Protopine protects chondrocytes from undergoing ferroptosis by activating Nrf2 pathway.

Osteoarthritis is a highly prevalent joint disease; however, effective treatments are lacking. Protopine (PTP) is an isoquinoline alkaloid with potent anti-inflammatory and antioxidant properties; however, it has not been studied in osteoarthritis. This study aimed to investigate whether PTP can effectively protect chondrocytes from ferroptosis. Primary mouse chondrocytes were treated with tert-butyl hydroperoxide (TBHP) to simulate oxidative stress in an in vitro model of osteoarthritis. Two concentrations of PTP (10 and 20 µg/mL) were validated for in vitro experiments. Cellular inflammation and metabolism were detected using RT-qPCR and western blotting (WB). Ferroptosis was assessed via WB, qPCR, reactive oxygen species (ROS) levels, lipid ROS, and immunofluorescence staining. In vitro, PTP significantly ameliorated chondrocyte inflammation and cytolytic metabolism and significantly suppressed chondrocyte ferroptosis through the activation of the Nrf2 pathway. The anterior cruciate ligament transection (ACLT) mouse model was used to validate the in vivo effects of PTP. The joint cartilage was assessed using the Osteoarthritis Research Society International (OARSI) score, Safranin O staining, and immunohistochemistry. The intra-articular administration of PTP alleviated cartilage inflammation and ferroptosis, as evidenced by the expression of MMP3, MMP13, COL2A1, GPX4, and Nrf2. Overall, we find that PTP exerted anti-ferroptosis and anti-inflammatory effects on chondrocytes to protect the articular cartilage.

Pulley Effect in the Capture of DNA Translocation through Solid-State Nanopores.

Nanopores are powerful single-molecule sensors for analyzing biomolecules such as DNA and proteins. Understanding the dynamics of DNA capture and translocation through nanopores is essential for optimizing their performance. In this study, we examine the effects of applied voltage and pore diameter on current blockage, translocation time, collision, and capture location by translocating λ-DNA through 5.7 and 16 nm solid-state nanopores. Ionic current changes are used to infer DNA conformations during translocation. We find that translocation time increases with pore diameter, which can be attributed to the decrease of the stall force. Linear and exponential decreases of collision frequency with voltage are observed in the 16 and 5.7 nm pores, respectively, indicating a free energy barrier in the small pore. Moreover, the results reveal a voltage-dependent bias in the capture location toward the DNA ends, which is explained by a "pulley effect" deforming the DNA as it approaches the pore. This study provides insights into the physics governing DNA capture and translocation, which can be useful for promoting single-file translocation to enhance nanopore sensing.

Analysis of the effect of cations on protein conformational stability using solid-state nanopores.

The conformation of proteins is closely related to their biological functions, and it is affected by many factors, including the type of cations in solution. However, it is difficult to detect the conformational changes of a protein in situ. As a single-molecule sensing technology, nanopores can convert molecular structural information into analyzable current signals within a reasonable time range. Herein, we detect and analyze the effects of two different types of monovalent cations (Na+ and Li+) on a model protein bovine serum albumin (BSA) conformation using SiNx nanopores with different diameters. The quantitative analysis results show that the excluded volume of BSA in LiCl salt solutions is larger than the value in NaCl solution, indicating that Li+ is more prone to unfolding the proteins and making them unstable. This study demonstrated that nanopores enable the in situ detection of the structure of proteins at the single-molecule level and provide a new approach for the quantitative analysis of proteins.

Development of a dual fluorescent reporter system to identify inhibitors of Staphylococcus aureus virulence factors.

IMPORTANCE: Staphylococcus aureus is a formidable pathogen responsible for a wide range of infections, and the emergence of antibiotic-resistant strains has posed significant challenges in treating these infections. In this study, we have established a novel dual reporter system capable of concurrently monitoring the activities of two critical virulence regulators in S. aureus. By incorporating both reporters into a single screening platform, we provide a time- and cost-efficient approach for assessing the activity of compounds against two distinct targets in a single screening round. This innovative dual reporter system presents a promising strategy for the identification of molecules capable of modulating virulence gene expression in S. aureus, potentially expediting the development of antivirulence therapies.

Superhydrophobic and easy-to-clean full-packing nanopatterned microlens array with high-quality imaging.

The high-quality imaging and easy cleaning property of microlens array (MLA) are two very important factors for its outdoor work. Herein, a superhydrophobic and easy-to-clean full-packing nanopatterned MLA with high-quality imaging is prepared by thermal reflow together with sputter deposition. Scanning electronic microscopy (SEM) images demonstrate that the sputter deposition method can improve 84% packing density of MLA prepared by thermal reflow to 100% and add nanopattern on the surface of microlens. The prepared full-packing nanopatterned MLA (npMLA) possess clear imaging with a significant increase of signal-to-noise ratio and higher transparency compared with the MLA prepared by thermal reflow. Besides for excellent optical properties, the full-packing surface displays a superhydrophobic property with a contact angle of 151.3°. Further, the full-packing contaminated by chalk dust become easier to be cleaned by nitrogen blowing and deionized water. As a result, the prepared full-packing is considered to be potential for various applications in the outdoor.

Flavone inhibits Staphylococcus aureus virulence via inhibiting the sae two component system.

The rising prevalence of antibiotic resistance in Staphylococcus aureus calls for the development of innovative antimicrobial agents targeting novel pathways. S. aureus generates various virulence factors that compromise host defense mechanisms. Flavone, a core structure of flavonoids, has been shown to diminish the production of staphyloxanthin and alpha-hemolysin. Nonetheless, the influence of flavone on the majority of other virulence factors in S. aureus and its underlying molecular mechanism remain elusive. In this study, we examined the impact of flavone on the transcriptional profile of S. aureus using transcriptome sequencing. Our findings revealed that flavone substantially downregulated the expression of over 30 virulence factors implicated in immune evasion by the pathogen. Gene set enrichment analysis of the fold change-ranked gene list in relation to the Sae regulon indicated a robust association between flavone-induced downregulation and membership in the Sae regulon. Through the analysis of Sae target promoter-gfp fusion expression patterns, we observed a dose-dependent inhibition of Sae target promoter activity by flavone. Moreover, we discovered that flavone protected human neutrophils from S. aureus-mediated killing. Flavone also decreased the expression of alpha-hemolysin and other hemolytic toxins, resulting in a reduction in S. aureus' hemolytic capacity. Additionally, our data suggested that the inhibitory effect of flavone on the Sae system operates independently of its capacity to lower staphyloxanthin levels. In conclusion, our study proposes that flavone exhibits a broad inhibitory action on multiple virulence factors of S. aureus by targeting the Sae system, consequently diminishing the bacterium's pathogenicity.

Enhanced recovery after surgery in congenital duodenal obstruction.

BACKGROUND: The present study aims to explore the clinical application of enhanced recovery after surgery (ERAS) in pediatric patients with congenital upper gastrointestinal obstruction (CUGIO). METHODS: A total of 82 pediatric patients with CUGIO admitted to the neonatal intensive care unit in Kunming Children's Hospital between June 2017 and June 2021 were enrolled in the present study and divided into two groups: the ERAS group (n = 46) and the control group (n = 36). The ERAS management mode was adopted in the ERAS group, and the conventional perioperative management mode was adopted in the control group. RESULTS: In the ERAS group and the control group, the time to the first postoperative bowel movement was 49.2 ± 16.6 h and 58.4 ± 18.8 h, respectively, and the time to the first postoperative feeding was 79 ± 7.1 h and 125.2 ± 8.3 h, respectively. The differences in the above two indicators between the two groups were statistically significant (P < 0.05). In the ERAS group, the days of parenteral nutrition and the length of hospital stay were 14.5 ± 2.3 d and 18.8 ± 6.4 d, respectively. In the control group, 17.6 ± 2.2 d and 23.1 ± 8.1 d, respectively. The differences in these two indicators between the two groups were statistically significant (P < 0.05). CONCLUSION: The ERAS management model had a positive effect on early postoperative recovery in pediatric patients with CUGIO.

CoW Bimetallic Carbide Nanocatalysts: Computational Exploration, Confined Disassembly-Assembly Synthesis and Alkaline/Seawater Hydrogen Evolution.

Earth-abundant tungsten carbide exhibits potential hydrogen evolution reaction (HER) catalytic activity owing to its Pt-like d-band electronic structure, which, unfortunately, suffers from the relatively strong tungsten-hydrogen binding, deteriorating its HER performance. Herein, a catalyst design concept of incorporating late transition metal into early transition metal carbide is proposed for regulating the metal-H bonding strength and largely enhancing the HER performance, which is employed to synthesize CoW bi-metallic carbide Co6 W6 C by a "disassembly-assembly" approach in a confined environment. Such synthesized Co6 W6 C nanocatalyst features the optimal Gibbs free energy of *H intermediate and dissociation barrier energy of H2 O molecules as well by taking advantage of the electron complementary effect between Co and W species, which endows the electrocatalyst with excellent HER performance in both alkaline and seawater/alkaline electrolytes featuring especially low overpotentials, elevated current densities, and much-enhanced operation durability in comparison to commercial Pt/C catalyst. Moreover, a proof-of-concept Mg/seawater battery equipped with Co6 W6 C-2-600 as cathode offers a peak power density of 9.1 mW cm-2 and an open-circuit voltage of ≈1.71 V, concurrently realizing hydrogen production and electricity output.

Nangibotide attenuates osteoarthritis by inhibiting osteoblast apoptosis and TGF-ß activity in subchondral bone.

Osteoarthritis (OA) is a chronic joint disorder that causes cartilage degradation and subchondral bone abnormalities. Nangibotide, also known as LR12, is a dodecapeptide with considerable anti-inflammatory properties, but its significance in OA is uncertain. The aim of the study was to determine whether nangibotide could attenuate the progression of OA, and elucidate the underlying mechanism. In vitro experiments showed that nangibotide strongly inhibited TNF-α-induced osteogenic reduction, significantly enhanced osteoblast proliferation and prevented apoptosis in MC3T3-E1 cells. Male C57BL/6 J mice aged 2 months were randomly allocated to three groups: sham, ACLT, and ACLT with nangibotide therapy. Nangibotide suppressed ACLT-induced cartilage degradation and MMP-13 expression. MicroCT analysis revealed that nangibotide attenuated in vivo subchondral bone loss induced by ACLT. Histomorphometry results showed that nangibotide attenuated ACLT-induced osteoblast inhibition; TUNEL assays and immunohistochemical staining of cleaved-caspase3 further confirmed the in vivo anti-apoptotic effect of nangibotide on osteoblasts. Furthermore, we found that nangibotide exerted protective effects by suppressing TGF-ß signaling mediated by Smad2/3 to restore coupled bone remodeling in the subchondral bone. In conclusion, the findings suggest that nangibotide might exert a protective effect on the bone-cartilage unit and maybe an alternative treatment option for OA.

Survival outcomes and prognostic factors of papillary serous adenocarcinoma and papillary squamous cell carcinoma of the uterine cervix.

The aim of this retrospective population-based study was to investigate the survival outcomes and prognostic factors of patients with the two cervical carcinomas. A cohort of patients diagnosed with papillary serous adenocarcinoma of the uterine cervix (PSAC) and papillary squamous cell carcinoma (PSCC) between 1973 and 2015 were drawn from the National Cancer Institute's Surveillance Epidemiology and End Results (SEER) database. Overall survival (OS) and cancer-specific survival (CSS) were estimated using the Kaplan-Meier method, and prognostic factors were assessed using Cox proportional hazards survival regression analysis. The 5-year and 10-year OS rates were 38.4 and 33.1% for PSAC and 64.6 and 50.8% for PSCC, respectively. The 2-year and 5-year CSS rates were 60.6 and 45.9% for PSAC and 79.6 and 69.0% for PSCC, respectively. Patients with PSCC survive longer than PSAC patients and have other well-described prognostic factors for improved survival rates, including an early cancer stage, a younger patient age and standardised surgery.Impact statementWhat is already known on this subject? Papillary serous adenocarcinoma of the uterine cervix (PSAC) and papillary squamous cell carcinoma (PSCC)are both very rare subtypes of cervical carcinomas.What do the results of this study add? This retrospective population-based analysis has evaluated the survival outcomes and prognostic indicators of patients with PSAC and PSCC.What the implications are of these findings for clinical practice and/or further research? Knowing the survival outcomes and prognostic indicators of PSAC and PSCC patients, we can better follow up patients.

Fe2+ /Fe3+ Cycling for Coupling Self-Powered Hydrogen Evolution and Preparation of Electrode Catalysts.

A novel Zn-Fe flow battery featuring an Fe3+ reduction reaction (Fe3+ RR)-coupled zinc oxidation, and an Fe2+ oxidation reaction (Fe2+ OR)-coupled hydrogen evolution reaction (HER) system as well, was established. This battery is capable of driving two Fe2+ OR-coupled HER systems in series based on the above Fe2+ /Fe3+ cycling, for efficient self-powered hydrogen evolution. Meanwhile, this Fe2+ /Fe3+ cycling enables the preparation of a multifunctional catalyst, Pt-3@SXNS (siloxene nanosheet), by the Fe2+ OR-promoted dispersion of Pt nanoparticles on SXNS; alternatively, this support could be obtained by Fe3+ RR-assisted exfoliation using Fe3+ from the anolyte of Fe2+ OR-coupled HER. The Pt-3@SXNS catalyst exhibits excellent catalytic activities toward Fe3+ RR in the Zn-Fe flow battery, HER, and Fe2+ OR in the electrolyzer, which is attributed to the strong electronic interaction between Pt and Si. This work offers a new strategy for energy storage and low-cost hydrogen production from acidic wastewater.

Recepteur d'origine nantais contributes to the development of endometriosis via promoting epithelial-mesenchymal transition of a endometrial epithelial cells.

Endometriosis is a benign, chronic inflammatory disease that commonly occurs in reproductive-aged women. Epithelial-mesenchymal transition (EMT) of endometrial epithelial cells plays an important role in the development of endometriosis. Recepteur d'origine nantais (RON), a receptor tyrosine kinase, has been reported to promote EMT and progression in tumours. However, whether and how RON mediates the EMT and endometriosis development is not known. Here, we found that RON activation could improve the migratory and invasive capabilities, change cellular morphologies, and decrease expression of E-cadherin and increase expression of N-cadherin in endometrial epithelial cells. Inhibition or knockdown of RON expression suppressed the migration and invasion of endometrial epithelial cells. Our studies also indicated that RON played its part in endometrial epithelial cells through protein kinase B (Akt) and mitogen-activated protein kinase (MAPK) pathways. Treatment with a RON inhibitor could decrease the number of ectopic lesions in a mouse model of endometriosis and mediate expression of EMT markers in endometriotic lesions. These data suggest that RON contributed to endometriosis development by promoting EMT of endometrial epithelial cells. Therefore, RON may be a new therapeutic target for endometriosis.

Characterization of deep sub-wavelength nanowells by imaging the photon state scattering spectra.

Optical-matter interactions and photon scattering in a sub-wavelength space are of great interest in many applications, such as nanopore-based gene sequencing and molecule characterization. Previous studies show that spatial distribution features of the scattering photon states are highly sensitive to the dielectric and structural properties of the nanopore array and matter contained on or within them, as a result of the complex optical-matter interaction in a confined system. In this paper, we report a method for shape characterization of subwavelength nanowells using photon state spatial distribution spectra in the scattering near field. Far-field parametric images of the near-field optical scattering from sub-wavelength nanowell arrays on a SiN substrate were obtained experimentally. Finite-difference time-domain simulations were used to interpret the experimental results. The rich features of the parametric images originating from the interaction of the photons and the nanowells were analyzed to recover the size of the nanowells. Experiments on nanoholes modified with Shp2 proteins were also performed. Results show that the scattering distribution of modified nanoholes exhibits significant differences compared to empty nanoholes. This work highlights the potential of utilizing the photon status scattering of nanowells for molecular characterization or other virus detection applications.

Bikini Incision Increases the Incidence of Lateral Femoral Cutaneous Nerve Injury in Direct Anterior Approach Hip Arthroplasty: A Prospective Ultrasonic, Electrophysiological, and Clinical Study.

BACKGROUND: Lateral femoral cutaneous nerve (LFCN) injury has been widely reported as one of the most common complications of direct anterior approach (DAA) hip arthroplasty. Bikini incision is considered to increase the incidence of this complication. METHODS: A prospective randomized study was conducted after including ninety-nine bikini and ninety-six longitudinal incision DAA cases from May to November 2020. The occurrence of LFCN was examined using ultrasound before and after surgery. The recovery of injury symptoms was evaluated by continuous clinical follow-up until six months, and the patients were treated with mecobalamin and/or celecoxib. Sensory conduction velocity and sensory action potential amplitude of the LFCN were measured after surgery in symptomatic patients. RESULTS: Eighty five (43.6%), sixty seven (34.4%), and forty three (22.0%) cases of LFCN were of the anterior trunk, posterior trunk, and fan types, respectively, before surgery. All one hundred ninety five patients completed the follow-up period. Fifty-seven patients had symptoms of LFCN injury, including thirty six and twenty one patients in the bikini group and longitudinal group, respectively, with significantly different incidence rates (36.4% and 21.9%, respectively; P < .05). Of these, thirty two (56.1%), thirteen (22.8%), and twelve (21.1%) cases were of the anterior trunk, posterior trunk, and fan types, respectively. Sensory conduction velocity and sensory action potential amplitude significantly decreased after surgery in both groups (P < .05). Seventeen cases showed reduction of symptoms within three months. Forty six cases showed self-recovery within six months and eleven cases showed persistent symptoms at the final follow-up. CONCLUSION: Bikini incision DAA hip arthroplasty may increase the incidence of LFCN injury, and the anterior trunk distribution type is most likely to be affected. (Clinical Trial Registration Number: CHICTR2000035107).

Management of a Complex Peristomal Fistula: A Case Study.

BACKGROUND: We describe our experiences caring for a patient with a peristomal fistula (PF), characterized by suppuration from a peristomal abscess. The challenges associated with this case included management of a complex fistula and prevention of abdominal necrotizing fasciitis and peritonitis. CASE: A 63-year-old man presented with severe peristomal swelling and pain resulting from an abscess adjacent to his ileostomy. He was malnourished and depressed. He underwent a low anterior resection (Dixon procedure) for rectal cancer 2 years ago and an abdominoperineal resection (Miles procedure) for the recurrence of rectal carcinoma 1 year later. In addition, he underwent bowel resection with the creation of an ileostomy due to intestinal obstruction caused by a second recurrence approximately 1 month prior to this admission. Following evaluation of the fistula anatomy, incision and drainage of the abscess was performed. Diversion of the effluent was used to control infection and promote fistula closure. A registered dietitian and a psychologist were consulted to optimize nutrition and treat his depression. After 20 days of treatment, the patient recovered and was safely discharged. CONCLUSION: Peristomal fistula management should include anatomical assessment, incision and drainage of the abscess, diversion to control effluent, and skin protection. For complex cases, the coordinated efforts of the interdisciplinary team are imperative.

Deformation-Mediated Translocation of DNA Origami Nanoplates through a Narrow Solid-State Nanopore.

With the development in DNA self-assembly technology, DNA origami nanostructures have been widely applied in biomedical research. Solid-state nanopores represent an emerging single-molecule sensing platform for studying nanostructures with arbitrary dimensions and physical characteristics, including DNA origami. Here, we employed relatively narrow silicon nitride nanopores to detect the deformation and translocation of DNA origami nanoplates with dimensions of approximately 60 × 54 nm. We performed translocation experiments using three nanopore diameters that are all smaller than the plat dimensions. Analysis of current blockade signals and the representative events reveals three types of translocation orientations for the nanoplates. Furthermore, by studying the electrical signal characteristics (current change and dwell time) for the different diameter pores, we obtained information about the translocation behaviors for the DNA nanoplates through different constrictions. Our investigation provides an approach to analyze the deformation and translocation of DNA origami structures.

Activation of ATF3/AP-1 signaling pathway is required for P2X3-induced endometriosis pain.

STUDY QUESTION: Does P2X ligand-gated ion channel 3 (P2X3) play a role in endometriosis pain? SUMMARY ANSWER: Upregulation of P2X3 in dorsal root ganglia (DRG) tissues via the activating transcription factor 3 (ATF3)/activator protein (AP)-1 pathway contributed to endometriosis-associated hyperalgesia, which could be attenuated by the chitosan oligosaccharide stearic acid (CSOSA)/liposomes (LPs)/SP600125 delivery system. WHAT IS KNOWN ALREADY: Infiltrating nerve fibers and elevated nociceptors in endometriotic lesions are associated with endometriosis pain. P2X3 has been demonstrated to play an important role in neuropathic pain. STUDY DESIGN, SIZE, DURATION: A rat model of endometriosis was used to investigate the signaling pathways involved in P2X3-induced pain. PARTICIPANTS/MATERIALS, SETTING, METHODS: Degrees of hyperalgesia, endogenous adenosine 5'-triphosphate (ATP) contents and P2X3 expression levels in endometriotic lesions and DRG tissues were detected in a rat model of endometriosis. The expression levels of ATF3 and P2X3 were measured using qRT-PCR, western blot analysis and immunofluorescence analysis after adenosine 5'-diphosphate (ADP) exposure in DRG cells. Plasmids encoding ATF3 and its siRNA were used to investigate the role of ATF3 on ADP-induced P2X3 upregulation. The activity of ATF binding to the P2X3 promoter was evaluated by using chromatin immunoprecipitation (CHIP) and luciferase assays. SP600125, an inhibitor of c-JUN N-terminal kinase, was wrapped in CSOSA/LPs delivery system and its inhibitory effects on ADP-induced upregulation of P2X3 in DRG cells and endometriosis-induced hyperalgesia in rats were tested. MAIN RESULTS AND THE ROLE OF CHANCE: The concentrations of endogenous ATP and expression levels of P2X3 were significantly increased in both endometriotic lesions and DRG tissues in endometriosis rat models and were found to be positively correlated with the severity of hyperalgesia. In DRG cells, P2X3 expression levels were elevated by ADP stimulation, but dramatically inhibited by blocking ATF3 with its siRNA and SP600125. CHIP and luciferase assay showed that ADP increased the binding of ATF3 to the P2X3 promoter, resulting in an increase in P2X3 expression levels. In the CSOSA/LPs/SP600125 delivery system, the drug could be effectively concentrated in endometriotic lesions, and it could alleviate endometriosis-induced hyperalgesia, reduce the size of endometriotic lesions and attenuate upregulated P2X3 expression levels in endometriosis rat models. LARGE SCALE DATA: N/A. LIMITATIONS, REASONS FOR CAUTION: Changes in the sensitivity and function of P2X3 caused by endometriosis need to be further investigated. WIDER IMPLICATIONS OF THE FINDINGS: This study indicates that ATP and the P2X3 receptor are involved in endometriosis pain, thus providing a novel therapeutic approach for the treatment of endometriosis pain by targeting the P2X3 receptor. STUDY FUNDING/COMPETING INTEREST(S): This work was funded by National Key R&D Program of China (Grant No. 2017YFC1001202) and National Natural Science Foundation of China (Grant Nos. 81974225, 81671429 and 81471433). There are no competing interests.

Recognition of Bimolecular Logic Operation Pattern Based on a Solid-State Nanopore.

Nanopores have a unique advantage for detecting biomolecules in a label-free fashion, such as DNA that can be synthesized into specific structures to perform computations. This method has been considered for the detection of diseased molecules. Here, we propose a novel marker molecule detection method based on DNA logic gate by deciphering a variable DNA tetrahedron structure using a nanopore. We designed two types of probes containing a tetrahedron and a single-strand DNA tail which paired with different parts of the target molecule. In the presence of the target, the two probes formed a double tetrahedron structure. As translocation of the single and the double tetrahedron structures under bias voltage produced different blockage signals, the events could be assigned into four different operations, i.e., (0, 0), (0, 1), (1, 0), (1, 1), according to the predefined structure by logic gate. The pattern signal produced by the AND operation is obviously different from the signal of the other three operations. This pattern recognition method has been differentiated from simple detection methods based on DNA self-assembly and nanopore technologies.

CDK9 attenuation exerts protective effects on catabolism and hypertrophy in chondrocytes and ameliorates osteoarthritis development.

Osteoarthritis (OA) is generally considered to be characterized by progressive articular cartilage destruction. Increasing evidence demonstrates that CDK9, which is a member of cyclin-dependent kinase family, plays a significant role in the regulation of acute and chronic inflammatory diseases. IL-1ß, a major proinflammatory cytokine, was used to establish a model of OA in vitro after stimulating chondrocytes. We found that CDK9 was highly expressed in in vitro and in vivo models of inflammation. The role of LDC000067 (abbreviated as LDC067), a specific inhibitor of CDK9, in protecting articular cartilage from immune response has not been fully clarified. Intriguingly, in this study, we demonstrated that LDC067 prevented IL-1ß-induced production of metalloproteinases (MMPs) and inflammatory cytokines, including MMP3, MMP9, MMP13, IL-6, IL-8 and TNF-ɑ. Furthermore, we revealed that LDC067 inhibited IL-1ß-induced NF-κB signaling pathway activation in chondrocytes. The inhibition of CDK9 could also delay cartilage degeneration in an anterior cruciate ligament transection (ACLT) mouse model in vivo. Taken together, these results highlighted the significance of this CDK9 inhibitor in preventing cartilage destruction and indicated that LDC067 might serve as a potential therapeutic agent for OA.

Survival Outcomes of Patients with Primary Breast Cancer Following Primary Ovarian Cancer.

BACKGROUND Patients with primary breast cancer following primary ovarian cancer do not comprise a large clinical entity, and reports of the survival outcomes of this cohort are rare. The purpose of this retrospective population-based research was to investigate the survival outcomes of patients with primary breast cancer after primary ovarian cancer. MATERIAL AND METHODS A cohort of patients diagnosed with primary breast cancer following primary ovarian cancer between 1973 and 2014 was drawn from the National Cancer Institute's Surveillance Epidemiology and End Results (SEER) database. Cox proportional hazards survival regression analysis and Kaplan-Meier were applied to calculate overall survival (OS), cancer-specific survival (CSS), and independent predictors of CSS. RESULTS A total of 1455 patients with primary breast cancer following primary ovarian cancer were identified. The 5-year and 10-year OS rates for the entire cohort were 81.7% and 67.4%, respectively. The 5-year and 10-year CSS rates were 84.2% and 74.3% for ovarian cancer, and 76.0% and 67.8% for breast cancer, respectively. Multivariate analysis revealed that independent predictors of ovarian cancer CSS include age, cancer stage, diagnosis time, and histological subtype. CONCLUSIONS Patients diagnosed with breast cancer following ovarian cancer have better survival rates. Patients age, ovarian cancer stage, ovarian cancer histological type, and time of diagnose affect the survival rate.