Kai-Ren Chen) ...
Taiwan gong gong wei sheng za zhi (Taiwan gong gong wei sheng xue hui),
10/2021, Letnik:
40, Številka:
5
Journal Article
Since November 2019, COVID-19 has spread rapidly around the world. In order to control the epidemic, countries have resorted to measures such as social distance, reducing gatherings, and isolation, ...ranging from community blockades, school closures, and lockdowns. Various epidemic prevention measures have affected the national economy and society, and have also had a major impact on the education system. According to statistics from the United Nations Educational, Scientific and Cultural Organization (UNESCO), as of March 2021, more than 168 million schoolchildren around the world have not attended school for a year. The impact of school suspension is both deep and wide.
Some clinically used anti-cancer drugs are obtained from natural products. Allyl isothiocyanate (AITC), a plant-derived compound abundant in cruciferous vegetables, has been shown to possess an ...anti-cancer ability in human cancer cell lines in vitro, including human brain glioma cells. However, the anti-cancer effects of AITC in human glioblastoma (GBM) cells in vivo have not yet been examined. In the present study, we used GBM8401/luc2 human glioblastoma cells and a GBM8401/luc2-cell-bearing animal model to identify the treatment efficacy of AITC. Here, we confirm that AITC reduced total cell viability and induced cell apoptosis in GBM8401/luc2 cells in vitro. Furthermore, Western blotting also showed that AITC induced apoptotic cell death through decreased the anti-apoptotic protein BCL-2, MCL-1 expression, increased the pro-apoptotic protein BAX expression, and promoted the activities of caspase-3, -8, and -9. Therefore, we further investigated the anti-tumor effects of AITC on human GBM8401/luc2 cell xenograft mice. The human glioblastoma GBM8401/luc2 cancer cells were subcutaneously injected into the right flank of BALB/c nude mice to generate glioblastoma xenograft mice. The animals were randomly divided into three groups: group I was treated without AITC (control); group II with 0.1 mg/day of AITC; and group III with 0.2 mg/day of AITC every 3 days for 27 days. Bodyweight, and tumor volume (size) were recorded every 3 days. Tumors exhibiting Luc2 intensity were measured, and we quantified intensity using Living Image software on days 0, 12, and 24. After treatment, tumor weight from each mouse was recorded. Tumor tissues were examined for histopathological changes using H&E staining, and we analyzed the protein levels via immunohistochemical analysis. Our results indicate that AITC significantly inhibited tumor growth at both doses of AITC due to the reduction in tumor size and weight. H&E histopathology analysis of heart, liver, spleen, and kidney samples revealed that AITC did not significantly induce toxicity. Body weight did not show significant changes in any experiment group. AITC significantly downregulated the protein expression levels of MCL-1, XIAP, MMP-9, and VEGF; however, it increased apoptosis-associated proteins, such as cleaved caspase-3, -8, and -9, in the tumor tissues compared with the control group. Based on these observations, AITC exhibits potent anti-cancer activity in the human glioblastoma cell xenograft model via inhibiting tumor cell proliferation and the induction of cell apoptosis. AITC may be a potential anti-GBM cancer drug that could be used in the future.
碩士
國立臺灣大學
機械工程學研究所
91
In semiconductor manufacturing, photolithography (PL), being a most repeated process, is a critical process, since meeting tolerance on critical dimensions and alignment with ...the previous layers. In order to check conformance to process specifications, test runs are made regularly, and machine dedication rule is used. Akcali et al.2001 proposed three test run policies and two stepper dispatch rules for experimental study. The study revealed that the parallel testing policy and the flexible stepper dispatch rule performed the best under a certain production conditions. The authors pointed the optimal test run policy might not be the same under different production conditions, and they didn’t consider the effect of alignment that led the result of choosing the flexible dispatch one.
The main purpose of this study is to propose an evaluation method to determine the optimal test run policy and the stepper dispatch rule under different production conditions for PL, if they are case-dependen
Under the impact of the financial tsunami, global economy was weaken, lots of luxury brands¡¦ profits decreased, but trendy brands rise at that time. There are many kinds of trendy brands appear in ...Taiwan since 2008, and become famous between young people immediately. Trendy brands emphasize with uniqueness¡Bself-expression, not only become the fashion tendency, they also play an important role in teenagers¡¦ sub culture. As trendy brands get popular, some companies want to attract more young people by cooperating with trendy brands. Crossover with trendy brands is the main topic for companies.There is a lack of research about trendy or crossover so far, so this study is based on co-branding theory, analysis the change of consumers¡¦ evaluations about Positive brand emotions, negative brand emotions, involvement, and brand identity after company crossovers with different kinds of trendy brand. Then the study adds fitness between company and trendy brand and self-construal types of consumer as mediators, trying to comprehend the influence.This study finds consumers¡¦ evaluations about positive brand emotions and negative brand emotions will be better if company crossover with trendy brand founded by famous people. But consumers¡¦ evaluations about brand identity will be better if company crossover with both trendy brand founded by famous people and ordinary people. However, fitness between company and trendy brand and consumer¡¦s self-construal types don¡¦t change evaluations after crossover.
Abstract
Canakinumab is a fully human monoclonal antibody that specifically neutralizes human interleukin (IL)-1β and has been approved by the US Food and Drug Administration for treating different ...types of autoinflammatory disorders such as cryopyrin-associated periodic syndrome, tumor necrosis factor receptor-associated periodic syndrome and systemic juvenile idiopathic arthritis. However, long-term systemic neutralization of IL-1β by Canakinumab may cause severe adverse events such as serious upper respiratory tract infections and inflammation, thereby decreasing the quality of life of patients. Here, we used an IgG1 hinge as an Ab lock to cover the IL-1β-binding site of Canakinumab by linking with matrix metalloprotease 9 (MMP-9) substrate to generate pro-Canakinumab that can be specifically activated in the inflamed regions in autoinflammatory diseases to enhance the selectivity and safety of treatment. The Ab lock significantly inhibited the IL-1β-binding by 68-fold compared with Canakinumab, and MMP-9 completely restored the IL-1β neutralizing ability of pro-Canakinumab within 60 min and blocked IL-1β-downstream signaling and IL-1β-regulated genes (i.e., IL-6). It is expected that MMP-9 cleavable and efficient Ab lock will be able to significantly enhance the selective reaction of Canakinumab at the disease site and reduce the on-target toxicities of Canakinumab during systemic circulation, thereby showing potential for development to improve the safety and quality of life of patients with autoinflammatory disorders in the future.
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Irinotecan (CPT-11), a first-line chemotherapy for advanced colorectal cancer, causes serious diarrhea in patients receiving treatment. The underlying mechanism has been shown that ...the active metabolite of CPT-11, SN-38, is metabolized to the inactive metabolite SN-38 glucuronide (SN-38 G) during hepatic glucuronidation, and subsequently is exported into the intestine, where SN-38 G is hydrolyzed by bacterial β-glucuronidase (βG) to be SN-38, thus leading to intestinal toxicity. Thus, inhibition of the intestinal bacterial βG activity is expected to prevent CPT-11-induced diarrhea. However, the effects of such inhibition on serum pharmacokinetics of SN-38, the key determinant of CPT-11 treatment, are uncertain. Here, we determined the effects of a potent E. coli βG (eβG)-specific inhibitor pyrazolo4,3-cquinoline derivative (TCH-3562) for the potential use in preventing CPT-11-induced diarrhea. TCH-3562 exhibited efficacious inhibitory potency of endogenous βG activity in two anaerobes, Eubacteriumsp. and Peptostreptococcus anaerobius. Oral administration of TCH-3562 also effectively reduced the bacterial βG activity in mice intestine. Moreover, pharmacokinetic analysis of TCH-3562 revealed a relatively low amount of TCH-3562 was detected in the plasma whereas the majority of TCH-3562 was found in the feces. Importantly, co-treatment of CPT-11 and TCH-3562 did not decrease active SN-38 level in mice plasma. Finally, we established that TCH-3562 as an adjuvant treatment showed protective effects on CPT-11-induced diarrhea and had no negative effects on the therapeutic efficacy of CPT-11 in tumor-bearing mice. Therefore, inhibition of the intestinal bacterial βG activity by the specific inhibitor, TCH-3562, is promising to prevent CPT-11-induced diarrhea while maintaining its anti-tumor efficacy that may have clinical potentials for the treatment with CPT-11.
Membrane antigens (mAgs) are important targets for the development of antibody (Ab) drugs. However, native mAgs are not easily prepared, causing difficulties in acquiring functional Abs. In this ...study, we present a platform in which human mAgs were expressed in native form on cell adjuvants made with membrane-bound cytokines that were then used immunize syngeneic mice directly. The membrane-bound cytokines were used as immune stimulators to enhance specific Ab responses against the desired mAgs. Then, mAgs-expressing xenogeneic cells were used for Ab characterization to reduce non-specific binding. We established cell adjuvants by expressing membrane-bound cytokines (mIL-2, mIL-18, or mGM-CSF) on BALB/3T3 cells, which were effective in stimulating splenocyte proliferation in vitro. We then transiently expressed ecotropic viral integration site 2B (EVI2B) on the adjuvants and used them to directly immunize BALB/c mice. We found that 3T3/mGM-CSF cells stimulated higher specific anti-EVI2B Ab response in the immunized mice than the other cell adjuvants. A G-protein coupled receptor (GPCR), CXCR2, was then transiently expressed on 3T3/mGM-CSF cell adjuvant to immunize mice. The immune serum exhibited relatively higher binding to xenogeneic 293 A/CXCR2 cells than 293 A cells (~3.5-fold). Several hybridoma clones also exhibited selective binding to 293 A/CXCR2 cells. Therefore, the cell adjuvant could preserve the native conformation of mAgs and exhibit anti-mAg Ab stimulatory ability, providing a more convenient and effective method to generate functional Abs, thus possibly accelerating Ab drug development.
3D bioprinting is a pioneering technology that enables fabrication of biomimetic, multiscale, multi-cellular tissues with highly complex tissue microenvironment, intricate cytoarchitecture, ...structure-function hierarchy, and tissue-specific compositional and mechanical heterogeneity. Given the huge demand for organ transplantation, coupled with limited organ donors, bioprinting is a potential technology that could solve this crisis of organ shortage by fabrication of fully-functional whole organs. Though organ bioprinting is a far-fetched goal, there has been a considerable and commendable progress in the field of bioprinting that could be used as transplantable tissues in regenerative medicine. This paper presents a first-time review of 3D bioprinting in regenerative medicine, where the current status and contemporary issues of 3D bioprinting pertaining to the eleven organ systems of the human body including skeletal, muscular, nervous, lymphatic, endocrine, reproductive, integumentary, respiratory, digestive, urinary, and circulatory systems were critically reviewed. The implications of 3D bioprinting in drug discovery, development, and delivery systems are also briefly discussed, in terms of in vitro drug testing models, and personalized medicine. While there is a substantial progress in the field of bioprinting in the recent past, there is still a long way to go to fully realize the translational potential of this technology. Computational studies for study of tissue growth or tissue fusion post-printing, improving the scalability of this technology to fabricate human-scale tissues, development of hybrid systems with integration of different bioprinting modalities, formulation of new bioinks with tuneable mechanical and rheological properties, mechanobiological studies on cell-bioink interaction, 4D bioprinting with smart (stimuli-responsive) hydrogels, and addressing the ethical, social, and regulatory issues concerning bioprinting are potential futuristic focus areas that would aid in successful clinical translation of this technology.
Objective: A global consensus meeting was held to review current evidence and knowledge gaps and propose collaborative studies on population-wide screening and eradication of Helicobacter pylori for ...prevention of gastric cancer (GC). Methods 28 experts from 11 countries reviewed the evidence and modified the statements using the Delphi method, with consensus level predefined as >= 80% of agreement on each statement. The Grading of Recommendation Assessment, Development and Evaluation (GRADE) approach was followed. Results Consensus was reached in 26 statements. At an individual level, eradication of H. pylori reduces the risk of GC in asymptomatic subjects and is recommended unless there are competing considerations. In cohorts of vulnerable subjects (eg, first-degree relatives of patients with GC), a screen-and-treat strategy is also beneficial. H. pylori eradication in patients with early GC after curative endoscopic resection reduces the risk of metachronous cancer and calls for a re-examination on the hypothesis of 'the point of no return'. At the general population level, the strategy of screen-and-treat for H. pylori infection is most cost-effective in young adults in regions with a high incidence of GC and is recommended preferably before the development of atrophic gastritis and intestinal metaplasia. However, such a strategy may still be effective in people aged over 50, and may be integrated or included into national healthcare priorities, such as colorectal cancer screening programmes, to optimise the resources. Reliable locally effective regimens based on the principles of antibiotic stewardship are recommended. Subjects at higher risk of GC, such as those with advanced gastric atrophy or intestinal metaplasia, should receive surveillance endoscopy after eradication of H. pylori. Conclusion Evidence supports the proposal that eradication therapy should be offered to all individuals infected with H. pylori. Vulnerable subjects should be tested, and treated if the test is positive. Mass screening and eradication of H. pylori should be considered in populations at higher risk of GC.
Serological responses (Seroresponse) and durability of hepatitis A virus (HAV) vaccination are reduced among human immunodeficiency virus (HIV)‐positive patients. Incidence of and associated factors ...with early seroreversion (loss of seroresponse) among HIV‐positive patients who have achieved seroresponses after two doses of HAV vaccination remain unclear. In this multicenter study, we followed HIV‐positive adults who had mounted seroresponses after completing two doses of HAV vaccination during a recent outbreak of acute hepatitis A between 2015 and 2017, a 1:4 case‐control study was conducted to identify factors associated with seroreversion. Case patients were those with seroreversion, and controls were those with similar follow‐up durations who were able to maintain seroresponses. During the study period, 49 of the 1,256 patients (3.9%) seroreverted after a median follow‐up of 611 days. In a case‐control study, seroreversion was more likely to occur in patients with a higher weight (adjusted odds ratio aOR, 1.703; 95% confidence interval CI, 1.292‐2.323, per 10‐kg increment) and HIV viremia at the time of vaccination (aOR, 2.922; 95% CI, 1.067‐7.924), whereas positive seroresponse at 6 months of HAV vaccination and higher CD4 lymphocyte counts at vaccination were inversely associated with early seroreversion with an aOR of 0.059 (95% CI, 0.020‐0.154) and 0.837 (95% CI, 0.704‐0.979, per 100‐cell/mm3 increment), respectively, in multivariable analyses. Conclusion: During an outbreak setting, early seroreversion following two‐dose HAV vaccination occurred in 3.9% of HIV‐positive patients. Lower and delayed seroresponses to HAV vaccination, a higher weight, and HIV viremia and lower CD4 lymphocyte counts at the time of HAV vaccination were associated with early seroreversion. Regular monitoring of seroresponse and booster vaccination might be warranted, especially in HIV‐positive adults with predictors of early seroreversion.
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