CDK5 inhibition promotes osteoblastic differentiation of MSCs and blocks the migration of osteosarcoma MG-63 cells

CDK5 belongs to the cyclin-dependent kinase family. CDK5 is multifunctional and plays an important role in neural differentiation. However, the role of CDK5 in osteoblastic differentiation remains unclear. The present study investigated functions and molecular mechanism of CDK5 in osteoblastic differentiation. It was found that, CDK5 inhibition promoted the expression of Runx2, ALP, OCN and OPN of MSCs and the mineralization of MC-3T3E1 cells and MSCs. CDK5 inhibition enhanced the development of F-actin, nuclear localization of β-catenin and YAP, as well as the expression of RMRP RNA. When F-actin was suppressed by Blebbistatin, the nuclear localization of YAP and β-catenin, and expression of RMRP RNA as well as Runx2 and ALP were decreased. These indicate Seliciclib promotes osteoblastic differentiation mainly by F-actin. Moreover, Seliciclib also suppressed the migration of MG-63, suggesting a potential application for Seliciclib in bone defect repair and inhibition of the migration of osteosarcoma cells after osteosarcoma surgical resection.     

Serine Protease Inhibitors as Good Predictors of Meat Tenderness: Which Are They and What Are Their Functions?

Since years, serine proteases and their inhibitors were an enigma to meat scientists. They were indeed considered to be extracellular and to play no role in postmortem muscle proteolysis. In the 1990's, we observed that protease inhibitors levels in muscles are a better predictor of meat tenderness than their target enzymes. From a practical point of view, we therefore choose to look for serine protease inhibitors rather than their target enzymes, i.e. serine proteases and the purpose of this report was to overview the findings obtained. Fractionation of a muscle crude extract by gel filtration revealed three major trypsin inhibitory fractions designed as F1 (Mr:50–70 kDa), F2 (Mr:40–60 kDa) and F3 (Mr:10–15kD) which were analyzed separately. Besides antithrombin III, an heparin dependent thrombin inhibitor, F1 and F2 comprised a large set of closely related trypsin inhibitors encoded by at least 8 genes bovSERPINA3-1 to A3-8 and able to inhibit also strongly initiator and effector caspases. They all belong to the serpin superfamily, known to form covalent complexes with their target enzymes, were located within muscle cells and found in all tissues and fluids examined irrespective of the animal species. Potential biological functions in living and postmortem muscle were proposed for all of them. In contrast to F1 and F2 which have been more extensively investigated only preliminary findings were provided for F3. Taken together, these results tend to ascertain the onset of apoptosis in postmortem muscle. However, the exact mechanisms driving the cell towards apoptosis and how apoptosis, an energy dependent process, can be completed postmortem remain still unclear.     

Socio-spatial differentiation and residential segregation in the Chinese city based on the 2000 community-level census data: A case study of the inner city of Nanjing

Socio-spatial differentiation and residential segregation have been studied extensively in numerous cities and have contributed significantly to the understanding of urban spatial and social structures. Analyses of diverse data sets at varied spatial scales have supported the development of theoretical frameworks. However, the majority of Chinese case studies published in recent decades were dominantly based on either non-spatial data or population census data at sub-district (or jiedao in Chinese) level. These analyses have been limited through using low-resolution aggregate data resulting in incomplete or biased findings. This paper aims to examine the fine-scale socio-spatial structure of the inner city of Nanjing using the fifth population census data of 2000 at the lowest spatial scale – community (or juweihui in Chinese) level. Our findings reveal that the policies of the socialist era and the initial outcomes of the introduction of a free market, particularly with regard to the creation of new elite spaces within the inner city, have shaped a complex pattern of socio-spatial differentiation and residential segregation.     

红河流域径流演变分异及其特征

红河流域径流演变分异研究对于揭示流域径流的形成、演变规律及跨境水管理具有重要意义。选取红河流域9个代表站点,利用累积距平法、滑动t检验和Mann-Kendall-Sneyers法研究了红河流域的径流演变分异。结果表明,径流演变空间差异显著,各控制断面波动不一致;流域各站点(除大东勇站)均出现径流突变,但突变时间不一致,且越往下游,突变时间越晚;此外,各站点丰枯转化时段不一致。     

Nanosensors for Continuous and Noninvasive Monitoring of Mesenchymal Stem Cell Osteogenic Differentiation

Assessing mesenchymal stem cell (MSC) differentiation status is crucial to verify therapeutic efficacy and optimize treatment procedures. Currently, this involves destructive methods including antibody‐based protein detection and polymerase chain reaction gene analysis, or laborious and technically challenging genetic reporters. Development of noninvasive methods for real‐time differentiation status assessment can greatly benefit MSC‐based therapies. This report introduces a nanoparticle‐based sensing platform that encapsulates two molecular beacon (MB) probes within the same biodegradable polymeric nanoparticles. One MB targets housekeeping gene glyceraldehyde‐3‐phosphate dehydrogenase (GAPDH) as an internal reference, while another detects alkaline phosphatase (ALP), a functional biomarker. Following internalization, MBs are gradually released as the nanoparticle degrades. GAPDH MBs provide a stable reference signal throughout the monitoring period (18 days) regardless of differentiation induction. Meanwhile, ALP mRNA undergoes well‐defined dynamics with peak expression observed during early stages of osteogenic differentiation. By normalizing ALP‐MB signal with GAPDH‐MB, changes in ALP expression can be monitored, to noninvasively validate osteogenic differentiation. As proof‐of‐concept, a dual‐colored nanosensor is applied to validate MSC osteogenesis on 2D culture and polycaprolactone films containing osteo‐inductive tricalcium phospate.     

电力外绝缘污秽颗粒等效模型和粒径分布探讨

为今后实现自然积污规律研究和防污的差异化,对污秽颗粒等效简化模型、大气总悬浮颗粒物(TSP)的粒径分布函数、绝缘表面污秽主要化学成分对应TSP的粒径分布进行了综述和分析,认为可以污秽颗粒可等效简化为球体,使用空气动力学粒径衡量其粒径;建立TSP粒径分布函数拟合模型;分析认为化学成分Ca2+、SO42-、Cl-、SiO2、Al2O3在TSP中的粒径主要分布在1.8~10μm,0~10μm,1.8~10μm,30-40μm,40μm~50μm的范围内,最后对自然积污规律研究和防污的差异化进行了展望。     

Effect of Transition Metals on Polysialic Acid Structure and Functions

Polysialic acid (PSA) is one of the most abundant glycopolymer present in embryonic brain, and it is known to be involved in key roles such as plasticity in the central nervous system, cell adhesion, migration and localization of neurotrophins. However, in adult brain, its expression is quite low. The exception to this is in Alzheimer′s disease (AD) brain, where significantly increased levels of polysilylated neural cell adhesion molecule (PSA‐NCAM) have been reported. Here, we confirm the role of PSA as a metal chelator, allowing it to decrease cytotoxicity caused by high levels of transition metals, commonly found in AD brain, and as a regulator of cell behavior. UV‐visible (UV‐vis) and circular dichroism (CD) spectroscopy, atomic force microscopy (AFM), and isothermal titration calorimetry (ITC) techniques were used to investigate the assembly of PSA–metals complexes. These PSA–metal complexes exhibited less toxicity compared to free metal ions, and in particular, the PSA–Cu²⁺ complex synergistically promoted neurite outgrowth in PC12 cells.     

Silicon-Doped Titanium Dioxide Nanotubes Promoted Bone Formation on Titanium Implants

While titanium (Ti) implants have been extensively used in orthopaedic and dental applications, the intrinsic bioinertness of untreated Ti surface usually results in insufficient osseointegration irrespective of the excellent biocompatibility and mechanical properties of it. In this study, we prepared surface modified Ti substrates in which silicon (Si) was doped into the titanium dioxide (TiO₂) nanotubes on Ti surface using plasma immersion ion implantation (PIII) technology. Compared to TiO₂ nanotubes and Ti alone, Si-doped TiO₂ nanotubes significantly enhanced the expression of genes related to osteogenic differentiation, including Col-I, ALP, Runx2, OCN, and OPN, in mouse pre-osteoblastic MC3T3-E1 cells and deposition of mineral matrix. In vivo, the pull-out mechanical tests after two weeks of implantation in rat femur showed that Si-doped TiO₂ nanotubes improved implant fixation strength by 18% and 54% compared to TiO₂-NT and Ti implants, respectively. Together, findings from this study indicate that Si-doped TiO₂ nanotubes promoted the osteogenic differentiation of osteoblastic cells and improved bone-Ti integration. Therefore, they may have considerable potential for the bioactive surface modification of Ti implants.     

MicroRNA-331-3p Suppresses Cervical Cancer Cell Proliferation and E6/E7 Expression by Targeting NRP2

Aberrant expression of microRNAs (miRNAs) is involved in the development and progression of various types of cancers. In this study, we investigated the role of miR-331-3p in cell proliferation and the expression of keratinocyte differentiation markers of uterine cervical cancer cells. Moreover, we evaluated whether neuropilin 2 (NRP2) are putative target molecules that regulate the human papillomavirus (HPV) related oncoproteins E6 and E7. Cell proliferation in the human cervical cancer cell lines SKG-II, HCS-2, and HeLa was assessed using the 3-(4,5-dimethylthiazol-2-yl)-5-(3-carboxymethoxyphenyl)-2-(4-sulfophenyl)-2H-tetrazolium, inner salt (MTS) assay. Cellular apoptosis was measured using the TdT-mediated dUTP nick end labeling (TUNEL) and Annexin V assays. Quantitative RT-PCR was used to measure the messenger RNA (mRNA) expression of the NRP2, E6, E7, p63, and involucrin (IVL) genes. A functional assay for cell growth was performed using cell cycle analyses. Overexpression of miR-331-3p inhibited cell proliferation, and induced G2/M phase arrest and apoptosis in SKG-II, HCS-2 and HeLa cells. The luciferase reporter assay of the NRP2 3′-untranslated region revealed the direct regulation of NRP2 by miR-331-3p. Gene expression analyses using quantitative RT-PCR in SKG-II, HCS-2, and HeLa cells overexpressing miR-331-3p or suppressing NRP2 revealed down-regulation of E6, E7, and p63 mRNA and up-regulation of IVL mRNA. Moreover, miR-331-3p overexpression was suppressed NRP2 expression in protein level. We showed that miR-331-3p and NRP2 were key effectors of cell proliferation by regulating the cell cycle, apoptosis. NRP-2 also regulates the expression of E6/E7 and keratinocyte differentiation markers. Our findings suggest that miR-331-3p has an important role in regulating cervical cancer cell proliferation, and that miR-331-3p may contribute to keratinocyte differentiation through NRP2 suppression. miR-331-3p and NRP2 may contribute to anti-cancer effects.     

湖北宜昌镁橄榄岩矿床地质特征及其成因探讨

矿床位于宜昌大平溪超基性岩体中段,由弱蛇纹石化或未蚀变的巨晶纯橄榄岩组成。按氧化镁含量及灼失量圈定的镁橄榄岩,为一向西侧伏的扁豆体。岩石为巨晶不等粒、似斑状结构,快状构造,矿物以镁橄榄石为主,粒径一般20～30mm,最大>100mm,多为半自形晶。岩石化学成分:MgO4O.88％～48.41％,CaO<0.95％,Al_2O_3<0.87％,灼失量一般<6.77％。耐火度一般为1630°～1710℃,最高达1770℃,与国内外镁橄榄岩相同。本文以实际资料,证实镁橄榄岩是较均一的超基性岩浆,在温度缓慢下降时,结晶分异生成的折离体,属岩浆分异矿床。