Exercise-induced irisin in bone and systemic irisin administration reveal new regulatory mechanisms of bone metabolism

Irisin is a polypeptide hormone derived from the proteolytic cleavage of fibronectin-type III domaincontaining 5(FNDC5) protein. Once released to circulation upon exercise or cold exposure, irisin stimulates browning of white adipose tissue(WAT) and uncoupling protein 1(UCP1) expression, leading to an increase in total body energy expenditure by augmented UCP1-mediated thermogenesis. It is currently unknown whether irisin is secreted by bone upon exercise or whether it regulates bone metabolism in vivo. In this study, we found that 2 weeks of voluntary wheel-running exercise induced high levels of FNDC5 messenger RNA as well as FNDC5/irisin protein expression in murine bone tissues. Increased immunoreactivity due to exercise-induced FNDC5/irisin expression was detected in different regions of exercised femoral bones,including growth plate, trabecular bone, cortical bone, articular cartilage, and bone–tendon interface. Exercise also increased expression of osteogenic markers in bone and that of UCP1 in WAT, and led to bodyweight loss. Irisin intraperitoneal(IP) administration resulted in increased trabecular and cortical bone thickness and osteoblasts numbers, and concurrently induced UCP1 expression in subcutaneous WAT. Lentiviral FNDC5 IP administration increased cortical bone thickness. In vitro studies in bone cells revealed irisin increases osteoblastogenesis and mineralization, and inhibits receptor activator of nuclear factor-k B ligand(RANKL)-induced osteoclastogenesis. Taken together, our findings show that voluntary exercise increases irisin production in bone, and that an increase in circulating irisin levels enhances osteogenesis in mice.

Comparative Genomic Analysis of Enterovirus 71 Revealed Six New Potential Neurovirulence-associated Sites

在现在的学习，完全的染色体四普通(4/EV71/Wenzhou/CHN/2014， 15/EV71/Wenzhou/CHN/2014， 116/EV71/Wenzhou/CHN/2014，和 120/EV71/Wenzhou/CHN/2014 ) 并且二剧毒(11/EV71/Wenzhou/CHN/2014 和 109/EV71/Wenzhou/CHN/2014 ) enterovirus (EV71 ) 71 孤立被定序并且描述。他们是在长度的 7405 bp 并且属于 EV71 亚遗传型 C4 (C4a 簇) 。核苷酸顺序排列揭示了六个核苷酸变化( G P151 T P151 , G P199 P199 , G P261 T P261 , A P328 C P328 , G P422 P422 ,和 G P437 T P437 )在二剧毒在 IRES 元素的 5UTR 以内孤立。怒火和 FCE 的 RNA 第二等的结构预言显示普通孤立分享的类似的结构，它与那些不同剧毒孤立。而且， G P114 C P114 和 G P151 T P151 变化在剧毒孤立在 SL II 贡献了唯一的 RNA 第二等的结构的形成。而且， EV71 孤立的 82 的 nucleotide/amino 酸顺序排列显示了那六个地点(T P488 和 C 在 5UTR 的 P577 ；Asn 在 2A 的 P57 ；Ile 在 3C 的 P56 ；C P10 和 A 在 3UTR 的 P47 ) 潜在地与 EV71 的 neurovirulence 被联系。最后， 2A 的 3D 结构是类似的，而 VP1 和 3C 的结构是可变的。

Angiography reveals early hiding iris neovascularization after ischemic CRVO

Dear Sir, I am Dr. Zhi-Qing Li from Tianjin Medical University Eye Hospital, Tianjin City, China. I write to present a case with hiding iris neovascularization (INV) following central retinal vein occlusion (CRVO) can be detected early by iris angiography (IA) and neovascular glaucoma (NVG)

Unintended targeting of Dmp1-Cre reveals a critical role for Bmpr1a signaling in the gastrointestinal mesenchyme of adult mice

Cre/lox P technology has been widely used to study cell type-specific functions of genes. Proper interpretation of such data critically depends on a clear understanding of the tissue specificity of Cre expression. The Dmp1-Cre mouse, expressing Cre from a 14-kb DNA fragment of the mouse Dmp1 gene, has become a common tool for studying gene function in osteocytes, but the presumed cell specificity is yet to be fully established. By using the Ai9 reporter line that expresses a red fluorescent protein upon Cre recombination, we find that in2-month-old mice, Dmp1-Cre targets not only osteocytes within the bone matrix but also osteoblasts on the bone surface and preosteoblasts at the metaphyseal chondro-osseous junction. In the bone marrow, Cre activity is evident in certain stromal cells adjacent to the blood vessels, but not in adipocytes. Outside the skeleton, Dmp1-Cre marks not only the skeletal muscle fibers, certain cells in the cerebellum and the hindbrain but also gastric and intestinal mesenchymal cells that express Pdgfra. Confirming the utility of Dmp1-Cre in the gastrointestinal mesenchyme, deletion of Bmpr1 a with Dmp1-Cre causes numerous large polyps along the gastrointestinal tract, consistent with prior work involving inhibition of BMP signaling.Thus, caution needs to be exercised when using Dmp1-Cre because it targets not only the osteoblast lineage at an earlier stage than previously appreciated, but also a number of non-skeletal cell types.

Mutagenesis reveals that the rice OsMPT3 gene is an important osmotic regulatory factor

Plant mitochondrial phosphate transporters regulate phosphate transport and ATP synthesis. Determining whether they function in abiotic stress response process would shed light on their response to salt stress. We used the CRISPR/Cas9 gene-editing system to mutagenize two mitochondrial phosphate transporters, OsMPT3;1 and OsMPT3;2, to investigate their regulatory roles under salt stress. Two cas9(CRISPR-associated protein9)-free homozygous mutants, mpt33 and mpt30, were confirmed to be stable. Both OsMPT3;1 and OsMPT3;2 were markedly induced by salt stress, and their mutagenesis strongly inhibited growth and development, especially under salt stress. Mutagenesis sharply reduced the accumulation of ATP, phosphate, calcium, soluble sugar, and proline and increased osmotic potential, malondialdehyde, and Na^+ /K^+ ratio under salt stress. Both mutants demonstrate normal growth and development in the presence of ATP, revealing high sensitivity to exogenous ATP under salt stress. The mutants showed lowered rates of Na^+ efflux but also of K^+ and Ca^(2+) influx under salt stress. Mutagenesis of OsMPT3;2 altered the enrichment profiles of differentially expressed genes involved mainly in synthesis of secondary metabolites, metabolism of glycolysis, pyruvate, tricarboxylic acid cycle, in response to salt stress. The mutant displayed significant accumulation differences in 14 metabolites involved in 17 metabolic pathways, and strongly up-regulated the accumulation of glutamine, a precursor in proline synthesis, under salt stress. These findings suggest that the OsMPT3 gene modulates phosphate transport and energy supply for ATP synthesis and triggers changes in accumulation of ions and metabolites participating in osmotic regulation in rice under salt stress, thus increasing rice salt tolerance. This study demonstrates the effective application of CRISPR/Cas9 gene-editing to the investigation of plant functional genes.

On Mars, Location and Orientation of Dykes Exposed along the Valles Marineris Walls Reveal Expected and Unexpected Stress Fields

Structural and geomorphological analysis of the Martian surface in the visible spectral range using the NASA/Viking images in the 90’s,complemented by experimental modelling(Mège and Masson,1996a;Mège et al.,2003)suggested that the Valles Marineris trough(chasma)system is aligned with a mafic dyke swarm,named the Syria Planum Dyke Swarm.Cross-cutting relationships

Differential Proteomics Reveals the Potential Injury Mechanism Induced by Heavy Ion Radiation in Mice Ovaries

在现在的学习，我们基于在 pubertal Swiss-Webster 鼠标的卵巢的纸巾调查蛋白质表示的引用地图使遭到了到碳离子放射(CIR ) 的二维的电气泳动(2-DE ) 使用了一条 proteomics 途径。在识别蛋白质之中， ubiquitin carboxy 终端 hydrolase L1 (UCH-L1 ) 与房间周期 [1] 和那被联系它在卵巢的纸巾影响增长。我们分析了 UCH-L1 和增长标记增长房间的表示用 immunoblotting 和 immunofluorescence 跟随 CIR 的原子抗原(PCNA ) 。proteomics 和生物化学的结果在卵巢的纸巾提供卓见进 CIR 毒性的内在的机制。

Force Spectrum of Single CsgA Nanofiber Reveal Surprising Properties

CsgA protein monomers consist of aβ-helix of five repeat units possessing several conservative residues and thus,inherently fibrillate.CsgA protein monomers could self-assemble into hierarchical nanofiber structure cross multiple scales after expression and secretion by E.Coli cells.Previous researches show that CsgA nanofibers could provide adhesion,stiffness,and mechanical homogeneity for the biofilms,host cells’fibronectin binding for internalization,or protection against phage attack.CsgA nanofibers have obtained various applications in material science and synthetic biology.To illustrate,CsgA nanofibers have characteristics of intrinsic hierarchical structures across multiple scales,robustness in harsh environments and programmable functionality via biological tools.Studying the force spectrum or mechanical properties of the nanofiber can provide fundamental information of self-assembly process and ultra-stability in extreme conditions.Single molecule techniques such as atomic force microscopy,optical tweezers,and magnetic tweezers have been widely applied to study proteins.In these studies,proteins are usually chemically conjugated or genetically constructed to have a tag such as histidine,cysteine or biotin.Genetic engineering requires modification of the plasmids encoding the specific protein,and also involve special protein expression and purification.Such study needs collaboration from multi-disciplinary.It normally studies one protein at a time which gives out clear signal but lacks throughput and efficiency.Here we have established a simple method to measure all kinds of proteins without labels.The carboxyl terminus of a protein is attached to the amine group on a magnetic bead,and the amine terminus of the protein is attached to glutaraldehyde on the glass slide.Then we used magnetic tweezers to manipulate and stretched the bead and protein.Extension versus rotation relation was used to identify a single protein or protein fibril.The fiber under tension is also observed by Scanning Electronic Microcopy which convinces that single CsgA-His fibril is linked to a microbead.The peak of diameter distribution is around 15 nm.The fracture of fibers was observed in real time on SEM.Force-extension curves of single fibers are obtained in real time.The force-extension curves generally agree with the worm like chain model.The persistence lengths from the fitting are from 0.9 to 49.8 nm.The elongation ratio increases gradually with force until reaches a plateau.The maximum elongation ratio of 78 nanofibers were made into an elongation ratio distribution diagram,more than half of CsgA-His nanofibers has an elongation ratio from 0 to 2,some are distributed in 2~10,and a few are distributed in 10~18.The maximum elongation ratio of CsgA-His nanofibers is 17.1,indicating that the fibril’s flexibility is much higher than DNA or silk fiber.For forces less than 20 pN,the extension was reversible.With a 42.1 pN holding force,the extension jumped in steps of from 30 to 365 nm and was irreversible.At the scale tested,the jumps corresponded to the unfolding of multiple beta sheets in the fiber.Work for CsgA-His nanofibers during stretching increase with the normalized strain fractions.The experimental data agree with a theoretical prediction for a single CsgA protein from a SMD calculation.Therefore,our results provide key information for the understandings of CsgA protein nanofiber assembly and biofilm robustness.

Organization and Ultra-Structural Components of Endothelial Surface Glycocalyx Revealed by Stochastic Optical Reconstruction Microscopy(STORM)

Introduction The endothelial cells(ECs)lining every blood vessel wall constantly expose to the mechanical forces generated by the blood flow.The EC responses to these hemodynamic forces play a critical role in the homeostasis of the circulatory system.In addition to forming a transport barrier between the blood and vessel wall,vascular ECs play important roles in regulating circulation functions.Besides biochemical stimuli,blood flow induced(hemodynamic)mechanical stimuli,such as shear stress,pressure and circumferential stretch,modulate EC morphology and functions by activating mechanosensors,signaling pathways,and gene and protein expressions.The EC responses to the hemodynamic forces(mechano-sensing and transduction)are critical to maintaining normal vascular functions.Failure in the mechano-sensing and transduction leads to serious vascular diseases including hypertension,atherosclerosis,aneurysms and thrombosis,to name a few[1].On the luminal surface of our blood vessels,there is a thin layer called endothelial surface glycocalyx(ESG)which consists of proteoglycans,glycosaminoglycans(GAGs)and glycoproteins.The GAGs in the ESG are heparan sulfate(HS),hyaluronic acid(HA),chondroitin sulfate(CS),and sialic acid(SA)[2].In order to play important roles in vascular functions,such as being a mechanosensor and transducer for the endothelial cells(ECs)to sense the blood flow,a molecular sieve to maintain normal microvessel permeability and a barrier between the circulating cells and endothelial cells forming the vessel wall,the ESG should have an organized structure at the molecular level.Due to the limitations of optical and electron microscopy,the ultra-structure and organization of ESG has not been revealed until recent development of a super high resolution fluorescence optical microscope,STORM(Stochastic Optical Reconstruction Microscopy).The diffraction of a single fluorescence molecule can be described as the point spread function(PSF).When the light of wavelengthλexcites the fluorophore(emitter),the intensity profile of the spot is defined as the PSF with the width^0.6λ/NA,NA is the numerical aperture of the objective.The diffraction-limited image resolution,for a high numerical aperture objective lens,is^200 nm in the lateral direction and^500 nm in the axial direction,for a conventional fluorescence microscope.The key idea of the single-molecule localization microscopy is to light the molecule,in turn,to achieve the nanometer-level accuracy of their position and reconstruction into a super-resolution image,such as STORM.STORM employs photo-switching mechanisms to stochastically activate individual molecules(photo-switchable or photoactivatable fluorophores)within the diffraction-limited region at different times.Then images with sub-diffraction limit resolution are reconstructed from the measured positions of individual fluorophores[3].To trade the super spatial resolution(accuracy),STORM sacrifices its temporal resolution(efficiency)by switching the state and sequentially exciting the emitters at a high density.Rust et al[3]employed organic dyes and fluorescent proteins as photo-switchable emitters to trade temporal resolution for a super spatial resolution(~20 nm lateral and^50 nm axial at present,can go down to a couple of nanometers if using smaller peptides or antibody fragments instead of currently used whole anti-bodies),which is an order of magnitude higher than conventional confocal microscopy.In the current study,we employed STORM to reveal the major ultra-structural components of the ESG,HS and HA,and their organization at the surface of the cultured EC monolayer[4].Materials and methods We used newly acquired Nikon-STORM system to observe the ESG on in vitro EC(bEnd3,mouse brain microvascular endothelial cells)monolayers.After confluency,the bEnd3 cells were immunolabeled with anti-HS,fol-lowed by an ATT0488 conjugated goat anti-mouse IgG,and with biotinylated HA binding protein,followed by an AF647 conjugated anti-biotin.The ESG was then imaged by the STORM with a 100x/1.49 oil immersed lens.Multiple Reporters of ATT0488 and AF647 with alternating illumination were used to acquire the 3D images of HS and HA.The field of 256×256(40×40μm2)of HS and HA at the surface of ECs was obtained based on totally 40,000 of EM-CCD captured images for each reporter at a capturing speed of 19 ms/frame.Results HA is a long molecule weaving into a network which covers the endothelial luminal surface.The diameter of the HA segments is 185.3±44.7 nm,155.5±57.2 nm,and 156.9±56.1 nm,respectively,at the top,middle and bottom regions of the cell luminal surface.In contrast,HS is a shorter molecule,perpendicular to the cell surface.HA and HS are partially overlapped with each other at the endothelial luminal surface.We quantified the length,diameter,orientation,and density of HS at the top,middle and bottom regions of the endothelial surface.The diameter of the observed HS is 191.0±46.0 nm,284.3±71.1 nm,and 184.2±59.6 nm,and the length of the HS is 621.0±75.7 nm,651.0±118.0 nm,and 575.2±105.6 nm,respectively,at the top,middle and bottom regions of the cell luminal surface.For the HS orientation,its angle with the cell surface is 92.9±1.9,88.7±8.2,and 96.2±10.9 degree,respectively,at the top,middle and bottom regions.The angle of 90 degree is perfectly perpendicular to the cell surface.For the HS distribution,the average density is0.398 elements/μm2,0.345 elements/μm2 and 0.665 elements/μm2,respectively,and the distance between the adjacent HS is 1 694.4±628.1 nm,1 844.8±758.5 nm,and 1 221.9±450.7 nm,respectively,at the top,middle and bottom regions.Conclusions Our results suggest that HS plays a major role in mechanosensing and HA plays a major role in the molecular sieve,due to their organization,ultra-structure and distribution.

Hybridization Effects Revealed by Angle-Resolved Photoemission Spectroscopy in Heavy-Fermion Ce2IrIn8

We utilize high-resolution resonant angle-resolved photoemission spectroscopy(ARPES)to study the band structure and hybridization effect of the heavy-fermion compound Ce2 IrIn8.We observe a nearly flat band at the binding energy of 7 meV below the coherent temperature Tcoh^40 K,which characterizes the electrical resistance maximum and indicates the onset temperature of hybridization.However,the Fermi vector and the Fermi surface volume have little change around Tcoh,which challenges the widely believed evolution from a hightemperature small Fermi surface to a low-temperature large Fermi surface.Our experimental results of the band structure fit well with the density functional theory plus dynamic mean-field theory calculations.

Revealed Cores: Characterizations and Structure

Characterizations of the classes of all choice functions that select the cores or the externally stable cores induced by an underlying revealed dominance digraph are provided. Relying on such characterizations, the basic order-theoretic structure of the corresponding sets of revealed cores is also analyzed. In particular, it is shown that the poset of all revealed cores ordered by set inclusion is a median meet semilattice: therefore, any profile of revealed cores may be aggregated by means of the simple majority rule.

Data Transmission Delay in Medtronic Reveal LINQ^TMImplantable Cardiac Monitor: Clinical Experience in 520 Patients

Background: The Implantable Cardiac Monitor (ICM) is an invaluable tool for detecting cardiac arrhythmias by providing physicians. Critical to the success of ICMs depends on how quickly and accurately the data can be transmitted to a physician’s office after an arrhythmic event. Then, the clinical event can be analyzed and the treatment will be provided accordingly. However, no reports have been published as to how efficiently the ICM data is transmitted. Methods: There is a retrospective review of 520 patients who received a Medtronic Reveal LINQTM between 2/01/2015 and 6/01/2017. The time from the arrhythmic event to the time of physician notification was calculated and reason for delay was noted. Results: One hundred and twenty patients out of 520 patients (23%) had arrhythmic events transmitted over a mean follow up of 14 ± 4 months. The mean time between cardiac events and physician notification was 15 ± 8 days. Sixty-three percent (63%) of data transmission delay (defined as >24 hours) was due to the MyCareLinkTM Monitor not being in proximity to the patient. Connection failure between the monitor and the network accounted for 34% of data transmission delay. Conclusion: Significant delay in data transmission from Medtronic Reveal LINQTM cardiac monitor occurs frequently impacting patient care. Newer generations of the implantable cardiac monitors utilize Bluetooth technology, enabling immediate transfer of data from ICM to a patient’s cellular phone and subsequently to their physician’s office. This technology could potentially improve efficiency and reliability eliminating the issues of proximity and connectivity.

Revealing the Pressure-Induced Softening/Weakening Mechanism in Representative Covalent Materials

Diamond, cubic boron nitride(c-BN), silicon(Si), and germanium(Ge), as examples of typical strong covalent materials, have been extensively investigated in recent decades, owing to their fundamental importance in material science and industry. However, an in-depth analysis of the character of these materials' mechanical behaviors under harsh service environments, such as high pressure, has yet to be conducted. Based on several mechanical criteria, the effect of pressure on the mechanical properties of these materials is comprehensively investigated.It is demonstrated that, with respect to their intrinsic brittleness/ductile nature, all these materials exhibit ubiquitous pressure-enhanced ductility. By analyzing the strength variation under uniform deformation, together with the corresponding electronic structures, we reveal for the first time that the pressure-induced mechanical softening/weakening exhibits distinct characteristics between diamond and c-BN, owing to the differences in their abnormal charge-depletion evolution under applied strain, whereas a monotonous weakening phenomenon is observed in Si and Ge. Further investigation into dislocation-mediated plastic resistance indicates that the pressure-induced shuffle-set plane softening in diamond(c-BN), and weakening in Si(Ge), can be attributed to the reduction of antibonding states below the Fermi level, and an enhanced metallization, corresponding to the weakening of the bonds around the slipped plane with increasing pressure, respectively. These findings not only reveal the physical mechanism of pressure-induced softening/weakening in covalent materials, but also highlights the necessity of exploring strain-tunable electronic structures to emphasize the mechanical response in such covalent materials.

Annual Meeting Reveals Competitiveness of Chinese Enterprises

This is the fifth year since the first "Chinese Enterprises Competitiveness Annual Meeting" convened in 2003. During those five years,we have witnessed a period of remarkable performance by Chinese enterprises. These last five years have seen a reaping of the fruits brought about by China's three-decade-long reform and opening, as evidenced by the increasing growth and maturity of Chinese enterprises and the rising competitiveness of publicly listed Chinese enterprises. Along with the development of globalization initiatives, Chinese enterprises are moving firmly and solidly towards internationalization and have begun to have a profound impact on the world economy. The roadmap of Chinese enterprises has now become a focus of global attention.

Auditory Hopf Amplification Revealed by an Energy Method

We report on the auditory Hopf amplification contributed by the electrical energy of the hair cell during its bundle deflecting. An energy method to calculate the active force is adopted according to the electrical energy consumption of the hair cell. After some experimental data was analyzed and simulated, we find that the electrical energy determines the value of the active force and enlarges the mechanical response of the hair bundle.This amplification is controlled by the cell voltage and makes the sensor a Hopf vibrator with hearing nonlinear characteristics. A velocity-dependent active force derived previously from the force-gating channel operation strongly reinforces our conclusion.

Critical Transitions of Microviscosity in Concentrated Polystyrene Solutions Revealed by Excimer Formation of Pyrenyl Probes

Excimer formation of pyrene and benzyl 4-(1-pyrenyl) butanoate was used to study the microviscosity of polystyrene/toluene solutions over the entire concentration range. Two critical concentrations (CPS～0.32, 0.82g/ml) have been observed from the log-log plot of IE/IM vs CPS. The results are explained in terms of the onset of cohesional interaction and the glass transition of the polymer chains.

A Blackish Gingiva Revealing a Metastatic Melanoma of the Oral Mucosa

Background and Objective: Malignant melanoma is the most aggressive skin cancer because it has very strong metastatic power. Endobuccal localization is very rare. Its discovery is often made in the late stage, which leads to a consistently pessimistic diagnostic. We report a case of palatal melanoma at the metastatic stage. Case Report: A 43-year-old woman presented left lateral cervical swelling associated with dyspnea for 5 months. She had regularly taken chewing tobacco for 4 years and had developed blackish gums. The endobuccal examination showed a blackish non-haemorrhagic swelling of 5 cm of the long axis, located at the level of the palatal vault, associated with pigmentation in teeth 21, 22, and 23. The anatomopathological examination confirmed the melanoma. The spreading assessment revealed pleural and hepatic metastasis. The proposed treatment was palliative treatment. The patient died 2 months later. Conclusion: Melanoma of the oral mucosa is a very aggressive tumor. The scarcities of dental care among the Malagasy people exacerbate the delay in diagnosis. Its management is still challenging in Madagascar.

Facebook——Are You Revealing Too Much?

Most young people know what Facebook is:a free-access Internet social networking website popular among teenagers,and adults,too.It was founded by a Harvard University student named Mark Zuckerberg and launched on February 4,2004.

Fossils Reveal Flowers Originated 50 Million Years Earlier than Thought

The discovery in China of fossil specimens of a flower called Nanjinganthus from the Early Jurassic suggests that flowers originated 50 million years earlier than previously thought.Scientists have discovered the earliest flower specimens dating back to the Early Jurassic。