Histone demethylase JMJD3 downregulation protects against aberrant force-induced osteoarthritis through epigenetic control of NR4A1

Osteoarthritis(OA)is a prevalent joint disease with no effective treatment strategies.Aberrant mechanical stimuli was demonstrated to be an essential factor for OA pathogenesis.Although multiple studies have detected potential regulatory mechanisms underlying OA and have concentrated on developing novel treatment strategies,the epigenetic control of OA remains unclear.Histone demethylase JMJD3 has been reported to mediate multiple physiological and pathological processes,including cell differentiation,proliferation,autophagy,and apoptosis.However,the regulation of JMJD3 in aberrant force-related OA and its mediatory effect on disease progression are still unknown.In this work,we confirmed the upregulation of JMJD3 in aberrant forceinduced cartilage injury in vitro and in vivo.Functionally,inhibition of JMJD3 by its inhibitor,GSK-J4,or downregulation of JMJD3 by adenovirus infection of sh-JMJD3 could alleviate the aberrant force-induced chondrocyte injury.Mechanistic investigation illustrated that aberrant force induces JMJD3 expression and then demethylates H3K27me3 at the NR4A1 promoter to promote its expression.Further experiments indicated that NR4A1 can regulate chondrocyte apoptosis,cartilage degeneration,extracellular matrix degradation,and inflammatory responses.In vivo,anterior cruciate ligament transection(ACLT)was performed to construct an OA model,and the therapeutic effect of GSK-J4 was validated.More importantly,we adopted a peptide-si RNA nanoplatform to deliver si-JMJD3 into articular cartilage,and the severity of joint degeneration was remarkably mitigated.Taken together,our findings demonstrated that JMJD3 is flow-responsive and epigenetically regulates OA progression.Our work provides evidences for JMJD3 inhibition as an innovative epigenetic therapy approach for joint diseases by utilizing p5RHH-si RNA nanocomplexes.

Co-axial depth sensor with an extended depth range for AR/VR applications

Background Depth sensor is an essential element in virtual and augmented reality devices to digitalize users'environment in real time.The current popular technologies include the stereo,structured light,and Time-of-Flight(ToF).The stereo and structured light method require a baseline separation between multiple sensors for depth sensing,and both suffer from a limited measurement range.The ToF depth sensors have the largest depth range but the lowest depth map resolution.To overcome these problems,we propose a co-axial depth map sensor which is potentially more compact and cost-effective than conventional structured light depth cameras.Meanwhile,it can extend the depth range while maintaining a high depth map resolution.Also,it provides a high-resolution 2 D image along with the 3 D depth map.Methods This depth sensor is constructed with a projection path and an imaging path.Those two paths are combined by a beamsplitter for a co-axial design.In the projection path,a cylindrical lens is inserted to add extra power in one direction which creates an astigmatic pattern.For depth measurement,the astigmatic pattern is projected onto the test scene,and then the depth information can be calculated from the contrast change of the reflected pattern image in two orthogonal directions.To extend the depth measurement range,we use an electronically focus tunable lens at the system stop and tune the power to implement an extended depth range without compromising depth resolution.Results In the depth measurement simulation,we project a resolution target onto a white screen which is moving along the optical axis and then tune the focus tunable lens power for three depth measurement subranges,namely,near,middle and far.In each sub-range,as the test screen moves away from the depth sensor,the horizontal contrast keeps increasing while the vertical contrast keeps decreasing in the reflected image.Therefore,the depth information can be obtained by computing the contrast ratio between features in orthogonal directions.Conclusions The proposed depth map sensor could implement depth measurement for an extended depth range with a co-axial design.

Multi-focus non-periodic scanning method for femtosecond lasers based on DMD and galvanometer scanners[Invited]

Multi-focus parallel scanning can effectively increase laser fabrication throughput.However,the conventional approach of using a spatial light modulator(SLM)to generate multi-foci and scan this fixed number of foci with galvanometer scanners can only achieve a periodic scanning trajectory due to the low switching speed of the SLM.Here we demonstrate a multifocus non-periodic scanning method for femtosecond lasers by using,instead,a fast-switching digital micromirror device(DMD)to generate a dynamic number of foci.The number of effective foci is quickly switched by introducing aberration to the undesired focus.In this way,the intensity allocated to each focus will not be affected by the number of foci,and a uniformity of 98%with different numbers of foci is achieved without adjusting the total laser energy.Finally,we validate the effectiveness of this scanning method by demonstrating corneal flap fabrication of porcine cornea in vitro.