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| 1 | Exosomal PD-L1 induces osteogenic differentiation and promotes fracture healing by acting as an immunosuppressant显示文摘A moderate inflammatory response at the early stages of fracture healing is necessary for callus formation.Over-active and continuous inflammation,however,impairs fracture healing and leads to excessive tissue damage.Adequate fracture healing could be promoted through suppression of local over-active immune cells in the fracture site.In the present study,we achieved an enriched concentration of PD-L1 from exosomes(Exos)of a genetically engineered Human Umbilical Vein Endothelial Cell(HUVECs),and demonstrated that exosomes overexpressing PD-L1 specifically bind to PD-1 on the T cell surface,suppressing the activation of T cells.Furthermore,exosomal PD-L1 induced Mesenchymal Stem Cells(MSCs)towards osteogenic differentiation when pre-cultured with T cells.Moreover,embedding of Exos into an injectable hydrogel allowed Exos delivery to the surrounding microenvironment in a time-released manner.Additionally,exosomal PD-L1,embedded in a hydrogel,markedly promoted callus formation and fracture healing in a murine model at the early over-active inflammation phase.Importantly,our results suggested that activation of T cells in the peripheral lymphatic tissues was inhibited after local administration of PD-L1-enriched Exos to the fracture sites,while T cells in distant immune organs such as the spleen were not affected.In summary,this study provides the first example of using PD-L1-enriched Exos for bone fracture repair,and highlights the potential of Hydrogel@Exos systems for bone fracture therapy through immune inhibitory effects. | Ze Lin Yuan Xiong Weilin Meng Yiqiang Hu Lili Chen Lang Chen Hang Xue Adriana CPanayi Wu Zhou Yun Sun Faqi Cao Guodong Liu Liangcong Hu Chenchen Yan Xudong Xie Chuanchuan Lin Kaiyong Cai Qian Feng Bobin Mi Guohui Liu | 2022 | Bioactive Materials2022，7，7： | 4 |
| 2 | Advances and perspective on animal models and hydrogel biomaterials for diabetic wound healing显示文摘Diabetic wounds are a common complication in diabetes patients.Due to peripheral nerve damage and vascular dysfunction,diabetic wounds are prone to progress to local ulcers,wound gangrene and even to require amputation,bringing huge psychological and economic burdens to patients.However,the current treatment methods for diabetic wounds mainly include wound accessories,negative pressure drainage,skin grafting and surgery;there is still no ideal treatment to promote diabetic wound healing at present.Appropriate animal models can simulate the physiological mechanism of diabetic wounds,providing a basis for translational research in treating diabetic wound healing.Although there are no animal models that can fully mimic the pathophysiological mechanisms of diabetic wounds in humans,it is vital to explore animal simulation models used in basic research and preclinical studies of diabetic wounds.In addition,hydrogel materials are regarded as a promising treatment for diabetic wounds because of their good antimicrobial activity,biocompatibility,biodegradation and appropriate mechanical properties.Herein,we review and discuss the different animal models used to investigate the pathological mechanisms of diabetic wounds.We further discuss the promising future application of hydrogel biomaterials in diabetic wound healing. | Yiqiang Hu Yuan Xiong Ranyang Tao Hang Xue Lang Chen Ze Lin Adriana C.Panayi Bobin Mi Guohui Liu | 2022 | Biomaterials Translational2022，3，3： | 2 |
| 3 | Abdominal Obesity and Its Attribution to All-cause Mortality in the General Population with 14 Years Follow-up:Findings from Shanxi Cohort in China显示文摘Objective This study aimed to assess the association of waist circumference(WC)with all-cause mortality among Chinese adults.Methods The baseline data were from Shanxi Province of 2002 China Nutrition and Health Survey.The death investigation and follow-up visit were conducted from December 2015 to March 2016.The visits covered up to 5,360 of 7,007 participants,representing a response rate of 76.5%.The Cox regression model and floating absolute risk were used to estimate hazard ratio and 95%floating CI of death by gender and age groups(≥60 and<60 years old).Sensitivity analysis was performed by excluding current smokers;participants with stroke,hypertension,and diabetes;participants who accidentally died;and participants who died during the first 2 years of follow-up.Results This study followed 67,129 person-years for 12.5 years on average,including 615 deaths.The mortality density was 916 per 100,000 person-years.Low WC was associated with all-cause mortality among men.Multifactor-adjusted hazard ratios(HR)were 1.60(1.35–1.90)for WC<75.0 cm and 1.40(1.11–1.76)for WC ranging from 75.0 cm to 79.9 cm.Low WC(<70.0 cm and 70.0–74.9 cm)and high WC(≥95.0 cm)groups had a high risk of mortality among women.The adjusted HRs of death were 1.43(1.11–1.83),1.39(1.05–1.84),and 1.91(1.13–3.22).Conclusion WC was an important predictor of death independent of body mass index(BMI).WC should be used as a simple rapid screening and predictive indicator of the risk of death. | ZHAI Yi REN Ze Ping ZHANG Mei ZHANG Jian JIANG Yong MI Sheng Quan WANG Zhuo Qun ZHAO Yan Fang SONG Peng Kun YIN Zhao Xue ZHAO Wen Hua | 2020 | Biomedical and Environmental Sciences2020，33，4： | 2 |
| 4 | Extracellular Polysaccharide from Rhizopus nigricans Inhibits Hepatocellular Carcinoma via miR-494-3p/TRIM36 Axis and Cyclin E Ubiquitination显示文摘Background and Aims:This study was designed to uncov-er the mechanism for extracellular polysaccharide(EPS1-1)-mediated effects on hepatocellular carcinoma(HCC)devel-opment.Methods:HCC cells were treated with EPS1-1,miR-494-3p mimic,sh-TRIM36,and pcDNA3.1-TRIM36.The levels of miR-494-3p and TRIM36 were measured in nor-mal hepatocytes,THLE-2,and HepG2 and HuH7HCC cell lines,along with the protein expression of cyclin D/E and p21.The proliferation,cell cycle,and apoptosis of HCC cells were assayed.The interactions between miR-494-3p and TRIM36,and between TRIM36 and cyclin E were assessed.Finally,the expression and localization of TRIM36 and cyclin E were monitored,and tumor apoptosis was detected,in tumor xenograft model.Results:EPS1-1 suppressed HCC cell proliferation and cyclin D/E expression and promoted apoptosis and p21 expression.miR-494-3p was upregulated and TRIM36 was downregulated in HCC cells.Transfection with miR-494-3p mimic or sh-TRIM36 facilitated HCC cell proliferation and the expression of cyclin D/E protein but they inhibited apoptosis and p21 expression in the pres-ence of EPS1-1.Overexpression of TRIM36 further con-solidated EPS1-1-mediated inhibition of HCC proliferation,cyclin D/E,and the promotion of apoptosis and p21 expres-sion.Those effects were reversed by miR-494-3p overex-pression.TRIM36 was a target gene of miR-494-3p,and TRIM36 induced cyclin E ubiquitination.EPS1-1 suppressed cyclin E expression,promoted TRIM36 expression and tu-mor apoptosis,all of which were abrogated by increasing the expression of miR-494-3p in vivo.Conclusions:EPS1-1 protected against HCC by limiting its proliferation and sur-vival through the miR-494-3p/TRIM36 axis and by inducing cyclin E ubiquitination. | Haixiong Yan XiaoQian Ma Ze Mi Zhenhu He Pengfei Rong | 2022 | Journal of Clinical and Translational Hepatology2022，10，4： | 2 |
| 5 | Salmonella-mediated blood-brain barrier penetration,tumor homing and tumor microenvironment regulation for enhanced chemo/bacterial glioma therapy显示文摘Chemotherapy is an important adjuvant treatment of glioma,while the efficacy is far from satisfactory,due not only to the biological barriers of blood-brain barrier(BBB)and blood-tumor barrier(BTB)but also to the intrinsic resistance of glioma cells via multiple survival mechanisms such as upregulation of P-glycoprotein(P-gp).To address these limitations,we report a bacteria-based drug delivery strategy for BBB/BTB transportation,glioma targeting,and chemo-sensitization.Bacteria selectively colonized into hypoxic tumor region and modulated tumor microenvironment,including macrophages repolarization and neutrophils infiltration.Specifically,tumor migration of neutrophils was employed as hitchhiking delivery of doxorubicin(DOX)-loaded bacterial outer membrane vesicles(OMVs/DOX).By virtue of the surface pathogen-associated molecular patterns derived from native bacteria,OMVs/DOX could be selectively recognized by neutrophils,thus facilitating glioma targeted delivery of drug with significantly enhanced tumor accumulation by 18-fold as compared to the classical passive targeting effect.Moreover,the P-gp expression on tumor cells was silenced by bacteria typeⅢsecretion effector to sensitize the efficacy of DOX,resulting in complete tumor eradication with 100%survival of all treated mice.In addition,the colonized bacteria were finally cleared by anti-bacterial activity of DOX to minimize the potential infection risk,and cardiotoxicity of DOX was also avoided,achieving excellent compatibility.This work provides an efficient trans-BBB/BTB drug delivery strategy via cell hitchhiking for enhanced glioma therapy. | Ze Mi Qing Yao Yan Qi Jinhai Zheng Jiahao Liu Zhenguo Liu Hongpei Tan Xiaoqian Ma Wenhu Zhou Pengfei Rong | 2023 | Acta Pharmaceutica Sinica B2023，13，2： | 1 |
| 6 | Role of unfolded protein response in lipogenesis显示文摘The signal transduction network in regulating lipid metabolism is a hot topic of biomedical research. Recent research endeavors reveal that intracellular stress signaling from a cellular organelle called endoplasmic reticulum (ER) is critically involved in lipid homeostasis and the development of metabolic disease. The ER is a site where newly-synthesized proteins are folded and assembled into their three-dimensional structures, modified and transported to their precise cellular destinations. A wide range of biochemical, physiological and pathological stimuli can interrupt the protein folding process in the ER and cause accumulation of unfolded or misfolded proteins in the ER lumen, a condition referred to as ER stress. To cope with this stress condition, the ER has evolved highly-specifi c signaling pathways collectively termed Unfolded Protein Response (UPR) or ER stress response. The UPR regulates transcriptionaland translational programs, affecting broad aspects of cellular metabolism and cell fate. Lipogenesis, the metabolic process of de novo lipid biosynthesis, occurs primarily in the liver where metabolic signals regulate expression of key enzymes in glycolytic and lipogenic pathways. Recent studies suggest that the UPR plays crucial roles in modulating lipogenesis under metabolic conditions. Here we address some of recent representative evidence regarding the role of the UPR in lipogenesis. | Ze Zheng, Chunbin Zhang, Kezhong Zhang, Center for Molecular Medicine and Genetics, Wayne State University School of Medicine, Detroit, MI 48201, United States , Department of Immunology and Mic robiology, Wayne State University School of Medicine, Detroit, MI 48201, United States | 2010 | World Journal of Hepatology2010，2，6： | 1 |
| 7 | Enhanced tissue regeneration through immunomodulation of angiogenesis and osteogenesis with a multifaceted nanohybrid modified bioactive scaffold显示文摘Major traumatic tissue defects are common clinical problems often complicated by infection and local vascular dysfunction, processes which hinder the healing process. Although local application of growth factors or stem cells through various tissue engineering techniques are promising methods for the repair of tissue defects, limitations in their clinical application exist. Herein, we synthesized multifaceted nanohybrids composed of Quaternized chitosan (QCS), Graphene oxide (GO), and Polydopamine (PDA;QCS-GO-PDA). Covalent grafting of QCS and GO at a mass ratio of 5:1 (5QCS-1GO) displayed excellent biocompatibility and enhanced osteogenic ability, while addition of PDA (5QCS-1GO-PDA) reduced the level of reactive oxygen species (ROS). 5QCS-1GO-PDA was able to achieve wound tissue regeneration by reducing the inflammatory response and enhancing angiogenesis. Furthermore, Polylactic acid/hydroxyapatite (PLA/HA) composite scaffolds were printed using Selective Laser Sintering (SLS) and the hybrid nanomaterial (5QCS-1GO-PDA) was used to coat the PLA/HA scaffold (5QCS-1GO-PDA@PLA/HA) to be used for rapid bone regeneration. 5QCS-1GO-PDA not only improved angiogenesis and osteogenic differentiation, but also induced M2-type polarization of macrophages and promoted bone regeneration via the BMP2/BMPRs/Smads/Runx2 signaling pathway. The bidirectional enhanced healing ability of the multifaceted nanohybrids 5QCS-1GO-PDA provides a promising method of effectively treating tissue defects. | Hang Xue Zhenhe Zhang Ze Lin Jin Su Adriana CPanayi Yuan Xiong Liangcong Hu Yiqiang Hu Lang Chen Chenchen Yan Xudong Xie Yusheng Shi Wu Zhou Bobin Mi Guohui Liu | 2022 | Bioactive Materials2022，7，12： | 1 |
| 8 | Hydrothermal synthesis and thermoelectric properties of nanostructured Bi 0.5 Sb 1.5 Te 3 compounds显示文摘 | Yanhua Zhang Guiying Xu Jianli Mi Fei Han Ze Wang Changchun Ge | 2011 | Materials Research Bulletin2011，，5： | 1 |
| 9 | Association between Baseline SBP/DBP and All-Cause Mortality in Residents of Shanxi,China:A Population-based Cohort Study from 2002 to 2015显示文摘Objective To investigate the association between blood pressure and all-cause mortality in Shanxi,China.Methods The‘2002 China Nutrition and Health Survey’baseline data in Shanxi province was used.A retrospective investigation was performed in 2015.The effects of SBP and DBP on the all-cause mortality were analyzed using the Cox regression model.The hazard ratio(HR)and 95%confidence interval(CI)were estimated by the sex and age groups.Results The follow-up rate was 76.52%over 13 years,while the cumulative mortality rate for all participants was 917.12/100,000 person-years.The mortality rose with an increasing SBP(χ_(trend)^(2)=270.537,P<0.001)or DBP level(χ_(trend)^(2)=57.240,P<0.001).After adjustment for the confounding factors,a significant association between mortality and high SBP(≥160 mm Hg)and high DBP(≥100 mm Hg),with adjusted HR ranging from 1.405-to 2.179-fold for SBP and 1.550-to 2.854-fold for DBP,was noted.Significant HRs for most DBP subgroups were found in>60-year-old participants.Males with DBP≥100 mm Hg had a significantly higher mortality,with an HR(95%CI)of 2.715(1.377–5.351).Conclusion Adults with SBP>160 mm Hg and DBP>100 mm Hg had a higher mortality risk.Sex and age difference was noted in both DBP and mortality risk. | WANG Zhuo Qun ZHAI Yi LI Man YANG Xiu Feng ZHANG Jian REN Ze Ping ZHANG Mei SONG Peng Kun ZHAO Yan Fang MI Sheng Quan ZHANG Lu YANG Mao Xiang ZHAO Wen Hua | 2021 | Biomedical and Environmental Sciences2021，34，1： | 0 |
| 10 | Glucose-responsive,antioxidative HA-PBA-FA/EN106 hydrogel enhanced diabetic wound healing through modulation of FEM1b-FNIP1 axis and promoting angiogenesis显示文摘The diabetic wounds remain to be unsettled clinically,with chronic wounds characterized by drug-resistant bacterial infections,compromised angiogenesis and oxidative damage to the microenvironment.To ameliorate oxidative stress and applying antioxidant treatment in the wound site,we explore the function of folliculininteracting protein 1(FNIP1),a mitochondrial gatekeeper protein works to alter mitochondrial morphology,reduce oxidative phosphorylation and protect cells from unwarranted ROS accumulation.And our in vitro experiments showed the effects of FNIP1 in ameliorating oxidative stress and rescued impaired angiogenesis of HUVECs in high glucose environment.To realize the drug delivery and local regulation of FNIP1 in diabetic wound sites,a novel designed glucose-responsive HA-PBA-FA/EN106 hydrogel is introduced for improving diabetic wound healing.Due to the dynamic phenylboronate ester structure with a phenylboronic acid group between hyaluronic acid(HA)and phenylboronic acid(PBA),the hydrogel is able to realize a glucose-responsive release of drugs.Fulvic acid(FA)is added in the hydrogel,which not only severs as crosslinking agent but also provides antibacterial and anti-inflammatory abilities.Moreover,the release of FEM1b-FNIP1 axis inhibitor EN106 ameliorated oxidative stress and stimulated angiogenesis through FEM1b-FNIP1 axis regulation.These in vivo and in vitro results demonstrated that accelerated diabetic wounds repair with the use of the HA-PBA-FA/EN106 hydrogel,which may provide a promising strategy for chronic diabetic wound repair. | Wenqian Zhang Kangkang Zha Yuan Xiong Weixian Hu Lang Chen Ze Lin Chenyan Yu Wu Zhou Faqi Cao Hankun Hu Bobin Mi Guohui Liu | 2023 | Bioactive Materials2023，，12： | 0 |
| 11 | Assessing the severity of cotton Verticillium wilt disease from in situ canopy images and spectra using convolutional neural networks显示文摘Verticillium wilt(VW)is a common soilborne disease of cotton.It occurs mainly in the seedling and bollopening stages and severely impairs the yield and quality of the fiber.Rapid and accurate identification and evaluation of VW severity(VWS)forms the basis of field cotton VW control,which has great significance to cotton production.Cotton VWS values are conventionally measured using in-field observations and laboratory test diagnoses,which require abundant time and professional expertise.Remote and proximal sensing using imagery and spectrometry have great potential for this purpose.In this study,we performed in situ investigations at three experimental sites in 2019 and 2021 and collected VWS values,in situ images,and spectra of 361 cotton canopies.To estimate cotton VWS values at the canopy scale,we developed two deep learning approaches that use in situ images and spectra,respectively.For the imagery-based method,given the high complexity of the in situ environment,we first transformed the task of healthy and diseased leaf recognition to the task of cotton field scene classification and then built a cotton field scenes(CFS)dataset with over 1000 images for each scene-unit type.We performed pretrained convolutional neural networks(CNNs)training and validation using the CFS dataset and then used the networks after training to classify scene units for each canopy.The results showed that the Dark Net-19 model achieved satisfactory performance in CFS classification and VWS values estimation(R^(2)=0.91,root-mean-square error(RMSE)=6.35%).For the spectroscopy-based method,we first designed a one-dimensional regression network(1D CNN)with four convolutional layers.After dimensionality reduction by sensitive-band selection and principal component analysis,we fitted the 1D CNN with varying numbers of principal components(PCs).The 1D CNN model with the top 20 PCs performed best(R^(2)=0.93,RMSE=5.77%).These deep learning-driven approaches offer the potential of assessing crop disease severity from spatial and spectral perspectives. | Xiaoyan Kang Changping Huang Lifu Zhang Mi Yang Ze Zhang Xin Lyu | 2023 | The Crop Journal2023，11，3： | 0 |
| 12 | Immunomodulatory Nanosystems:Advanced Delivery Tools for Treating Chronic Wounds显示文摘The increasingly aging society led to a rise in the prevalence of chronic wounds(CWs),posing a significant burden to public health on a global scale.One of the key features of CWs is the presence of a maladjusted immune microenvironment characterized by persistent and excessive(hyper)inflammation.A variety of immunomodulatory therapies have been proposed to address this condition.Yet,to date,current delivery systems for immunomodulatory therapy remain inadequate and lack efficiency.This highlights the need for new therapeutic delivery systems,such as nanosystems,to manage the pathological inflammatory imbalance and,ultimately,improve the treatment outcomes of CWs.While a plethora of immunomodulatory nanosystems modifying the immune microenvironment of CWs have shown promising therapeutic effects,the literature on the intersection of immunomodulatory nanosystems and CWs remains relatively scarce.Therefore,this review aims to provide a comprehensive overview of the pathogenesis and characteristics of the immune microenvironment in CWs,discuss important advancements in our understanding of CW healing,and delineate the versatility and applicability of immunomodulatory nanosystems-based therapies in the therapeutic management of CWs.In addition,we herein also shed light on the main challenges and future perspectives in this rapidly evolving research field. | Xiangyu Chu Yuan Xiong Samuel Knoedler Li Lu Adriana CPanayi Michael Alfertshofe Dongsheng Jiang Yuval Rinkevich Ze Lin Zhiming Zhao Guandong Daia Bobin Mi Guohui Liu | 2023 | Research2023，，4： | 0 |
| 13 | Bone-targeting engineered small extracellular vesicles carrying anti-miR-6359-CGGGAGC prevent valproic acid-induced bone loss显示文摘The clinical role and underlying mechanisms of valproic acid(VPA)on bone homeostasis remain controversial.Herein,we confirmed that VPA treatment was associated with decreased bone mass and bone mineral density(BMD)in both patients and mice.This effect was attributed to VPA-induced elevation in osteoclast formation and activity.Through RNA-sequencing,we observed a significant rise in precursor miR-6359 expression in VPA-treated osteoclast precursors in vitro,and further,a marked upregulation of mature miR-6359(miR-6359)in vivo was demonstrated using quantitative real-time PCR(qRT-PCR)and miR-6359 fluorescent in situ hybridization(miR-6359-FISH).Specifically,the miR-6359 was predominantly increased in osteoclast precursors and macrophages but not in neutrophils,T lymphocytes,monocytes and bone marrow-derived mesenchymal stem cells(BMSCs)following VPA stimulation,which influenced osteoclast differentiation and bone-resorptive activity.Additionally,VPA-induced miR-6359 enrichment in osteoclast precursors enhanced reactive oxygen species(ROS)production by silencing the SIRT3 protein expression,followed by activation of the MAPK signaling pathway,which enhanced osteoclast formation and activity,thereby accelerating bone loss.Currently,there are no medications that can effectively treat VPA-induced bone loss.Therefore,we constructed engineered small extracellular vesicles(E-sEVs)targeting osteoclast precursors in bone and naturally carrying anti-miR-6359 by introducing of EXOmotif(CGGGAGC)in the 3’-end of the anti-miR-6359 sequence.We confirmed that the E-sEVs exhibited decent bone/osteoclast precursor targeting and exerted protective therapeutic effects on VPA-induced bone loss,but not on ovariectomy(OVX)and glucocorticoid-induced osteoporotic models,deepening our understanding of the underlying mechanism and treatment strategies for VPA-induced bone loss. | Xudong Xie Peng Cheng Liangcong Hu Wu Zhou Detai Zhang Samuel Knoedler Guodong Liu Yuan Xiong Hang Xue Yiqiang Hu Barbara Kern Doha Obed Adriana CPanayi Lang Chen Chenchen Yan Ze Lin Guandong Dai Bobin Mi Yingze Zhang Guohui Liu | 2024 | Signal Transduction and Targeted Therapy2024，9，2： | 0 |
| 14 | Role of the immune microenvironment in bone,cartilage,and soft tissue regeneration:from mechanism to therapeuticopportunity显示文摘Bone,cartilage,and soft tissue regeneration is a complex spatiotemporal process recruiting a variety of cell types,whose activity and interplay must be precisely mediated for effective healing post-injury.Although extensive strides have been made in the understanding of the immune microenvironment processes governing bone,cartilage,and soft tissue regeneration,effective clinical translation of these mechanisms remains a challenge.Regulation of the immune microenvironment is increasingly becoming a favorable target for bone,cartilage,and soft tissue regeneration;therefore,an in-depth understanding of the communication between immune cells and functional tissue cells would be valuable.Herein,we review the regulatory role of the immune microenvironment in the promotion and maintenance of stem cell states in the context of bone,cartilage,and soft tissue repair and regeneration.We discuss the roles of various immune cell subsets in bone,cartilage,and soft tissue repair and regeneration processes and introduce novel strategies,for example,biomaterial-targeting of immune cell activity,aimed at regulating healing.Understanding the mechanisms of the crosstalk between the immune microenvironment and regeneration pathways may shed light on new therapeutic opportunities for enhancing bone,cartilage,and soft tissue regeneration through regulation of the immune microenvironment. | Yuan Xiong Bo‑Bin Mi Ze Lin Yi‑Qiang Hu Le Yu Kang‑Kang Zha Adriana CPanayi Tao Yu Lang Chen Zhen‑Ping Liu Anish Patel Qian Feng Shuan‑Hu Zhou Guo‑Hui Liu | 2023 | Military Medical Research2023，10，4： | 0 |
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