Structural characterization of four Rhododendron spp.chloroplast genomes and comparative analyses with other azaleas

Azalea is a general designation of Rhododendron in the Ericaceae family.Rhododendron not only has high ornamental value but also has application value in ecological protection,medicine,and scientific research.In this study,we used Illumina and PacBio sequencing to assemble and annotate the entire chloroplast genomes(cp genomes)of four Rhododendron species.The chloroplast genomes of R.concinnum,R.henanense subsp.lingbaoense,R.micranthum,and R.simsii were assembled into 207,236,208,015,207,233,and 206,912 bp,respectively.All chloroplast genomes contain eight rRNA genes,with either 88 or 89 protein-coding genes.The four cp genomes were compared and analyzed by bioinformatics,and the phylogenetic analysis based on chloroplast genomes of 26 species of Ericaceae,Actinidiaceae,and Primulaceae under Ericales was conducted.A comparison of the linear structure of cp genomes of four Rhododendron showed that there were substantial sequence similarities in coding regions,but high differences in non-coding regions.A phylogenetic analysis,based on chloroplast whole genome sequences,showed that all Rhododendron species are in the clade Ericaceae.This study provides valuable genetic information for the study of population genetics and evolutionary relationships in Rhododendron and other azalea species.

基于FLO-2D的核桃沟泥石流数值模拟分析

铁路沿线泥石流灾害将对铁路隧道和桥梁施工和运营造成极大危害。文章选取核桃沟为研究对象,运用FLO-2D软件模拟不同周期的降雨过程,并提取降雨过程线计算泥石流洪峰流量。通过与雨洪法计算结果对比,验证了根据降雨过程线确定泥石流洪峰流量的合理性,进而对不同暴雨重现周期下核桃沟支沟和主沟泥石流发生过程进行模拟。核桃沟支沟泥石流模拟结果与分析表明,不同重现周期下,泥石流对支沟2~#斜井、沟谷居民安置点以及工程项目部的威胁较大,建议加强对支沟的泥石流监测预警。核桃沟主沟泥石流模拟结果与分析表明,不同重现周期下,核桃沟大桥处泥石流流速与堆积厚度有增大趋势;在50或100a一遇情况下,泥石流对核桃沟大桥的影响较大。

Application of next-generation sequencing technology to precision medicine in cancer: joint consensus of the Tumor Biomarker Committee of the Chinese Society of Clinical Oncology

Next-generation sequencing(NGS) technology is capable of sequencing millions or billions of DNA molecules simultaneously.Therefore, it represents a promising tool for the analysis of molecular targets for the initial diagnosis of disease, monitoring of disease progression, and identifying the mechanism of drug resistance. On behalf of the Tumor Biomarker Committee of the Chinese Society of Clinical Oncology(CSCO) and the China Actionable Genome Consortium(CAGC), the present expert group hereby proposes advisory guidelines on clinical applications of NGS technology for the analysis of cancer driver genes for precision cancer therapy. This group comprises an assembly of laboratory cancer geneticists, clinical oncologists, bioinformaticians,pathologists, and other professionals. After multiple rounds of discussions and revisions, the expert group has reached a preliminary consensus on the need of NGS in clinical diagnosis, its regulation, and compliance standards in clinical sample collection. Moreover, it has prepared NGS criteria, the sequencing standard operation procedure(SOP), data analysis, report, and NGS platform certification and validation.

Study on calculation of rock pressure for ultra-shallow tunnel in poor surrounding rock and its tunneling procedure

A computational method of rock pressure applied to an ultra-shallow tunnel is presented by key block theory, and its mathematical formula is proposed according to a mechanical tunnel model with super-shallow depth. Theoretical analysis shows that the tunnel is subject to asymmetric rock pressure due to oblique topography. The rock pressure applied to the tunnel crown and sidewall is closely related to the surrounding rock bulk density, tunnel size, depth and angle of oblique ground slope. The rock pressure applied to the tunnel crown is much greater than that to the sidewalls, and the load applied to the left side-wall is also greater than that to the right sidewall. Mean-while, the safety of the lining for an ultra-shallow tunnel in strata with inclined surface is affected by rock pressure and tunnel support parameters. Steel pipe grouting from ground surface is used to consolidate the unfavorable surrounding rock before tunnel excavation, and the reinforcing scope is proposed according to the analysis of the asymmetric load induced by tunnel excavation in weak rock with inclined ground surface. The tunneling procedure of bench cut method with pipe roof protection is still discussed and carried out in this paper according to the special geological condition. The method and tunneling procedure have been successfully utilized to design and drive a real expressway tunnel. The practice in building the super-shallow tunnel＆amp;nbsp;has proved the feasibility of the calculation method and tunneling procedure presented in this paper.

Expressions of genes related to genome stability and DNA repair in nasopharyngeal carcinoma clustering families

Objective： The aim of the study was to observe the expressions of genes related to genome stability and DNA repair in the members of nasopharyngeal carcinoma （NPC） clustedng families. Methods： In the Zhongshan City where there is highly incidence rate of NPC, we chose the members of the NPC clustering families as objects, and the patients of nasopharyngitis and NPC as the control group. We isolated the RNA from the nasopharyngeal tissue, and synthesized its cRNA, the genome stability and DNA repair genes chip technique, chemiluminescent detection and real-time fluorescence quantita- tive technique were used to examine the genome stability and DNA repair genes in the nasopharyngeal tissue. Results： More genome stability and DNA repair genes were up-regulated in the members of the NPC clustering families than the NPC patients, and the range of up-regulated was high, with the over up-regulated 100 times genes including TEP1, MSH4, PMS2LI. Fewer genome stability and DNA repair genes were down-regulated in the members of the NPC clustering families than the NPC patients, the ubiquitin genes almost were down-regulated, the results also could be confirmed by real-time fluorescence quantitative PCR. Conclusion： There are specially expression character of genome stability and DNA repair genes in the members of NPC clustering families.

Development of polymorphic SSR markers and their applicability in genetic diversity evaluation in Euptelea pleiosperma

Euptelea pleiosperma is a characteristic species of East Asian flora with both ornamental and scientific values.Based on the reduced-representation sequencing(RRS)technology of RAD-Seq,this study conducted high-throughput Illumina paired-end sequencing to find SSR marker information in the genome of E.pleiosperma,and to screen and verify polymorphism of SSR markers.We obtained 5.5G of high-quality data using RAD-Seq.The total number of contigs of the RAD tags was 299,376,with the maximum contig length of 2,062 bp and the average length of 445 bp.From these sequences,we identified 20,718 SSR loci,with a distribution density of one SSR per 6.45 kb(1/6.45 kb).Among all SSRs,dinucleotides(52.00%)were the most detected SSRs,followed by mononucleotides(21.63%).AG/CT was the dominant motif in the SSR loci,accounting for 34.8%.Primers were successfully designed for 14,593 loci,and 100 pairs of these primers were randomly selected for chemical synthesis and validated by SSR-PCR amplification in 20 individuals of E.pleiosperma.Seventy-nine primers were able to amplify the target bands.Cervus 3.0 software was used to analyze the selected 20 SSR loci with good polymorphism.For the 20 SSR markers,the number of alleles ranged from 4 to 9,and the observed heterozygosity and expected heterozygosity were from 0.35 to 0.75 and 0.541 to 0.875,respectively.The information content of polymorphic loci ranged from 0.463 to 0.848,with an average value of 0.638.Among them,there were 18 highly polymorphic loci,and 20 SSR loci did not deviate from the Hardy-Weinberg equilibrium.Furthermore,the 20 pairs of SSR primers were used to conduct PCoA analysis based on Nei’s genetic distance of 51 individuals from three populations.The results showed that these SSR markers could distinguish genetic differences based on different geographical locations.

Experimental and Theoretical Analysis of the Drag Torque in Wet Clutches

Traditional mathematical models cannot predict and explain the phenomenon by which the drag torque(DT)in wet clutches rises in the high-speed zone.In order to evaluate the DT in such conditions,a two-phase air-fluid mathematical model for a DT with grooves was elaborated.The mathematical model was based on the theory of viscous fluid flow.A two-phase volume of fluid model was also used to investigate the distribution and volume fraction of air and fluid.Experiments on three friction plates with different grooves were conducted to validate the resulting mathematical model.It was found that the gap between plates decreased in the high-speed zone,thereby producing an increase of the DT in the high-speed zone.These results support the understanding of the physical phenomena relating to disengaged wet clutches,and provide a theoretical basis for the future improvement of drive systems.

Expression of DNA-dependent protein kinase in the nasopharyngeal tissue during carcinogenesis

Objective： To observe the expression of DNA-dependent protein kinase （DNA-PKcs） in the nasopharyngeal tissues during carcinogenesis. Methods： Patients including 30 cases of nasopharyngitis, 42 cases of nasopharyngeal atypical hyperplasia and 34 cases of nasopharyngeal carcinoma （NPC） were chosen from Zhongshan area in which there is high incidence rate of NPC. The expression of DNA-PKcs in the nasopharyngeal tissue was examined by immunohistochemistry. Results： The expression rates of DNA-PKcs in the nasopharyngitis tissue, the nasopharyngeal precancerous lesion and the NPC were 6.7%, 64.3% and 55.9%, respectively （P〈 0.001）. Conclusion： The expression of DNA-dependent protein kinase may play an important role in nasopharyngeal tissue carcinogenesis.

Research Center of 3D Bioprinting in Shanghai Ninth People’s Hospital

The center was first established in 2013 and affiliated to the Shanghai Ninth People’s Hospital,Shanghai Jiao Tong University School of Medicine.In 2015,the center was entitled as 3D Bioprinting Clinical Transformation Collaborative Innovation Center.In 2016,the center was renamed as Medical 3D Printing Innovation Research Center of Shanghai Jiao Tong University School of Medicine.Although the center was established in 2013,the clinical application of 3D printing in Shanghai Ninth People’s Hospital can be traced back to the 1990s.As early as 30 years ago,Prof.Kerong Dai had tried to rebuild patients pelvic by manually cutting the foam boards and layering them together based on the theory of 3D printing for preoperative planning model of abnormal skeleton structures and development of personalized prosthesis.That was the first application of 3D printing in the area of medicine in China.Now,The Research Center of 3D Bioprinting in Shanghai Ninth People’s Hospital comprised of subcenters including the outpatient department of 3D printing,medical 3D printing innovation research center and Shanghai key laboratory of orthopedic implant.

Expression of mir-34c-5p and mir-150-5pin nasopharyngeal carcinoma and up-regulated expression after invasion and apoptosis of nasopharyngeal carcinoma cells

Objective MiRNAs are closely related to tumors,and we hypothesized there is specific miR expression in nasopharyngeal carcinoma(NPC).We intended to investigate the expression of mir-34c-5p and mir-150-5p in NPC and to investigate the effects of mir-34c-5p and mir-150-5p on apoptosis and invasion following up-regulated expression in HNE1 NPC cells.Methods MiR-34c-5p and miR-150-5p expression levels in 30 individual cases of NPC and nasopharyngitis were detected with gene chip and qRT-PCR techniques.miR-34c-5p and miR-150-5p were transfected into the NPC cell line HNE1 via liposomes.Their expression levels were detected with qRT-PCR,apoptosis was evaluated by flow cytometry,and invasion ability was assessed via Transwell migration assay.Results MiR-150-5p expression levels in NPC and nasopharyngitis were 0.165±0.092 and 1.062±0.280 respectively,and miR-34c-5p expression levels in NPC and nasopharyngitis were 0.417±0.220 and 1.385±0.739,respectively,which indicated miR-34c-5p and miR-150-5p were weakly expressed in NPC.Apoptosis rates in HNE1 cells transfected by miR-34c-5p and miR-150-5p were increased,by 12.7%and 7.6%,respectively,which were significantly higher compared to blank control(3.9%).The Transwell assay demonstrated that invasive HNE1 cell counts were 32.00±2.00 and 28.33±2.08,respectively,compared to 60.66±8.50 in the blank control(P<0.001).Conclusion MiR-34c-5p and miR-150-5p are lowly expressed in NPC,and their down-regulation may be associated with NPC.

High-performance formaldehyde prediction for indoor air quality assessment using time series deep learning

Indoor air pollution resulting from volatile organic compounds(VOCs),especially formaldehyde,is a significant health concern needed to predict indoor formaldehyde concentration(Cf)in green intelligent building design.This study develops a thermal and wet coupling calculation model of porous fabric to account for the migration of formaldehyde molecules in indoor air and cotton,silk,and polyester fabric with heat flux in Harbin,Beijing,Xi’an,Shanghai,Guangzhou,and Kunming,China.The time-by-time indoor dry-bulb temperature(T),relative humidity(RH),and Cf,obtained from verified simulations,were collated and used as input data for the long short-term memory(LSTM)of the deep learning model that predicts indoor multivariate time series Cf from the secondary source effects of indoor fabrics(adsorption and release of formaldehyde).The trained LSTM model can be used to predict multivariate time series Cf at other emission times and locations.The LSTM-based model also predicted Cf with mean absolute percentage error(MAPE),symmetric mean absolute percentage error(SMAPE),mean absolute error(MAE),mean square error(MSE),and root mean square error(RMSE)that fell within 10%,10%,0.5,0.5,and 0.8,respectively.In addition,the characteristics of the input dataset,model parameters,the prediction accuracy of different indoor fabrics,and the uncertainty of the data set are analyzed.The results show that the prediction accuracy of single data set input is higher than that of temperature and humidity input,and the prediction accuracy of LSTM is better than recurrent neural network(RNN).The method’s feasibility was established,and the study provides theoretical support for guiding indoor air pollution control measures and ensuring human health and safety.

Multi-modal imaging for dynamic visualization of osteogenesis and implant degradation in 3D bioprinted scaffolds

In situ monitoring of bone regeneration enables timely diagnosis and intervention by acquiring vital biological parameters.However,an existing gap exists in the availability of effective methodologies for continuous and dynamic monitoring of the bone tissue regeneration process,encompassing the concurrent visualization of bone formation and implant degradation.Here,we present an integrated scaffold designed to facilitate real-time monitoring of both bone formation and implant degradation during the repair of bone defects.Laponite(Lap),CyP-loaded mesoporous silica(CyP@MSNs)and ultrasmall superparamagnetic iron oxide nanoparticles(USPIO@SiO2)were incorporated into a bioink containing bone marrow mesenchymal stem cells(BMSCs)to fabricate functional scaffolds denoted as C@M/GLU using 3D bioprinting technology.In both in vivo and in vitro experiments,the composite scaffold has demonstrated a significant enhancement of bone regeneration through the controlled release of silicon(Si)and magnesium(Mg)ions.Employing near-infrared fluorescence(NIR-FL)imaging,the composite scaffold facilitates the monitoring of alkaline phosphate(ALP)expression,providing an accurate reflection of the scaffold’s initial osteogenic activity.Meanwhile,the degradation of scaffolds was monitored by tracking the changes in the magnetic resonance(MR)signals at various time points.These findings indicate that the designed scaffold holds potential as an in situ bone implant for combined visualization of osteogenesis and implant degradation throughout the bone repair process.

Meticulously engineered three-dimensional-printed scaffold with microarchitecture and controlled peptide release for enhanced bone regeneration

The repair of large load-bearing bone defects requires superior mechanical strength,a feat that a single hydrogel scaffold cannot achieve.The objective is to seamlessly integrate optimal microarchitecture,mechanical robustness,vascularisation,and osteoinductive biological responses to effectively address these critical load-bearing bone defects.To confront this challenge,three-dimensional(3D)printing technology was employed to prepare a polycaprolactone(PCL)-based integrated scaffold.Within the voids of 3D printed PCL scaffold,a methacrylate gelatin(GelMA)/methacrylated silk fibroin(SFMA)composite hydrogel incorporated with parathyroid hormone(PTH)peptide-loaded mesoporous silica nanoparticles(PTH@MSNs)was embedded,evolving into a porous PTH@MSNs/GelMA/SFMA/PCL(PM@GS/PCL)scaffold.The feasibility of fabricating this functional scaffold with a customised hierarchical structure was confirmed through meticulous chemical and physical characterisation.Compression testing unveiled an impressive strength of 17.81±0.83 MPa for the composite scaffold.Additionally,in vitro angiogenesis potential of PM@GS/PCL scaffold was evaluated through Transwell and tube formation assays using human umbilical vein endothelium,revealing the superior cell migration and tube network formation.The alizarin red and alkaline phosphatase staining assays using bone marrow-derived mesenchymal stem cells clearly illustrated robust osteogenic differentiation properties within this scaffold.Furthermore,the bone repair potential of the scaffold was investigated on a rat femoral defect model using micro-computed tomography and histological examination,demonstrating enhanced osteogenic and angiogenic performance.This study presents a promising strategy for fabricating a microenvironment-matched composite scaffold for bone tissue engineering,providing a potential solution for effective bone defect repair.

Effect of down-regulation of let-7c/g on triggering a double-negative feedback loop and promoting restenosis

Background:Excessive proliferation and migration of vascular smooth muscle cells(VSMCs)are the main causes of restenosis(RS)in diabetic lower extremity arterial disease(LEAD).However,the relevant pathogenic mechanisms are poorly understood.Methods:In this study,we introduced a“two-step injury protocol”rat RS model,which started with the induction of atherosclerosis(AS)and was followed by percutaneous transluminal angioplasty(PTA).Hematoxylin-eosin(HE)staining and immunohistochemistry staining were used to verify the form of RS.Two-step transfection was performed,with the first transfection of Lin28a followed by a second transfection of let-7c and let-7g,to explore the possible mechanism by which Lin28a exerted effects.5-ethynyl-2΄-deoxyuridine(EdU)and Transwell assay were performed to evaluate the ability of proliferation and migration of VSMCs.Western blotting and quantitative real-time polymerase chain reaction(qRT-PCR)were performed to detect the expression of Lin28a protein and let-7 family members.Results:Using a combination of in vitro and in vivo experiments,we discovered that let-7c,let-7g,and microRNA98(miR98)were downstream targets of Lin28a.More importantly,decreased expression of let-7c/let-7g increased Lin28a,leading to further inhibition of let-7c/let-7g.We also found an increased level of let-7d in the RS pathological condition,suggesting that it may function as a protective regulator of the Lin28a/let-7 loop by inhibiting the proliferation and migration of VSMCs.Conclusion:These findings indicated the presence of a double-negative feedback loop consisting of Lin28a and let-7c/let-7g,which may be responsible for the vicious behavior of VSMCs in RS.

Interaction between OCT1 and LPIN1 polymorphisms and response to pioglitazone-metformin tablets in patients with polycystic ovary syndrome

To the Editor:Polycystic ovary syndrome(PCOS)is a common endocrine disorder among women of reproductive age.PCOS is characterized by infrequent or absent ovulation,high androgen levels,and hyperinsulinaemia.Androgenic excess is the main pathophysiological mechanism of the disease.Metformin can lower insulin and androgen levels,increase estradiol levels,and induce ovulation.^([1])Pioglitazone can increase the sensitivity of peripheral tissues to insulin,improve insulin resistance,reduce androgen levels,restore the menstrual cycle,and promote ovulation.^([2])Despite extensive research,the molecular mechanisms that mediate the beneficial effects of metformin or pioglitazone in the treatment of PCOS are still unclear.There are also differences in individual patient responses to drugs.

高光谱成像激光雷达系统辐射定标和地物信息获取

提出一种高光谱成像激光雷达系统的光学结构设计,并对系统的光学辐射定标方法进行研究。利用单色仪对出射光的精细扫描,确定高光谱成像雷达每个探测通道的带宽和中心波长。根据高光谱成像激光雷达方程,在实验室定标过程中,不考虑大气对定标的影响,得到系统每一个通道的定标系数。系统定标过程中合成不确定度为0.87%,扩展不确定度(k=2)为1.73%。最后对超连续谱高重复频率激光器出射的脉冲能量进行监测,使该高光谱激光雷达在机载飞行过程中,依据探测器输出的回波信号强度信息,能够实时得到地物的反射光谱信息,进而实现高精度地形获取和地表超精细分类。

Three-dimensional bioprinting of multicell-laden scaffolds containing bone morphogenic protein-4 for promoting M2 macrophage polarization and accelerating bone defect repair in diabetes mellitus

Critical-sized bone defect repair in patients with diabetes mellitus remains a challenge in clinical treatment because of dysfunction of macrophage polarization and the inflammatory microenvironment in the bone defect region.Three-dimensional(3D)bioprinted scaffolds loaded with live cells and bioactive factors can improve cell viability and the inflammatory microenvironment and further accelerating bone repair.Here,we used modified bioinks comprising gelatin,gelatin methacryloyl(GelMA),and 4-arm poly(ethylene glycol)acrylate(PEG)to fabricate 3D bioprinted scaffolds containing BMSCs,RAW264.7 macrophages,and BMP-4-loaded mesoporous silica nanoparticles(MSNs).Addition of MSNs effectively improved the mechanical strength of GelMA/gelatin/PEG scaffolds.Moreover,MSNs sustainably released BMP-4 for long-term effectiveness.In 3D bioprinted scaffolds,BMP-4 promoted the polarization of RAW264.7 to M2 macrophages,which secrete anti-inflammatory factors and thereby reduce the levels of pro-inflammatory factors.BMP-4 released from MSNs and BMP-2 secreted from M2 macrophages collectively stimulated the osteogenic differentiation of BMSCs in the 3D bioprinted scaffolds.Furthermore,in calvarial critical-size defect models of diabetic rats,3D bioprinted scaffolds loaded with MSNs/BMP-4 induced M2 macrophage polarization and improved the inflammatory microenvironment.And 3D bioprinted scaffolds with MSNs/BMP-4,BMSCs,and RAW264.7 cells significantly accelerated bone repair.In conclusion,our results indicated that implanting 3D bioprinted scaffolds containing MSNs/BMP-4,BMSCs,and RAW264.7 cells in bone defects may be an effective method for improving diabetic bone repair,owing to the direct effects of BMP-4 on promoting osteogenesis of BMSCs and regulating M2 type macrophage polarization to improve the inflammatory microenvironment and secrete BMP-2.

Cartilage-targeting peptide-modified dual-drug delivery nanoplatform with NIR laser response for osteoarthritis therapy

Cartilage-targeting delivery of therapeutic agents is still an effective strategy for osteoarthritis(OA)therapy.Recently,scavenging for reactive oxygen species(ROS)and activating autophagy have been increasingly reported to treat OA effectively.In this study,we designed,for the first time,a dual-drug delivery system based on metal organic framework(MOF)-decorated mesoporous polydopamine(MPDA)which composed of rapamycin(Rap)loaded into the mesopores and bilirubin(Br)loaded onto the shell of MOF.The collagen II-targeting peptide(WYRGRL)was then conjugated on the surface of above nanocarrier to develop a cartilage-targeting dual-drug delivery nanoplatform(RB@MPMW).Our results indicated the sequential release of two agents from RB@MPMW could be achieved via near-infrared(NIR)laser irritation.Briefly,the rapid release of Br from the MOF shell exhibited excellent ROS scavenging ability and anti-apoptosis effects,however responsively reduced autophagy activity,to a certain extent.Meanwhile,following the NIR irradiation,Rap was rapidly released from MPDA core and further enhanced autophagy activation and chondrocyte protection.RB@MPMW continuously phosphorylated AMPK and further rescued mitochondrial energy metabolism of chondrocytes following IL-1βstimulation via activating SIRT1-PGC-1αsignaling pathway.Additionally,the cartilage-targeting property of peptide-modified nanocarrier could be monitored via Magnetic Resonance(MR)and IVIS imaging.More significantly,RB@MPMW effectively delayed cartilage degeneration in ACLT rat model.Overall,our findings indicated that the as-prepared dual-drug delivery nanoplatform exerted potent anti-inflammation and anti-apoptotic effects,rescued energy metabolism of chondrocytes in vitro and prevented cartilage degeneration in vivo,which thereby showed positive performance for OA therapy.

Preparation of a tantalum-based MoSi_(2)–Mo coating resistant to ultra-high-temperature thermal shock by a new two-step process

To develop an ultra-high-temperature resistant coating for a reusable thermal protection system,the preparation of a tantalum-based MoSi_(2)-Mo coating by a new two-step process of multi-arc ion plating and halide activated pack cementation is presented.The coating has a dense structure and is well compatible with the tantalum substrate,which can be thermally shocked from room temperature to 1750℃ for 360 cycles without failure.The mechanism of the coating’s excellent resistance to high-temperature thermal shocks is that a strong-binding gradient interface and a dense SiO_(2) oxide scale with good oxygen resistance are formed by the high-temperature self-diffusion of Si.

Tumor cell membrane-camouflaged responsive nanoparticles enable MRI-guided immuno-chemodynamic therapy of orthotopic osteosarcoma

Osteosarcoma is a refractory bone disease in young people that needs the updating and development of effective treatment.Although nanotechnology is widely applied in cancer therapy,poor targeting and inadequate effi-ciency hinder its development.In this study,we prepared alendronate(ALD)/K7M2 cell membranes-coated hollow manganese dioxide(HMnO_(2))nanoparticles as a nanocarrier to load Ginsenoside Rh2(Rh2)for Mag-netic Resonance imaging(MRI)-guided immuno-chemodynamic combination osteosarcoma therapy.Subse-quently,the ALD and K7M2 cell membranes were successively modified on the surface of HMnO_(2) and loaded with Rh2.The tumor microenvironment(TME)-activated Rh2@HMnO_(2)-AM nanoparticles have good bone tumor-targeting and tumor-homing capabilities,excellent GSH-sensitive drug release profile and MRI capability,and attractive immuno-chemodynamic combined therapeutic efficiency.The Rh2@HMnO_(2)-AM nanoparticles can effectively trigger immunogenic cell death(ICD),activate CD4^(+)/CD8^(+)T cells in vivo,and upregulate BAX,BCL-2 and Caspase-3 in cellular level.Further results revealed that Rh2@HMnO_(2)-AM enhanced the secretion of IL-6,IFN-γand TNF-αin serum and inhibited the generation of FOXP3^(+)T cells(Tregs)in tumors.Moreover,the Rh2@HMnO_(2)-AM treatment significant restricted tumor growth in-situ tumor-bearing mice.Therefore,Rh2@HMnO_(2)-AM may serve as an effective and bio-friendly nanoparticle platform combined with immuno-therapy and chemodynamic therapy to provide a novel approach to osteosarcoma therapy.