Effects of Roughly Focused Extracorporeal Shock Waves Therapy on the Expressions of Bone Morphogenetic Protein-2 and Osteoprotegerin in Osteoporotic Fracture in Rats

Background：Roughly focused extracorporeal shock waves therapy （ESWT） is characterized by a wide focal area,a large therapy zone,easy positioning,and less pain during treatment.The purpose of this study was to investigate the effects of roughly focused ESWT on the expression of osteoprotegerin （OPG） and bone morphogenetic protein-2 （BMP-2） in osteoporotic fractures in rats.Methods：Seventy-two female Sprague-Dawley （SD） rats,3 months old,were divided into sham-operated group （n =6） and an ovariectomized （OVX） group （n =66）.Sixty OVX SD rats were used as a model of double proximal tibial osteotomy and inner fixation.The osteotomy site in the left tibia was treated with roughly focused ESWT once at an energy density of 0.26 mJ/mm^2,60 doses/min,and 2000 pact quantities.The contralateral right tibia was left untreated and served as a control.Expression of OPG and BMP-2 in the callus of the osteoporotic fracture area was assessed using immunohistochemistry,real-time polymerase chain reaction （PCR）,and Western blotting analysis.Results：Bone mineral density （BMD） at the proximal tibia,femur,and L5 spine was significantly reduced after ovariectomy.BMD of proximal tibia was 12.9% less in the OVX group than that in the sham-operated group.Meanwhile,bilateral oophorectomy resulted in a lower trabecular bone volume fraction （BV/TV） in the proximal tibia of the sham-OVX animals.Three months after bilateral oophorectomy,BV/TV was 14.29% of baseline BV/TV in OVX legs versus 45.91% in the sham-OVX legs （P 〈 0.001）.These data showed that the SD rats became a suitable model of osteoporosis,3 months after they were OVX.Immunohistochemical analysis showed higher levels of BMP-2 and OPG expression in the treatment group than those in the control group.Compared with the contralateral controls,decreased expression of OPG and BMP-2 at 3 days after roughly focused ESWT,followed by a later increase at 7 days,was indicated by real-time PCR and Western blotting analysis.The OPG messenger RNA （mRNA） expression levels peaked at 6 weeks after the shock wave treatment,paired with a much earlier （at 4 weeks） increase of BMP-2,and declined close to normal at 8 weeks.Conclusions：Roughly focused ESWT may promote the expression of OPG and BMP-2 in the osteoporotic fracture area in rats.BMP-2 and OPG may act synergistically and may lead to a significant enhancement of bone formation and remodeling.

Tumor heterogeneity and the potential role of liquid biopsy in bladder cancer

Bladder cancer(BC)is a heterogeneous disease that characterized by genomic instability and a high mutation rate.Heterogeneity in tumor may partially explain the diversity of responses to targeted therapies and the various clinical outcomes.A combination of cytology and cystoscopy is the standard methodology for BC diagnosis,prognosis,and disease surveillance.However,genomics analyses of single tumor-biopsy specimens may underestimate the mutational burden of heterogeneous tumors.Liquid biopsy,as a promising technology,enables analysis of tumor components in the bodily fluids,such as blood and urine,at multiple time points and provides a minimally invasive approach that can track the evolutionary dynamics and monitor tumor heterogeneity.In this review,we describe the multiple faces of BC heterogeneity at the genomic and transcriptional levels and how they affect clinical care and outcomes.We also summarize the outcomes of liquid biopsy in BC,which plays a potential role in revealing tumor heterogeneity.Finally,we discuss the challenges that must be addressed before liquid biopsy can be widely used in clinical treatment.

Synergistic enhancement of spin-phonon interaction in a hybrid system

An investigation to significantly enhance coupling to nitrogen-vacancy(NV)centers at a single-quanta level is of great interest to further explore its applications in quantum information processing(QIP).This study explores a joint scheme to further enhance NV-phonon coherent coupling with two methods working together in hybrid optomechanical systems.Both methods are mechanics-induced mode field coupling(MFC)that lead,respectively,to the modification of the spatial distribution of the optical field and the mechanical parametric amplification(MPA)realized by modulating the mechanical spring constant in time.With the joint assistance of MFC and MPA,the coherent coupling between the NV spin and one supermode of the mechanical resonators(MRs)can be further significantly enhanced with the rate∝n_(cav)e^(r).Several potential applications are also discussed in this work.With the ultimate goal to enhance the coupling to NV spin at a single-quanta level,this attempt may provide a promising spin-phonon platform to implement more active control.