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Manjunatha S. Muttigi Byoung Ju Kim Bogyu Choi Inbo Han Hansoo Park Soo-Hong Lee 《International journal of molecular sciences》2020,21(23)
Adipose-derived mesenchymal stromal cells (Ad-MSCs) are a promising tool for articular cartilage repair and regeneration. However, the terminal hypertrophic differentiation of Ad-MSC-derived cartilage is a critical barrier during hyaline cartilage regeneration. In this study, we investigated the role of matrilin-3 in preventing Ad-MSC-derived chondrocyte hypertrophy in vitro and in an osteoarthritis (OA) destabilization of the medial meniscus (DMM) model. Methacrylated hyaluron (MAHA) (1%) was used to encapsulate and make scaffolds containing Ad-MSCs and matrilin-3. Subsequently, the encapsulated cells in the scaffolds were differentiated in chondrogenic medium (TGF-β, 1–14 days) and thyroid hormone hypertrophic medium (T3, 15–28 days). The presence of matrilin-3 with Ad-MSCs in the MAHA scaffold significantly increased the chondrogenic marker and decreased the hypertrophy marker mRNA and protein expression. Furthermore, matrilin-3 significantly modified the expression of TGF-β2, BMP-2, and BMP-4. Next, we prepared the OA model and transplanted Ad-MSCs primed with matrilin-3, either as a single-cell suspension or in spheroid form. Safranin-O staining and the OA score suggested that the regenerated cartilage morphology in the matrilin-3-primed Ad-MSC spheroids was similar to the positive control. Furthermore, matrilin-3-primed Ad-MSC spheroids prevented subchondral bone sclerosis in the mouse model. Here, we show that matrilin-3 plays a major role in modulating Ad-MSCs’ therapeutic effect on cartilage regeneration and hypertrophy suppression. 相似文献
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Zhang Huawei Yang Zhi Wu Zhaoyu Hong Xiaoyu Li Zhong Xu Yulai Li Jun Ni Gaojin Xiao Xueshan 《Oxidation of Metals》2019,92(1-2):49-65
Oxidation of Metals - The isothermal oxidation behavior and oxide-scale evolution on a newly developed Ni–Fe-based superalloy were investigated. Three oxidation stages were generally... 相似文献
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Dr. Yahu A. Liu Dr. Qihui Jin Qiang Ding Dr. Xueshi Hao Tingting Mo Shanshan Yan Dr. Yefen Zou Dr. Zhihong Huang Xiaoyue Zhang Wenqi Gao Dr. Tom Y.-H. Wu Chun Li Dr. Badry Bursalaya Dr. Michael Di Donato Dr. You-Qing Zhang Lisa Deaton Dr. Weijun Shen Dr. Brandon Taylor Anwesh Kamireddy Dr. George Harb Dr. Jing Li Dr. Yong Jia Dr. Andrew M. Schumacher Dr. Bryan Laffitte Dr. Richard Glynne Dr. Shifeng Pan Dr. Peter McNamara Dr. Valentina Molteni Dr. Jon Loren 《ChemMedChem》2020,15(16):1562-1570
Loss of β-cell mass and function can lead to insufficient insulin levels and ultimately to hyperglycemia and diabetes mellitus. The mainstream treatment approach involves regulation of insulin levels; however, approaches intended to increase β-cell mass are less developed. Promoting β-cell proliferation with low-molecular-weight inhibitors of dual-specificity tyrosine-regulated kinase 1A (DYRK1A) offers the potential to treat diabetes with oral therapies by restoring β-cell mass, insulin content and glycemic control. GNF4877, a potent dual inhibitor of DYRK1A and glycogen synthase kinase 3β (GSK3β) was previously reported to induce primary human β-cell proliferation in vitro and in vivo. Herein, we describe the lead optimization that lead to the identification of GNF4877 from an aminopyrazine hit identified in a phenotypic high-throughput screening campaign measuring β-cell proliferation. 相似文献
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Baizhan Li Chenqiu Du Hong Liu Wei Yu Jie Zheng Meilan Tan Zhenxing Jin Wenjie Li Jing Wu Lu Chen Runming Yao 《Indoor air》2019,29(2):308-319
The extensive research interests in environmental temperature can be linked to human productivity / performance as well as comfort and health; while the mechanisms of physiological indices responding to temperature variations remain incompletely understood. This study adopted a physiological sensory nerve conduction velocity (SCV) as a temperature‐sensitive biomarker to explore the thermoregulatory mechanisms of human responding to annual temperatures. The measurements of subjects’ SCV (over 600 samples) were conducted in a naturally ventilated environment over all four seasons. The results showed a positive correlation between SCV and annual temperatures and a Boltzmann model was adopted to depict the S‐shaped trend of SCV with operative temperatures from 5°C to 40°C. The SCV increased linearly with operative temperatures from 14.28°C to 20.5°C and responded sensitively for 10.19°C‐24.59°C, while tended to be stable beyond that. The subjects’ thermal sensations were linearly related to SCV, elaborating the relation between human physiological regulations and subjective thermal perception variations. The findings reveal the body SCV regulatory characteristics in different operative temperature intervals, thereby giving a deeper insight into human autonomic thermoregulation and benefiting for built environment designs, meantime minimizing the temperature‐invoked risks to human health and well‐being. 相似文献
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中间包上水口环形吹氩可以在塞棒周围形成清洗钢液的环形气幕,同时部分氩气泡随钢液进入上水口内,可以减少非金属夹杂物在水口内壁的黏附,起到防止水口堵塞的作用。然而,不合理的吹氩量会导致中间包内液面渣层受过强的气液羽流冲击而形成渣眼,使得钢液裸露并发生二次氧化,严重影响铸坯质量。采用标准 k ε 湍流模型研究中间包内流体流动,采用DPM模型和VOF模型耦合方法,研究上水口环形吹氩条件下渣眼的形成及演化规律。结果表明,上水口环形吹氩在塞棒周围形成较强的上升流,塞棒上部邻近区域存在多个涡流区;在钢液涡流的影响下,中间包液渣下层远离塞棒区域,上层向塞棒区域迁移;随着吹氩量的增大,平均湍动能增大,塞棒附近钢液速度逐渐增大,钢渣界面钢液速度先增大后减小,渣眼边缘钢液速度先增大后减小然后再增大,速度与垂直方向夹角逐渐减小;增大吹氩量,中间包熔池液面形成以塞棒为中心的渣眼,渣眼面积逐渐增大。试验条件下不产生渣眼的临界吹氩量为4.2 L/min,对应的钢渣界面最大速度为0.247 m/s,与垂直方向夹角为70°。 相似文献
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利用猪毛、风化煤和腐植酸钠的水解液为增效剂制备了一种增效过磷酸钙,探讨了增效过磷酸钙的增效机制及其对玉米生长的影响。结果表明,蒸馏水浸提条件下,增效过磷酸钙能减缓水溶磷的释放,具备较高的pH值缓冲性。与普通过磷酸钙相比,增效过磷酸钙处理的玉米生物量平均增加了41.9%,吸磷量和吸钙量分别增加了61.7%和27.8%,根系活力增加了24.3%。该研究结果对过磷酸钙生产的技术改进具有指导意义。 相似文献