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Ovarian cancer is a malignant tumor that seriously endangers health. Early ovarian cancer symptoms are frequently challenging to detect, resulting in a large proportion of patients reaching an advanced stage when diagnosed. Conventional diagnosis relies heavily on serum biomarkers and pathological examination, but their sensitivity and specificity require improvement. Targeted therapy inhibits tumor growth by targeting certain characteristics of tumor cells, such as signaling pathways and gene mutations. However, the effectiveness of targeted therapy varies among individuals due to differences in their unique biological characteristics and requires individualized strategies. Immunotherapy is a promising treatment for ovarian cancer due to its long-lasting antitumor effect. Nevertheless, issues such as variable efficacy, immune-associated adverse effects and drug resistance remain to be resolved. The present review discusses the diagnostic strategies, rationale, treatment strategies and prospects of targeted therapy and immunotherapy for ovarian cancer.
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Background: Predicting the response to neoadjuvant chemoradiotherapy (nCRT) before initiating treatment is essential for tailoring therapeutic strategies and monitoring prognosis in locally advanced rectal cancer (LARC). In this study, we aimed to develop and validate radiomic-based models to predict clinical and pathological complete responses (cCR and pCR, respectively) by incorporating the Shapley Additive exPlanations (SHAP) method for model interpretation. Methods: A total of 285 patients with complete pretreatment clinical characteristics and T1-weighted (T1W) and T2-weighted (T2W) magnetic resonance imaging (MRI) at 3 centers were retrospectively recruited. The features of tumor lesions were extracted by PyRadiomics and selected using least absolute shrinkage and selection operator (LASSO) algorithm. The selected features were used to build multilayer perceptron (MLP) models alone or combined with clinical features. Area under the receiver operating characteristic curve (AUC), decision curve, and calibration curve were applied to evaluate performance of models. The SHAP method was adopted to explain the prediction models. Results: The radiomic-based models all showed better performances than clinical models. The clinical-radiomic models showed the best differentiation on cCR and pCR with mean AUCs of 0.718 and 0.810 in the validation set, respectively. The decision curves of the clinical-radiomic models showed its values in clinical application. The SHAP method powerfully interpreted the prediction models both at a holistic and individual levels. Conclusions: Our study highlights that the radiomic-based prediction models have more excellent abilities than clinical models and can effectively predict treatment response and optimize therapeutic strategies for patients with LARCs.
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Intervertebral disc degeneration (IVDD) is a common degenerative disease which is closely related to low back pain (LBP) and brings huge economic and social burdens. In this study, we explored the therapeutic effects of Homoplantaginin (Hom) for IVDD due to its convincing anti-inflammatory and antioxidant functions. TNF-α was used to simulate the inflammatory environment for nucleus pulposus (NP) cells in vitro. We verified that Hom could alleviate the TNF-α-induced inflammation and disturbance of ECM homeostasis through blocking the NF-κB/MAPK signaling pathways. Subsequently, we screened the binding targets of Hom and confirmed that Hom could directly bind to TAK1 and inhibit its phosphorylation to down-regulate the inflammation-related pathways. The therapeutic effects of Hom on IVDD were further validated through a needle puncture rat model in vivo. Overall, Hom was a promising small molecule for IVDD early intervention, possessing huge clinical translational value.
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Degeneración del Disco Intervertebral , Quinasas Quinasa Quinasa PAM , FN-kappa B , Animales , Humanos , Masculino , Ratas , Células Cultivadas , Degeneración del Disco Intervertebral/tratamiento farmacológico , Degeneración del Disco Intervertebral/metabolismo , Quinasas Quinasa Quinasa PAM/metabolismo , Quinasas Quinasa Quinasa PAM/antagonistas & inhibidores , Sistema de Señalización de MAP Quinasas/efectos de los fármacos , Sistema de Señalización de MAP Quinasas/fisiología , FN-kappa B/metabolismo , FN-kappa B/antagonistas & inhibidores , Núcleo Pulposo/metabolismo , Núcleo Pulposo/efectos de los fármacos , Núcleo Pulposo/patología , Unión Proteica/fisiología , Unión Proteica/efectos de los fármacos , Ratas Sprague-Dawley , Factor de Necrosis Tumoral alfa/metabolismoRESUMEN
Potyviridae, the largest family of plant RNA viruses, includes many important pathogens that significantly reduce the yields of many crops worldwide. In this study, we report that the 6-kilodalton peptide 1 (6K1), one of the least characterized potyviral proteins, is an endoplasmic reticulum-localized protein. AI-assisted structure modeling and biochemical assays suggest that 6K1 forms pentamers with a central hydrophobic tunnel, can increase the cell membrane permeability of Escherichia coli and Nicotiana benthamiana, and can conduct potassium in Saccharomyces cerevisiae. An infectivity assay showed that viral proliferation is inhibited by mutations that affect 6K1 multimerization. Moreover, the 6K1 or its homologous 7K proteins from other viruses of the Potyviridae family also have the ability to increase cell membrane permeability and transmembrane potassium conductance. Taken together, these data reveal that 6K1 and its homologous 7K proteins function as viroporins in viral infected cells.
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Nicotiana , Nicotiana/virología , Nicotiana/metabolismo , Potyviridae/genética , Potyviridae/metabolismo , Proteínas Virales/metabolismo , Proteínas Virales/genética , Permeabilidad de la Membrana Celular , Retículo Endoplásmico/metabolismo , Retículo Endoplásmico/virología , Saccharomyces cerevisiae/genética , Saccharomyces cerevisiae/metabolismo , Proteínas Viroporinas/metabolismo , Proteínas Viroporinas/genética , Escherichia coli/genética , Escherichia coli/metabolismo , Virus de Plantas/genética , Virus de Plantas/fisiología , Enfermedades de las Plantas/virología , Potasio/metabolismoRESUMEN
Intervertebral disc is a highly rhythmical tissue. As a key factor linking biorhythm and inflammatory response, the shielding effect of NR1D1 in the process of intervertebral disc degeneration remains unclear. Here, we first confirmed that NR1D1 in the nucleus pulposus tissue presents periodic rhythmic changes and decreases in expression with intervertebral disc degeneration. Second, when NR1D1 was activated by SR9009 in vitro, NLRP3 inflammasome assembly and IL-1ß production were inhibited, while ECM synthesis was increased. Finally, the vivo experiments further confirmed that the activation of NR1D1 can delay the process of disc degeneration to a certain extent. Mechanistically, we demonstrate that NR1D1 can bind to IL-1ß and NLRP3 promoters, and that the NR1D1/NLRP3/IL-1ß pathway is involved in this process. Our results demonstrate that the activation of NR1D1 can effectively reduce IL-1ß secretion, alleviate LPS-induced NPMSC pyroptosis, and protect ECM degeneration.
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Plant viruses must move through plasmodesmata (PD) to complete their life cycles. For viruses in the Potyviridae family (potyvirids), three viral factors (P3N-PIPO, CI, and CP) and few host proteins are known to participate in this event. Nevertheless, not all the proteins engaging in the cell-to-cell movement of potyvirids have been discovered. Here, we found that HCPro2 encoded by areca palm necrotic ring spot virus (ANRSV) assists viral intercellular movement, which could be functionally complemented by its counterpart HCPro from a potyvirus. Affinity purification and mass spectrometry identified several viral factors (including CI and CP) and host proteins that are physically associated with HCPro2. We demonstrated that HCPro2 interacts with both CI and CP in planta in forming PD-localized complexes during viral infection. Further, we screened HCPro2-associating host proteins, and identified a common host protein in Nicotiana benthamiana-Rubisco small subunit (NbRbCS) that mediates the interactions of HCPro2 with CI or CP, and CI with CP. Knockdown of NbRbCS impairs these interactions, and significantly attenuates the intercellular and systemic movement of ANRSV and three other potyvirids (turnip mosaic virus, pepper veinal mottle virus, and telosma mosaic virus). This study indicates that a nucleus-encoded chloroplast-targeted protein is hijacked by potyvirids as the scaffold protein to assemble a complex to facilitate viral movement across cells.
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Potyvirus , Proteínas Virales , Proteínas Virales/metabolismo , Ribulosa-Bifosfato Carboxilasa/metabolismo , Potyvirus/metabolismo , Enfermedades de las PlantasRESUMEN
Colorectal cancer liver metastasis (CRLM) presents a clinical challenge, and optimizing treatment strategies is crucial for improving patient outcomes. Surgical resection, a key element in achieving prolonged survival, is often linked to a heightened risk of recurrence. Acknowledging the potential benefits of preoperative neoadjuvant chemotherapy in managing resectable liver metastases, this approach has gained attention for its role in tumor downsizing, assessing biological behavior, and reducing the risk of postoperative recurrence. However, the use of neoadjuvant chemotherapy in initially resectable CRLM sparks ongoing debates. The balance between tumor reduction and the risk of hepatic injury, coupled with concerns about delaying surgery, necessitates a nuanced approach. This article explores recent research insights and draws upon the practical experiences at our center to address critical issues regarding considerations for initially resectable cases. Examining the criteria for patient selection and the judicious choice of neoadjuvant regimens are pivotal areas of discussion. Striking the right balance between maximizing treatment efficacy and minimizing adverse effects is imperative. The dynamic landscape of precision medicine is also reflected in the evolving role of gene testing, such as RAS/BRAF and PIK3CA, in tailoring neoadjuvant regimens. Furthermore, the review emphasizes the need for a multidisciplinary approach to navigate the complexities of CRLM. Integrating technical expertise and biological insights is crucial in refining neoadjuvant strategies. The management of progression following neoadjuvant chemotherapy requires a tailored approach, acknowledging the diverse biological behaviors that may emerge. In conclusion, this review aims to provide a comprehensive perspective on the considerations, challenges, and advancements in the use of neoadjuvant chemotherapy for initially resectable CRLM. By combining evidence-based insights with practical experiences, we aspire to contribute to the ongoing discourse on refining treatment paradigms for improved outcomes in patients with CRLM.
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Neoplasias Colorrectales , Neoplasias Hepáticas , Humanos , Terapia Neoadyuvante , Hepatectomía/efectos adversos , Neoplasias Colorrectales/patología , Resultado del Tratamiento , Neoplasias Hepáticas/tratamiento farmacológico , Neoplasias Hepáticas/cirugíaRESUMEN
Apple latent spherical virus (ALSV) is widely used as a virus-induced gene silencing (VIGS) vector for function genome study. However, the application of ALSV to soybeans is limited by the resistance of many varieties. In this study, the genetic locus linked to the resistance of a resistant soybean variety Heinong 84 was mapped by high-throughput sequencing-based bulk segregation analysis (HTS-BSA) using a hybrid population crossed from Heinong 84 and a susceptible variety, Zhonghuang 13. The results showed that the resistance of Heinong 84 to ALSV is controlled by two genetic loci located on chromosomes 2 and 11, respectively. Cleaved amplified polymorphic sequence (CAPS) markers were developed for identification and genotyping. Inheritance and biochemical analyses suggest that the resistance locus on chromosome 2 plays a dominant dose-dependent role, while the other locus contributes a secondary role in resisting ALSV. The resistance locus on chromosome 2 might encode a protein that can directly inhibit viral proliferation, while the secondary resistance locus on chromosome 11 may encode a host factor required for viral proliferation. Together, these data reveal novel insights on the resistance mechanism of Heinong 84 to ALSV, which will benefit the application of ALSV as a VIGS vector.
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Glycine max , Secoviridae , Glycine max/genética , Vectores Genéticos , Enfermedades de las Plantas/genéticaRESUMEN
This procedure provides a comprehensive method for isolating double-stranded RNA (dsRNA) that relies on the different solubility of various nucleic acids in lithium chloride (LiC1). The approach offers several notable advantages including simplicity, avoidance of enzymatic treatments, and the ability to obtain relatively high yields of undegraded dsRNA over other conventional techniques. Moreover, it allows for the separation of different groups of cellular and viral nucleic acids from a single tissue sample. This method was further improved to increase the purity of dsRNA using plant tissues infected by RNA viruses.
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Cloruro de Litio , Ácidos Nucleicos , ARN Bicatenario , Fraccionamiento Químico , SolubilidadRESUMEN
Double-stranded RNA (dsRNA) is the replicate intermediate of all RNA viruses, and is also recognized by their host cells as a virus-invading molecule signal. Analysis of the localization and dynamic of virus-induced dsRNA can reveal crucial information concerning the molecular mechanism of virus replication and host responses to viral infection. In this chapter, we provide an easy and efficient protocol called dsRNA binding-dependent fluorescence complementation (dRBFC) assay for labeling the dsRNAs in living plant cells using two different plant RNA viruses, namely potato virus X and turnip mosaic virus. Moreover, both YFP- and mRFP-based dRBFC plasmids are available for the flexibility of experiment design.
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Potexvirus , ARN Bicatenario , ARN Bicatenario/genética , Células Vegetales , Bioensayo , Potexvirus/genética , ARN de PlantaRESUMEN
Acridine orange is a nucleic acid binding dye that emits green fluorescence when bound to double-stranded DNA or RNA and red fluorescence when bound to single-stranded DNA or RNA under ultraviolet light. This unique characterization allows it to be used for distinguishing or visualization of dsRNA. Here, we present a convenient and efficient protocol for detecting dsRNA in polyacrylamide gels.
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Naranja de Acridina , ARN Bicatenario , Coloración y Etiquetado , ADN de Cadena Simple , Rayos UltravioletaRESUMEN
RNA silencing (also known as gene silencing) is an evolutionary conserved mechanism that is involved in regulating gene expression, suppressing mobile elements, and defensing virus infection. RNA silencing is triggered by double-stranded RNA via Dicer or Dicer-like riboendonucleases. DsRNAs are also the replication intermediates of all RNA viruses; as a result, plant RNA viruses are ideal candidates to induce RNA silencing. A large body of plant viruses have been modified into vectors for RNA silencing in varied plant species. Here, we described a simple, time-saving, and operable system for gene function and genetic breeding study of potato and Nicotiana benthamiana using a potato mop-top (MPTV)-based vector.
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Virus de Plantas , ARN Bicatenario , ARN Bicatenario/genética , Virus de Plantas/genética , Enfermedades de las Plantas/genética , Fitomejoramiento , Silenciador del GenRESUMEN
Transgenic expression of hairpin RNA or artificial microRNA is widely used for genetic studies in plant science. However, induction of RNA silencing by transgenic method may have a problem when studying essential genes. Here, we provide an in planta transient double-stranded RNA (dsRNA) producing system using a tobacco necrosis virus A (TNV-A)-based replicon for efficiently inducing RNA silencing in plants. In this system, the target sequence is placed between the cauliflower mosaic virus 35S promoter and the 3'-terminal part of viral genomic RNA, while the C-terminal part of TNV-A RNA-dependent RNA polymerase (p82C) is expressed by a different promoter. The endogenous RNA polymerase-synthesized target sequence is recruited by p82C to produce dsRNA to induce RNA silencing.
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MicroARNs , Tombusviridae , Interferencia de ARN , ARN Bicatenario/genética , Tombusviridae/genética , MicroARNs/genética , ARN Viral/genéticaRESUMEN
Colorectal melanoma (CRM) is a rare malignant tumor with severe complications, and there is currently a lack of systematic research. We conducted a study that combined proteomics and mutation data of CRM from a cohort of three centers over a 16-years period (2005-2021). The patients were divided into a training set consisting of two centers and a testing set comprising the other center. Unsupervised clustering was conducted on the training set to form two molecular subtypes for clinical characterization and functional analysis. The testing set was used to validate the survival differences between the two subtypes. The comprehensive analysis identified two subtypes of CRM: immune exhausted C1 cluster and DNA repair C2 cluster. The former subtype exhibited characteristics of metabolic disturbance, immune suppression, and poor prognosis, along with APC mutations. A machine learning algorithm named Support Vector Machine (SVM) was applied to predict the classification of CRM patients based on protein expression in the external testing cohort. Two subtypes of primary CRM with clinical and proteomic characteristics provides a reference for subsequent diagnosis and treatments.
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Neoplasias Colorrectales , Melanoma , Humanos , Melanoma/genética , Multiómica , Estudios Prospectivos , Proteómica , PronósticoRESUMEN
BACKGROUND CONTEXT: Cervical laminoplasty is a common approach for the treatment of multilevel cervical spondylotic myelopathy (CSM). Postoperative loss of cervical lordosis (LCL) was associated with lower extension motion of the cervical spine before laminoplasty. PURPOSE: To analyze the possible causes of preoperative cervical extension capacity affecting LCL after laminoplasty by evaluating the changes in cervical lordosis (CL) at different stages. STUDY DESIGN/SETTING: Retrospective study. PATIENT SAMPLE: Seventy-two patients undergoing laminoplasty due to multilevel CSM. OUTCOME MEASURES: Radiographic parameters included CL, extension CL (eCL), flexion CL (fCL), range of motion (ROM), extension ROM (eROM), flexion ROM (fROM) and LCL. Clinical outcomes were assessed using the Japanese Orthopedic Association (JOA) and neck disability index (NDI) score. METHODS: The data were recorded before surgery and at 3- and 24-month follow-up. All patients completed a cervical extension test preoperatively. A receiver operating characteristic (ROC) curve of eROM was constructed to discriminate the patients with and without postoperative kyphotic deformity. RESULTS: According to the optimal cut-off value of eROM, the patients were divided into two groups: extension group (eROM≥9.3°) and control group (eROM<9.3°). The radiographic outcomes demonstrated no significant differences in CL, eCL, fCL and ROM between the two groups. Both eROM and fROM were significantly different in the two groups. There was a significant change in CL in the extension group at 3-month follow-up and in the control group at 24-month follow-up. The extension group exhibited significantly lower LCL compared with the control group at follow-up. No significant difference between the two groups was noted in the JOA recovery rate, while the NDI score was significantly different at 24-month follow-up. The positivity ratio of the extension test was significantly greater in the extension group than that in the control group. CONCLUSIONS: eROM in patients with favorable preoperative cervical extension capacity (eROM≥9.3°) consisted of the actual extension capacity and compensatory flexion. The cervical alignment would be spontaneously restored to its initial lordosis in the short term after laminoplasty. These patients had no substantial LCL at 24-month follow-up and would be good candidates for laminoplasty.
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Laminoplastia , Lordosis , Enfermedades de la Médula Espinal , Espondilosis , Humanos , Lordosis/diagnóstico por imagen , Lordosis/etiología , Lordosis/cirugía , Laminoplastia/efectos adversos , Estudios Retrospectivos , Cuello , Enfermedades de la Médula Espinal/cirugía , Vértebras Cervicales/diagnóstico por imagen , Vértebras Cervicales/cirugía , Espondilosis/diagnóstico por imagen , Espondilosis/cirugía , Espondilosis/complicaciones , Resultado del TratamientoRESUMEN
It is widely accepted that the minus strands of positive single-strand RNA (+ssRNA) viruses function as replication templates only. Gong et al. revealed that the minus strand of two unrelated +ssRNA viruses encodes proteins. This textbook-changing discovery calls for the reconsideration of the molecular mechanisms underlying the infection cycle of +ssRNA viruses.
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Virus ARN , ARN Viral , ARN Viral/genética , ARN Viral/metabolismo , Replicación Viral , Virus ARN Monocatenarios Positivos/genética , Virus ARN Monocatenarios Positivos/metabolismo , Virus ARN/genética , Virus ARN/metabolismoRESUMEN
Plant viruses have been engineered to express proteins and induce gene silencing for decades. Recently, plant viruses have also been used to deliver components into plant cells for genome editing, a technique called virus-induced genome editing (VIGE). Although more than a dozen plant viruses have been engineered into VIGE vectors and VIGE has been successfully accomplished in some plant species, application of VIGE to crops that are difficult to tissue culture and/or have low regeneration efficiency is still tough. This paper discusses factors to consider for an ideal VIGE vector, including insertion capacity for foreign DNA, vertical transmission ability, expression level of the target gene, stability of foreign DNA insertion, and biosafety. We also proposed a step-by-step schedule for excavating the suitable viral vector for VIGE.
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Edición Génica , Virus de Plantas , Edición Génica/métodos , Sistemas CRISPR-Cas , Virus de Plantas/genética , Productos Agrícolas , ADN , Genoma de PlantaRESUMEN
Background: The changes in the microenvironment of degenerative intervertebral discs cause oxidative stress injury and excessive apoptosis of intervertebral disc endogenous stem cells. The purpose of this study was to explore the possible mechanism of the protective effect of melatonin on oxidative stress injury in NPMSCs induced by H2O2. Methods: The Cell Counting Kit-8 assay was used to evaluate the cytotoxicity of hydrogen peroxide and the protective effects of melatonin. ROS content was detected by 2'7'-dichlorofluorescin diacetate (DCFH-DA). Mitochondrial membrane potential (MMP) was detected by the JC-1assay. Transferase mediated d-UTP Nick end labeling (TUNEL) and Annexin V/PI double staining were used to determine the apoptosis rate. Additionally, apoptosis-associated proteins and PI3K/Akt signaling pathway-related proteins were evaluated by immunofluorescence, immunoblotting and PCR. ECMs were evaluated by RTâPCR and immunofluorescence. In vivo, X-ray, Magnetic resonance imaging (MRI) and Histological analyses were used to evaluate the protective effect of melatonin. Results: Melatonin had an obvious protective effect on NPMSCs treated with 0-10 µM melatonin for 24 h. In addition, melatonin also had obvious protective effects on mitochondrial dysfunction, decreased membrane potential and cell senescence induced by H2O2. More importantly, melatonin could significantly reduce the apoptosis of nucleus pulposus mesenchymal stem cells induced by H2O2 by regulating the expression of apoptosis-related proteins and decreasing the rate of apoptosis. After treatment with melatonin, the PI3K/Akt pathway was significantly activated in nucleus pulposus mesenchymal stem cells, while the protective effect was significantly weakened after PI3K-IN-1 treatment. In vivo, the results of X-ray, MRI and histological analyses showed that therapy with melatonin could partially reduce the degree of intervertebral disc degeneration. Conclusion: Our research demonstrated that melatonin can effectively alleviate the excessive apoptosis and mitochondrial dysfunction of nucleus pulposus mesenchymal stem cells induced by oxidative stress via the PI3K/Akt pathway, which provides a novel idea for the therapy of intervertebral disc degeneration. The translational potential of this article: This study indicates that melatonin can effectively alleviate the excessive apoptosis and mitochondrial dysfunction of NPMSCs through activating the PI3K/Akt pathway. Melatonin might serve as a promising candidate for the prevention and treatment of Intervertebral disc degeneration disease (IVDD) in the future.
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Drug resistance remains a significant challenge in the treatment of colorectal cancer (CRC). In recent years, the emerging field of ferroptosis, a unique form of regulated cell death characterized by iron-dependent lipid peroxidation, has offered new insights and potential therapeutic strategies for overcoming drug resistance in CRC. This review examines the role of ferroptosis in CRC and its impact on drug resistance. It highlights the distinctive features and advantages of ferroptosis compared to other cell death pathways, such as apoptosis and necrosis. Furthermore, the review discusses current research advances in the field, including novel treatment approaches that target ferroptosis. These approaches involve the use of ferroptosis inducers, interventions in iron metabolism and lipid peroxidation, and combination therapies to enhance the efficacy of ferroptosis. The review also explores the potential of immunotherapy in modulating ferroptosis as a therapeutic strategy. Additionally, it evaluates the strengths and limitations of targeting ferroptosis, such as its selectivity, low side effects, and potential to overcome resistance, as well as challenges related to treatment specificity and drug development. Looking to the future, this review discusses the prospects of ferroptosis-based therapies in CRC, emphasizing the importance of further research to elucidate the interaction between ferroptosis and drug resistance. It proposes future directions for more effective treatment strategies, including the development of new therapeutic approaches, combination therapies, and integration with emerging fields such as precision medicine. In conclusion, harnessing ferroptosis represents a promising avenue for overcoming drug resistance in CRC. Continued research efforts in this field are crucial for optimizing therapeutic outcomes and providing hope for CRC patients.
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Spondyloepiphyseal dysplasia (SEMD) is a rare disease in which cartilage growth is disrupted, and the DDRGK1 mutation is one of the causative genes. In our study, we established Ddrgk1fl/fl, Col2a1-ERT Cre mice, which showed a thickened hypertrophic zone (HZ) in the growth plate, simulating the previous reported SEMD pathology in vivo. Instead of the classical modulation mechanism towards SOX9, our further mechanism study found that DDRGK1 stabilizes the stress sensor endoplasmic reticulum-to-nucleus signaling 1 (IRE1α) to maintain endoplasmic reticulum (ER) homoeostasis. The loss of DDRGK1 decreased the UFMylation and subsequently led to increased ubiquitylation-mediated IRE1α degradation, causing ER dysfunction and activating the PERK/CHOP/Caspase3 apoptosis pathway. Further DDRGK1 K268R-mutant mice revealed the importance of K268 UFMylation site in IRE1α degradation and subsequent ER dysfunction. In conclusion, DDRGK1 stabilizes IRE1α to ameliorate ER stress and following apoptosis in chondrocytes, which finally promote the normal chondrogenesis.