Single-cell transcriptome analysis upon ECM-remodeling meningioma cells.

Meningiomas are the most common tumours that primarily arise in the central nervous system, but their intratumoural heterogeneity has not yet been thoroughly studied. We aimed to investigate the transcriptome characteristics and biological properties of ECM-remodeling meningioma cells. Single-cell RNA sequencing (ScRNA-seq) data from meningioma samples were acquired and used for analyses. We conducted comprehensive bioinformatics analyses, including screening for differentially expressed genes (DEGs), Kyoto Encyclopedia of Genes and Genomes (KEGG) signaling pathway and Gene Ontology (GO) term enrichment analyses, Gene Set Enrichment Analysis (GSEA), protein-protein interaction (PPI) analysis, and copy number variation (CNV) analysis on single-cell sequencing data from meningiomas. Eighteen cell types, including six meningioma subtypes, were identified in the data. ECM-remodeling meningioma cells (MGCs) were mainly distributed in brain-tumour interface tissues. KEGG and GO enrichment analyses revealed that 908 DEGs were mainly related to cell adhesion, extracellular matrix organization, and ECM-receptor interaction. GSEA analysis demonstrated that homophilic cell adhesion via plasma membrane adhesion molecules was significantly enriched (NES = 2.375, P < 0.001). CNV analysis suggested that ECM-remodeling MGCs showed considerably lower average CNV scores. ECM-remodeling MGCs predominantly localized at the brain-tumour interface area and adhere stably to the basement membrane with a lower degree of malignancy. This study provides novel insights into the malignancy of meningiomas.

Meta-analysis of the global prevalence and risk factors of Enterocytozoon bieneusi infection in pigs from 1999 to 2021.

Enterocytozoon bieneusi (E. bieneusi), which is one of the most common microsporidia, has been identified as an important obligate intracellular pathogen that commonly colonizes in a variety of animal species and humans worldwide, including humans. In this study, the statistical analyses of E. bieneusi infection and prevalence were performed to clarify the relationship between different genotypes in different countries. The databases Chinese National Knowledge Infrastructure (CNKI), VIP Chinese Journal Database, Wanfang Data, PubMed, Web of Science and ScienceDirect were used for data collection. The research data were subjected to subgroup, univariate regression, and correlation, to reveal factors related to the high prevalence of E. bieneusi. A total of, 34 of the 498 articles published before April 2022 met the inclusion criteria. The global prevalence of E. bieneusi in pigs was 37.69% (5175/12672). The prevalence of E. bieneusi in nursery pigs was 58.87% (588/946). In developing countries and Asia, the highest prevalence of E. bieneusi in pigs were 37.62% (4752/11645) and 40.14% (4715/11345), respectively. Moreover, humans and pigs have been found to be infected with the same genotype of E. bieneusi in some cases, as evidenced by the consolidation of genotype information. The results showed that pigs are susceptible to E. bieneusi during the nursery period. The prevalence of E. bieneusi is high in developing countries, and its genotype prevalence varies in each country. Thus, it is essential to strengthen the health inspection of vulnerable groups and customs quarantine inspection.

Global prevalence and risk factors of Enterocytozoon bieneusi infection in humans: a systematic review and meta-analysis.

Enterocytozoon bieneusi is one of the most important zoonotic pathogens. In this study, we present a systematic review and meta-analysis of the prevalence of human E. bieneusi infection in endemic regions and analyze the various potential risk factors. A total of 75 studies were included. Among 31,644 individuals tested, 2,291 (6.59%) were E. bieneusi-positive. The highest prevalence of E. bieneusi in the male population was 5.50%. The prevalence of E. bieneusi in different age groups was varied, with 10.97% in teenagers. The prevalence of E. bieneusi in asymptomatic patients (6.49%) is significantly lower than that in HIV-infected patients (11.49%), and in patients with diarrheal symptoms (16.45%). Rural areas had a higher rate (7.58%) than urban ones. The prevalence of E. bieneusi in humans was the highest (6.42%) at altitudes <10 m. Moreover, the temperate zone marine climate (13.55%) had the highest prevalence. A total of 69 genotypes of E. bieneusi have been found in humans. This is the first global study regarding E. bieneusi prevalence in humans. Not only people with low immunity (such as the elderly, children, people with HIV, etc.), but also people in Europe in temperate marine climates should exercise caution to prevent infection with E. bieneusi during contact process with animals.

Title: Prévalence mondiale et facteurs de risque de l'infection à Enterocytozoon bieneusi chez l'homme : revue systématique et méta-analyse. Abstract: Enterocytozoon bieneusi est l'un des agents pathogènes zoonotiques les plus importants. Dans cette étude, nous présentons une revue systématique et une méta-analyse de la prévalence de l'infection humaine à E. bieneusi dans les régions endémiques et analysons les différents facteurs de risque potentiels. Au total, 75 études ont été incluses. Parmi 31 644 individus, 2 291 (6,59 %) étaient positifs à E. bieneusi. La prévalence la plus élevée d'E. bieneusi dans la population masculine était de 5,50 %. La prévalence d'E. bieneusi dans différents groupes d'âge variait, avec 10,97 % chez les adolescents. La prévalence d'E. bieneusi chez les patients asymptomatiques (6,49 %) était significativement inférieure à celle des patients VIH (11,49 %) et des patients présentant des symptômes de diarrhée (16,45 %). Les zones rurales avaient un taux plus élevé (7,58 %) que les zones urbaines. La prévalence d'E. bieneusi chez les humains était la plus élevée (6,42 %) à une altitude <10 m. De plus, le climat marin de la zone tempérée (13,55 %) avait la prévalence la plus élevée. Au total, 69 génotypes d'E. bieneusi ont été trouvés chez l'homme. Il s'agit de la première étude mondiale concernant la prévalence d'E. bieneusi chez l'homme. Non seulement les personnes ayant une faible immunité (telles que les personnes âgées, les enfants, les patients atteints du VIH, etc.), mais également les personnes vivant en Europe dans un climat marin tempéré doivent veiller à prévenir l'infection par E. bieneusi lors du contact avec des animaux.

Design and impact assessment of policies to overcome oversupply in China's national carbon market.

China has adopted a national carbon emissions trading market to promote emission reductions, but until now, overallocation of allowances suffer low carbon prices and thus to unfulfilled emission reduction goals. We report a general equilibrium modeling that indicates the flexible compliance and price adjustment mechanism of the carbon market, along with explores the solution to the oversupply of allowances in the China's national carbon market. We find that, under the current policy, the initial loose allowance allocation decreases the overall carbon price, and simultaneously the total amount of banked carbon allowances reaches 4.880 billion tons in 2030, resulting in the level of carbon price cannot achieve NDC (Nationally Determined Contribution) targets. However, by introducing carbon market price adjustment schemes, we observe that the cumulative amount of allowances can effectively reduce, enabling the carbon price rising. Importantly, the amount of the supply of allowances decreases most under the benchmark decrease scenario, which increases the emission reduction pressure of the enterprises from the beginning, leading to the largest economic losses, the price-based adjustment mechanism raises the carbon price to expected level at the minimize economic losses, and the quantity-based adjustment mechanism is more sensitive to policy parameters compared to the price -based adjustment mechanism. These findings offer a promising avenue for selecting cost-effective price adjustment mechanism to improve price mechanism design for national carbon markets.

Tandem bispecific CD123/CLL-1 CAR-T cells exhibit specific cytolytic effector functions against human acute myeloid leukaemia.

OBJECTIVES: The treatment of refractory and recurrent acute myeloid leukaemia (AML) is still a challenge with poor response rates and short survival times. In an attempt to solve this problem, we constructed a tandem bispecific chimeric antigen receptor (CAR) targeting CD123 and C-type lectin-like molecule 1 (CLL-1), two different AML antigens, and verified its cytotoxic effects in vitro. METHODS: We established and cultured K562 cell lines expressing both CD123 and CLL1 antigens. Single-target CAR-T cells specific to CD123 and CLL1 were engineered, alongside tandem CD123/CLL1 bispecific CAR-T cells. Flow cytometry was used to determine cell phenotypes, transfection efficiencies, cytokine release, and CAR-T-cell proliferation, and an lactate dehydrogenase assay was used to detect the cytotoxicity of CD123/CLL-1 bispecific tandem CAR-T cells in vitro. RESULTS: Two types of tandem CAR-T cells exhibited significant killing effects on CLL-1 + CD123+ leukaemia cell lines and primary AML tumour cells. The killing efficiency of tandem CAR-T cells in the case of single antigen expression is comparable to that of single target CAR-T cells. When faced with dual target tumour cells, dual target CAR-T cells significantly surpass single target CAR-T cells. CD123/CLL-1 CAR-T cells in tandem targeted and killed CD123- and CLL-1-positive leukaemia cell lines and released a large number of cytokines. CONCLUSIONS: CD123/CLL-1 CAR-T cells in tandem can simultaneously target CD123 and CLL-1 on AML cells, demonstrating a significant ability to kill single antigens and multi-target tumour cells. This suggests that CD123/CLL-1 CAR-T cells exhibit significant advantages in the expression of multiple antigens in a wide range of target cells, which may help overcome the challenges posed by tumour heterogeneity and evasion mechanisms.

How to use the Surveillance, Epidemiology, and End Results (SEER) data: research design and methodology.

In the United States (US), the Surveillance, Epidemiology, and End Results (SEER) program is the only comprehensive source of population-based information that includes stage of cancer at the time of diagnosis and patient survival data. This program aims to provide a database about cancer incidence and survival for studies of surveillance and the development of analytical and methodological tools in the cancer field. Currently, the SEER program covers approximately half of the total cancer patients in the US. A growing number of clinical studies have applied the SEER database in various aspects. However, the intrinsic features of the SEER database, such as the huge data volume and complexity of data types, have hindered its application. In this review, we provided a systematic overview of the commonly used methodologies and study designs for retrospective epidemiological research in order to illustrate the application of the SEER database. Therefore, the goal of this review is to assist researchers in the selection of appropriate methods and study designs for enhancing the robustness and reliability of clinical studies by mining the SEER database.

Development and validation of a mutation-annotated prognostic score for intrahepatic cholangiocarcinoma after resection: a retrospective cohort study.

BACKGROUND: The value of existing prognostic models for intrahepatic cholangiocarcinoma is limited. The inclusion of prognostic gene mutations would enhance the predictive efficacy. METHODS: In the screening cohorts, univariable Cox regression analysis was applied to investigate the effect of individual mutant genes on overall survival (OS). In the training set, multivariable analysis was performed to evaluate the independent prognostic roles of the clinicopathological and mutational parameters, and a prognostic model was constructed. Internal and external validations were conducted to evaluate the performance of this model. RESULTS: Among the recurrent mutations, only TP53 and KRASG12 were significantly associated with OS across all three screening cohorts. In the training cohort, TP53 and KRASG12 mutations in combination with seven other clinical parameters (tumor size, tumor number, vascular invasion, lymph node metastasis, adjacent invasion, CA19-9, and CEA), were independent prognostic factors for OS. A mutation-annotated prognostic score (MAPS) was established based on the nine prognosticators. The C-indices of MAPS (0.782 and 0.731 in the internal and external validation cohorts, respectively) were statistically higher than those of other existing models ( P <0.05). Furthermore, the MAPS model also demonstrated significant value in predicting the possible benefits of upfront surgery and adjuvant therapy. CONCLUSIONS: The MAPS model demonstrated good performance in predicting the OS of intrahepatic cholangiocarcinoma patients. It may also help predict the possible benefits of upfront surgery and adjuvant therapy.

The significance of the best puncture side bone cement/vertebral volume ratio to prevent paravertebral vein leakage of bone cement during vertebroplasty: a retrospective study.

OBJECTIVES: To verify the clinical significance of the best puncture-side bone cement/vertebral volume ratio (PSBCV/VV%) and bone cement leakage in paravertebral veins during vertebroplasty. METHODS: This was a retrospective analysis of a total of 210 patients from September 2021 to December 2022, who were divided into an observation group (110 patients) and a control group (100 patients). In the observation group, patients' preoperative computed tomography (CT) data were imported into Mimics software, and the VV was calculated using the three-dimensional (3D) reconstruction function. Then, based on the best PSBCV/VV% of 13.68% determined in a previous study, the optimal PSBCV to be injected during vertebroplasty was calculated. In the control group, vertebroplasty was performed directly using the conventional method. The incidence of cement leakage into paravertebral veins was observed postoperatively in both groups. RESULTS: There were no statistically significant differences (P > 0.05) in the evaluated indicators between the two groups pre- or postoperatively, including the anterior vertebral margin height, mid-vertebral height, injured vertebral Cobb angle, visual analogue scale (VAS) score, and Oswestry Disability Index (ODI). Intragroup comparisons showed improvements in the anterior vertebral height, mid-vertebral height, injured vertebral Cobb angle, VAS score, and ODI after surgery compared with before surgery (P < 0.05). In the observation group, there were 3 cases of cement leakage into the paravertebral veins, for a leakage rate of 2.7%. In the control group, there were 11 cases of cement leakage into the paravertebral veins, for a leakage rate of 11%. The difference in the leakage rate between the two groups was statistically significant (P = 0.016). CONCLUSION: In vertebroplasty, preoperative VV calculations using Mimics software, combined with calculation of the PSBCV according to the best PSBCV/VV% (13.68%), can effectively prevent leakage of bone cement into paravertebral veins and further prevent serious life-threatening complications such as pulmonary embolism.

Early Circulating Tumor DNA Dynamics Predict Neoadjuvant Therapy Response and Recurrence in Colorectal Liver Metastases: A Prospective Study.

BACKGROUND: For patients with colorectal liver metastases (CRLM) who receive neoadjuvant therapy (NAT), reliable indicators that can early and accurately predict treatment response are lacking. This study was conducted to prospectively investigate the potential of early circulating tumor DNA (ctDNA) dynamics as a precise predictor of NAT response and recurrence in CRLM. METHODS: This study prospectively enrolled 34 patients with CRLM who received NAT, with blood samples collected and subjected to deep targeted panel sequencing at two time points: 1 day before the first and the second cycles of NAT. Correlations of ctDNA mean variant allele frequency (mVAF) dynamics and treatment response were assessed. The performance of early ctDNA dynamics in predicting treatment response was assessed and compared with those of carcinoembryonic antigen (CEA) and cancer antigen 19-9 (CA19-9). RESULTS: The baseline ctDNA mVAF was significantly associated with pre-NAT tumor diameter (r = 0.65; P < 0.0001). After one cycle of NAT, the ctDNA mVAF declined remarkably (P < 0.0001). The dynamic change in ctDNA mVAF of 50% or more was significantly correlated with better NAT responses. The discriminatory capacity of ctDNA mVAF changes was superior to that of CEA or CA19-9 in predicting radiologic response (area under the curve [AUC], 0.90 vs 0.71 vs 0.61) and pathologic tumor regression grade (AUC, 0.83 vs 0.64 vs 0.67). The early changes in ctDNA mVAF but not CEA or CA19-9 were an independent indicator of recurrence-free survival (RFS) (hazard ratio, 4.0; P = 0.023). CONCLUSIONS: For CRLM patients receiving NAT, an early ctDNA change is a superior predictor of treatment response and recurrence compared with conventional tumor markers.

Amplicon-based metagenomic association analysis of gut microbiota in relation to egg-laying period and breeds of hens.

BACKGROUND: The gut microbiota plays an essential role in maintaining gut homeostasis and improving performance, with the composition of microbial communities visibly differing across different laying stages in hens and significantly correlating with egg production. To gain further insights into the association between microbial community characteristics and laying periods in Hy-Line variety brown and Isa brown laying hens, we conducted a 16S rRNA amplicon sequencing survey. RESULTS: Our result revealed the diversity of bacteria in the early laying period was commonly higher than peak, and in Hy-Line variety brown laying hens were generally higher than Isa brown. Principal coordinate analysis (PCoA) and permutational multivariate analysis of variance (PERMANOVA) revealed that the structure and composition of the gut microbiota of laying hens exhibited significant differences among different groups. Phylum Firmicutes, Bacteroidota, Proteobacteria, and Fusobacteriota were found that dominant in the host's feces. Therein, the abundance of Fusobacteriota was higher in the peak period than in the early period, while the abundance of Cyanobacteria in the early period was higher in two breeds of hens. Furthermore, random forest based on machine learning showed that there were several distinctly abundant genera, which can be used as potential biomarkers to differentiate the different groups of laying periods and breeds. In addition, the prediction of biological function indicated the existing discrepancy in microbial function among the microbiota of four groups. CONCLUSIONS: Our findings offer new insights into the bacterial diversity and intestinal flora composition of different strains of laying hens during various laying periods, contributing significantly to the improvement of production performance and the prevention of chicken diseases.

Intraoperative Diagnosis of Serosal Invasion in Gastric Cancer by Magnifying Endoscopy with Narrow-Band Imaging for Intraoperative Measurement Decision.

Purpose: To establish a precise diagnostic method for serosal invasion in gastric cancer (GC) during surgery using therapeutic measures, and facilitate quick decision-making. Methods: A total of 19 GC patients treated in the department of gastrointestinal surgery of Fujian Provincial Hospital between April 2019 and December 2020 were enrolled. An electronic gastroscopy with a magnifying endoscope with narrow-band imaging was used to photograph the serosal surface of the GC lesion site and the normal gastric wall around the lesion during surgery. The endoscopic diagnosis was confirmed on the basis of the microvascular phenotype of the serosal surface and validated by comparison with the pathological diagnosis. Results: Under the specific endoscopy, serosal invasion, including subserosal tissue invasion and serosal layer invasion, was diagnosed by observing the capillary morphology change, and capillary diameter and density increase. According to the pathological diagnosis, the accuracy of serosal invasion diagnosis was 94.7%, the sensitivity was 100%, the specificity was 75%, the positive predictive value was 93.8%, and the negative predictive value was 100%. To further distinguish the subserosal tissue invasion and serosal layer invasion, the magnifying endoscope with narrow-band imaging possessed a 78.9% accuracy by distinguishing irregular changes in microvessels. Conclusions: Magnifying endoscope with narrow-band imaging is less time-consuming than pathological diagnosis. Intraoperative diagnosis using microvascular observation can accurately detect serosal invasion. It is of value for the intraoperative diagnosis in GC patients.

Effect of melatonin on ATG2B-mediated autophagy regulation in sheep granulosa cells with different FecB genotypes.

Melatonin (MLT) protects cells by reducing reactive oxygen species (ROS) levels, which are key for inducing cellular autophagy. The aim of this study was to investigate the molecular mechanisms underlying MLT regulation of autophagy in granulosa cells (GCs) with BMPR-1B homozygous (FecB BB) and wild type (FecB ++) mutations. GCs collected from small-tailed Han sheep with different FecB genotypes were typed using a TaqMan probe assay, and autophagy levels were found to be significantly higher in GCs with FecB BB than the levels in those with FecB ++. Autophagy-related 2 homolog B (ATG2B) was associated with cell autophagy and was highly expressed in GCs with the FecB BB genotype in small-tailed Han sheep. Overexpression of ATG2B in the GCs of sheep with both FecB genotypes promoted GC autophagy, and the contrary was observed after the inhibition of ATG2B expression. Subsequently, treatment of GCs with different genotypes of FecB and MLT revealed a significant decrease in cellular autophagy and an increase in ATG2B expression. Addition of MLT to GCs with inhibited ATG2B expression revealed that MLT could protect GCs by decreasing ROS levels, especially in GCs with FecB ++ genotype. In conclusion, this study determined that autophagy levels were significantly higher in sheep GCs with FecB BB genotype than the levels in those with FecB ++ genotype, which may have contributed to the difference in lambing numbers between the two FecB genotypes. Autophagy was regulated by ATG2B and was able to protect GCs by reducing the high levels of ROS produced following inhibition of ATG2B through the addition of MLT in vitro.

Progress on the effect of FecB mutation on BMPR1B activity and BMP/SMAD pathway in sheep.

BMPR1B is the first major gene of litter size identified in sheep. However, the molecular mechanism of the FecB mutation that increases the ovulation rate in sheep is still unclear. In recent years, it has been demonstrated that BMPR1B activity is regulated by the small molecule repressor protein FKBP1A, which acts as a key activity switch of the BMPR1B in the BMP/SMAD pathway. The FecB mutation is located close to the binding site of FKBP1A and BMPR1B. In this review, we summarize the structure of BMPR1B and FKBP1A proteins, and clarify the spatial interactive domains of the two proteins with respect to the location of the FecB mutation. Then the relationship between the FecB mutation and the degree of affinity of the two proteins are predicted. Finally, the hypothesis that FecB mutation causes change of activity in BMP/SMAD pathway by affecting the intensity of the interactions between BMPR1B and FKBP1A is proposed. This hypothesis provides a new clue to investigate the molecular mechanism of FecB mutation affecting ovulation rate and litter size in sheep.

Near-Infrared Fluorescent Probe for Imaging Upregulated Hydrogen Sulfide Levels in Rice under Salt and Drought Stress.

Hydrogen sulfide (H2S) is a hazardous gas found in living organisms and is directly tied to our daily lives. Recent studies show that it plays a significant role in plant growth, development, and response to environmental stresses. However, few of the reported near-infrared (NIR) fluorescent probes have been applied to rice and deeply investigated the influence of the external environment on the biological molecules in its internal environment. Therefore, our team created BSZ-H2S, which has the advantage of an emission wavelength of up to 720 nm with fast response, successfully applying it to cell and zebrafish imaging. More importantly, the probe detected H2S in rice roots by in situ imaging in a facile manner and verified the existence of an upregulation process of H2S in response to salt and drought stress. This work provides a concept for the intervention of external stresses in rice culture.

Localization and density of tertiary lymphoid structures associate with molecular subtype and clinical outcome in colorectal cancer liver metastases.

BACKGROUND: Tertiary lymphoid structures (TLSs) have been proposed to assess the prognosis of patients with cancer. Here, we investigated the prognostic value and relevant mechanisms of TLSs in colorectal cancer liver metastases (CRCLM). METHODS: 603 patients with CRCLM treated by surgical resection from three cancer centers were included. The TLSs were categorized according to their anatomic subregions and quantified, and a TLS scoring system was established for intratumor region (T score) and peritumor region (P score). Differences in relapse-free survival (RFS) and overall survival (OS) between groups were determined. Multiplex immunohistochemical staining (mIHC) was used to determine the cellular composition of TLSs in 40 CRCLM patients. RESULTS: T score positively correlated with superior prognosis, while P score negatively associated with poor survival (all p<0.05). Meanwhile, T score was positively associated with specific mutation subtype of KRAS. Furthermore, TLSs enrichment gene expression was significantly associated with survival and transcriptomic subtypes of CRCLM. Subsequently, mIHC showed that the densities of Treg cells, M2 macrophages and Tfh cells were significantly higher in intratumor TLSs than in peritumor TLSs (p=0.029, p=0.047 and p=0.041, respectively), and the frequencies of Treg cells and M2 macrophages were positively correlated with P score, while the frequencies of Tfh cells were positively associated with T scores in intratumor TLSs (all p<0.05). Next, based on the distribution and abundance of TLSs, an Immune Score combining T score and P score was established which categorized CRCLM patients into four immune classes with different prognosis (all p<0.05). Among them, patients with higher immune class have more favorable prognoses. The C-index of Immune Class for RFS and OS was higher than Clinical Risk Score statistically. These results were also confirmed by the other two validation cohorts. CONCLUSIONS: The distribution and abundance of TLSs is significantly associated with RFS and OS of CRCLM patients, and a novel immune class was proposed for predicting the prognosis of CRCLM patients.

Nanomedicines Reprogram Synovial Macrophages by Scavenging Nitric Oxide and Silencing CA9 in Progressive Osteoarthritis.

Osteoarthritis (OA) is a progressive joint disease characterized by inflammation and cartilage destruction, and its progression is closely related to imbalances in the M1/M2 synovial macrophages. A two-pronged strategy for the regulation of intracellular/extracellular nitric oxide (NO) and hydrogen protons for reprogramming M1/M2 synovial macrophages is proposed. The combination of carbonic anhydrase IX (CA9) siRNA and NO scavenger in "two-in-one" nanocarriers (NAHA-CaP/siRNA nanoparticles) is developed for progressive OA therapy by scavenging NO and inhibiting CA9 expression in synovial macrophages. In vitro experiments demonstrate that these NPs can significantly scavenge intracellular NO similar to the levels as those in the normal group and downregulate the expression levels of CA9 mRNA (≈90%), thereby repolarizing the M1 macrophages into the M2 phenotype and increasing the expression levels of pro-chondrogenic TGF-ß1 mRNA (≈1.3-fold), and inhibiting chondrocyte apoptosis. Furthermore, in vivo experiments show that the NPs have great anti-inflammation, cartilage protection and repair effects, thereby effectively alleviating OA progression in both monoiodoacetic acid-induced early and late OA mouse models and a surgical destabilization of medial meniscus-induced OA rat model. Therefore, the siCA9 and NO scavenger "two-in-one" delivery system is a potential and efficient strategy for progressive OA treatment.