Roles of mechanosensitive channel Piezo 1/2 proteins in skeleton and other tissues

Mechanotransduction is a fundamental ability that allows living organisms to receive and respond to physical signals from both the external and internal environments.The mechanotransduction process requires a range of special proteins termed mechanotransducers to convert mechanical forces into biochemical signals in cells.The Piezo proteins are mechanically activated nonselective cation channels and the largest plasma membrane ion channels reported thus far.The regulation of two family members,Piezol and Piezo2#has been reported to have essential functions in mechanosensation and transduction in different organs and tissues.Recently,the predominant contributions of the Piezo family were reported to occur in the skeletal system,especially in bone development and mechano-stimulated bone homeostasis.Here we review current studies focused on the tissue-specific functions of Piezol and Piezo2 in various backgrounds with special highlights on their importance in regulating skeletal cell mechanotransduction.In this review,we emphasize the diverse functions of Piezol and Piezo2 and related signaling pathways in osteoblast lineage cells and chondrocytes.We also summarize our current understanding of Piezo channel structures and the key findings about PIEZO gene mutations in human diseases.

Circular RNA circStag1 promotes bone regeneration by interacting with HuR

Postmenopausal osteoporosis is a common bone metabolic disorder characterized by deterioration of the bone microarchitecture,leading to an increased risk of fractures.Recently,circular RNAs(circ RNAs)have been demonstrated to play pivotal roles in regulating bone metabolism.However,the underlying functions of circ RNAs in bone metabolism in postmenopausal osteoporosis remain obscure.Here,we report that circ Stag1 is a critical osteoporosis-related circ RNA that shows significantly downregulated expression in osteoporotic bone marrow mesenchymal stem cells(BMSCs)and clinical bone tissue samples from patients with osteoporosis.Overexpression of circ Stag1 significantly promoted the osteogenic capability of BMSCs.Mechanistically,we found that circ Stag1 interacts with human antigen R(Hu R),an RNA-binding protein,and promotes the translocation of Hu R into the cytoplasm.A high cytoplasmic level of Hu R led to the activation of the Wnt signaling pathway by stabilizing and enhancing low-density lipoprotein receptor-related protein 5/6(Lrp5/6)andβ-catenin expression,thereby stimulating the osteogenic differentiation of BMSCs.Furthermore,overexpression of circ Stag1 in vivo by circ Stag1-loaded adeno-associated virus(circ Stag1-AAV)promoted new bone formation,thereby preventing bone loss in ovariectomized rats.Collectively,we show that circ Stag1 plays a pivotal role in promoting the regeneration of bone tissue via Hu R/Wnt signaling,which may provide new strategies to prevent bone metabolic disorders such as postmenopausal osteoporosis.

Electropolishing of NiTi for Improving Biocompatibility

A modified electrolyte （CH3COOH-HClO4-A-B） for electropolishing （EP） of NiTi was presented for improving the corrosion resistance and biocompatibility of the alloy. Using the proposed parameters, a homogeneous and uniform surface was obtained. Atomic force microscopy （AFM） revealed that the surface roughness （Ra） for EP sample （23.21 nm） was close to mechanical polishing （MP） sample （19.36 nm）. Analysis by X-ray photoelectron spectroscopy （XPS） showed that Ti/Ni ratio increased from 3.1 for MP sample to 27.6 for EP sample. Measurements using potentiodynamic polarization in Hanks＇ solution showed that no pitting occurred for EP sample even though the applied potential increased up to 1500 mV （vs SCE）, while the MP sample was broken down at 650 mV. The present study indicates that electropolishing NiTi with this modified electrolyte contributes to the improved biocompatibility of NiTi.

A Concise Overview on Solar Resource Assessment and Forecasting

China’s recently announced directive on tackling climate change,namely,to reach carbon peak by 2030 and to achieve carbon neutrality by 2060,has led to an unprecedented nationwide response among the academia and industry.Under such a directive,a rapid increase in the grid penetration rate of solar in the near future can be fully anticipated.Although solar radiation is an atmospheric process,its utilization,as to produce electricity,has hitherto been handled by engineers.In that,it is thought important to bridge the two fields,atmospheric sciences and solar engineering,for the common good of carbon neutrality.In thisüberreview,all major aspects pertaining to solar resource assessment and forecasting are discussed in brief.Given the size of the topic at hand,instead of presenting technical details,which would be overly lengthy and repetitive,the overarching goal of this review is to comprehensively compile a catalog of some recent,and some not so recent,review papers,so that the interested readers can explore the details on their own.

A novel sprayable thermosensitive hydrogel coupled with zinc modified metformin promotes the healing of skin wound

A novel sprayable adhesive is established(ZnMet-PF127)by the combination of a thermosensitive hydrogel(Pluronic F127,PF127)and a coordination complex of zinc and metformin(ZnMet).Here we demonstrate that ZnMet-PF127 potently promotes the healing of traumatic skin defect and burn skin injury by promoting cell proliferation,angiogenesis,collagen formation.Furthermore,we find that ZnMet could inhibit reactive oxygen species(ROS)production through activation of autophagy,thereby protecting cell from oxidative stress induced damage and promoting healing of skin wound.ZnMet complex exerts better effects on promoting skin wound healing than ZnCl2 or metformin alone.ZnMet complex also displays excellent antibacterial activity against Staphylococcus aureus or Escherichia coli,which could reduce the incidence of skin wound infections.Collectively,we demonstrate that sprayable PF127 could be used as a new drug delivery system for treatment of skin injury.The advantages of this sprayable system are obvious:(1)It is convenient to use;(2)The hydrogel can cover irregular skin defect sites evenly in a liquid state.In combination with this system,we establish a novel sprayable adhesive(ZnMet-PF127)and demonstrate that it is a potential clinical treatment for traumatic skin defect and burn skin injury.

Targeting Kindlin-2 in adipocytes increases bone mass through inhibiting FAS/PPARγ/FABP4 signaling in mice

Osteoporosis(OP)is a systemic skeletal disease that primarily affects the elderly population,which greatly increases the risk of fractures.Here we report that Kindlin-2 expression in adipose tissue increases during aging and high-fat diet fed and is accompanied by decreased bone mass.Kindlin-2 specific deletion(K2KO)controlled by Adipoq-Cre mice or adipose tissue-targeting AAV(AAV-Rec2-CasRx-sgK2)significantly increases bone mass.Mechanistically,Kindlin-2 promotes peroxisome proliferator-activated receptor gamma(PPARγ)activation and downstream fatty acid binding protein 4(FABP4)expression through stabilizing fatty acid synthase(FAS),and increased FABP4 inhibits insulin expression and decreases bone mass.Kindlin-2 inhibition results in accelerated FAS degradation,decreased PPARγactivation and FABP4 expression,and therefore increased insulin expression and bone mass.Interestingly,we find that FABP4 is increased while insulin is decreased in serum of OP patients.Increased FABP4 expression through PPARγactivation by rosiglitazone reverses the high bone mass phenotype of K2KO mice.Inhibition of FAS by C75 phenocopies the high bone mass phenotype of K2KO mice.Collectively,our study establishes a novel Kindlin-2/FAS/PPARγ/FABP4/insulin axis in adipose tissue modulating bone mass and strongly indicates that FAS and Kindlin-2 are new potential targets and C75 or AAV-Rec2-CasRx-sgK2 treatment are potential strategies for OP treatment.

计算思维教育的困惑与博弈

在周以真的倡导下,国内外一些教育机构积极推进计算思维教育,其教学工具、测量工具得到发展,同时也暴露出各种教育活动之间差异较大、教育效果实证不足等问题。从对计算思维内涵的认识、计算思维教学内容、教学工具、教学策略、测量工具、测量结果、迁移效果等方面对国际社会计算思维教育活动现状进行了分析,认为目前计算思维教育研究与实践成果不足以有效支持计算思维教育,存在许多困惑和博弈;计算思维教育不能速成,反对零基础的计算思维教育,应从知识传递入手,结合学习者的认知基础,遵从思维发展规律开展教学活动;不赞成分离式教育,提倡融入式教育;建议形成研究团队开展多项研究和实验,形成逐层递进的教学体系,注重教师队伍建设,反对将计算思维教育简单化。

Modification of polycarbonateurethane surface with poly （ethylene glycol） monoacrylate and phosphorylcholine glyceraldehyde for anti-platelet adhesion

Poly（ethylene glycol） monoacrylate （PEGMA） is grafted onto polycarbonateurethane （PCU） surface via ultraviolet initiated photopolymerization. The hydroxyl groups of poly（PEGMA） on the surface react with one NCO group of isophorone diisocyanate （IPD1） and another NCO group of IPDI is then hydrolyzed to form amino terminal group, which is further grafted with phosphorylcholine glyceraldehyde to establish a biocompatible hydrophilic structure on the surface. Fourier transform infrared spectroscopy and X-ray photoelectron spectroscopy confirm the successful grafting of both PEG and phosphorylcholine functional groups on the surface. The decrease of the water contact angle for the modified film is caused by synergic effect of PEG and phosphorylcholine, which both have the high hydrophilicity. Furthermore, the number of platelets adhered is relative low on the synergetically modified PCU film compared with the PCU film modified only by poly（PEGMA）. Our synergic modification method using both PEG and phosphorylcho- line may be applied in surface modification of bloodcontacting biomaterials and some relevant devices.