Fabrication and Characterization of Collagen-Immobilized Porous PHBV/HA Nanocomposite Scaffolds for Bone Tissue Engineering

The porous composite scaffolds (PHBV/HA) consisting of poly (3-hydroxybutyrate-co-3-hydroxyvalerate) (PHBV) and hydroxyapatite (HA) were fabricated using a hot-press machine and salt-leaching. Collagen (type I) was then immobilized on the surface of the porous PHBV/HA composite scaffolds to improve tissue compatibility. The structure and morphology of the collagen-immobilized composite scaffolds (PHBV/HA/Col) were investigated using a scanning electron microscope (SEM), Fourier transform infrared (FTIR), and electron spectroscopy for chemical analysis (ESCA). The potential of the porous PHBV/HA/Col composite scaffolds for use as a bone scaffold was assessed by an experiment with osteoblast cells (MC3T3-E1) in terms of cell adhesion, proliferation, and differentiation. The results showed that the PHBV/HA/Col composite scaffolds possess better cell adhesion and significantly higher proliferation and differentiation than the PHBV/HA composite scaffolds and the PHBV scaffolds. These results suggest that the PHBV/HA/Col composite scaffolds have a high potential for use in the field of bone regeneration and tissue engineeringclose2

Yoga Training Improves Metabolic Parameters in Obese Boys

Yoga has been known to have stimulatory or inhibitory effects on the metabolic parameters and to be uncomplicated therapy for obesity. The purpose of the present study was to test the effect of an 8-week of yoga-asana training on body composition, lipid profile, and insulin resistance (IR) in obese adolescent boys. Twenty volunteers with body mass index (BMI) greater than the 95th percentile were randomly assigned to yoga (age 14.7±0.5 years, n=10) and control groups (age 14.6±1.0 years, n=10). The yoga group performed exercises three times per week at 40~60% of heart-rate reserve (HRR) for 8 weeks. IR was determined with the homeostasis model assessment of insulin resistance (HOMA-IR). After yoga training, body weight, BMI, fat mass (FM), and body fat % (BF %) were significantly decreased, and fat-free mass and basal metabolic rate were significantly increased than baseline values. FM and BF % were significantly improved in the yoga group compared with the control group (p\u3c0.05). Total cholesterol (TC) was significantly decreased in the yoga group (p\u3c0.01). HDL-cholesterol was decreased in both groups (p\u3c0.05). No significant changes were observed between or within groups for triglycerides, LDL-cholesterol, glucose, insulin, and HOMA-IR. Our findings show that an 8-week of yoga training improves body composition and TC levels in obese adolescent boys, suggesting that yoga training may be effective in controlling some metabolic syndrome factors in obese adolescent boys

Treatment shortening of drug-sensitive pulmonary tuberculosis using high-dose rifampicin for 3 months after culture conversion (Hi-DoRi-3): a study protocol for an open-label randomized clinical trial

Background : The standard treatment regimen for drug-sensitive tuberculosis (TB), comprising four companion drugs, requires a minimum duration of 6 months, and this lengthy treatment leads to poor adherence and increased toxicity. To improve rates of adherence, reduce adverse events, and lower costs, a simplified and shortened treatment regimen is warranted. Methods : This study is a multicenter, open-label randomized clinical trial of non-inferiority design that compares a new regimen with the conventional regimen for drug-sensitive pulmonary TB. The investigational group will use a regimen of high-dose rifampicin (30 mg/kg/day) with isoniazid and pyrazinamide, and the treatment will be maintained for 12 weeks after the achievement of negative conversion of sputum culture. The control group will be treated for 6 months with a World Health Organization-endorsed regimen consisting of isoniazid, rifampicin (10 mg/kg/day), ethambutol, and pyrazinamide. The primary endpoint is the proportion of unfavorable outcomes at 18 months after randomization. Secondary outcomes include time to unfavorable treatment outcome, time to culture conversion on liquid medium, treatment success rate at the end of treatment, proportion of recurrence at 18 months after randomization, time to recurrence after treatment completion, and adverse events of grade 3 or higher during the treatment. We predict a 10% unfavorable outcome for the control group, and 0% difference from the investigational group. Based on 80% verification power and a 2.5% one-sided significance level for a non-inferiority margin of 6%, 393 participants per group are required. Considering the 15% dropout rate, a total of 926 participants (463 in each group) will be recruited. Discussion : This study will inform on the feasibility of the treatment regimen using high-dose rifampicin with a shortened and individualized treatment duration for pulmonary TB. Trial registration : ClinicalTrials.gov NCT04485156.Registered on July 24, 2020.This work was supported by a grant from the Korea National Institute of Health (2020-ER5201-01), Republic of Korea. High-dose rifampicin tablets and capsules were donated from Yuhan (Seoul, Republic of Korea) for this study. The funder and donor had no role in the study design, data collection and analysis, decision to publish, or preparation of the manuscript

글리세롤로부터 1, 2-propanediol (1,2-PDO) 생산을 위한 구리 기반의 나노 촉매 제조 및 특성 연구

With the increasing crisis regarding crude-oil reserves and air pollution caused by the combustion of petroleum-derived fuel, the focus has recently turned towards a more intensive utilization of renewable energy resources. Among the renewable energy resources, biomass is an abundant and carbon-neutral renewable energy resource that can be used for the production of biofuels and valuable chemicals. This biomass represents a potential for producing value-added products, which is an alternative biodiesel to feedstocks for the production of chemicals and other materials. Glycerol, a representative biomass, was produced as a 10 % byproduct of biodiesel production. A number of catalytic conversion processes have been reported for converting glycerol into other useful chemicals and a broad overview is presented here. Among the various value-added chemicals,1,2-propanediol (abbreviated hereafter as 1,2-PDO) is a major commodity that is widely used in the production of unsaturated polyester resins, functional fluids (antifreeze, de-icing, and heat transfer), pharmaceuticals, foods, cosmetics, liquid detergents, tobacco humectants, flavors and fragrances, personal care, paints and animal feed. In this study, we developed a high performance catalyst and support for the production of 1,2-PDO from glycerol. In the first part, Zn-promoted CuCr2O4 catalysts prepared by a co-precipitation method and evaluated. A variety of techniques, including TPR, H2-TPD, XRD and XPS, were used to characterize the samples. The presence of Zn as a promoter results in the enhancement of the copper reducibility compared to a pure CuCr2O4 catalyst. In addition, it affected to the cubic spinel structure of reduced CuCr2O4, which became more active due to the increase in the amounts of occluded hydrogen. These results indicate that the reducibility and amounts of occluded hydrogen in spinel structure of CuCr2O4 played significant roles in the catalytic activity for hydrogenolysis of glycerol. Among the catalysts tested, a CuCr2O4 catalyst with 5 wt. % Zn added (ZnCuCr-5) showed the highest catalytic activity, with about a 90% yield of a conversion of 94% of 1,2-PDO under the reaction conditions (220 oC, 5 MPa initial H2 pressure for 12 h). For the second part, samples of nanocrystalline copper aluminate (CuAl2O4) were prepared using various calcination temperatures and surfactant concentrations of citric acid via a sol-gel method for the hydrogenolysis of glycerol. A variety of techniques, including TPR, H2-TPD, XRD and XPS, were used to characterize the samples. Crystallized CuAl2O4 was initially observed after calcination at the temperature of 600 oC and only peaks corresponding to CuAl2O4 spinel crystal were observed at 800 oC, as evidenced by the XRD results. The citric acid concentration also influenced the size of the CuAl2O4 crystal (ca. 10-30 nm) and the electron state of Cu after reduction, which optimized the ratio of metal precursor cations and citric acid with 1 to 2. Catalytic activities of the prepared catalysts were examined for the hydrogenolysis of glycerol to 1,2-PDO. CuAl2O4 catalyst calcined at 800 oC, which contains only the CuAl2O4 crystalline phase, showed the highest catalytic performance with over a 90 % conversion and selectivity. This can be attributed to the exceptional reducibility of Cu species and hydrogen adsorption/desorption ability among the catalysts studied, as determined by TPR and H2-TPD analysis. Finally, we also prepared bimetallic CuNi catalysts supported on mesoporous alumina (MA) with different Cu and Ni ratios by a one-pot sol-gel method. The CuNi/MA catalysts showed well developed framework mesoporosity and a relatively high degree of metal dispersion (ca. 30 wt. %). Hydrogen mobility between Cu and Ni metal in the catalysts was analyzed by TPR and H2-TPD. The catalytic activity of these catalysts were evaluated for the hydrogenolysis of glycerol to 1,2-PDO without the addition of hydrogen gas from an external source. The Cu7Ni3/MA catalyst showed the best catalytic activity (18.9 %) with the highest conversion of glycerol and selectivity for 1,2-PDO. This result is due to the optimized metal contents, which are favorable for hydrogen mobility and successive hydrogenation after the dehydration reaction using aqueous phase reforming by a Ni catalyst. Based on the findings reported herein, a mechanism is proposed for the hydrogenolysis of glycerol with the simultaneous generation of hydrogen gas using CuNi/MA catalysts.최근의 에너지 위기에 대한 해결 방안으로써 기존의 석유화학 산업을 대체하며 지속 가능한 에너지 자원 중 하나인 바이오매스에 대하여 많은 관심이 집중되고 있다. 이러한 바이오매스로부터 생산되는 바이오디젤의 부산물로 생산되는 글리세롤은 바이오디젤의 생산량의 급증에 따라 이를 활용하여 다양한 고부가가치 물질을 생산하는 기술들에 대한 연구가 필요한 실정이다. 다양한 고부가가치 물질 중에서 1,2-Propanediol (1,2-PDO)은 다양한 고기능성 물질 (부동액, 윤활제, 계면활성제, 보습제, 화장품 등)의 기초원료로 사용되며 계속적으로 소비량이 증가하고 있어 산업의 발전가능성이 확대되고 있다. 글리세롤로부터 1,2-PDO를 생산하는 대표적으로 알려진 반응은 수소첨가분해반응으로 글리세롤로부터 아세톨로 전환되는 탈수 반응, 아세톨로부터 1,2-PDO로 전환되는 수소화 반응의 두 단계 반응으로 진행되고 있으며, 활용되는 촉매들은 두 가지의 기능성을 갖는 촉매들에 대한 연구가 많이 진행되고 있다. 또한, 이 반응을 상업적으로 이용하기 위해서 수소화 반응에서 사용되는 수소의 사용량을 감소시켜 낮은 수소압 및 온도 조건에서 반응을 진행하는 연구들이 많이 진행되고 있다. 이 학위논문에서는 글리세롤로부터 1,2-PDO로의 전환에서 높은 수율을 얻을 수 있는 스피넬 구조의 촉매에 대한 개발과 특성 연구 및 수소가 첨가되지 않는 전환 반응에서의 촉매의 개발 및 반응 mechanism의 해석을 다루었다. 첫 번째 연구로 높은 수율의 1,2-PDO를 생산하기 위한 촉매로써 스피넬(spinel) 구조의 CuCr2O4 촉매와 CuAl2O4 촉매를 제조하였다. 기존에 약 60 %의 높은 활성을 보였던 CuCr2O4촉매에 조촉매로 적은 양의 Zn을 첨가하여 촉매를 제조하였으며, 이 촉매를 XRD, H2-TPD, TPR 등의 기법을 사용하여 분석하였다. 제조된 촉매의 반응 실험 결과, 전환율과 선택도가 약 90 % 이상의 높은 수율을 보이는 것으로 나타났다. 이러한 반응성 결과를 다양한 분석법을 사용하여 분석한 결과, 조촉매가 약 5 ~ 10 % 정도 첨가 되었을 때, 스피넬 구조 내의 산화구리의 환원력 및 스피넬 구조의 내부로 포함되는 수소의 양의 증가에 의한 영향인 것으로 판단하였다. 또한, 솔-젤 방법을 사용하여 낮은 소성온도에서도 높은 스피넬 결정을 갖는 나노 구조의 CuAl2O4 촉매를 제조하였다. 다양한 소성온도와 유기산인 Citric 산의 농도를 조절하여 촉매의 입자 크기 및 촉매 내에서의 전자 구조를 조절할 수 있었다. 제조된 촉매의 반응실험 결과, 스피넬 구조의 CuAl2O4 결정의 형성이 증가함에 따라 반응의 선택성이 점차적으로 증가하는 것으로 나타났다. 이러한 반응성 결과를 TPR, H2-TPD를 통해 분석한 결과, 스피넬 구조의 촉매에서 증가되는 수소 흡탈착 특성이 글리세롤의 수소첨가분해반응의 활성을 결정하는데 큰 역할을 한 것으로 해석하였다. 1,2-PDO로의 전환반응이 경제성을 갖기 위해서는 기존의 공정 조건보다 낮은 온도와 수소압이 필요하다. 이를 해결하고자 높은 표면적을 갖는 중형기공 구조성 알루미나에 Cu와 Ni 금속을 담지시켜 촉매를 제조하였다. 이를 이용하여 수소가 첨가되지 않는 조건에서 수소의 생산 및 수소첨가분해반응을 동시에 일으키는 연구를 진행하여 보았다. Ni이 첨가된 촉매의 경우, 글리세롤로부터 수소가 생산되고, 이렇게 발생되는 수소가 동시적으로 반응에 사용되어 1,2-PDO의 생산되는 것을 보였다. Cu와 Ni의 비율을 다양하게 조절하여 연구한 결과, 글리세롤의 전환율과 1,2-PDO의 선택성이 최적화되는 비율이 약 7:3을 나타내는 것을 볼 수 있었다. 그리고 수소의 생산 및 수소첨가분해 반응이 동시에 진행되어 글리세롤로부터 1,2-PDO가 생성되는 반응에 대한 메커니즘을 해석하였다. 이 연구에서는 높은 성능 및 안정성을 보이는 구리 기반의 촉매를 제조하여 이를 통해 1,2-PDO를 제조하는 반응을 진행하였다. 그 결과, 스피넬 구조를 갖는 CuCr2O4 와 CuAl2O4 촉매에서는 촉매의 환원성 및 높은 수소함량율을 통해 1,2-PDO의 수율이 증가하는 것을 확인하였다. 또한, 수소를 첨가하지 않은 상태에서 촉매의 활성을 통해 글리세롤로부터 수소의 생산 및 수소첨가분해반응이 동시에 진행되는 반응을 진행하여 글리세롤로부터 1,2-PDO로의 전환반응에 대한 새로운 메커니즘을 적절하게 제시할 수 있었다.Docto

A Small Molecule Promoting Neural Differentiation Suppresses Cancer Stem Cells in Colorectal Cancer

Cancer stem cells (CSCs) are a tumor cell subpopulation that drives tumor progression and metastasis, leading to a poor overall survival of patients. In colorectal cancer (CRC), the hyper-activation of Wnt/β-catenin signaling by a mutation of both adenomatous polyposis coli (APC) and K-Ras increases the size of the CSC population. We previously showed that CPD0857 inactivates Wnt/β-catenin signaling by promoting the ubiquitin-dependent proteasomal degradation of β-catenin and Ras proteins, thereby decreasing proliferation and increasing the apoptosis of CRC lines. CPD0857 also decreased the growth and invasiveness of CRC cells harboring mutant K-Ras resistant to EGFR mAb therapy. Here, we show that CPD0857 treatment decreases proliferation and increases the neuronal differentiation of neural progenitor cells (NPCs). CDP0857 effectively reduced the expression of CSC markers and suppressed self-renewal capacity. CPD0857 treatment also inhibited the proliferation and expression of CSC markers in D-K-Ras MT cells carrying K-Ras, APC and PI3K mutations, indicating the inhibition of PI3K/AKT signaling. Moreover, CPD0857-treated xenograft mice showed a regression of tumor growth and decreased numbers of CSCs in tumors. We conclude that CPD0857 could serve as the basis of a drug development strategy targeting CSCs activated through Wnt/β-catenin-Ras MAPK-PI3K/AKT signaling in CRCs

Thermodynamic Control of Amorphous Precursor Phases for Calcium Carbonate via Additive Ions

Calcium carbonate is an earth-abundant biomineral that exists in a variety of marine environments, including corals, shells of mollusks, sea urchins, and so forth. Particularly, amorphous calcium carbonate (ACC) phases have increasingly received scientific attention because their local order in the short range can affect the subsequent pathways for phase transition. In this regard, various types of additives have been employed to tailor the local structures and stability of ACC; however, their precise roles in controlling the phase transition pathways are still unclear. To address this ambiguity problem, the effects of additive ions on the structure and stability of amorphous precursor phases were theoretically traced using molecular dynamics simulation. Starting from the nucleation cluster in aqueous solution, the hydrated and anhydrous forms of ACC were systematically examined by varying the hydration levels and molar compositions of additive ions (e.g., Mg2+, Fe2+, Sr2+, and Ba2+). Our results revealed that each ion can exert promoting or inhibiting effect by tuning the local structures and stability of amorphous precursor phases depending on their hydrophilicity and ionic radii. Moreover, our findings suggested that the thermodynamic spontaneity of the overall phase transition process can be determined by the balance between two opposing factors???endothermic dehydration and exothermic crystallization

Theoretical investigation on crystallization mechanism of ???carbonate minerals using molecular dynamics simulation???

Mineral carbonation, which refers to the reaction of CO2 with calcium or magnesium containing minerals to form a stable phase, is important CO2 storage technology against greenhouse gas emission along with the industrial development. However, their crystallization mechanisms are still in dispute. Particularly for calcium carbonate, it has been reported that various crystallization mechanisms exist through the formation of pre-nucleation cluster (PNC) or dense liquid phase. In this work, we investigated the crystallization mechanisms of calcium carbonate involving PNCs depending on various control factors (i.e., pH, temperature, concentration) using molecular dynamics simulation. At the initial phase of the carbonate reaction, PNC was formed as dynamically ordered liquid like oxyanion polymer (DOLLOP), representing a mixture of Ca and carbonate ions as polymer chains. To scrutinize the PNC structure that varies depending on the control factor, the average coordination number and the average number of Ca ions in the cluster, radius of gyration and local density were analyzed. Also, the change in Gibbs free energy was compared to determine the spontaneity of the carbonation reaction