Matrix stiffening promotes chondrocyte senescence and the osteoarthritis development through downregulating HDAC3

Extracellular matrix(ECM)stiffening is a typical characteristic of cartilage aging,which is a quintessential feature of knee osteoarthritis(KOA).However,little is known about how ECM stiffening affects chondrocytes and other molecules downstream.This study mimicked the physiological and pathological stiffness of human cartilage using polydimethylsiloxane(PDMS)substrates.It demonstrated that epigenetic Parkin regulation by histone deacetylase 3(HDAC3)represents a new mechanosensitive mechanism by which the stiffness matrix affected chondrocyte physiology.We found that ECM stiffening accelerated cultured chondrocyte senescence in vitro,while the stiffness ECM downregulated HDAC3,prompting Parkin acetylation to activate excessive mitophagy and accelerating chondrocyte senescence and osteoarthritis(OA)in mice.Contrarily,intra-articular injection with an HDAC3-expressing adeno-associated virus restored the young phenotype of the aged chondrocytes stimulated by ECM stiffening and alleviated OA in mice.The findings indicated that changes in the mechanical ECM properties initiated pathogenic mechanotransduction signals,promoted the Parkin acetylation and hyperactivated mitophagy,and damaged chondrocyte health.These results may provide new insights into chondrocyte regulation by the mechanical properties of ECM,suggesting that the modification of the physical ECM properties may be a potential OA treatment strategy.

Numerical Study on the Effect of Current Profiles on Vortex-Induced Vibrations in a Top-Tension Riser

In this paper, numerical simulations of vortex-induced vibrations in a vertical top-tension riser with a length-to-diameter ratio of 500 using our in-house code viv-FOAM-SJTU are presented. The time-dependent hydrodynamic forces on two-dimensional strips are obtained by solving the Navier-Stokes equations, which are, in turn, integrated into a finite-element structural model to obtain the riser deflections. The riser is discretized into 80 elements with its two ends set as pinned and 20 strips are located equidistant along the risers. Flow and structure are coupled by hydrodynamic forces and structural displacements. In order to study the effects of the shear rate, of the current profiles on the vortex-induced vibrations in the riser, vibrations, with varying shear rates, in both the in-line and cross-flow directions, are simulated. In addition to the time domain analysis, spectral analysis was conducted in both the temporal and spatial domains. Multi-mode vibration characteristics were observed in the riser. The relationship between dominant vibration mode number and the shear rate of current profiles is discussed. In general, the overall vibrations in the riser pipe include contributions from several modes and each mode persists over a range of shear rates. Moreover, the results suggest that with a larger shear rate the position of the maximum in-line time-averaged displacement will move closer to the end where the largest velocity is located.

Effect of internal defects on tensile strength in SLM additively-manufactured aluminum alloys by simulation

This research investigates the effect of internal defects on the tensile strength of Selective Laser Melting(SLM)additively-manufactured aluminum alloy(AlSi10Mg)test parts used for civil aircraft light weight design.A Finite Element Analysis(FEA)model containing internal defects was established by combining test data and the stress concentration factor comparison method.The effect of variation in the number,location and shape of defects on the finite element results was analyzed.Its results show that it is reasonable to use spherical defect modeling.The finite element modeling and analysis methods are also applied to the study of the effect of internal defects on tensile strength in additive manufacturing of other metallic materials.According to the FEA results of single defects at different scales,the formula for calculating the weakening degree of tensile strength applicable to the defective area of less than 15%was established.The result of the procedure is reliable and conservative.This research results can guide the selection of process parameters for the additive manufacturing of aluminum alloys.Further,the research results can promote the application of metal additive manufacturing in designing light-weight civil aircraft structures.

Co-doping strategy enhanced the ionic conductivity and excellent lithium stability of garnet-type Li_(7)La_(3)Zr_(2)O_(12)electrolyte in all solidstate lithium batteries

Garnet-type Li_(7)La_(3)Zr_(2)O_(12)(LLZO)is one of the most promising solid-state electrolytes(SSEs).However,the application of LLZO is limited by structural instability,low ionic conductivity,and poor lithium stability.To obtain a garnet-type solid electrolyte with a stable structure and high ionic conductivity,a series of TaeCe co-doping cubic Li_(6.4)La_(3)Zr_(1.4-x)Ta_(0.6)Ce_(x)O_(12)(LLZTCO,x=,0.02,0.04,0.06,0.08,0.10,0.20,0.30)electrolytes were successfully synthesized through conventional solid-phase method.The Ta^(5+)doping can introduce more lithium vacancies and effectively maintain the stability of the cubic phase.The Ce^(4+)with a larger ionic radius is introduced into the lattice to widen the Lit migration bottleneck size,which significantly increased the ionic conductivity to 1.05×10^(-3)S/cm.It also shows excellent stability to lithium metal by the optimization of Lit transport channel.Li||LLZTCO||Li symmetric cells can cycle stably for more than 6000 h at a current density of 0.1 mA/cm^(2)without any surface modifications.The commercialization potential of LLZTCO samples in all solid-state lithium batteries(ASSLBs)is confirmed by the prepared LiFePO_(4)||LLZTCO||Li cells with a capacity retention rate of 98%after 100 cycles at 0.5C.This new co-doping method presents a practical solution for the realization of high-performance ASSLBs.

Integration of microfluidic injection analysis with carbon nanomaterials/gold nanowire arrays-based biosensors for glucose detection

Carbon nanotubes(CNTs) and reduced graphene oxide(r GO) nanosheets were utilized to construct glucose biosensors in combination with gold nanowire arrays(Au NWAs), and microfluidic injection analysis driven by gravity force was used to investigate the performances of as-prepared glucose biosensors. The results demonstrated glucose biosensors based on carbon nanomaterials/Au NWAs presented excellent performance at low working potential of-0.2 V versus Ag/Ag Cl(3 mol/L KCl), such as high sensitivity, good anti-interference ability and high throughput(45 h^(-1)). The glucose biosensor based on glucose oxidase(GOx)–CNT–Au NWAs showed a wide linear range from 100 to 3,000 lmol/L with a sensitivity of 4.12 l A/cm^2 mmol/L. Furthermore, the linear range and sensitivity of GOx–r GO–Au NWAs-based glucose biosensor were 50–4,000 lmol/L and 8.59 l A/(cm^2 mmol/L), respectively, which were better than those of glucose biosensor based on GOx–CNT–Au NWAs,suggesting r GO nanosheets in combination with Au NWAs being a good platform for the construction of glucose biosensors.

Numerical study of vibrations of a vertical tension riser excited at the top end

This paper presents numerical simulations of vortex-induced vibrations of a vertical riser which is sinusoidally excited at its top end in both one and two directions in still water.A computational fluid dynamics method based on the strip theory is used.The riser’s responses to both top-end and two-end excitations are carefully examined.In low reduced velocity cases,the in-line vibrations consist of three components,the low-frequency oscillation,the first-natural-frequency vibration during the riser reversal,and the second-natural-frequency vibration due to vortex shedding.The sheared oscillatory flow along the span causes low-frequency oscillations in higher modes in the in-line direction,thus forming‘X’shaped,‘II’shaped,and‘O’shaped trajectories at various positions along the span when the riser is excited at its top end in one direction.In the presence of excitations in the other direction,more complex trajectories appear.