Anticipated cancer burden of low individual fruit and vegetable consumption under climate change: A modelling study in China.

BACKGROUND: Dietary patterns with a high intake of fruits and vegetables (FV) are associated with a reduced risk of various cancers. It is not yet clear where and to what extent a decline in crop productivity caused by climate change may modify the distribution of related cancer burdens through reducing FV consumption in China. To design policies and interventions aimed at improving FV intake, regional monitoring is required on how consumption-changing factors might impact the associated cancer burdens by socio-demographic subpopulations. METHODS: A microsimulation study was conducted from a societal perspective to project the effects of cancers associated with inadequate FV intake attributable to climate change. We linked the International Model for Policy Analysis of Agricultural Commodities and Trade to a health modelling framework for obesity, gastric cancer, lung cancer, and oesophageal cancer in a close-to-reality synthetic population. RESULTS: In the presence of climate constantly change, the relative reduction in FV consumption would induce an additional 9.73 million disability-adjusted life years (DALYs) nationally over the period 2010-2050 ([CrI]: 7.83-12.13). The climate change-induced cancer burden is projected to disproportionately affect socio-demographic index regions from 0.65 to 5.06 million DALYs. CONCLUSIONS: Effects of climate change on FV consumption are anticipated to exacerbate intra-regional inequalities in the associated cancer burdens of China by 2050. By quantitatively analysing the impact of such dietary changes on regional health in light of climate change, our research can inform the design of public health interventions for heterogeneous populations, as health impact assessments based solely on the population as a whole cannot reflect significant differences across subpopulations.

Mitochondria-targeting graphene oxide nanocomposites for fluorescence imaging-guided synergistic phototherapy of drug-resistant osteosarcoma.

BACKGROUND: Osteosarcoma (OS) is the most common primary malignant bone tumor occurring in children and young adults. Drug-resistant osteosarcoma often results in chemotherapy failure. Therefore, new treatments aimed at novel therapeutic targets are urgently needed for the treatment of drug-resistant osteosarcoma. Mitochondria-targeted phototherapy, i.e., synergistic photodynamic/photothermal therapy, has emerged as a highly promising strategy for treating drug-resistant tumors. This study proposed a new nano-drug delivery system based on near-infrared imaging and multifunctional graphene, which can target mitochondria and show synergistic phototherapy, with preferential accumulation in tumors. METHODS AND RESULTS: Based on our previous study, (4-carboxybutyl) triphenyl phosphonium bromide (TPP), a mitochondria-targeting ligand, was conjugated to indocyanine green (ICG)-loaded, polyethylenimine-modified PEGylated nanographene oxide sheets (TPP-PPG@ICG) to promote mitochondrial accumulation after cellular internalization. Thereafter, exposure to a single dose of near-infrared irradiation enabled synergistic photodynamic and photothermal therapy, which simultaneously inhibited adenosine triphosphate synthesis and mitochondrial function. Induction of intrinsic apoptosis assisted in surmounting drug resistance and caused tumor cell death. After fluorescence imaging-guided synergistic phototherapy, the mitochondria-targeting, multifunctional graphene-based, drug-delivery system showed highly selective anticancer efficiency in vitro and in vivo, resulting in marked inhibition of tumor progression without noticeable toxicity in mice bearing doxorubicin-resistant MG63 tumor cells. CONCLUSION: The mitochondria-targeting TPP-PPG@ICG nanocomposite constitutes a new class of nanomedicine for fluorescence imaging-guided synergistic phototherapy and shows promise for treating drug-resistant osteosarcoma.

Design and application of terahertz metamaterial sensor based on DSRRs in clinical quantitative detection of carcinoembryonic antigen.

The terahertz (THz) metamaterial biosensor has great potential for label-free and rapid specificity testing. Here, we designed two highly sensitive structures to detect the carcinoembryonic antigen (CEA) of the cancer biomarker in early stages. There was about 29 GHz (500 ng/ml) resonance shift for CEA with an insert grate metamaterial, which was consistent with simulation results. Moreover, the concentration of CEA was gained through the relationship between the cancer marker concentration and frequency shift (Δƒ). Our design and detection methods may provide a potential route for the early warning stages of cancer.

Access to chiral α-substituted-ß-hydroxy arylphosphonates enabled by biocatalytic dynamic reductive kinetic resolution.

Ketoreductase (KRED)-catalyzed dynamic reductive kinetic resolution (DYRKR) of α-substituted-ß-keto arylphosphonates was developed as a generic and stereoselective approach to synthesize chiral α-substituted-ß-hydroxy arylphosphonates, with moderate-to-excellent isolated yield (up to 96%), good-to-excellent diastereoselectivity (up to >99 : <1 dr), and excellent enantioselectivity (up to >99% ee) being achieved.

Klotho deficiency aggravates diabetes-induced podocyte injury due to DNA damage caused by mitochondrial dysfunction.

Diabetic nephropathy (DN) is a progressive disease, the main pathogeny of which is podocyte injury inducing glomerular filtration barrier and proteinuria. The occurrence and development of DN could be partly attributed to the reactive oxygen species (ROS) generated by mitochondria. However, research on how mitochondrial dysfunction (MtD) ultimately causes DNA damage is poor. Here, we investigated the influence of Klotho deficiency on high glucose (HG)-induced DNA damage in vivo and in vitro. First, we found that the absence of Klotho aggravated diabetic phenotypes indicated by podocyte injury accompanied by elevated urea albumin creatinine ratio (UACR), creatinine and urea nitrogen. Then, we further confirmed that Klotho deficiency could significantly aggravate DNA damage by increasing 8-OHdG and reducing OGG1. Finally, we demonstrated Klotho deficiency may promote MtD to promote 8-OHdG-induced podocyte injury. Therefore, we came to a conclusion that Klotho deficiency may promote diabetes-induced podocytic MtD and aggravate 8-OHdG-induced DNA damage by affecting OOG1.

Ghrelin accelerates wound healing in combined radiation and wound injury in mice.

Impaired wound healing caused by radiation happens frequently in clinical practice, and the exact mechanisms remain partly unclear. Various countermeasures have been taken to tackle with this issue. Ghrelin was considered as a potent endogenous growth hormone-releasing peptide, and its role in enhancing wound repair and regeneration was firstly investigated in whole-body irradiated (γ-ray) mice in this study. Collagen deposition and neovascularization were mostly discussed. The results demonstrated that ghrelin administration promoted cutaneous wound healing in irradiated mice, followed with reduced average wound closure time, increased spleen index (SI) and improved haematopoiesis. After isolation and analysis of granulation tissues in combined radiation and wound injury (CRWI) mice treated with and without ghrelin, a phenomenon of increased DNA, hexosamine, nitrate and nitrite synthesis, elevated collagen content and enhanced neovascularization was observed after ghrelin treatment. Western blotting indicated that ghrelin also increased the expression of vascular endothelial growth factor (VEGF) and transforming growth factor-ß (TGF-ß), both responsible for wound healing. However, previous administration of growth hormone secretagogue receptor 1a (GHS-R1a) blocker blunted these therapeutic effects of ghrelin on CRWI mice. Our results identify ghrelin as a novel peptide that could be used for radiation-induced impaired wound healing.

Isolation of human lymphatic malformation endothelial cells, their in vitro characterization and in vivo survival in a mouse xenograft model.

Human lymphatic vascular malformations (LMs), also known as cystic hygromas or lymphangioma, consist of multiple lymphatic endothelial cell-lined lymph-containing cysts. No animal model of this disease exists. To develop a mouse xenograft model of human LM, CD34(Neg)CD31(Pos) LM lymphatic endothelial cells (LM-LEC) were isolated from surgical specimens and compared to foreskin CD34(Neg)CD31(Pos) lymphatic endothelial cells (LECs). Cells were implanted into a mouse tissue engineering model for 1, 2 and 4 weeks. In vitro LM-LECs showed increased proliferation and survival under starvation conditions (P < 0.0005 at 48 h, two-way ANOVA), increased migration (P < 0.001, two-way ANOVA) and formed fewer (P = 0.029, independent samples t test), shorter tubes (P = 0.029, independent samples t test) than foreskin LECs. In vivo LM-LECs implanted into a Matrigel™-containing mouse chamber model assembled to develop vessels with dilated cystic lumens lined with flat endothelium, morphology similar to that of clinical LMs. Human foreskin LECs failed to survive implantation. In LM-LEC implanted chambers the percent volume of podoplanin(Pos) vessels was 1.18 ± 2.24 % at 1 week, 6.34 ± 2.68 % at 2 weeks and increasing to 7.67 ± 3.60 % at 4 weeks. In conclusion, the significantly increased proliferation, migration, resistance to apoptosis and decreased tubulogenesis of LM-LECs observed in vitro is likely to account for their survival and assembly into stable LM-like structures when implanted into a mouse vascularised chamber model. This in vivo xenograft model will provide the basis of future studies of LM biology and testing of potential pharmacological interventions for patients with lymphatic malformations.

Efficiency enhancement of homoepitaxial InGaN/GaN light-emitting diodes on free-standing GaN substrate with double embedded SiO2 photonic crystals.

Homoepitaxially grown InGaN/GaN light emitting diodes (LEDs) with SiO2 nanodisks embedded in n-GaN and p-GaN as photonic crystal (PhC) structures by nanospherical-lens photolithography are presented and investigated. The introduction of SiO2 nanodisks doesn't produce the new dislocations and doesn't also result in the electrical deterioration of PhC LEDs. The light output power of homoepitaxial LEDs with embedded PhC and double PhC at 350 mA current is increased by 29.9% and 47.2%, respectively, compared to that without PhC. The corresponding light radiation patterns in PhC LEDs on GaN substrate show a narrow beam shape due to strong guided light extraction, with a view angle reduction of about 30°. The PhC LEDs are also analyzed in detail by finite-difference time-domain simulation (FDTD) to further reveal the emission characteristics.

Efficiency improvement by polarization-reversed electron blocking structure in GaN-based Light-emitting diodes.

Polarization-reversed electron-blocking structure, which had negative polarization charges localized at the interface between the last quantum barrier (LQB) and electron-blocking layer (EBL), was demonstrated to remarkably improve the light-emitting efficiency of GaN-based blue light-emitting diodes (LEDs) numerically and experimentally. The improvement was attributed to the enhanced electron-blocking effectiveness by the elevated conduction band nearby the LQB/EBL interface. Nevertheless, the efficiency droop was not mitigated because the decrease of electron-leakage was accompanied by the increase of Auger recombination.

Surface plasmon-enhanced nanoporous GaN-based green light-emitting diodes with Al2O3 passivation layer.

A surface plasmon (SP)-enhanced nanoporous GaN-based green LED based on top-down processing technology has been successfully fabricated. This SP-enhanced LED consists of nanopores passing through the multiple quantum wells (MQWs) region, with Ag nanorod array filled in the nanopores for SP-MQWs coupling and thin Al(2)O(3) passivation layer for electrical protection. Compared with nanoporous LED without Ag nanorods, the electroluminescence (EL) peak intensity for the SP-enhanced LED was greatly enhanced by 380% and 220% at an injection current density of 1 and 20A/cm(2), respectively. Our results show that the increased EL intensity is mainly attributed to the improved internal quantum efficiency of LED due to the SP coupling between Ag nanorods and MQWs.

[Raman spectra analysis of GaN : Er films prepared by ion implantation].

U-, n- and p-GaN : Er films were prepared by ion implantation method. Three carrier types of samples were studied by Raman spectra analysis. After Er+ ion implantation into GaN samples, new Raman peaks at wavenumber of 293, 362 (see text) 670 cm-1 appeared, where 293 cm-1 was considered as disordered activation of Raman scattering (DARS), 362 and 670 cm-1 may be associated with GaN lattice defects formed after ion implantation. The Ez (high) characteristic peak moves to the high frequency before and after GaN : Er samples annealing at 800 C, indicating that GaN lattice is under the compressive stress. The Lorenz fitting was used to analysed the occurrences of A1 (LO) peak in different samples which is composed of the uncoupled mode LO and the plasmon coupling mode LPP+, qualitatively pointing out the carrier concentration variation of a series of GaN : Er samples.

Multi-Source Data Fusion and Hydrodynamics for Urban Waterlogging Risk Identification.

The complex formation mechanism and numerous influencing factors of urban waterlogging disasters make the identification of their risk an essential matter. This paper proposes a framework for identifying urban waterlogging risk that combines multi-source data fusion with hydrodynamics (MDF-H). The framework consists of a source data layer, a model parameter layer, and a calculation layer. Using multi-source data fusion technology, we processed urban meteorological information, geographic information, and municipal engineering information in a unified computation-oriented manner to form a deep fusion of a globalized multi-data layer. In conjunction with the hydrological analysis results, the irregular sub-catchment regions are divided and utilized as calculating containers for the localized runoff yield and flow concentration. Four categories of source data, meteorological data, topographic data, urban underlying surface data, and municipal and traffic data, with a total of 12 factors, are considered the model input variables to define a real-time and comprehensive runoff coefficient. The computational layer consists of three calculating levels: total study area, sub-catchment, and grid. The surface runoff inter-regional connectivity is realized at all levels of the urban road network when combined with hydrodynamic theory. A two-level drainage capacity assessment model is proposed based on the drainage pipe volume density. The final result is the extent and depth of waterlogging in the study area, and a real-time waterlogging distribution map is formed. It demonstrates a mathematical study and an effective simulation of the horizontal transition of rainfall into the surface runoff in a large-scale urban area. The proposed method was validated by the sudden rainstorm event in Futian District, Shenzhen, on 11 April 2019. The average accuracy for identifying waterlogging depth was greater than 95%. The MDF-H framework has the advantages of precise prediction, rapid calculation speed, and wide applicability to large-scale regions.

Long-term results of synovectomy in total knee arthroplasty: a prospective, randomized controlled trial.

BACKGROUND: Synovectomy has been introduced into total knee arthroplasty (TKA) with the aim of relieving pain and inflammation of the synovium. However, there are no long-term, comparative data to evaluate the effect of synovectomy in TKA. This study was aimed at assessing pain, function, and complications in patients undergoing synovectomy during TKA for osteoarthritis (OA) at long-term follow-up. METHODS: This was a prospective randomized controlled trial of 42 consecutive patients who underwent staged bilateral TKA. Patients undergoing the first-side TKA were allocated to receive TKA with or without synovectomy followed by a 3-month washout period and crossover to the other strategy for the opposite-side TKA. The overall efficacy of both strategies was evaluated by determination of blood loss, the Knee Society score (KSS), and knee inflammation conditions during a 3-month postoperative period. The postoperative pain, range of motion (ROM), and complications were sequentially evaluated to compare the two groups until 10 years after surgery. RESULTS: At the 10-year follow-up, both groups had a similarly significantly improved ROM (114.88 ±â€Š9.84° vs. 114.02 ±â€Š9.43°, t  = 0.221, P  = 0.815) and pain relief with no differences between the two groups (1.0 [1.0] vs. 1.0 [1.5], U  = 789.500, P  = 0.613). Similar changes in total blood loss, KSS, and knee inflammation were found in both groups during 3 months postoperatively ( P  > 0.05). Additionally, there was no significant difference regarding complications and satisfaction between the two groups ( P  > 0.05). CONCLUSIONS: Synovectomy in conjunction with TKA for primary OA does not seem to provide any benefit regarding postoperative pain, ROM, and satisfaction during a 10-year follow-up. In addition, it may not result in more blood loss and increased incidence of long-term complications. Based on our long-term findings, it should not be performed routinely. TRIAL REGISTRATION: Chinese Clinical Trial Registry, ChiCTR-INR-16008245; https://www.chictr.org.cn/showproj.aspx?proj=13334 .

Antifungal effects and biocontrol potential of lipopeptide-producing Streptomyces against banana Fusarium wilt fungus Fusarium oxysporum f. sp. cubense.

Fusarium wilt of banana (FWB), caused by Fusarium oxysporum f. sp. cubense (Foc), especially tropical race 4 (TR4), presents the foremost menace to the global banana production. Extensive efforts have been made to search for efficient biological control agents for disease management. Our previous study showed that Streptomyces sp. XY006 exhibited a strong inhibitory activity against several phytopathogenic fungi, including F. oxysporum. Here, the corresponding antifungal metabolites were purified and determined to be two cyclic lipopeptide homologs, lipopeptin A and lipopeptin B. Combined treatment with lipopeptin complex antagonized Foc TR4 by inhibiting mycelial growth and conidial sporulation, suppressing the synthesis of ergosterol and fatty acids and lowering the production of fusaric acid. Electron microscopy observation showed that lipopeptide treatment induced a severe disruption of the plasma membrane, leading to cell leakage. Lipopeptin A displayed a more pronounced antifungal activity against Foc TR4 than lipopeptin B. In pot experiments, strain XY006 successfully colonized banana plantlets and suppressed the incidence of FWB, with a biocontrol efficacy of up to 87.7%. Additionally, XY006 fermentation culture application improved plant growth parameters and induced peroxidase activity in treated plantlets, suggesting a possible role in induced resistance. Our findings highlight the potential of strain XY006 as a biological agent for FWB, and further research is needed to enhance its efficacy and mode of action in planta.

Conserved signaling through vascular endothelial growth (VEGF) receptor family members in murine lymphatic endothelial cells.

Lymphatic vessels guide interstitial fluid, modulate immune responses by regulating leukocyte and antigen trafficking to lymph nodes, and in a cancer setting enable tumor cells to track to regional lymph nodes. The aim of the study was to determine whether primary murine lymphatic endothelial cells (mLECs) show conserved vascular endothelial growth factor (VEGF) signaling pathways with human LECs (hLECs). LECs were successfully isolated from murine dermis and prostate. Similar to hLECs, vascular endothelial growth factor (VEGF) family ligands activated MAPK and pAkt intracellular signaling pathways in mLECs. We describe a robust protocol for isolation of mLECs which, by harnessing the power of transgenic and knockout mouse models, will be a useful tool to study how LEC phenotype contributes to alterations in lymphatic vessel formation and function.

Analysis of the Interaction Mechanism of the Risk Factors of Gas Explosions in Chinese Underground Coal Mines.

Gas explosion accidents easily cause severe casualties in Chinese underground coal mines. Systematic analysis of accident causation is crucial for the prevention of gas explosions. This study identifies the representative risk factors of gas explosions and determines the interrelationship among these risk factors to highlight weak links and develop countermeasures. A total of 21 representative risk factors of gas explosions were identified through 128 case studies and front-line investigations. On this basis, a five-level hierarchical structure model of gas explosions was established to explore the complex interrelationships among the representative risk factors based on a combination of the Decision-Making Trial and Evaluation Laboratory (DEMATEL) and Interpretive Structural Modeling (ISM) methods. Moreover, the Matrix of Cross Impact Multiplications Applied to Classification (MICMAC) method was applied to achieve risk factor classification into four clusters, namely, driving factors, linkage factors, dependent factors and autonomous factors. The results indicated that the interrelationships and emergence properties among the risk factors may cause gas explosions, which should give more attention to the interrelationships among multiple factors and multiple subsystems for coal enterprises. Meanwhile, the complex geological conditions, poor safety supervision, inadequate safety education and training, incomplete execution safety regulations and poor safety technology and input are the long-term focus of risk management for coal enterprises. Finally, 10 countermeasures were proposed to control these representative risk factors and interrelationships. The results are helpful to the development of gas explosion risk management policies and to the preferential allocation of limited resources to resolve these issues.

Predicting the effectiveness of interventions on population-level sodium reduction: A simulation modeling study.

Background and Aims: Interventions that significantly reduce dietary sodium intake are anticipated to decrease gastric cancer (GCa) burden. However, the optimal restriction strategies remain unknown at present. This study aims to understand where and to what extent policies modifying sodium consumption change the distribution of GCa burden, and the effects of potential salt reduction strategies in China. Methods: The synthetic population in this microscopic simulation study is close to reality. We incorporated estimates of dietary patterns and GCa risk into the model of excess salt consumption. These estimates and simulated population were obtained from the China Health and Nutrition Survey, Global Burden of Disease Project, and the sixth census of China's National Bureau of Statistics, respectively. Results: In the no intervention scenario, we estimated that disease burdens due to excess sodium intake would be at 472.9 million disability-adjusted life years (DALYs) nationally between 2010 and 2030 (95% credible interval [CrI]: 371.1-567.7). The GCa burden caused by high sodium is projected to have a disproportionate impact on the central and southern provinces of China (9.2 and 4.5 million DALYs, respectively). Implementing a cooking salt substitute strategy would be expected to avoid a larger portion of GCa burden (about 67.2%, 95% CrI: 66.8%-67.6%) than the salt-restriction spoon program (about 16.7%, 95% CrI: 16.1%-17.4%). Conclusion: Dietary salt reduction policy is very powerfully effective in reducing the GCa burden overall. It is expected that proposed salt substitutes are more effective than traditional salt-restriction spoons to avoid increased inequality.

Improving light extraction of InGaN-based light emitting diodes with a roughened p-GaN surface using CsCl nano-islands.

InGaN-based light emitting diodes (LEDs) with a top nano-roughened p-GaN surface are fabricated using self-assembled CsCl nano-islands as etch masks. Following formation of hemispherical GaN nano-island arrays, electroluminescence (EL) spectra of roughened LEDs display an obvious redshift due to partial compression release in quantum wells through Inductively Coupled Plasma (ICP) etching. At a 350-mA current, the enhancement of light output power of LEDs subjected to ICP treatment with durations of 50, 150 and 250 sec compared with conventional LED have been determined to be 9.2, 70.6, and 42.3%, respectively. Additionally, the extraction enhancement factor can be further improved by increasing the size of CsCl nano-island. The economic and rapid method puts forward great potential for high performance lighting devices.

Impact of different control policies for COVID-19 outbreak on the air transportation industry: A comparison between China, the U.S. and Singapore.

Many countries have been implementing various control measures with different strictness levels to prevent the coronavirus disease 2019 (COVID-19) from spreading. With the great reduction in human mobility and daily activities, considerable impacts have been imposed on the global air transportation industry. This study applies a hybrid SARIMA-based intervention model to measure the differences in the impacts of different control measures implemented in China, the U.S. and Singapore on air passenger and air freight traffic. To explore the effect of time span for the measures to be in force, two scenarios are invented, namely a long-term intervention and a short-term intervention, and predictions are made till the end of 2020 for all three countries under both scenarios. As a result, predictive patterns of the selected metrics for the three countries are rather different. China is predicted to have the mildest economic impact on the air transportation industry in this year in terms of air passenger revenue and air cargo traffic, provided that the control measures were prompt and effective. The U.S. would suffer from a far-reaching impact on the industry if the same control measures are maintained. More uncertainties are found for Singapore, as it is strongly associated with international travel demands. Suggestions are made for the three countries and the rest of the world on how to seek a balance between the strictness of control measures and the potential long-term industrial losses.

Intra-articular Injection of Kartogenin-Enhanced Bone Marrow-Derived Mesenchymal Stem Cells in the Treatment of Knee Osteoarthritis in a Rat Model.

BACKGROUND: In this study, we investigated the in vitro and in vivo chondrogenic capacity of kartogenin (KGN)-enhanced bone marrow-derived mesenchymal stem cells (BMSCs) for cartilage regeneration. PURPOSE: To determine (1) whether functionalized nanographene oxide (NGO) can effectively deliver KGN into BMSCs and (2) whether KGN would enhance BMSCs during chondrogenesis in vitro and in vivo in an animal model. STUDY DESIGN: Controlled laboratory study. METHODS: Functionalized NGO with line chain amine-terminated polyethylene glycol (PEG) and branched polyethylenimine (BPEI) were used to synthesize biocompatible NGO-PEG-BPEI (PPG) and for loading hydrophobic KGN molecules noncovalently via π-π stacking and hydrophobic interactions (PPG-KGN). Then, PPG-KGN was used for the intracellular delivery of hydrophobic KGN by simple mixing and co-incubation with BMSCs to acquire KGN-enhanced BMSCs. The chondrogenic efficacy of KGN-enhanced BMSCs was evaluated in vitro. In vivo, osteoarthritis (OA) was induced by anterior cruciate ligament transection in rats. A total of 5 groups were established: normal (OA treated with nothing), phosphate-buffered saline (PBS; intra-articular injection of PBS), PPG-KGN (intra-articular injection of PPG-KGN), BMSCs (intra-articular injection of BMSCs), and BMSCs + PPG-KGN (intra-articular injection of PPG-KGN-preconditioned BMSCs). At 6 and 9 weeks after the surgical induction of OA, the rats received intra-articular injections of PPG-KGN, BMSCs, or KGN-enhanced BMSCs. At 14 weeks after the surgical induction of OA, radiographic and behavioral evaluations as well as histological analysis of the knee joints were performed. RESULTS: The in vitro study showed that PPG could be rapidly uptaken in the first 4 hours after incubation, reaching saturation at 12 hours and accumulating in the lysosome and cytoplasm of BMSCs. Thus, PPG-KGN could enhance the efficiency of the intracellular delivery of KGN, which showed a remarkably high chondrogenic differentiation capacity of BMSCs. When applied to an OA model of cartilage injuries in rats, PPG-KGN-preconditioned BMSCs contributed to protection from joint space narrowing, pathological mineralization, OA development, and OA-induced pain, as well as improved tissue regeneration, as evidenced by radiographic, weightbearing, and histological findings. CONCLUSION: Our results demonstrate that KGN-enhanced BMSCs showed markedly improved capacities for chondrogenesis and articular cartilage repair. We believe that this work demonstrates that a multifunctional nanoparticle-based drug delivery system could be beneficial for stem cell therapy. Our results present an opportunity to reverse the symptoms and pathophysiology of OA. CLINICAL RELEVANCE: The intracellular delivery of KGN to produce BMSCs with enhanced chondrogenic potential may offer a new approach for the treatment of OA.