Exosomes derived from mesenchymal stem cells in diabetes and diabetic complications.

Diabetes, a group of metabolic disorders, constitutes an important global health problem. Diabetes and its complications place a heavy financial strain on both patients and the global healthcare establishment. The lack of effective treatments contributes to this pessimistic situation and negative outlook. Exosomes released from mesenchymal stromal cells (MSCs) have emerged as the most likely new breakthrough and advancement in treating of diabetes and diabetes-associated complication due to its capacity of intercellular communication, modulating the local microenvironment, and regulating cellular processes. In the present review, we briefly outlined the properties of MSCs-derived exosomes, provided a thorough summary of their biological functions and potential uses in diabetes and its related complications.

Mechanosensitive protein polycystin-1 promotes periosteal stem/progenitor cells osteochondral differentiation in fracture healing.

Background: Mechanical forces are indispensable for bone healing, disruption of which is recognized as a contributing cause to nonunion or delayed union. However, the underlying mechanism of mechanical regulation of fracture healing is elusive. Methods: We used the lineage-tracing mouse model, conditional knockout depletion mouse model, hindlimb unloading model and single-cell RNA sequencing to analyze the crucial roles of mechanosensitive protein polycystin-1 (PC1, Pkd1) promotes periosteal stem/progenitor cells (PSPCs) osteochondral differentiation in fracture healing. Results: Our results showed that cathepsin (Ctsk)-positive PSPCs are fracture-responsive and mechanosensitive and can differentiate into osteoblasts and chondrocytes during fracture repair. We found that polycystin-1 declines markedly in PSPCs with mechanical unloading while increasing in response to mechanical stimulus. Mice with conditional depletion of Pkd1 in Ctsk+ PSPCs show impaired osteochondrogenesis, reduced cortical bone formation, delayed fracture healing, and diminished responsiveness to mechanical unloading. Mechanistically, PC1 facilitates nuclear translocation of transcriptional coactivator TAZ via PC1 C-terminal tail cleavage, enhancing osteochondral differentiation potential of PSPCs. Pharmacological intervention of the PC1-TAZ axis and promotion of TAZ nuclear translocation using Zinc01442821 enhances fracture healing and alleviates delayed union or nonunion induced by mechanical unloading. Conclusion: Our study reveals that Ctsk+ PSPCs within the callus can sense mechanical forces through the PC1-TAZ axis, targeting which represents great therapeutic potential for delayed fracture union or nonunion.

miR-188-3p targets skeletal endothelium coupling of angiogenesis and osteogenesis during ageing.

A specific bone capillary subtype, namely type H vessels, with high expression of CD31 and endomucin, was shown to couple angiogenesis and osteogenesis recently. The number of type H vessels in bone tissue declines with age, and the underlying mechanism for this reduction is unclear. Here, we report that microRNA-188-3p (miR-188-3p) involves this process. miRNA-188-3p expression is upregulated in skeletal endothelium and negatively regulates the formation of type H vessels during ageing. Mice with depletion of miR-188 showed an alleviated age-related decline in type H vessels. In contrast, endothelial-specific overexpression of miR-188-3p reduced the number of type H vessels, leading to decreased bone mass and delayed bone regeneration. Mechanistically, we found that miR-188 inhibits type H vessel formation by directly targeting integrin ß3 in endothelial cells. Our findings indicate that miR-188-3p is a key regulator of type H vessel formation and may be a potential therapeutic target for preventing bone loss and accelerating bone regeneration.

Senescent immune cells release grancalcin to promote skeletal aging.

Skeletal aging is characterized by low bone turnover and marrow fat accumulation. However, the underlying mechanism for this imbalance is unclear. Here, we show that during aging in rats and mice proinflammatory and senescent subtypes of immune cells, including macrophages and neutrophils, accumulate in the bone marrow and secrete abundant grancalcin. The injection of recombinant grancalcin into young mice was sufficient to induce premature skeletal aging. In contrast, genetic deletion of Gca in neutrophils and macrophages delayed skeletal aging. Mechanistically, we found that grancalcin binds to the plexin-b2 receptor and partially inactivates its downstream signaling pathways, thus repressing osteogenesis and promoting adipogenesis of bone marrow mesenchymal stromal cells. Heterozygous genetic deletion of Plexnb2 in skeletal stem cells abrogated the improved bone phenotype of Gca-knockout mice. Finally, we developed a grancalcin-neutralizing antibody and showed that its treatment of older mice improved bone health. Together, our data suggest that grancalcin could be a potential target for the treatment of age-related osteoporosis.

Metal Oxy-Hydroxides with a Hierarchical and Hollow Structure for Highly Efficient Solar-Thermal Water Evaporation.

Solar-thermal water evaporation is a promising technology for pure water production. However, the design of low-cost systems for efficient antifouling solar-thermal water evaporation remains a challenge. Herein, an evaporator based on metal oxy-hydroxides with a hierarchical and hollow structure is rationally designed through material selection and structural engineering. The obtained evaporator possesses good light absorption performance, excellent antifouling property against oil, and enhanced heat localization ability. Consequently, the water evaporation rate reaches as high as 1.65 kg m-2 h-1 with a solar-thermal conversion efficiency up to 82.3% under 1 sun illumination. More importantly, the evaporator exhibits almost identical evaporation performance in oily wastewater and natural seawater due to its superhydrophilicity and underwater superoleophobicity. This work provides a worth-adopted approach to prepare solar-thermal evaporators with high efficiency and anti-oil-fouling property, highlighting the new application of metal oxy-hydroxide-based materials and the importance of a hierarchical and hollow structure for efficient solar-thermal water evaporation.

Predicted high thermoelectric performance in a two-dimensional indium telluride monolayer and its dependence on strain.

In recent years, another two-dimensional (2D) family, monolayer metal monochalcogenides (group IIIA-VIA), has attracted extensive attention. In this work, we adopt density functional theory (DFT) and the non-equilibrium Green's function (NEGF) method to systematically investigate the ballistic thermoelectric properties of the IIIA-VIA family, including GaS, GaSe, GaTe, InS, InSe, and InTe. Among others, the InTe monolayer possesses the highest figure of merit, ZT = 2.03 at 300 K, due to its ultra-low thermal conductance. Biaxial strain in the range of -10% (compressive) to 10% (tensile) is applied to the InTe monolayer and the strain-induced electronic and thermal transport properties are discussed. The maximum ZT (up to 2.7) for the InTe monolayer at 300 K is achieved under an 8% tensile strain.

Theoretical design of a new family of two-dimensional topological insulators.

A new family of two-dimensional topological insulator, hydrogenated monolayer Pb2XY (X = Ga/In, Y = Sb/Bi), has been predicted using first-principles density functional theory. The electronic bulk band gap of the proposed systems can be induced in the presence of a spin-orbit coupling effect and its highest value (0.25 eV) was observed in the hydrogenated monolayer Pb2GaBi, which is suitable for practical application. Our simulation study points out that the nanoribbons derived from this new family harbor gapless edge channels. The non-trivial topological nature was further confirmed by calculating the Z2 topological invariant. These novel systems provide a new platform for topological phenomena observation and spintronic applications.

WSe2 nanoribbons: new high-performance thermoelectric materials.

In this work, for the first time, we systematically investigate the ballistic transport properties of WSe2 nanoribbons using first-principles methods. Armchair nanoribbons with narrow ribbon width are mostly semiconductive but the zigzag nanoribbons are metallic. Surprisingly, an enhancement in thermoelectric performance is discovered moving from monolayers to nanoribbons, especially armchair ones. The maximum room-temperature thermoelectric figure of merit of 2.2 for an armchair nanoribbon is discovered. This may be contributed to by the effects of the disordered edges, owing to the existence of dangling bonds at the ribbon edge. H-passivation has turned out to be an effective way to stabilize the edge atoms, which enhances the thermodynamic stability of the nanoribbons. In addition, after H-passivation, all of the armchair nanoribbons exhibit semiconductive properties with similar band gaps (∼1.3 eV). Our work provides instructional theoretical evidence for the application of armchair WSe2 nanoribbons as promising thermoelectric materials. The enhancement mechanism of the disordered edge effect can also encourage further exploration to achieve outstanding thermoelectric materials.

Downregulation of rho-associated protein kinase 1 by miR-124 in colorectal cancer.

AIM: To investigate the roles and interactions of rho-associated protein kinase (ROCK)1 and miR-124 in human colorectal cancer (CRC). METHODS: Expression of ROCK1 protein was examined by Western blotting, and quantitative reverse transcriptase PCR was performed to measure expression of ROCK1 mRNA and miR-124. Two cancer cell lines were transfected with pre-miR-124 (mimic) and anti-miR-124 (inhibitor) and the effects on ROCK1 protein and mRNA expression were observed. In addition, cell proliferation was assessed via a 5-ethynyl-2' deoxyuridine assay. Soft agar formation assay, and cell migration and invasion assays were used to determine the effect of survivin on the transformation and invasion activity of CRC cells. RESULTS: miR-124 was significantly downregulated in CRC compared to normal specimens (0.603 ± 0.092 vs 1.147 ± 0.286, P = 0.016) and in metastatic compared to nonmetastatic CRC specimens (0.416 ± 0.047 vs 0.696 ± 0.089, P = 0.020). Expression of miR-124 was significantly associated with CRC metastasis, tumor T and N stages, and tumor grade (all P < 0.05). ROCK1 protein was significantly increased in CRC compared to normal tissues (1.896 ± 0.258 vs 0.866 ± 0.136, P = 0.026), whereas ROCK1 mRNA expression was unaltered (2.613 ± 0.251 vs 2.325 ± 0.246). miR-124 and ROCK1 were inversely expressed in CRC tissues and cell lines. ROCK1 mRNA was unaltered in cells transfected with miR-124 mimic and miR-124 inhibitor, compared to normal controls. There was a significant reduction in ROCK1 protein in cells transfected with miR-124 mimic and a significant increase in cells transfected with miR-124 inhibitor (Ps < 0.05). Transformation and invasion of cells transfected with miR-124 inhibitor were significantly increased compared to those in normal controls (P < 0.05). Cells transfected with miR-124 inhibitor showed increased cell proliferation. CONCLUSION: miR-124 promotes hyperplasia and contributes to invasion of CRC cells, but downregulates ROCK1. ROCK1 and miR-124 may play important roles in CRC.