Unveiling the methionine cycle: a key metabolic signature and NR4A2 as a methionine-responsive oncogene in esophageal squamous cell carcinoma.

Esophageal squamous cell carcinoma (ESCC) is a deadly malignancy with notable metabolic reprogramming, yet the pivotal metabolic feature driving ESCC progression remains elusive. Here, we show that methionine cycle exhibits robust activation in ESCC and is reversely associated with patient survival. ESCC cells readily harness exogenous methionine to generate S-adenosyl-methionine (SAM), thus promoting cell proliferation. Mechanistically, methionine augments METTL3-mediated RNA m6A methylation through SAM and revises gene expression. Integrative omics analysis highlights the potent influence of methionine/SAM on NR4A2 expression in a tumor-specific manner, mediated by the IGF2BP2-dependent stabilization of methylated NR4A2 mRNA. We demonstrate that NR4A2 facilitates ESCC growth and negatively impacts patient survival. We further identify celecoxib as an effective inhibitor of NR4A2, offering promise as a new anti-ESCC agent. In summary, our findings underscore the active methionine cycle as a critical metabolic characteristic in ESCC, and pinpoint NR4A2 as a novel methionine-responsive oncogene, thereby presenting a compelling target potentially superior to methionine restriction.

Oxidation-enabled SnS conversion to two-dimensional porous SnO2 flakes towards NO2 gas sensing.

Tin dioxide (SnO2)-based electronic materials and gas sensors have attracted extensive attention from academia and industry. Herein we report the preparation of two-dimensional (2D) porous SnO2 flakes by thermal oxidation of 2D SnS flakes that serve as a self-sacrificial template. An oxidation-enabled, temperature-dependent matter conversion from SnS through three-phase SnS-SnS2-SnO2 (400 °C) and two-phase SnS2-SnO2 (600 °C) to pure-phase SnO2 (≥800 °C) is disclosed by means of combined XRD, TG-DSC and XPS studies. Meanwhile, the associated chemical reactions and the mass and heat changes during this solid-state conversion process are clarified. The as-prepared 2D SnO2 flakes exhibit structural porosity with tunable pore sizes and crystallite sizes/crystallinity, resulting in superior potential for NO2 sensing. At the optimized operating temperature of 200 °C, the prototype gas sensors made of porous SnO2 flakes show competitive sensing parameters in a broad NO2 concentration range of 50 ppb-10 ppm in terms of high response, faster response/recovery speeds, and good selectivity and stability. A sensing mechanism involving the adsorption and desorption of NO2/O2 molecules and the possible surface reactions is further rationalized for the SnO2 NO2 gas sensors.

ZnO-Au@ZIF-8 core-shell nanorod arrays for ppb-level NO2 detection.

ZnO-Au@ZIF-8 core-shell heterostructures were prepared by ZIF-8 encapsulation of sacrificial ZnO-Au nanorods. Because of the catalytic activity of the Au nanoparticles and the sieving effects of the ZIF-8, the ZnO-Au@ZIF-8 heterostructures showed an outstanding response of 1.8 to 5 ppb NO2, and exhibited higher selectivity, stability, anti-humidity and fast response and recovery properties. The combination of the gas-selective catalytic activity of noble metals with the MOF filter used in this work can be easily extended to synthesize other types of MOS@MOF sensors, opening a new avenue for the detection of hazardous gases.

Enhance Hydrogen Evolution Reaction Performance via Double-Stacked Edges of Black Phosphorene.

Based on the density functional theory (DFT) calculations, we explored the structures and HER catalytic properties of reconstructed and double-stacked black phosphorene (BP) edges. Ten bilayer BP edges were constructed by the double stacking of three typical monolayer edges, i.e., zigzag (ZZ) edge, armchair (AC) edge, skewed diagonal (SD) edge, and their reconstructed derivatives with their layer's configurations, edge deformations and thermodynamic stabilities were discussed. Based on these edges, five chemical sites on four bilayer BP edges were selected to be promising candidates for a HER catalyst, which present higher HER activities than that of Pt(111). Besides, among these four edges, two edges have even lower energetic barriers for the Tafel reaction. Compared with the monolayer edges, these selected bilayer BP edges confirm the remarkable enhancement of the HER catalytic properties, which can be attributed to their unique edge structures and the enhanced electronic densities after the hydrogen adsorptions. Finally, the thermostability of these edges at room temperature has also been proved by the DFT-MD simulations. This theoretic study deepens our fundamental understanding of the double-stacked edge structures of the BP and provides a new way for the rational design of highly efficient and noble-metal-free HER catalysts.

Exudate Absorbing and Antimicrobial Hydrogel Integrated with Multifunctional Curcumin-Loaded Magnesium Polyphenol Network for Facilitating Burn Wound Healing.

Burns are among the most common causes of trauma worldwide. Reducing the healing time of deep burn wounds has always been a major challenge. Traditional dressings not only require a lengthy medical procedure but also cause unbearable pain and secondary damage to patients. In this study, we developed an exudate-absorbing and antimicrobial hydrogel with a curcumin-loaded magnesium polyphenol network (Cur-Mg@PP) to promote burn wound healing. That hydrogel was composed of an ε-poly-l-lysine (ε-PLL)/polymer poly(γ-glutamic acid) (γ-PGA) hydrogel (PP) and curcumin-loaded magnesium polyphenol network (Cur-Mg). Because of the strong water absorption property of ε-PLL and γ-PGA, Cur-Mg@PP powder can quickly absorb the wound exudate and transform into a moist and viscous hydrogel, thus releasing payloads such as magnesium ion (Mg2+) and curcumin (Cur). The released Mg2+ and Cur demonstrated good therapeutic efficacy on analgesic, antioxidant, anti-inflammation, angiogenesis, and tissue regeneration. Our findings provide a strategy for accelerating burn wound healing.

Observation of Room-Temperature Exciton-Polariton Emission from Wide-Ranging 2D Semiconductors Coupled with a Broadband Mie Resonator.

Two-dimensional exciton-polaritons in monolayer transition metal dichalcogenides (TMDs) exhibit practical advantages in valley coherence, optical nonlinearities, and even bosonic condensation owing to their light-emission capability. To achieve robust exciton-polariton emission, strong photon-exciton couplings are required at the TMD monolayer, which is challenging due to its atomic thickness. High-quality (Q) factor optical cavities with narrowband resonances are an effective approach but typically limited to a specific excitonic state of a certain TMD material. Herein, we achieve on-demand exciton-polariton emission from a wide range of TMDs at room temperature by hybridizing excitons with broadband Mie resonances spanning the whole visible spectrum. By confining broadband light at the TMD monolayer, our one type of Mie resonator on different TMDs enables enhanced light-matter interactions with multiple excitonic states simultaneously. We demonstrate multi-Rabi splittings and robust polaritonic photoluminescence in monolayer WSe2, WS2, and MoS2. The hybrid system also shows the potential to approach the ultrastrong coupling regime.

D-mannose induces TFE3-dependent lysosomal degradation of EGFR and inhibits the progression of NSCLC.

In non-small cell lung cancer (NSCLC), the overexpression or abnormal activation of epidermal growth factor receptor (EGFR) is associated with tumor progression and drug resistance. EGFR tyrosine kinase inhibitors (TKIs) are currently the first-line treatment of NSCLC. However, patients inevitably acquired EGFR TKIs resistance mutations, which led to disease progression, so it is urgent to find new treatment. Here, we report that D-mannose up-regulates lysosomal activity by enhancing TFE3-mediated lysosomal biogenesis, thereby increasing the degradation of EGFR and significantly down-regulating its protein level. Therefore, D-mannose significantly inhibited the proliferation, migration and invasion of wild-type EGFR (WT-EGFR) and EGFR mutant cells (E746-A750 deletion, L858R and T790M mutations) in vitro. Oral administration of D-mannose strongly inhibited tumor growth in mice, showing similar effects with osimertinib. Taken together, these data suggest that D-mannose may represent a new strategy for clinical treatment of NSCLC.

Fibronectin promotes tumor progression through integrin αvß3/PI3K/AKT/SOX2 signaling in non-small cell lung cancer.

The tumor microenvironment, especially the extracellular matrix (ECM), is strongly associated with tumor cell proliferation and metastasis. Numerous studies have provided evidence suggesting that fibronectin (FN) in ECM supports cancer cell escape and contributes to cell migration, resulting in distant cancer metastasis and poor outcomes in patients. In our study, it was demonstrated that FN expression was elevated in tumor tissues from highly malignant NSCLC patients, compared to those with low malignancy (p = 0.0076). Importantly, FN promoted proliferative phenotypes and strengthened tumorigenesis capabilities in NSCLC cells, including A549 and Lewis cells, leading to sustained tumor growth in vivo. Mechanistically, it was identified that FN facilitated the activation of the integrin αvß3/PI3K/AKT signaling pathway, which subsequently upregulated tumor stemness through the downstream transcription factor SOX2. Blockade of integrin αvß3 signal efficiently suppressed NSCLC proliferation and tumorigenesis both in vitro and in vivo. In conclusion, our study demonstrated that extracellular FN could facilitate NSCLC development through the integrin αvß3/PI3K/AKT/SOX2 signaling pathway. Blockade of integrin αvß3 could efficiently enhance the anticancer effects of chemotherapy, offering an innovative approach for clinical NSCLC therapy.

Lymph node metastasis in cancer progression: molecular mechanisms, clinical significance and therapeutic interventions.

Lymph nodes (LNs) are important hubs for metastatic cell arrest and growth, immune modulation, and secondary dissemination to distant sites through a series of mechanisms, and it has been proved that lymph node metastasis (LNM) is an essential prognostic indicator in many different types of cancer. Therefore, it is important for oncologists to understand the mechanisms of tumor cells to metastasize to LNs, as well as how LNM affects the prognosis and therapy of patients with cancer in order to provide patients with accurate disease assessment and effective treatment strategies. In recent years, with the updates in both basic and clinical studies on LNM and the application of advanced medical technologies, much progress has been made in the understanding of the mechanisms of LNM and the strategies for diagnosis and treatment of LNM. In this review, current knowledge of the anatomical and physiological characteristics of LNs, as well as the molecular mechanisms of LNM, are described. The clinical significance of LNM in different anatomical sites is summarized, including the roles of LNM playing in staging, prognostic prediction, and treatment selection for patients with various types of cancers. And the novel exploration and academic disputes of strategies for recognition, diagnosis, and therapeutic interventions of metastatic LNs are also discussed.

Wet-adhesive γ-PGA/ε-PLL hydrogel loaded with EGF for tracheal epithelial injury repair.

Following the global COVID-19 pandemic, the incidence of tracheal epithelial injury is increasing. However, the repair of tracheal epithelial injury remains a challenge due to the slow renewal rate of tracheal epithelial cells (TECs). In traditional nebulized inhalation treatments, drugs are enriched in the lungs or absorbed into the blood, reducing drug concentration at the tracheal injury site. In this study, we prepared an epidermal growth factor (EGF)-loaded gamma-polyglutamic acid (γ-PGA)/epsilon-poly-L-lysine (ε-PLL) (PP) hydrogel (EGF@PP) to promote the repair of tracheal epithelial injury. Epidermal growth factor promotes the proliferation of TECs and enhances vascularization, thereby accelerating injury repair. The PP hydrogel exhibits outstanding wet adhesion, slow drug release, and antibacterial and anti-inflammatory properties, making it suitable for application in the airways and creating an environment conducive to epithelial repair. Here, we established a rabbit model of tracheal injury using a laser to destroy the tracheal epithelium and delivered EGF@PP powder to the injury site under fiberoptic bronchoscopy guidance. Our findings revealed that this was an effective therapeutic strategy for accelerating the repair of tracheal epithelial injury.

Exploring the gas-sensing properties of MOF-derived TiN@CuO as a hydrogen sulfide sensor.

In an effort to develop a long-lasting gas sensor, this article presents titanium nitride (TiN) as a potential substitute sensitive material in conjunction with (copper(II) benzene-1,3,5-tricarboxylate) Cu-BTC-derived CuO. The work focused on the gas-sensing characteristics of TiN/CuO nanoparticles in detecting H2S gas at various temperatures and concentrations. XRD, XPS, and SEM were utilized to analyze the composites with varied Cu molar ratios. The responses of TiN/CuO-2 nanoparticles to 50 and 100 ppm H2S gas at 50 °C and 250 °C are 34.8 and 60.0, respectively. The related sensor had high selectivity and stability towards H2S, and the response of TiN/CuO-2 is still 2.5-5 ppm H2S. The gas-sensing properties as well as the mechanism are fully explained in this study. TiN/CuO might be a choice for the detection of H2S gas, opening up new avenues for applications in industries, medical facilities, and homes.

Development and validation of a pulmonary complications prediction model based on the Yang's index.

Background: Blunt chest trauma patients with pulmonary contusion are susceptible to pulmonary complications, and severe cases may develop respiratory failure. Some studies have suggested the extent of pulmonary contusion to be the main predictor of pulmonary complications. However, no simple and effective method to assess the severity of pulmonary contusion has been available yet. A reliable prognostic prediction model would facilitate the identification of high-risk patients, so that early intervention can be given to reduce pulmonary complications; however, no suitable model based on such an assumption has been available yet. Methods: In this study, a new method for assessing lung contusion by the product of the three dimensions of the lung window on the computed tomography (CT) image was proposed. We conducted a retrospective study on patients with both thoracic trauma and pulmonary contusion admitted to 8 trauma centers in China from January 2014 to June 2020. Using patients from 2 centers with a large number of patients as the training set and patients from the other 6 centers as the validation set, a prediction model for pulmonary complications was established with Yang's index and rib fractures, etc., being the predictors. The pulmonary complications included pulmonary infection and respiratory failure. Results: This study included 515 patients, among whom 188 developed pulmonary complications, including 92 with respiratory failure. Risk factors contributing to pulmonary complications were identified, and a scoring system and prediction model were constructed. Using the training set, models for adverse outcomes and severe adverse outcomes were developed, and area under the curve (AUC) of 0.852 and 0.788 were achieved in the validation set. In the model performance for predicting pulmonary complications, the positive predictive value of the model is 0.938, the sensitivity of the model is 0.563 and the specificity of the model is 0.958. Conclusions: The generated indicator, called Yang's index, was proven to be an easy-to-use method for the evaluation of pulmonary contusion severity. The prediction model based on Yang's index could facilitate early identification of patients at risk of pulmonary complications, yet the effectiveness of the model remains to be validated and its performance remains to be improved in further studies with larger sample sizes.

METTL3 achieves lipopolysaccharide-induced myocardial injury via m6A-dependent stabilization of Myh3 mRNA.

Septic cardiomyopathy (SCM) was an important pathological component of severe sepsis and septic shock. N6-methyladenosine (m6A) modification was a common RNA modification in both mRNA and non-coding RNAs and was proved to be involved in sepsis and immune disorders. Therefore, the purpose of this study was to investigate the role and mechanism of METTL3 in lipopolysaccharide-induced myocardial injury. We firstly analyzed the expression changes of various m6A-related regulators in human samples in the GSE79962 data and the Receiver Operating Characteristic curve of significantly changed m6A enzymes, showing that METTL3 had a high diagnostic ability in patients with SCM. Western blotting confirmed the high expression of METTL3 in LPS-treated H9C2 cells, which was consistent with the above results in human samples. In vitro and in vivo, the deficiency of METTL3 could improve the cardiac function, cardiac tissue damage, myocardial cell apoptosis and reactive oxygen species levels in LPS-treated H9C2 cells and LPS-induced sepsis rats, respectively. In addition, we obtained 213 differential genes through transcriptome RNA-seq analysis, and conducted GO enrichment analysis and KEGG pathway analysis through DAVID. We also found that the half-life of Myh3 mRNA was significantly reduced after METTL3 deletion and that Myh3 carried several potential m6A modification sites. In conclusion, we found that downregulation of METTL3 reversed LPS-induced myocardial cell and tissue damage and reduced cardiac function, mainly by increasing Myh3 stability. Our study revealed a key role of METTL3-mediated m6A methylation in septic cardiomyopathy, which may offer a potential mechanism for the therapy of septic cardiomyopathy.

Active post-transcriptional regulation and ACLY-mediated acetyl-CoA synthesis as a pivotal target of Shuang-Huang-Sheng-Bai formula for lung adenocarcinoma treatment.

BACKGROUND: New therapeutic approaches are required to improve the outcomes of lung cancer (LC), a leading cause of cancer-related deaths worldwide. Chinese herbal medicine formulae widely used in China provide a unique opportunity for improving LC treatment, and the Shuang-Huang-Sheng-Bai (SHSB) formula is a typical example. However, the underlying mechanisms of action remains unclear. PURPOSE: This study aimed to confirm the efficacy of SHSB against lung adenocarcinoma (LUAD), which is a major histological type of LC, unveil the downstream targets of this formula, and assess the clinical relevance and biological roles of the newly identified target. METHODS: An experimental metastasis mouse model and a subcutaneous xenograft mouse model were used to evaluate the anti-cancer activity of SHSB. Multi-omics profiling of subcutaneous tumors and metabolomic profiling of sera were performed to identify downstream targets, especially the metabolic targets of SHSB. A clinical trial was conducted to verify the newly identified metabolic targets in patients. Next, the metabolites and enzymes engaged in the metabolic pathway targeted by SHSB were measured in clinical samples. Finally, routine molecular experiments were performed to decipher the biological functions of the metabolic pathways targeted by SHSB. RESULTS: Oral SHSB administration showed overt anti-LUAD efficacy as revealed by the extended overall survival of the metastasis model and impaired growth of implanted tumors in the subcutaneous xenograft model. Mechanistically, SHSB administration altered protein expression in the post-transcriptional layer and modified the metabolome of LUAD xenografts. Integrative analysis demonstrated that SHSB markedly inhibited acetyl-CoA synthesis in tumors by post-transcriptionally downregulating ATP-citrate lyase (ACLY). Consistently, our clinical trial showed that oral SHSB administration declined serum acetyl-CoA levels of patients with LC. Moreover, acetyl-CoA synthesis and ACLY expression were both augmented in clinical LUAD tissues of patients, and high intratumoral ACLY expression predicted a detrimental prognosis. Finally, we showed that ACLY-mediated acetyl-CoA synthesis is essential for LUAD cell growth by promoting G1/S transition and DNA replication. CONCLUSION: Limited downstream targets of SHSB for LC treatment have been reported in previous hypothesis-driven studies. In this study, we conducted a comprehensive multi-omics investigation and demonstrated that SHSB exerted its anti-LUAD efficacy by actively and post-transcriptionally modulating protein expression and particularly restraining ACLY-mediated acetyl-CoA synthesis.

Intelligent microneedle patch with prolonged local release of hydrogen and magnesium ions for diabetic wound healing.

Diabetes mellitus, an epidemic with a rapidly increasing number of patients, always leads to delayed wound healing associated with consistent pro-inflammatory M1 polarization, decreased angiogenesis and increased reactive oxygen species (ROS) in the microenvironment. Herein, a poly (lactic-co-glycolic acid) (PLGA)-based microneedle patch loaded with magnesium hydride (MgH2) (MN-MgH2) is manufactured for defeating diabetic wounds. The application of microneedle patch contributes to the transdermal delivery and the prolonged release of MgH2 that can generate hydrogen (H2) and magnesium ions (Mg2+) after reaction with body fluids. The released H2 reduces the production of ROS, transforming the pathological microenvironment induced by diabetes mellitus. Meanwhile, the released Mg2+ promotes the polarization of pro-healing M2 macrophages. Consequently, cell proliferation and migration are improved, and angiogenesis and tissue regeneration are enhanced. Such intelligent microneedle patch provides a novel way for accelerating wound healing through steadily preserving and releasing of H2 and Mg2+ locally and sustainably.

CuO-decorated MOF derived ZnO polyhedral nanostructures for exceptional H2S gas detection.

Considering that H2S is a hazardous gas that poses a significant risk to people's lives, research into H2S gas sensors has garnered a lot of interest. This work reports a CuO/ZnO multifaceted nanostructures(NS) created by heat treating Cu2+/ZIF-8 impregnation precursors, and their microstructure and gas sensing characteristics were examined using various characterization techniques (XRD, XPS, SEM, TEM, and BET). The as-prepared hollow CuO/ZnO multifunctional nanostructures had a high gas response value (425@50 ppm H2S gas), quick response and recovery times (57/191s @20 ppm), a low limit of detection (1.6@500 ppb H2S), good humidity resistance and highly selective towards H2S gas. The hollow CuO/ZnO multifaceted nanostructures possessed enhanced gas sensing capabilities which may be related to their porous hollow nanostructures, the manufactured p-CuO/n-ZnO heterojunctions, and the spillover effect between CuO and H2S.

Modified Nuss procedure for the treatment of pectus excavatum: Experience of 259 patients.

BACKGROUND: Pectus excavatum is not rare in China. Many treatments for this disease have proved to have many shortcomings. Nuss procedure has been a ground-breaking technology, but it also has some disadvantages. Hence, this study was conducted to review our experience in the use of modified Nuss procedure in our hospital. METHODS: Data from 259 patients suffered from pectus excavatum between August 2020 and August 2021 who were treated with modified Nuss procedure was analyzed retrospectively. RESULT: Age was from 3 to 37 years. The average was 15.54 years. The male was 213 cases and the female was 46 cases. The time patients or their family members found pectus excavatum varied. 10 cases had been repaired previously when patients were admitted in our hospital. The clinical symptoms also varied. Each case had an improvement in Haller index. The average of the postoperative hospitalization was 3.97 days. Most cases were inserted 1 bar. Complication rate was also very low. All patients or their parents or their guardians were satisfied with the appearance of the chest wall after operation. There was no death in the whole observation period. CONCLUSION: From our experience, this modified Nuss procedure have obtained optimistic outcomes with more minimal invasion and low complication rate. This surgical method may be applied to many other hospitals in the future.

Expert consensus on indocyanine green fluorescence imaging for thoracoscopic lung resection (The Version 2022).

The use of the white-light thoracoscopy is hampered by the low contrast between oncologic margins and surrounding normal parenchyma. As a result, many patients with in situ or micro-infiltrating adenocarcinoma have to undergo lobectomy due to a lack of tactile and visual feedback in the resection of solitary pulmonary nodules. Near-infrared (NIR) guided indocyanine green (ICG) fluorescence imaging technique has been widely investigated due to its unique capability in addressing the current challenges; however, there is no special consensus on the evidence and recommendations for its preoperative and intraoperative applications. This manuscript will describe the development process of a consensus on ICG fluorescence-guided thoracoscopic resection of pulmonary lesions and make recommendations that can be applied in a greater number of centers. Specifically, an expert panel of thoracic surgeons and radiographers was formed. Based on the quality of evidence and strength of recommendations, the consensus was developed in conjunction with the Chinese Guidelines on Video-assisted Thoracoscopy, and the National Comprehensive Cancer Network (NCCN) guidelines on the management of pulmonary lesions. Each of the statements was discussed and agreed upon with a unanimous consensus amongst the panel. A total of 6 consensus statements were developed. Fluorescence-guided thoracoscopy has unique advantages in the visualization of pulmonary nodules, and recognition and resection of the anterior plane of the pulmonary segment. The expert panel agrees that fluorescence-guided thoracoscopic surgery has the potential to become a routine operation for the treatment of pulmonary lesions.

Effects of pre-operative enteral immunonutrition for esophageal cancer patients treated with neoadjuvant chemoradiotherapy: protocol for a multicenter randomized controlled trial (point trial, pre-operative immunonutrition therapy).

BACKGROUND: Neoadjuvant chemoradiation followed by esophagectomy has been established as the first-line treatment for locally advanced esophageal cancer. Postoperative enteral nutrition has been widely used to improve perioperative outcomes. However, whether to implement preoperative nutritional intervention during neoadjuvant therapy is yet to be verified by prospective studies. METHODS: POINT trial is a multicenter, open-labeled, randomized controlled trial. A total of 244 patients with surgically resectable esophageal cancer are randomly assigned to nutritional therapy group (arm A) or control group (arm B) with a 2:1 ratio. Both groups receive neoadjuvant chemotherapy with concurrent radiotherapy based on the CROSS regimen followed by minimally invasive esophagectomy. The primary endpoint is the rate of nutrition and immune-related complications after surgery. Secondary endpoints include completion rate of neoadjuvant chemoradiation and related adverse events, rate of pathological complete response, perioperative outcomes, nutritional status, overall survival, progression-free survival and quality of life. DISCUSSION: This trial aims to verify whether immunonutrition during neoadjuvant chemoradiation can reduce the rate of complications and improve perioperative outcomes. Frequent communication and monitoring are essential for a multicenter investigator-initiated trial. TRIAL REGISTRATION: ClinicalTrials.gov: NCT04513418. The trial was prospectively registered on 14 August 2020, https://www. CLINICALTRIALS: gov/ct2/show/NCT04513418 .

Use of mesoporous polydopamine nanoparticles as a stable drug-release system alleviates inflammation in knee osteoarthritis.

Osteoarthritis drugs are often short-acting; therefore, to enhance their efficacy, long-term, stable-release, drug-delivery systems are urgently needed. Mesoporous polydopamine (MPDA), a natural nanoparticle with excellent biocompatibility and a high loading capacity, synthesized via a self-aggregation-based method, is frequently used in tumor photothermal therapy. Here, we evaluated its efficiency as a sustained and controlled-release drug carrier and investigated its effectiveness in retarding drug clearance. To this end, we used MPDA as a controlled-release vector to design a drug-loaded microsphere system (RCGD423@MPDA) for osteoarthritis treatment, and thereafter, tested the efficacy of the system in a rat model of osteoarthritis. The results indicated that at an intermediate drug-loading dose, MPDA showed high drug retention. Furthermore, the microsphere system maintained controlled drug release for over 28 days. Our in vitro experiments also showed that drug delivery using this microsphere system inhibited apoptosis-related cartilage degeneration, whereas MPDA-only administration did not show obvious cartilage degradation improvement effect. Results from an in vivo osteoarthritis model also confirmed that drug delivery via this microsphere system inhibited cartilage damage and proteoglycan loss more effectively than the non-vectored drug treatment. These findings suggest that MPDA may be effective as a controlled-release carrier for inhibiting the overall progression of osteoarthritis. Moreover, they provide insights into the selection of drug-clearance retarding vectors, highlighting the applicability of MPDA in this regard.