Abstract Mesenchymal stem cell (MSC) is a promising cell source candidate in tissue engineering (TE) and regenerative medicine. However, the inability to target MSCs in tissues of interest with high ...efficiency and engraftment has become a significant barrier for MSC-based therapies. The mobilization and transfer of MSCs to defective/damaged sites in tissues or organs in vivo with high efficacy and efficiency has been a major concern. In the present study, we identified a peptide sequence (E7) with seven amino acids through phage display technology, which has a high specific affinity to bone marrow-derived MSCs. Subsequent analysis suggested that the peptide could efficiently interact specifically with MSCs without any species specificity. Thereafter, E7 was covalently conjugated onto polycaprolactone (PCL) electrospun meshes to construct an “MSC-homing device” for the recruitment of MSCs both in vitro and in vivo. The E7-conjugated PCL electrospun meshes were implanted into a cartilage defect site of rat knee joints, combined with a microfracture procedure to mobilize the endogenous MSCs. After 7 d of implantation, immunofluorescence staining showed that the cells grown into the E7-conjugated PCL electrospun meshes yielded a high positive rate for specific MSC surface markers (CD44, CD90, and CD105) compared with those in arginine-glycine-aspartic acid (RGD)-conjugated PCL electrospun meshes (63.67% vs. 3.03%; 59.37% vs. 2.98%; and 61.45% vs. 3.82%, respectively). Furthermore, the percentage of CD68 positive cells in the E7-conjugated PCL electrospun meshes was much lower than that in the RGD-conjugated PCL electrospun meshes (5.57% vs. 53.43%). This result indicates that E7-conjugated PCL electrospun meshes absorb much less inflammatory cells in vivo than RGD-conjugated PCL electrospun meshes. The results of the present study suggest that the identified E7 peptide sequence has a high specific affinity to MSCs. Covalently conjugating this peptide on the synthetic PCL mesh significantly enhanced the MSC recruitment of PCL in vivo. This method provides a wide range of potential applications in TE.
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•An in-situ regenerated Cu/zeolite H2S adsorbent with high sulfur capacity was prepared.•Cu/zeolite adsorbent can be stable regenerated at lower temperatures (280 °C) in air.•MOR ...zeolite not only act as carriers, but also play critical role for regeneration.
Desulfurization of blast furnace gas (BFG) is essential for steel companies to achieve its cleaner utilization. In this study, an in-situ regeneratable H2S adsorbent with a high sulfur capacity was developed. Zeolites with specific silica-aluminum ratios were selected, and hybrid Cu/zeolites adsorbents were synthesized using an impregnation method. The optimal adsorbent (DSZ-2) exhibited a high breakthrough sulfur capacity of 39.0 mg/g at 80 °C. Moreover, this adsorbent can also be in-situ regenerated at lower temperatures (280 ℃) and the regenerated adsorbent has even a higher breakthrough sulfur capacity of 49.0 mg/g. The possible desulfurization and regeneration mechanism of the DSZ-2 absorbent are discussed. Due to its high sulfur capacity and good regenerability, this absorbent has great application prospect in the removal of H2S from BFG.
Noncatalytic carbohydrate binding modules (CBMs) have been demonstrated to play various roles with cognate catalytic domains. However, for polysaccharide lyases (PLs), the roles of CBMs remain mostly ...unknown. AlyB is a multidomain alginate lyase that contains CBM32 and a PL7 catalytic domain. The AlyB structure determined herein reveals a noncanonical alpha helix linker between CBM32 and the catalytic domain. More interestingly, CBM32 and the linker does not significantly enhance the catalytic activity but rather specifies that trisaccharides are predominant in the degradation products. Detailed mutagenesis, biochemical and cocrystallization analyses show “weak but important” CBM32 interactions with alginate oligosaccharides. In combination with molecular modeling, we propose that the CBM32 domain serves as a “pivot point” during the trisaccharide release process. Collectively, this work demonstrates a novel role of CBMs in the activity of the appended PL domain and provides a new avenue for the well-defined generation of alginate oligosaccharides by taking advantage of associated CBMs.
•A unique alpha helix linker between CBMs and the catalytic domain was discovered.•CBM32 and the helix linker are responsible for the preferred trisaccharide products.•CBM32 forms “weak but important” interactions with alginate oligosaccharide.•CBM32 serves as a “pivot point” during the trisaccharide release process.
ABSTRACT
As one of the most sensitive regions to climate change, the Qinghai‐Xizang Plateau has been widely investigated as one unity for impacts of climate change on alpine grassland. However, ...previous findings might be confounded by distinct climate sensitivities at different elevations and different regional climates between Qinghai Province and Xizang Province, which lie at the two sides of Tanggula Mountains. In this study, we explored change trends of grassland vegetation, temperature and precipitation in growing season from 1982 to 2011, and elevation‐dependent effects of climate change on grassland vegetation in the two provinces separately. The plateau grassland greenness gained improvement under climate warming and wetting during the past 30 years, especially in Qinghai Province. Temperature increased significantly with a warming magnitude of more than 1.5 °C over the plateau grassland. The interannual change of precipitation showed contrary trends between the two provinces. The main climate factor driving the grassland vegetation variation varied between the two provinces, with temperature being the main factor in Qinghai Province and precipitation being the main factor in Xizang Province. In particular, a more significant correlation between climate change and grassland vegetation variation was found at higher elevations, which reveals higher climate sensitivity in higher elevation areas of the plateau.
Initiation of T cell receptor (TCR) signaling involves the activation of the tyrosine kinase LCK; however, it is currently unclear how LCK is recruited and activated. Here, we have identified the ...membrane protein CD146 as an essential member of the TCR network for LCK activation. CD146 deficiency in T cells substantially impaired thymocyte development and peripheral activation, both of which depend on TCR signaling. CD146 was found to directly interact with the SH3 domain of coreceptor-free LCK via its cytoplasmic domain. Interestingly, we found CD146 to be present in both monomeric and dimeric forms in T cells, with the dimerized form increasing after TCR ligation. Increased dimerized CD146 recruited LCK and promoted LCK autophosphorylation. In tumor models, CD146 deficiency dramatically impaired the antitumor response of T cells. Together, our data reveal an LCK activation mechanism for TCR initiation. We also underscore a rational intervention based on CD146 for tumor immunotherapy.
Cancer is still one of the major problems threatening human health and the therapeutical efficacies of available treatment choices are often rather low. Due to their favorable biocompatibility, ...simplicity of modification, and improved therapeutic efficacy, peptide-based self-assembled delivery systems have undergone significant evolution. Physical encapsulation and covalent conjugation are two common approaches to load drugs for peptide assembly-based delivery, which are always associated with drug leaks in the blood circulation system or changed pharmacological activities, respectively. To overcome these difficulties, a more elegant peptide-based assembly strategy is desired. Notably, peptide-mediated co-assembly with drug molecules provides a new method for constructing nanomaterials with improved versatility and structural stability. The co-assembly strategy can be used to design various nanostructures for cancer therapy, such as nanotubes, nanofibrils, hydrogels, and nanovesicles. Recently, these co-assembled nanostructures have gained tremendous attention for their unique superiorities in tumor therapy. This article describes the classification of assembled peptides, driving forces for co-assembly, and specifically, the design methodologies for various drug molecules in co-assembly. It also highlights recent research on peptide-mediated co-assembled delivery systems for cancer therapy. Finally, it summarizes the pros and cons of co-assembly in cancer therapy and offers some suggestions for conquering the challenges in this field.
The Fault-Tolerant Permanent Magnet Rim Driven Motor (FTPM-RDM) is a high performance, high reliability marine driven motor. The short-circuit current and the mutual inductance voltage generated by ...the short-circuit current are important parameters to indicate the fault-tolerant performance of a motor. Increasing self-inductance and decreasing mutual inductance is an important method to improve fault tolerance of a FTPM-RDM. In this paper, the influence of positive wounded winding structure and positive and negative wounded winding structure of a 24-slot motor on the self-inductance and mutual inductance is analyzed by the winding function method. The conclusion that the positive and negative wounded winding structure has high self-inductance and low mutual inductance is revealed. This conclusion is generalized to the winding design in a general structure motor, and a generalized method of winding reconstruction is proposed. The simulation results show that the proposed winding reconstruction method can effectively increase self-inductance and significantly reduce mutual inductance to improve the fault tolerance of a FTPM-RDM. A motor prototype is produced and the experimental results have verified the correctness and feasibility of the proposed method.
OBJECTIVE: Low vitamin D status is common among healthy black and white adolescents residing at southern U.S. latitudes with a year-round sunny climate. Thus we aimed to study the relationships ...between circulating 25-hydroxyvitamin D 25(OH)D and cardiometabolic risk factors in this population. RESEARCH DESIGN AND METHODS: 25(OH)D concentrations were measured with liquid chromatography tandem mass spectroscopy in 701 girls and boys (14–18 years old, 54% blacks, 49% females). Cardiometabolic risk was indexed by adipokines, inflammatory markers, fasting glucose, homeostatic model assessment-insulin resistance (HOMA-IR), lipid profile, and blood pressure (BP). RESULTS: Controlling for age, sex, race, sexual maturation, season, physical activity, and percent body fat, 25(OH)D concentrations were significantly correlated with adiponectin (r = 0.06, P = 0.05), leptin (r = –0.32, P < 0.01), fibrinogen (r = –0.05, P = 0.03), glucose (r = –0.16, P = 0.02), HOMA-IR (r = –0.17, P < 0.01), HDL cholesterol (r = 0.14, P = 0.02), systolic BP (r = –0.10, P = 0.02), and diastolic BP (r = –0.21, P < 0.01). When 25(OH)D concentrations were stratified into increasing tertiles, there were significant linear upward trends for adiponectin (P = 0.01) and HDL cholesterol (P = 0.04), but significant linear down trends for glucose (P < 0.01), HOMA-IR (P < 0.01), and systolic BP (P < 0.01), after adjusting for the above covariates. CONCLUSIONS: Circulating 25(OH)D concentrations are associated with various adverse cardiometabolic risk factors, independent of adiposity. Clinical trials addressing the effects of vitamin D supplementation on cardiometabolic risk are warranted in adolescents irrespective of their geographical regions.
•The additions of Ca and Sr improve the softening resistance of the Cu-Cr alloy.•The Cu-Cr-Ca and Cu-Cr-Sr alloys have smaller Cr precipitates with FCC structure.•The Cu-Cr-Ca and Cu-Cr-Sr alloys ...recrystallize more difficultly.•Dislocations and precipitates make main contribution to high strengths of alloys.•Ca and Sr atoms tend to segregate at interface between precipitates and matrix.
Cu-0.57Cr-0.01Ca and Cu-0.58Cr-0.01Sr (wt.%) alloys were fabricated and processed by thermo-mechanical treatment. Their mechanical and electrical properties and microstructure were investigated in detail and compared with those of a Cu-0.57Cr (wt.%) alloy. The results showed that the softening resistance of the Cu-Cr alloy was significantly improved by the additions of Ca and Sr elements. Compared with the Cu-Cr alloy, the deformation microstructure of the Cu-Cr-Ca and Cu-Cr-Sr alloys was more difficult to recrystallize at elevated temperatures, and the Cr precipitates in the Cu-Cr-Ca and Cu-Cr-Sr alloys were smaller in size and had an FCC structure at any given aging state. The high strengths of the Cu-Cr-Ca and Cu-Cr-Sr alloys were mainly attributed to the dislocation strengthening provided by high-density dislocations and the precipitate strengthening provided by fine Cr precipitates. First-principles calculation showed that the segregations of Ca and Sr atoms at interface between Cr precipitates and copper matrix were favorable in energetics. This segregation effectively hindered the growth of Cr precipitates and significantly enhanced the pinning effect on the motion of dislocations and subgrain boundaries, eventually leading to the improvement in the softening resistance of the Cu-Cr alloy.
•CH4 emissions decreased during the rice-growing seasons after the conversion of RF to RW.•The Q10 of CH4 emissions was higher for RW-CN than that for RF-CN.•The soil DOC positively affected CH4 ...emissions in both RF-CN and RW-CN treatmnets, while the soil DIN negatively affected CH4 emissions.
To our knowledge, the conversion of winter flooded rice paddy (RF) to rice-wheat rotation (RW) has markedly decreased methane (CH4) emissions during the wheat-growing seasons. However, the effects of this conversion on CH4 emissions during the rice-growing seasons are unclear. To determine CH4 emissions during the rice-growing season and associated environmental factors under RF and RW systems, a split-plot design experiment was conducted in three RF fields in hilly areas of Sichuan province, China. One-half of each field was converted to RW, and the other half remained RF. Each plot of RW and RF was further divided into four subplots: three subplots for conventional nitrogen fertilization treatment (RW-CN and RF-CN) and one for unfertilized treatment (RW-NN and RF-NN). The study showed that the cumulative CH4 emissions from RW-CN during the rice-growing seasons were 192.77 ± 11.36 and 302.07 ± 28.34 kg C ha−1 in 2013 and 2014, respectively, which were decreased by 26.8% and 24.3% as compared to that from RF-CN. While for RW-NN, the cumulative CH4 emissions decreased by 54.1% and 24.0% as compared to that from RF-NN (372.49 ± 67.05 and 300.53 ± 13.49 kg C ha−1 in 2013 and 2014, respectively, P < 0.05). A higher Q10 (soil temperature sensitivity coefficient) of CH4 emissions during the whole experiment period was observed for RW-CN (6.69) than that for RF-CN (4.48). With rising soil temperature during the rice-growing seasons, the CH4 emissions for RW-CN escalated more rapidly than that for RF-CN. As expected, a positive correlation between CH4 fluxes and soil dissolved organic carbon (DOC) for both RF-CN and RW-CN was observed and DOC in RF-CN during the rice-growing seasons were higher than RW-CN. The soil dissolved inorganic nitrogen (DIN) was negatively correlated to CH4 emissions as the soil temperature ranged 22℃– 28℃. Moreover, rice yields in the RF-CN and RW-CN treatments were similar in both years of 2013 and 2014. These findings suggested that CH4 emissions were primarily controlled by soil environment, which was affected by water and fertilizer managements. The implication of this study is that the decreased CH4 emissions and increased crop yields could be achieved by conversion management from RF to RW.
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