Improvement of n-butanol tolerance in Escherichia coli by membrane-targeted tilapia metallothionein

Background: Though n-butanol has been proposed as a potential transportation biofuel, its toxicity oftencauses oxidative stress in the host microorganism and is considered one of the bottlenecks preventing itsefficient mass production.Results: To relieve the oxidative stress in the host cell, metallothioneins (MTs), which are known as scavengersfor reactive oxygen species (ROS), were engineered in E. coli hosts for both cytosolic and outer-membrane-targeted (osmoregulatory membrane protein OmpC fused) expression. Metallothioneins from human (HMT),mouse (MMT), and tilapia fish (TMT) were tested. The host strain expressing membrane-targeted TMT showed thegreatest ability to reduce oxidative stresses induced by n-butanol, ethanol, furfural, hydroxymethylfurfural, andnickel. The same strain also allowed for an increased growth rate of recombinant E. coli under n-butanol stress.Further experiments indicated that the TMT-fused OmpC protein could not only function in ROS scavenging butalso regulate either glycine betaine (GB) or glucose uptake via osmosis, and the dual functional fusion proteincould contribute in an enhancement of the host microorganism’s growth rate.Conclusions: The abilities of scavenging intracellular or extracellular ROS by these engineering E. coli wereexamined, and TMT show the best ability among three MTs. Additionally, the membrane-targeted fusion protein,OmpC-TMT, improved host tolerance up to 1.5% n-butanol above that of TMT which is only 1%. These resultspresented indicate potential novel approaches for engineering stress tolerant microorganism strains

Pioneering Astaxanthin-Tumor Cell Membrane Nanoparticles for Innovative Targeted Drug Delivery on Melanoma

BackgroundRecently, the use of the tumor or its secretions as drug carriers has gradually become popular, with the advantages of high biocompatibility and enhanced drug delivery to specific cells. Melanoma is the most malignant tumor of all skin cancers; it is the most metastatic and, therefore, the most difficult to treat. The main purpose of this study is to develop nanovesicles with tumor cell membrane secretion properties to encapsulate target substances to enhance the therapeutic effect of cancer.MethodsAstaxanthin was selected as an anticancer drug due to our previous research finding that astaxanthin has extremely high antioxidant, anti-ultraviolet damage, and anti-tumor properties. The manufacturing method of the astaxanthin nanovesicle carrier is to mix melanoma cells and astaxanthin in an appropriate ratio and then remove the genetic material and inflammatory factors of cancer cells by extrusion.ResultsIn terms of results, after the co-culture of astaxanthin nanovesicles and melanoma cancer cells, it was confirmed that the ability of astaxanthin nanovesicles to inhibit the growth and metastasis of melanoma cancer cells was significantly better than the same amount of astaxanthin alone, and it had no effect on normal Human cells are also effective. There was no apparent harm on normal cells, indicating the ability of the vesicles to be selectively transported.ConclusionOur findings illustrated the potential of astaxanthin nanovesicles as an anticancer drug

M-SpeechCLIP: Leveraging Large-Scale, Pre-Trained Models for Multilingual Speech to Image Retrieval

This work investigates the use of large-scale, pre-trained models (CLIP and HuBERT) for multilingual speech-image retrieval. For non-English speech-image retrieval, we outperform the current state-of-the-art performance by a wide margin when training separate models for each language, and show that a single model which processes speech in all three languages still achieves retrieval scores comparable with the prior state-of-the-art. We identify key differences in model behavior and performance between English and non-English settings, presumably attributable to the English-only pre-training of CLIP and HuBERT. Finally, we show that our models can be used for mono- and cross-lingual speech-text retrieval and cross-lingual speech-speech retrieval, despite never having seen any parallel speech-text or speech-speech data during training.Comment: Submitted to ICASSP 202

Bioactive Eunicellin-Based Diterpenoids from the Soft Coral Cladiella krempfi

Four new eunicellin-based diterpenoids, krempfielins A–D (1–4), along with two known compounds (5 and 6) have been isolated from a soft coral Cladiella krempfi. The structures of the new metabolites were elucidated by extensive spectroscopic analysis and by comparison with spectroscopic data of related known compounds. Compounds 5 and 6 were shown to exhibit cytotoxicity against a limited panel of cancer cell lines. Furthermore, compounds 2, 3, 5 and 6 were shown to exert significant in vitro anti-inflammatory activity against LPS-stimulated RAW264.7 macrophage cells

Assembling a cellulase cocktail and a cellodextrin transporter into a yeast host for CBP ethanol production

Background: Many microorganisms possess enzymes that can efficiently degrade lignocellulosic materials, but donot have the capability to produce a large amount of ethanol. Thus, attempts have been made to transform suchenzymes into fermentative microbes to serve as hosts for ethanol production. However, an efficient host for aconsolidated bioprocess (CBP) remains to be found. For this purpose, a synthetic biology technique that cantransform multiple genes into a genome is instrumental. Moreover, a strategy to select cellulases that interactsynergistically is needed.Results: To engineer a yeast for CBP bio-ethanol production, a synthetic biology technique, called “promoter-basedgene assembly and simultaneous overexpression” (PGASO), that can simultaneously transform and express multiplegenes in a kefir yeast, Kluyveromyces marxianus KY3, was recently developed. To formulate an efficient cellulasecocktail, a filter-paper-activity assay for selecting heterologous cellulolytic enzymes was established in this study andused to select five cellulase genes, including two cellobiohydrolases, two endo-β-1,4-glucanases and onebeta-glucosidase genes from different fungi. In addition, a fungal cellodextrin transporter gene was chosen totransport cellodextrin into the cytoplasm. These six genes plus a selection marker gene were one-step assembledinto the KY3 genome using PGASO. Our experimental data showed that the recombinant strain KR7 could expressthe five heterologous cellulase genes and that KR7 could convert crystalline cellulose into ethanol.Conclusion: Seven heterologous genes, including five cellulases, a cellodextrin transporter and a selection marker,were simultaneously transformed into the KY3 genome to derive a new strain, KR7, which could directly convertcellulose to ethanol. The present study demonstrates the potential of our strategy of combining a cocktailformulation protocol and a synthetic biology technique to develop a designer yeast host

Persistent Tissue Kinetics and Redistribution of Nanoparticles, Quantum Dot 705, in Mice: ICP-MS Quantitative Assessment

Background: Quantum dots (QDs) are autofluorescent semiconductor nanocrystals that can be used for in vivo biomedical imaging. However, we know little about their in vivo disposition and health consequences. Objectives: We assessed the tissue disposition and pharmacokinetics of QD705 in mice. Methods: We determined quantitatively the blood and tissue kinetics of QD705 in mice after single intravenous (iv) injection at the dose of 40 pmol for up to 28 days. Inductively coupled plasma–mass spectrometry (ICP-MS) measurement of cadmium was the primary method of quantification of QD705. Fluorescence light microscopy revealed the localization of QD705 in tissues. Results: Plasma half-life of QD705 in mice was short (18.5 hr), but ICP-MS analyses revealed QD705 persisted and even continued to increase in the spleen, liver, and kidney 28 days after an iv dose. Considerable time-dependent redistribution from body mass to liver and kidney was apparent between 1 and 28 days postdosing. The recoveries at both time points were near 100%; all QD705s reside in the body. Neither fecal nor urinary excretion of QD705 was detected appreciably in 28 days postdosing. Fluorescence microscopy demonstrated deposition of QD705 in the liver, spleen, and kidneys. Conclusion: Judging from the continued increase in the liver (29–42% of the administered dose), kidney (1.5–9.2%), and spleen (4.8–5.2%) between 1 and 28 days without any appreciable excretion, QD705 has a very long half-life, potentially weeks or even months, in the body and its health consequences deserve serious consideration

Impact Analysis of Earthquake-Induced Cracks in Deep Geological Repositories for Nuclear Waste Fuel

Based on the concept of deep geologic repositories, high-level radioactive waste will be stored in deep deposition holes away from the ground surface. The heat generated by the waste will induce both significant stress increments and ground water seepage in a multiple geologic barrier system. The long-term ability of a barrier system is significantly impacted by coupling between the thermal, hydrological, and mechanical processes. The stability of a system may also depend particularly upon unanticipated factors such as the development of post-earthquake macrocracks. Therefore, this study investigates the three-dimensional transient and long term thermo-hydro-mechanical behavior of a barrier system. The results can be used for future reference in practical engineering design.高放射性用過核燃料所產生之長期衰變熱會對生物圈造成極大衝擊，目前國際上多傾向以深層地質處置作為最終處置之方式。處置過程中，極可能因為地震或地層變動等不可預期之因素，在天然障壁中產生大形裂縫，由此伴隨的災損效應將會加速障壁之劣化。本研究依據我國深層地質處置的初步設計概念，針對天然障壁系統長期之熱-水力-力學耦合效應，利用依序耦合分析方法，考慮不同的裂縫尺寸，針對其可能引致之熱應力與地下水影響進行評估

A 64-week, multicenter, open-label study of aripiprazole effectiveness in the management of patients with schizophrenia or schizoaffective disorder in a general psychiatric outpatient setting

<p>Abstract</p> <p>Objective</p> <p>To evaluate the overall long-term effectiveness of aripiprazole in patients with schizophrenia in a general psychiatric practice setting in Taiwan.</p> <p>Methods</p> <p>This was a prospective, open-label, multicenter, post-market surveillance study in Taiwanese patients with a Diagnostic and Statistical Manual of Mental Disorders, Fourth Edition (DSM-IV) diagnosis of schizophrenia or schizoaffective disorder requiring a switch in antipsychotic medication because current medication was not well tolerated and/or clinical symptoms were not well controlled. Eligible patients were titrated to aripiprazole (5-30 mg/day) over a 12-week switching phase, during which their previous medication was discontinued. Patients could then enter a 52-week, long-term treatment phase. Aripiprazole was flexibly dosed (5-30 mg/day) at the discretion of the treating physicians. Efficacy was assessed using the Clinical Global Impression scale Improvement (CGI-I) score, the Clinical Global Impression scale Severity (CGI-S) score, The Brief Psychiatry Rating Scale (BPRS), and the Quality of Life (QOL) scale, as well as Preference of Medicine (POM) ratings by patients and caregivers. Safety and tolerability were also assessed.</p> <p>Results</p> <p>A total of 245 patients were enrolled and switched from their prior antipsychotic medications, and 153 patients entered the 52-week extension phase. In all, 79 patients (32.2%) completed the study. At week 64, the mean CGI-I score was 3.10 and 64.6% of patients who showed response. Compared to baseline, scores of CGI-S, QOL, and BPRS after 64 weeks of treatment also showed significant improvements. At week 12, 65.4% of subjects and 58.9% of caregivers rated aripiprazole as better than the prestudy medication on the POM. The most frequently reported adverse events (AEs) were headache, auditory hallucinations and insomnia. A total of 13 patients (5.3%) discontinued treatment due to AEs. No statistically significant changes were noted with respect to fasting plasma glucose, lipid profile, body weight, and body mass index after long-term treatment with aripiprazole.</p> <p>Conclusions</p> <p>Although the discontinuation rate was high, aripiprazole was found to be effective, safe and well tolerated in the long-term treatment of Taiwanese patients with schizophrenia who continued to receive treatment for 64 weeks.</p

The Relationship between Stasis-Stagnation Constitution and Peripheral Arterial Disease in Patients with Type 2 Diabetes

Objectives. In traditional Chinese medicine, Yu-Zhi (YZ, indicating stasis and stagnation) constitution describes a body that tends to express abnormal circulatory conditions. This study identified the linkage between YZ constitution and peripheral arterial disease (PAD) in patients with type 2 diabetes. Methods. Patients over 20 years of age who had had type 2 diabetes for 5 years or longer were recruited. PAD was diagnosed if the ankle-brachial index score was ≤0.9 in either leg. Level of YZ constitution was accessed by an YZ Constitution Questionnaire. Results. A total of 712 patients (354 men and 358 women) with a mean age of 61.5±10.6 years and diabetes duration of 13.1±6.7 years were recruited. The prevalence of PAD among our patients was 7.2%. Multivariate logistic regression revealed significant correlations between PAD and, respectively, YZ score, age, diabetes duration, current smoking, and hs-CRP. Conclusion. In addition to traditional risk factors, YZ constitution was statistically associated with PAD in patients with type 2 diabetes. This result invites further research into the effectiveness of traditional Chinese medicine to treat YZ constitution

Taiwan Oscillation Network

The Taiwan Oscillation Network (TON) is a ground-based network to measure solar intensity oscillations to study the internal structure of the Sun. K-line full-disk images of 1000 pixels diameter are taken at a rate of one image per minute. Such data would provide information onp-modes withl as high as 1000. The TON will consist of six identical telescope systems at proper longitudes around the world. Three telescope systems have been installed at Teide Observatory (Tenerife), Huairou Solar Observing Station (near Beijing), and Big Bear Solar Observatory (California). The telescopes at these three sites have been taking data simultaneously since October of 1994. Anl – v diagram derived from 512 images is included to show the quality of the data