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This was the first article reported a fatal case of chlorfenapyr poisoning in a child, and the typical symptoms before death include high fever, severe sweating, coma, and limb stiffness, and elevation of myocardial enzymes and myoglobin; neurological symptoms tend to appear earlier in children than in adults.
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Decoupling conductivity(σ)and Seebeck coefficient(S)by electronic topological transitions (ETT) under high pressure (2-4 GPa) is a promising method for bismuth telluride (Bi2Te3) to optimize thermoelectric (TE) performance. However, theScannot dramatically increase with increasingσwhen ETT occurs in Bi2Te3, which impedes optimizing TE performance by utilizing ETT in Bi2Te3. A new strategy of enhanced ETT by combining lattice distortions and high pressure is proposed in this work. The lattice distortions in Bi2Te3were introduced by high pressure and high temperature (HPHT) treatment to generate surplus dislocations. Thein-situmeasurements ofσandSat HPHT in Bi2Te3with lattice distortions show an enhanced ETT effect at 2 GPa, which causes decoupleσandSwith an anomalous increase in its|S|about 22%. The ETT effect causes the figure of merit (ZT) of Bi2Te3can be improved to 0.275 at 1.50-2.62 GPa, 460 K, it is more than 62% compared with 0.79 GPa, at 450 K. The excellent TE performance of Bi2Te3arising from the lattice distortions can result in local non-hydrostatic pressure which enhances ETT under high pressure. This work provides a new strategy to enhance ETT to decoupleσandS, and search for better TE materials from the pressure dimension in the future.
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Dimethyl fumarate (DMF) is an immunosuppressant commonly used to treat multiple sclerosis and other autoimmune diseases. Despite known side effects such as lymphopenia, the effect of DMF on cardiac development remains unclear. To assess this, we used zebrafish to evaluate the cardiac developmental toxicity of DMF. Our study showed that DMF reduced the survival rate of zebrafish embryos, with those exposed to 1, 1.3, and 1.6 mg/L exhibiting heart rate reduction, shortened body length, delayed yolk sac absorption, pericardial edema, increased distance from sinus venous to bulbus arteriosus, and separation of cardiomyocytes and endocardial cells at 72 hpf. Heart development-related genes showed disorder, apoptosis-related genes were up-regulated, and the oxidative stress response was down-regulated. Treatment with cysteamine ameliorated the heart development defects. Our study demonstrates that DMF induces cardiac developmental toxicity in zebrafish, possibly by down-regulating oxidative stress responses. This study provides a certain research basis for further study of DMF-induced cardiac developmental toxicity, and provides some experimental evidence for future clinical application and study of DMF.
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Cardiopatías Congénitas , Pez Cebra , Animales , Pez Cebra/fisiología , Dimetilfumarato/toxicidad , Dimetilfumarato/metabolismo , Regulación hacia Abajo , Embrión no Mamífero , Estrés Oxidativo , Cardiotoxicidad/metabolismoRESUMEN
Transparent nano-polycrystalline diamond (t-NPD) possesses superior mechanical properties compared to single and traditional polycrystalline diamonds. However, the harsh synthetic conditions significantly limit its synthesis and applications. In this study, a synthesis routine is presented for t-NPD under low pressure and low temperature conditions, 10 GPa, 1600 °C and 15 GPa, 1350 °C similar with the synthesis condition of organic precursor. Self-catalyzed hydrogenated carbon nano-onions (HCNOs) from the combustion of naphthalene enable synthesis under nearly industrial conditions, which are like organic precursor and much lower than that of graphite and other carbon allotropes. This is made possible thanks to the significant impact of hydrogen on the thermodynamics, as it chemically facilitates phase transition. Ubiquitous nanotwinned structures are observed throughout t-NPD due to the high concentration of puckered layers and stacking faults of HCNOs, which impart a Vickers hardness about 140 GPa. This high hardness and optical transparency can be attributed to the nanocrystalline grain size, thin intergranular films, absence of secondary phase and pore-free features. The facile and industrial-scale synthesis of the HCNOs precursor, and mild synthesis conditions make t-NPD suitable for a wide range of potential applications.
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The comorbidity of chronic pain and mental dysfunctions such as anxiety disorders has long been recognized, but the underlying mechanisms remained poorly understood. Here, using a mouse model of neuropathic pain, we demonstrated that the thalamic paraventricular nucleus (PVT) played a critical role in chronic pain-induced anxiety-like behavioral abnormalities. Fiber photometry and electrophysiology demonstrated that chronic pain increased the activities in PVT glutamatergic neurons. Chemogenetic manipulation revealed that suppression of PVT glutamatergic neurons relieved pain-like behavior and anxiety-like behaviors. Conversely, selective activation of PVT glutamatergic neurons showed algesic and anxiogenic effects. Furthermore, the elevated excitability of PVT glutamatergic neurons resulted in increased excitatory inputs to the basolateral complex (BLA) neurons. Optogenetic manipulation of the PVT-BLA pathway bilaterally modulates both the pain-like behavior and anxiety-like phenotypes. These findings shed light on how the PVT-BLA pathway contributed to the processing of pain-like behavior and maladaptive anxiety, and targeting this pathway might be a straightforward therapeutic strategy to both alleviate nociceptive hypersensitivity and rescue anxiety behaviors in chronic pain conditions.
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Complejo Nuclear Basolateral , Dolor Crónico , Neuralgia , Humanos , Ansiedad , Tálamo , Trastornos de Ansiedad , Enfermedad CrónicaRESUMEN
Hepatocellular carcinoma (HCC) is one of the most common malignant tumors in China, accounting for the majority of primary liver cancer cases. Liver resection is the preferred curative method for early-stage HCC. However, up to 80-85% of patients have already missed the opportunity of radical surgery due to tumor advances at the time of consultation. Conversion therapies are a series of medications and treatments for initially inoperable patients. For early-stage unresectable HCC (uHCC) patients, conversion therapies are designed to meet surgical requirements by increasing the volume of the residual liver. Meanwhile, for advanced cases, conversion therapies strive for tumor shrinkage and down-staging, creating the opportunity for liver resection or liver transplantation. This review summarizes the latest advances in conversion therapies and highlights their potential for improving the survival benefit of patients with uHCC.
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Nickel borides are promising multifunctional materials for high hardness and excellent properties in catalysis and magnetism. However, it is still a blank of intrinsic properties in Ni-B compounds, because crystallization of the single phases of Ni-B compounds with micro-size is a challenge. In this work, single phases of Ni2B (I4/mcm), α-Ni4B3 (Pnma), ß-Ni4B3 (C2/c), and NiB (Cmcm) are synthesized by high pressure and high temperature (HPHT). The results indicate that synthesizing α-Ni4B3 and ß-Ni4B3 requires more energy than Ni2B and NiB. The growth process of Ni-B compounds is that Ni covers B to form Ni-B compounds under HPHT, which also makes the slight excess of B necessary. So, generating homogeneous distribution of starting materials and increasing the interdiffusion between Ni and B are two keys to synthesize well crystallized and purer samples by HPHT. This work uncovers the growth process of Ni-B compounds, which is significant to guide the synthesis of highly crystalline transition metal borides (TMBs) in the future.
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Two-dimensional (2D) van der Waals heterostructures (VDWHs) containing a charge-density wave (CDW) and superconductivity (SC) have revealed rich tunability in their properties, which provide a new route for optimizing their novel exotic states. The interaction between SC and CDW is critical to its properties; however, understanding this interaction within VDWHs is very limited. A comprehensive in situ study and theoretical calculation on bulk 4Hb-TaSe2 VDWHs consisting of alternately stacking 1T-TaSe2 and 1H-TaSe2 monolayers are investigated under high pressure. Surprisingly, the superconductivity competes with the intralayer and adjacent-layer CDW order in 4Hb-TaSe2, which results in substantially and continually boosted superconductivity under compression. Upon total suppression of the CDW, the superconductivity in the individual layers responds differently to the charge transfer. Our results provide an excellent method to efficiently tune the interplay between SC and CDW in VDWHs and a new avenue for designing materials with tailored properties.
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This study aimed to investigate the impact of caloric restriction (CR) on cognitive function in aged C57BL/6 mice after surgery, as well as the underlying mechanisms. Forty 14-month-old male C57BL/6 mice were randomly assigned to the ad libitum (AL, n = 20) group and the CR (n = 20) group. After feeding for 12 weeks, they were subdivided into four groups: AL control (ALC, n = 10), AL with surgery (ALS, n = 10), CR control (CRC, n = 10), and CR with surgery (CRS, n = 10). The Morris Water Maze (MWM) test was used to assess learning and memory capacity. By using western blot and immunofluorescence, the expression of Sirt1, MeCP2, and BDNF in the hippocampus and hippocampal CA1 region was quantified. According to the behavioral test, the CRC and CRS groups had significantly better learning and memory abilities than the ALC and ALS groups, respectively. Sirt1, MeCP2, and BDNF expression in the hippocampus and CA1 region in the hippocampus of the ALC and CRC groups of mice were correlated with cognitive improvement. In conclusion, CR could enhance the postoperative cognitive function in aged mice, most likely by increasing the expression of Sirt1, MeCP2, and BDNF in the CA1 region of the hippocampus.
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High boron content transition metal (TM) borides (HB-TMBs) have recently been regarded as the promising candidate for superhard multifunctional materials. High hardness stems from the covalent bond skeleton formed by high content of boron (B) atoms to resist deformation. High valence electron density of TM and special electronic structure fromp-dhybridization of B and TM are the sources of multifunction. However, the reason of hardness variation in different HB-TMBs is still a puzzle because hardness is a complex property mainly associated with structures, chemical bonds, and mechanical anisotropy. Rich types of hybridization in B atoms (sp, sp2, sp3) generate abundant structures in HB-TMBs. Studying the intrinsic interaction of structures and hardness or multifunction is significant to search new functional superhard materials. In this review, the stable structure, hardness, and multifunctionality of HB-TMBs are summarized. It is concluded that the structures of HB-TMBs are mainly composed by sandwiched stacking of B and TM layers. The hardness of HB-TMBs shows a increasing tendency with the decreasing atom radius. The polyhedron in strong B skeleton provides hardness support for HB-TMBs, among which C2/mis the most possible structure to meet the superhard standard. The shear modulus (G0) generates a positive effect for hardness of HB-TMBs, but the effect from bulk modulus (G0) is complex. Importantly, materials with a value ofB0/G0less than 1.1 are more possible to achieve the superhard standard. As for the electronic properties, almost all TMB3and TMB4structures exhibit metallic properties, and their density of states near the Fermi level are derived from the d electrons of TM. The excellent electrical property of HB-TMBs with higher B ratio such as ZrB12comes from the channels between B-Bπ-bond and TM-d orbitals. Some HB-TMBs also indicate superconductivity from special structures, most of them have stronger hybridization of d electrons from TM atoms than p electrons from B atoms near the Fermi level. This work is meaningful to further understand and uncover new functional superhard materials in HB-TMBs.
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Hypoxia is an important tumor feature and hypoxia-inducible factor 1 (HIF-1) is a master regulator of cell response to hypoxia. Mouse double minute 2 homolog (MDM2) promotes cancer cell survival in retinoblastoma (RB), with the underlying mechanism remaining elusive. In this study, we investigated the role of MDM2 and its relation to HIF-1α in RB. Expression analysis on primary human RB samples showed that MDM2 expression was positively correlated with that of HIF-1α while negatively correlated with von Hippel-Lindau protein (pVHL), the regulator of HIF-1α. In agreement, RB cells with MDM2 overexpression showed increased expression of HIF-1α and decreased expression of pVHL, while cells with MDM2 siRNA knockdown or MDM2-specific inhibitor showed the opposite effect under hypoxia. Further immuno-precipitation analysis revealed that MDM2 could directly interact with pVHL and promotes its ubiquitination and degradation, which consequently led to the increase of HIF-1α. Inhibition of MDM2 and/or HIF-1α with specific inhibitors induced RB cell death and decreased the stem cell properties of primary RB cells. Taken together, our study has shown that MDM2 promotes RB survival through regulating the expression of pVHL and HIF-1α, and targeting MDM2 and/or HIF-1α represents a potential effective approach for RB treatment.
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Subunidad alfa del Factor 1 Inducible por Hipoxia , Proteínas Proto-Oncogénicas c-mdm2 , Neoplasias de la Retina , Retinoblastoma , Humanos , Hipoxia de la Célula/fisiología , Supervivencia Celular , Hipoxia , Subunidad alfa del Factor 1 Inducible por Hipoxia/genética , Proteínas Proto-Oncogénicas c-mdm2/genética , Neoplasias de la Retina/genética , UbiquitinaciónRESUMEN
Vascular fibrosis is a widespread pathologic condition that arises during vascular remodeling in cardiovascular dysfunctions. According to previous studies, vascular fibrosis is characterized by endothelial matrix deposition and vascular wall thickening. The RAAS and TGF-ß/Smad signaling pathways have been frequently highlighted. It is, however, far from explicit in terms of understanding the cause and progression of vascular fibrosis. In this review, we collected and categorized a large number of molecules which influence the fibrosing process, in order to acquire a better understanding of vascular fibrosis, particularly of pathologic dysfunction. Furthermore, several mediators that prevent vascular fibrosis are discussed in depth in this review, with the aim that this will contribute to the future prevention and treatment of related conditions.
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Transition metal diborides (TMdBs,P6/mmm, AlB2-type) have attracted much attention for decades, due to TMdBs can be conductors, superconductors, magnetism materials, and catalysts. The layered structure caused by the borophene subunit is the source of functions and also makes TMdBs a potential bank of Mbene. However, TMdBs also exhibit high hardness which is not supposed to have in the layered structure. The high hardness of TMdBs arises from covalent bonds of boron-boron (B-B) and strongp-dorbit hybridization of B and TM. While strong B-TM bonds will eliminate the layered structure which may damage the functional properties. Understanding the basic mechanism of hardness and function is significant to achieve optimal TMdBs. This work summarizes the basic properties of TMdBs including hardness, superconductor, and catalytic properties. It can be found that Young's modulus (E) and Shear modulus (G) are beneficial for the hardness of TMdBs and the Poisson's ratio is the opposite. Increasing the atomic radius of TM brings an improvement in the hardness of TMdBs before it reaches the highest value of 1.47 Å, beyond which hardness decreases. Besides, TMdBs also have excellent activity comparable with some noble metals for hydrogen evolution reaction, which is closely related to the d-band center. More importantly, higher valence electron concentrations were found to be adverse to the hardness and superconductivity of TMdBs and greatly affect their catalytic properties. This review is of guiding significance for further exploring the relationship between structures and properties of TMdBs.
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Regulating electron structure and electron-phonon coupling by means of pressure and temperature is an effective way to optimize thermoelectric properties. However, in situ testing of thermoelectric transport performance under pressure and temperature is hindered by technical constraints that obscure the intrinsic effects of pressure and temperature on thermoelectric properties. In the present study, a new reliable assembly was developed for testing the in situ thermoelectric transport performance of materials at high pressure and high temperature (HPHT). This reduces the influence of thermal effects on the test results and improves the success rate of in situ experiments at HPHT. The Seebeck coefficient and electrical resistivity of α-Cu2Se were measured under HPHT, and the former was found to increase with increasing pressure and temperature; for the latter, although an increase in the pressure acted to lower the electrical resistivity, an increase in the temperature acted to increase it. On increasing pressure from 0.8 to 3 GPa at 333 K, the optimal power factor of α-Cu2Se was increased by â¼76% from 2.36 × 10-4-4.15 × 10-4 W m-1 K-2, and the higher pressure meant that α-Cu2Se had its maximum power factor at lower temperature. The present work is particularly important for understanding the thermoelectric mechanism under HPHT.
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High-quality P6322 Mn2N0.86 samples were synthesised using a high-pressure metathesis reaction, and the properties of the material were investigated. The measurements revealed that the Vickers hardness was 7.47 GPa, which is less than that predicted by commonly used theoretical models. At low air pressure, Mn2N0.86 and MnO coexist at 500 to 600 °C, and by excluding air, we succeeded in producing Mn4N by heating Mn2N0.86 in nitrogen atmosphere; we carefully studied this process with thermogravimetry and differential scanning calorimetry (TG-DSC). This gives a hint that to control temperature, air pressure and gas concentration might be an effective way to prepare fine Mn-N-O catalysis. Magnetic measurements indicated that ferromagnetism and antiferromagnetism coexist within Mn2N0.86 at room temperature and that these magnetic properties are induced by nitrogen vacancies. Ab intio simulation was used to probe the nature of the magnetism in greater detail. The research contributes to the available data and the understanding of Mn2N0.86 and suggests ways to control the formation of materials based on Mn2N0.86.
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PURPOSE: To compare the efficacy and safety of immunotherapy plus regorafenib versus regorafenib only in patients with pretreated hepatocellular carcinoma (HCC). METHODS: Immunotherapy plus regorafenib or regorafenib alone was analyzed in patients with advanced HCC with documented tumor progression on front-line therapy. Progression-free survival (PFS), overall survival (OS), disease control rate (DCR), and treatment-related adverse events (TRAEs) were assessed. RESULTS: Of the 125 patients enrolled in this study, 50 patients received combination (pCOM) treatment as front-line treatment, and 60 patients received monotherapy (pMONO) as front-line treatment. In the pCOM cohort, median OS was significantly longer with for patients regorafenib plus immunotherapy than regorafenib alone treatment (15.0 vs. 2.0 months; P = 0.035). The DCR numerically increased in the regorafenib plus immunotherapy treatment in both cohorts (40.6 % vs. 22.2 %, 72.7 % vs. 54.7 %, respectively). There were no differences in PFS with regorafenib according to whether or not regorafenib was combined with immunotherapy in the pCOM and pMONO cohorts (PFS, P = 0.17, P = 0.91, respectively). Regarding the number of TRAEs occurred, regorafenib plus immunotherapy group was comparable to regorafenib group in the pCOM cohort (65.6 % vs. 72.2 %). In the pMONO cohort, TRAEs occurred in fewer patients receiving regorafenib than regorafenib plus immunotherapy (69.8 % vs. 95.5 %). CONCLUSIONS: Immunotherapy plus regorafenib may significantly improve clinical outcomes and have a manageable safety profile compared with regorafenib monotherapy in advanced HCC after front-line therapy failure. The efficacy of combination therapy needs to be validated in prospective studies with large samples.
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Carcinoma Hepatocelular , Neoplasias Hepáticas , Humanos , Carcinoma Hepatocelular/tratamiento farmacológico , Estudios Prospectivos , Neoplasias Hepáticas/tratamiento farmacológico , Inmunoterapia , Factores InmunológicosRESUMEN
Novel transition-metal borides have attracted considerable attention because they exhibit high stability under extreme conditions. Compared with binary borides, ternary transition-metal borides (TTMBs) exhibit novel boron substructures and diverse properties, which result in excellent designability. In this study, we synthesized the MAB-like (where M = iron, A = molybdenum, and B = boron) phase Fe(MoB)2 using a high-pressure and high-temperature method. Fe(MoB)2 exhibited ferromagnetic metastable characteristics with a saturation magnetization of 8.35 emu/g at room temperature. Microhardness measurement revealed an indentation hardness of 10.72 GPa, which was higher than those of conventional magnetic materials. First-principles calculations revealed excellent mechanical properties, which mainly originated from the strong covalent short B2 chains. Furthermore, magnetism was attributed to the Fe 3d electrons. Numerous d-d hybridizations existed between the Fe 3d eg and Mo 4d orbitals, and the antibonding/nonbonding state difference for up/down-spin electrons in the hybridization orbitals led to the local magnetic moment of Fe(MoB)2. The magnetic anisotropy energy analyses reveal that Fe(MoB)2 prefers the easy magnetization axis along the z direction, and Mo atom acts as a medium to realize the exchange action between two Fe atoms. The B-B and Fe-B bonds were considerably stronger than the Fe-Mo and Mo-B bonds, and Fe(MoB)2 exhibited a class of atomically laminate composed of FeB2 and Mo layers. These results may provide guidance for the design of novel multifunctional TTMBs by adjusting the interactions between binary metal components.
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Objective: To study and develop a predictive model for the differential diagnosis of acute appendicitis (AA) and Henoch-Schonlein purpura (HSP) in children and to validate the model internally and externally. Methods: The complete data of AA and HSP cases were retrospectively analyzed and divided into internal and external verification groups. SPSS software was used for single-factor analysis and screening of independent variables, and R software was used for the development and verification of the diagnostic model. Lasso regression analysis was used to screen predictors and Lasso-logistic regression model was constructed, and K-fold cross-validation was used for the internal verification. In addition, nonfever patients were selected for model development and validation in the same way. Receiver operating characteristic (ROC) curves and calibration curves were drawn, respectively, to evaluate the 2 models. Results: Internal development and validation of the model showed that fever, neutrophil ratio (NEUT%), albumin (ALB), direct bilirubin (DBIL), C-reactive protein (CRP), and K were predictive factors for the diagnosis of HSP. The model was presented in the form of a nomogram, and the area under ROC curve of the development group and verification group was 0.9462 (95% confidence interval [CI] = 0.9402-0.9522) and 0.8931 (95% CI = 0.8724-0.9139), respectively. In the model of patients without fever, NEUT%, platelets (PLT), ALB, DBIL, alkaline phosphatase (ALP), CRP, and K were predictive factors for the diagnosis of HSP, and the area under ROC curve of the development group and verification group was 0.9186 (95% CI = 0.908-0.9293) and 0.8591 (95% CI = 0.8284-0.8897), respectively. Conclusion: In this study, 2 diagnostic models were constructed for fever or not, both of which had good discrimination and calibration, and were helpful to distinguish AA and HSP in children.
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Apendicitis , Vasculitis por IgA , Apendicitis/diagnóstico , Proteína C-Reactiva/análisis , Proteína C-Reactiva/metabolismo , Niño , Diagnóstico Diferencial , Humanos , Vasculitis por IgA/diagnóstico , Estudios RetrospectivosRESUMEN
Background: Total pancreatectomy (TP) for pancreatic cancer (PC) has been limited historically for fear of elevated perioperative morbidity and mortality. With advances in perioperative care, TP may be an alternative option to partial pancreatectomy (PP). Limited evidence clarified the indication for these two procedures in PC patients, especially in patients with different tumor staging and location. Thus, this study aims to compare the outcomes after TP and PP for PCs of different T stages and locations. Methods: The study identified 14,456 PC patients with potentially curable primary tumor (T1-3) who received TP or PP from the Surveillance, Epidemiology, and End Results (SEER) database during 2000 to 2016. Detailed clinical and tumor covariates were all collected. Overall survival (OS) and cancer-specific survival (CSS) were the primary endpoints of interest in this study. OS and CSS were compared between patients after TP and PP using log-rank analysis. Results: For all patients, except for tumor location, TP group was comparable to the PP group. OS and CSS of the TP group were worse than of the PP group (median OS: 19 vs. 20 months, P=0.0058; median CSS: 24 vs. 26 months, P=0.00098, respectively). In stratifying analyses, TP was significantly related to worse OS and CSS than PP in pancreatic head and neck cancer patients with T2-stage tumors (median OS: 18 vs. 19 months, P=0.0016; median CSS: 22 vs. 24 months, P=0.00055, respectively), whereas for patients with T1- or T3-stage pancreatic head and neck cancer as well as T1- to T3-stage pancreatic body and tail cancer or overlapping location cancer, OS and CSS of the two groups were similar (all P>0.05). Conclusions: Compared with PP, TP offered worse prognosis in pancreatic head and neck cancer patients with T2-stage tumors, furthermore, TP and PP achieved comparable prognosis in patients with T1- or T3-stage pancreatic head and neck cancer as well as T1- to T3-stage pancreatic body and tail cancer or overlapping location cancer.
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Chemotherapy is the first-line treatment for human retinoblastoma (RB), but the occurrence of drug resistance greatly limited its efficacy in practice. RING-finger protein 6 (RNF6) is an E3 ubiquitin ligase that is aberrantly upregulated in a range of cancers and plays important roles in cancer progression. However, the role of RNF6 in RB is largely unknown. In this study, we investigated the role of RNF6 in RB drug resistance. Two carboplatin-resistant RB cells, Y-79/CR and SO-Rb50/CR, were generated based on Y-79 and SO-Rb50 cells. RT-PCR and western blot analyses showed that RNF6 expression on both mRNA and protein levels was significantly increased in Y-79/CR and SO-Rb50/CR cells comparing to their parental cells. Knockdown of RNF6 using siRNA in Y-79/CR and SO-Rb50/CR cells resulted in cells sensitive to carboplatin on a RNF6 siRNA dose dependent manner. Similarly, RNF6 overexpression in parental Y-79 and SO-Rb50 cells could help cells gain resistance to carboplatin on a RNF6 expression dependent manner. Signaling pathway analyses revealed that JAK2/STAT3 pathway was involved in the RNF6-induced carboplatin resistance in RB cells. We further revealed that RNF6 expression in both Y-79 and SO-Rb50 cells could render cells resistant to multiple anti-cancer drugs including carboplatin, vincristine and etoposide, an implication of RNF6 as a biomarker for RB drug resistance. Taken together, our study has revealed that RNF6 is upregulated in drug-resistant RB cells and RNF6 promotes drug resistance through JAK2/STAT3 signaling pathway. The importance of RNF6 in RB cells drug resistance may represent this protein as a potential biomarker and treatment target for drug resistance in RB.