Mechanotransduction pathways in articular chondrocytes and the emerging role of estrogen receptor-α

In the synovial joint,mechanical force creates an important signal that influences chondrocyte behavior.The conversion of mechanical signals into biochemical cues relies on different elements in mechanotransduction pathways and culminates in changes in chondrocyte phenotype and extracellular matrix composition/structure.Recently,several mechanosensors,the first responders to mechanical force,have been discovered.However,we still have limited knowledge about the downstream molecules that enact alterations in the gene expression profile during mechanotransduction signaling.Recently,estrogen receptorα(ERα)has been shown to modulate the chondrocyte response to mechanical loading through a ligand-independent mechanism,in line with previous research showing that ERαexerts important mechanotransduction effects on other cell types,such as osteoblasts.In consideration of these recent discoveries,the goal of this review is to position ERαinto the mechanotransduction pathways known to date.Specifically,we first summarize our most recent understanding of the mechanotransduction pathways in chondrocytes on the basis of three categories of actors,namely mechanosensors,mechanotransducers,and mechanoimpactors.Then,the specific roles played by ERαin mediating the chondrocyte response to mechanical loading are discussed,and the potential interactions of ERαwith other molecules in mechanotransduction pathways are explored.Finally,we propose several future research directions that may advance our understanding of the roles played by ERαin mediating biomechanical cues under physiological and pathological conditions.

Formability determination of AZ31B tube for IHPF process at elevated temperature

Ring hoop tension test and tube bulging test were carried out at elevated temperatures up to 480 ℃to evaluate the formability of AZ31B extruded tube for internal high pressure forming （IHPF） process. The total elongation along hoop direction and the maximum expansion ratio （MER） of the tube were obtained. The fracture surface after bursting was also analyzed. The results show that the total elongation along hoop direction and the MER value have a similar changing tendency as the testing temperature increases, which is quite different from the total elongation along axial direction. Both the total elongation along hoop direction and the MER value increase to a peak value at about 160 ℃. After that, they begin to decrease quickly until a certain rebounding temperature is reached. From the rebounding temperature, they begin to increase rapidly again. Burnt structure appears on the fracture surface when tested at temperatures higher than 420 ℃. Therefore, the forming temperature of the tested tube should be lower than 420 ℃, even though bigger formability can be achieved at higher temperature.

Assessing the accuracy of arthroscopic and open measurements of the size of rotator cuff tears: A simulation-based study

BACKGROUND Arthroscopic procedures are commonly performed for rotator cuff pathology.Repair of rotator cuff tears is a commonly performed procedure.The intraoperative evaluation of the tear size and pattern contributes to the choice and completion of the technique and the prognosis of the repair.AIM To compare the arthroscopic and open measurements with the real dimensions of three different patterns of simulated rotator cuff tears of known size using a plastic shoulder model.METHODS We created three sizes and patterns of simulated supraspinatus tears on a plastic shoulder model(small and large U-shaped,oval-shaped).Six orthopaedic surgeons with three levels of experience measured the dimensions of the tears arthroscopically,using a 5 mm probe,repeating the procedure three times,and then using a ruler(open technique).Arthroscopic,open and computerized measurements were compared.RESULTS A constant underestimation of specific dimensions of the tears was found when measured with an arthroscope,compared to both the open and computerized measurements(mean differences up to-7.5±5.8 mm,P<0.001).No differences were observed between the open and computerized measurements(mean difference-0.4±1.6 mm).The accuracy of arthroscopic and open measurements was 90.5%and 98.5%,respectively.When comparing between levels of experience,senior residents reported smaller tear dimensions when compared both to staff surgeons and fellows.CONCLUSION This study suggests that arthroscopic measurements of full-thickness rotator cuff tears constantly underestimate the dimensions of the tears.Development of more precise arthroscopic techniques or tools for the evaluation of the size and type of rotator cuff tears are necessary.

Use of sensory substitution devices as a model system for investigating cross-modal neuroplasticity in humans

Blindness provides an unparalleled opportunity to study plasticity of the nervous system in humans.Seminal work in this area examined the often dramatic modifications to the visual cortex that result when visual input is completely absent from birth or very early in life（Kupers and Ptito,2014）.More recent studies explored what happens to the visual pathways in the context of acquired blindness.This is particularly relevant as the majority of diseases that cause vision loss occur in the elderly.

Professor Yuan Cheng (Bert) Fung:My Respected Mentor and Cherished Friend

On September 14,2008,Drs.Shu Chien,Peter Chen,Geert Schmid-Schonbein,Pin Tong and I had the great pleasure of organizing a beautiful event in San Diego,California to celebration Dr.Fung’s 90thbirthday with his students,friends and family[1].The team gave me the honor and privilege to be the banquet speaker.I titled my speech as“Dr.Fung:My Respected Mentor and Cherished Friend”-something for those of you who have known Dr.Fung well can“resonate”.Still,I would like to take this opportunity to share with you an excerpt of the story I told about this great gentle man.

Analysis of Deformation in a High Entropy Alloy Using an Internal State Variable Model

Deformation in the model high entropy alloy CoCrFeMnNi is assessed using an internal state variable constitutive model. A remarkable property of these alloys is the extraordinarily high strain hardening rates they experience in the plastic region of the stress strain curve. Published stress-strain measurements over a range of temperatures are analyzed. Dislocation obstacle interactions and the observed high rate of strain hardening are characterized in terms of state variables and their evolution. A model that combines a short-range obstacle and a long-range obstacle is shown to match experimental measurements over a wide range of temperatures and grain sizes. The long-range obstacle is thought to represent interactions of dislocations with regions of incomplete mixing or partial segregation. Dynamic strain aging also is observed at higher temperatures. Comparisons with measurements in austenitic stainless steel show some common trends.

推拿手法对腰椎间盘突出症腰椎结构三维位移的影响

目的通过观察推拿手法对腰突症患者腰椎三维空间位移的影响,探讨推拿手法治疗腰突症"骨错缝"的干预机制。方法选取10名腰突症患者,分为理筋手法组(5例,简称理筋组)和理筋手法加调整手法组(5例,简称理调组)进行治疗;正常志愿者5例为理筋手法(简称正常组)。应用ITK重建软件重建腰椎椎体并进行有限元分析,比较3组手法干预前后腰椎椎体三维位移变化情况。结果 3组腰突症患者推拿手法治疗后L1～5各椎体的空间位置发生了一定改变。理调组L3在X轴角位移为(1.77±0.46)°;L4在X、Y轴角位移分别为(1.78±0.53)°、(1.89±0.75)°,显著大于理筋组和正常组(P<0.05);理调组L1～5在X轴三维角位移分别为(1.50±0.47)°、(1.55±0.57)°、(1.77±0.46)°、(1.78±0.53)°、(1.61±0.39)°,均显著大于正常组(P<0.05);理调组L3在Y轴三维位移为(2.87±0.74)mm,L4在X轴三维位移为(1.68±0.64)mm,显著大于理筋组和正常组(P<0.05);理调组L1、L4、L5在X轴三维位移分别为(1.28±0.21)、(1.68±0.64)、(1.30±0.51)mm,L1～3在Y轴三维位移分别为(1.92±0.42)、(2.25±0.61)、(2.87±0.74)mm,均显著大于正常组(P<0.05)。理筋手法组L1～5各节段三维角位移和位移与正常组相比,均呈现大于正常组的趋势。结论理调手法比理筋手法更能调整失稳或退变节段的空间位置,使腰椎椎体产生水平及旋转移位,而非上下移位,对纠正腰椎"骨错缝"产生重要作用。理筋手法对腰突症患者腰椎结构有一定的影响,但不显著。

Immunomodulatory approaches to CNS injury:extracellular matrix and exosomes from extracellular matrix conditioned macrophages

After central nervous system（CNS）injury,a pro-inflammatory,innate immune response contributes to permanently lost neuronal function by promoting changes in the micro-environment and extracellular matrix（ECM）that lead to CNS neuronal degeneration and death and permanent scarring.

Matrix bound vesicles and miRNA cargoes are bioactive factors within extracellular matrix bioscaffolds

Injury to central nervous system （CNS） tissues in adult mam- mals often leads to neuronal loss, scarring, and permanently lost neurologic functions, and this default healing response is increasingly linked to a pro-inflammatory innate immune response. Extracellular matrix （ECM） technology can reduce inflammation, while increasing functional tissue remodeling in various tissues and organs, including the CNS.

In vitro and in vivo evaluation of cerium oxide nanoparticles in respiratory syncytial virus infection

Respiratory syncytial virus(RSV)is the most common cause of viral bronchiolitis among children worldwide,yet there is no vaccine for RSV disease.This study investigates the potential of cube and sphere-shaped cerium oxide nanoparticles(CNP)to modulate reactive oxygen(ROS)and nitrogen(RNS)species and immune cell phenotypes in the presence of RSV infection in vitro and in vivo.Cube and sphere-shaped CNP were synthesized by hydrothermal and ultrasonication methods,respectively.Physico-chemical characterization confirmed the shape of sphere and cube CNP and effect of various parameters on their particle size distribution and zeta potential.In vitro results revealed that sphere and cube CNP differentially modulated ROS and RNS levels in J774 macrophages.Specifically,cube CNP significantly reduced RSV-induced ROS levels without affecting RNS levels while sphere CNP increased RSV-induced RNS levels with minimal effect on ROS levels.Cube CNP drove an M1 phenotype in RSV-infected macrophages in vitro by increasing macrophage surface expression of CD80 and CD86 with a concomitant increase in TNFαand IL-12p70,while simultaneously decreasing M2 CD206 expression.Intranasal administration of sphere and cube-CNP were well-tolerated with no observed toxicity in BALB/c mice.Notably,cube CNP preferentially accumulated in murine alveolar macrophages and induced their activation,avoiding enhanced uptake and activation of other inflammatory cells such as neutrophils,which are associated with RSV-mediated inflammation.In conclusion,we report that sphere and cube CNP modulate macrophage polarization and innate cellular responses during RSV infection.

Engineering osteoarthritic cartilage model through differentiating senescent human mesenchymal stem cells for testing disease-modifying drugs

Significant cellular senescence has been observed in cartilage harvested from patients with osteoarthritis(OA).In this study,we aim to develop a senescence-relevant OA-like cartilage model for developing disease-modifying OA drugs(DMOADs).Spe-cifically,human bone marrow-derived mesenchymal stromal cells(MSCs)were expanded in vitro up to passage 10(P10-MSCs).Following their senescent phenotype formation,P10-MSCs were subjected to pellet culture in chondrogenic medium.Results from qRT-PCR,histology,and immunostaining indicated that cartilage generated from P10-MSCs displayed both senescent and OA-like phenotypes without using other OA-inducing agents,when compared to that from normal passage 4(P4)-MSCs.Interestingly,the same gene expression differences observed between P4-MSCs and P10-MSC-derived cartilage tissues were also observed between the preserved and damaged OA cartilage regions taken from human samples,as demonstrated by RNA sequencing data and other analysis methods.Lastly,the utility of this senescence-initiated OA-like cartilage model in drug development was assessed by testing several potential DMOADs and senolytics.The results suggest that pre-existing cellular senescence can induce the generation of OA-like changes in cartilage.The P4-and P10-MSCs derived cartilage models also represent a novel platform for predicting the efficacy and toxicity of potential DMOADs on both preserved and damaged cartilage in humans.

A rapid solid-state synthesis of electrochemically active Chevrel phases （Mo6T8; T = S, Se） for rechargeable magnesium batteries

High energy mechanical milling （HEMM） of a stoichiometric mixture of molybdenum and metal chalcogenides （CuT and MOT2; T = S, Se） followed by heat treatment at elevated temperatures was successfully applied to synthesize Chevrel phases （Cu2Mo6T8; T = S, Se） as positive electrodes for rechargeable magnesium batteries. Differential scanning calorimetry （DSC）, thermogravimetric analyses （TGA）, X-ray diffraction （XRD）, and scanning electron microscopy （SEM） were used to understand the phase formation following milling and heat treatment. CuS and Mo were observed to react at 714-800 K and formed an intermediate ternary Chevrel phase （Cu1.83Mo3S4）, which further reacted with residual Mo and MoS2 to form the desired Cu2MosSs. Quantitative XRD analysis shows the formation of a -96%-98% Chevrel phase at 30 min following the milling and heat treatment. The electrochemical performance of de-cuprated Mo6S8 and Mo6Ses phases were evaluated by cyclic voltammetry （CV）, galvanostatic cycling, and electrochemical impedance spectroscopy （EIS）. The results of the CV and galvanostatic cycling data showed the expected anodic/cathodic behavior and a stable capacity after the first cycle with the formation of MgxMo6T8 （T = S, Se; 1 ≤ x 〈 2）. EIS at -0.1 V intervals for the Mo6Ss electrode during the first and second cycle shows that partial Mg-ion trapping resulted in an increase in charge transfer resistance Re. In contrast, the interfacial resistance Ri remained constant, and no significant trapping was evident during the galvanostatic cycling of the Mo6,Se8 electrode. Importantly, the ease of preparation, stable capacity, high Coulombic efficient35 and excellent rate capabilities render HEMM a viable route to laboratory-scale production of Chevrel phases for use as positive electrodes for rechargeable magnesium batteries.

Synthesis and biocompatibility of a biodegradable and functionalizable thermo-sensitive hydrogel

Injectable thermal gels are a useful tool for drug delivery and tissue engineering.However,most thermal gels do not solidify rapidly at body temperature(37C).We addressed this by synthesizing a thermo-sensitive,rapidly biodegrading hydrogel.Our hydrogel,poly(ethylene glycol)-co-poly(propanol serinate hexamethylene urethane)(EPSHU),is an ABA block copolymer comprising A,methoxy poly ethylene glycol group and B,poly(propanol L-serinate hexamethylene urethane).EPSHU was characterized by gel permeation chromatography for molecular weight and 1H NMR and Fourier transformed infrared for structure.Rheological studies measured the phase transition temperature.In vitro degradation in cholesterol esterase and in Dulbecco’s phosphate buffered saline(DPBS)was tracked using the average molecular weight measured by gel permeation chromatography.LIVE/DEAD and resazurin reduction assays performed on NIH 3T3 fibroblasts exposed to EPSHU extracts demonstrated no cytotoxicity.Subcutaneous implantation into BALB/cJ mice indicated good biocompatibility in vivo.The biodegradability and biocompatibility of EPSHU together make it a promising candidate for drug delivery applications that demand carrier gel degradation withinmonths.

Effect of Environmental Contaminants on the Interfacial Properties of Two-Dimensional Materials

CONSPECTUS:The surface of 2D materials can spontaneously adsorb and react with molecules in the environment during their processing and storage.This effect,while having a significant impact on many properties of 2D materials,is not always recognized and accounted for in the research involving them.This Account summarizes our recent work in understanding how the ambient environment impacts the properties of 2D materials and its mitigation strategies.We highlight graphene and hydrocarbons in our discussion and complement it with selected studies involving other 2D materials as well as water and oxygen.

Understanding the wettability of nanometer-thick room temperature ionic liquids(RTILs) on solid surfaces

Many important applications of room temperature ionic liquids （RTILs）, e.g., lubrication, energy storage and catalysis, involve RTILs confined to solid surfaces. In order to optimize the performance, it is critical to understand the wettability of nanometer-thick RTILs on solid surfaces. In this review, the recent progress in this filed is presented. First, the macroscopic wettability of RTILs on solids will be discussed briefly. Afterwards, the wetting of nanometer-thick RTILs will be discussed with the emphasis on RTIL/mica and RTIL/graphite interfaces since mica and graphite not only are mostly studied but also have important real-life applications. For RTIL/mica interface, the extended layering that promotes the wetting has been extensively reported and it is generally accepted that the electrostatic interaction at the RTIL/mica interface is the key. However, recent works from others and us highlight the unexpected effect of water： Water enables ion exchange between K^＋ and the cations of RTILs on the mica surface and thus triggers the ordered packing of cations/anions in RTILs, resulting in extended layering. Different from mica, there is no electrical charge on the graphite surface. Interestingly, previous reports showed inconsistent results on the wettability of RTILs on graphite. Recent research from others and us suggested that π-π^＋ stacking between sp2 carbon and the imidazoliumcation in