Changes in serum inflammatory factors after hip arthroplasty and analysis of risk factors for prosthesis loosening.

OBJECTIVE: To explore the relationship of serum levels of IL-1ß, IL-6, and TNF-α with prosthesis loosening after hip arthroplasty, and to establish a predictive model for prosthesis loosening. METHODS: We retrospectively analyzed the data of 501 patients who underwent hip arthroplasty in Xi'an International Medical Center Hospital from January 2020 to August 2022. Based on radiological diagnosis, the patients were divided into a prosthesis loosening group and a non-loosening group. Clinical data including postoperative serum levels of inflammatory cytokines were collected. Univariant analysis, Lasso regression, decision tree, and random forest models were used to screen feature variables. Based on the screening results, a nomogram model for predicting the risk of prosthesis loosening was established and then validated using ROC curve, and calibration curve, and other methods. RESULTS: There were 50 cases in the loosening group and 451 cases in the non-loosening group. Postoperative levels of IL-1ß, IL-6, and TNF-α were found to be significantly higher in the loosening group (P<0.0001). Univariant analysis showed that osteoporosis and postoperative infection were risk factors for prosthesis loosening (P<0.001). The machine learning algorithm identified osteoporosis, postoperative infection, IL-1ß, IL-6, and TNF-α as 5 relevant variables. The predictive model based on these 5 variables exhibited an area under the ROC curve of 0.763. The calibration curve and DCA curve verified the accuracy and practicality of the model. CONCLUSION: Serum levels of IL-1ß, IL-6, and TNF-α were significantly elevated in patients with postoperative prosthesis loosening. Osteoporosis, postoperative infection, and inflammatory cytokines are independent risk factors for prosthesis loosening. The predictive model we established through machine learning can effectively determine the risk of prosthesis loosening. Monitoring inflammatory cytokines and postoperative infections, combined with prevention of osteoporosis, can help reduce the risk of prosthesis loosening.

Construction of an ER stress-related prognostic signature for predicting prognosis and screening the effective anti-tumor drug in osteosarcoma.

BACKGROUND: Osteosarcoma is the most common malignant primary bone tumor in infants and adolescents. The lack of understanding of the molecular mechanisms underlying osteosarcoma progression and metastasis has contributed to a plateau in the development of current therapies. Endoplasmic reticulum (ER) stress has emerged as a significant contributor to the malignant progression of tumors, but its potential regulatory mechanisms in osteosarcoma progression remain unknown. METHODS: In this study, we collected RNA sequencing and clinical data of osteosarcoma from The TCGA, GSE21257, and GSE33382 cohorts. Differentially expressed analysis and the least absolute shrinkage and selection operator regression analysis were conducted to identify prognostic genes and construct an ER stress-related prognostic signature (ERSRPS). Survival analysis and time dependent ROC analysis were performed to evaluate the predictive performance of the constructed prognostic signature. The "ESTIMATE" package and ssGSEA algorithm were utilized to evaluate the differences in immune cells infiltration between the groups. Cell-based assays, including CCK-8, colony formation, and transwell assays and co-culture system were performed to assess the effects of the target gene and small molecular drug in osteosarcoma. Animal models were employed to assess the anti-osteosarcoma effects of small molecular drug. RESULTS: Five genes (BLC2, MAGEA3, MAP3K5, STC2, TXNDC12) were identified to construct an ERSRPS. The ER stress-related gene Stanniocalcin 2 (STC2) was identified as a risk gene in this signature. Additionally, STC2 knockdown significantly inhibited osteosarcoma cell proliferation, migration, and invasion. Furthermore, the ER stress-related gene STC2 was found to downregulate the expression of MHC-I molecules in osteosarcoma cells, and mediate immune responses through influencing the infiltration and modulating the function of CD8+ T cells. Patients categorized by risk scores showed distinct immune status, and immunotherapy response. ISOX was subsequently identified and validated as an effective anti-osteosarcoma drug through a combination of CMap database screening and in vitro and in vivo experiments. CONCLUSION: The ERSRPS may guide personalized treatment decisions for osteosarcoma, and ISOX holds promise for repurposing in osteosarcoma treatment.

Overexpression of lncRNA LINC00665 inhibits the proliferation and chondroblast differentiation of bone marrow mesenchymal stem cells by targeting miR-214-3p.

BACKGROUND: Osteoarthritis is a chronic disease mainly involving the damage of articular cartilage and the whole articular tissue, which is the main cause of disability in the elderly. To explore more effective treatment measures, this study analyzed the regulatory role and molecular mechanism of lncRNA LINC00665 (LINC00665) in the chondrogenic differentiation of bone marrow mesenchymal stem cells (BMSCs), providing a valuable theoretical basis for the pathogenesis and patient treatment of osteoarthritis. METHODS: Osteoarthritis tissues and healthy tissues were obtained from 52 patients with osteoarthritis and 34 amputated patients without osteoarthritis, and the levels of LINC00665 and miR-214-3p were assessed by RT-qPCR. BMSCs were cultured and induced chondrogenic differentiation. The proliferation ability of BMSCs was detected by CCK-8 method, and the apoptosis level of BMSCs was evaluated by flow cytometry. The content of proteoglycan-glycosaminoglycan (GAG) in cartilage matrix was determined by Alcian blue staining. In addition, the binding relationship between LINC00665 and miR-214-3p was verified by luciferase reporter assay, and the molecular mechanism was further analyzed. RESULTS: In osteoarthritis tissues, LINC00665 was elevated and miR-214-3p was down-regulated. With the chondrogenic differentiation of BMSCs, the level of GAG increased, and LINC00665 expression gradually decreased, while miR-214-3p level was on the contrary. After transfection of pcDNA3.1-LINC00665 in BMSCs, cell proliferation capacity was decreased, apoptosis rate was increased, and GAG content was reduced. Moreover, LINC00665 sponged miR-214-3p and negatively regulate its expression. Transfection of pcDNA3.1-LINC00665-miR-214-3p mimic changed the regulation of pcDNA3.1-LINC00665 on the viability and chondrogenic differentiation of BMSCs. CONCLUSIONS: Overexpression of lncRNA LINC00665 inhibited the proliferation and chondrogenic differentiation of BMSCs by targeting miR-214-3p. The LINC00665/miR-214-3p axis may improve joint damage and alleviate the progression of osteoarthritis.

RPL38 knockdown inhibits the inflammation and apoptosis in chondrocytes through regulating METTL3-mediated SOCS2 m6A modification in osteoarthritis.

BACKGROUND: Ribosomal protein L38 (RPL38) was found upregulated in osteoarthritic peripheral blood mononuclear cells, however, its role in progression of osteoarthritis has not been characterized. METHODS: The protein levels of RPL38 and SOCS2 in cartilage tissues from OA patients and controls were detected with Western blotting. IL-1ß was used to stimulate primary chondrocytes to establish an OA cell model, and RPL38 siRNA (si-RPL38) was transfected into chondrocytes to investigate the effect of RPL38 knockdown on cell viability, apoptosis, inflammatory factor secretion and extracellular matrix degradation. Then, the mechanism that RPL38 regulate the SOCS2 expression and SOCS2-induced chondrocyte dysfunction was explored. The methyltransferase-like 3 (METTL3)-mediated m6A modification of SOCS2 mRNA was confirmed, and the interaction of RPL38 and METTL3 was verified. Moreover, the effects of SOCS2 overexpression on IL-1ß-induced chondrocyte dysfunction and SOCS2 knockdown on the restoration of chondrocyte function by siRPL38 were investigated. Finally, RPL38 was knocked down in vivo and its role in OA progression was validated. RESULTS: RPL38 was upregulated and SOCS2 was downregulated in OA cartilages. RPL38 knockdown or SOCS2 overexpression either attenuated IL-1ß-induced chondrocyte apoptosis, inflammatory cytokine secretion, and ECM degradation. RPL38 directly interacted with METTL3 and it inhibited SOCS2 expression through METTL3-mediated m6A modification. SOCS2 knockdown activated the JAK2/STAT3 proinflammatory pathway and reversed the effects of RPL38 knockdown on IL-1ß-induced chondrocyte apoptosis, inflammation and ECM degradation. RPL38 knockdown alleviated cartilage tissue damage and ECM degradation in OA mice. CONCLUSION: RPL38 knockdown inhibited osteoarthritic chondrocyte dysfunction and alleviated OA progression through promoting METTL3-m6A-mediated SOCS2 expression.

Design of nickel cobalt molybdate regulated by boronizing for high-performance supercapacitor applications.

Nickel-cobalt-based molybdates have been intensively investigated because of their high theoretical specific capacitance and multifarious oxidation states. Here, we have successfully synthesized hierarchical structures (Ni3B/Ni(BO2)2@NixCoyMoO4) by boronizing NixCoyMoO4 nanosheets on flexible carbon cloth substrates. Benefitting from the synergistic effect among Ni3B, Ni(BO2)2 and NixCoyMoO4 in hybrid architectures, the electrode material possesses higher capacity of 394.7 mA h g-1 at 1 A g-1 and a good rate performance (309.5 mA h g-1 maintained at 20 A g-1). Then, a hybrid supercapacitor assembled with Ni3B/Ni(BO2)2@NixCoyMoO4 and activated carbon as the positive and the negative electrode, displays a high specific capacitance of 370.7 F g-1 at 1 A g-1 (210 F g-1 at 10 A g-1), a high voltage of 1.7 V, and a high energy density of 131.8 W h kg-1 at the power density of 800 W kg-1 (still 74.7 W h kg-1 maintained at 8000 W kg-1). This study widens the research scope of boronizing pseudocapacitance materials and reveals a high application potential of Ni3B/Ni(BO2)2@NixCoyMoO4 for energy storage devices in the future.

Constructing highly dispersed 0D Co3S4 quantum dots/2D g-C3N4 nanosheets nanocomposites for excellent photocatalytic performance.

The development of noble-metal-free catalysts with high efficiency photocatalytic properties is critical to the heterogeneous catalysis. Herein, zero-dimensional (0D) metal sulfide quantum dots/two-dimensional (2D) g-C3N4 nanosheets (Co3S4/CNNS) nanocomposites are synthesized by a two-step method, including the ways of in-situ deposition and water bath. The highly dispersed Co3S4 quantum dots (particle size is 2-4 nm) are evenly and tightly fixed on CNNS, which can be used as co-catalyst to effectively replace noble metals to improve the photocatalytic properties of CNNS. Co3S4/CNNS-900 has the apparent quantum efficiency, which is up to 7.85% at 400 nm. At the same time, the H2 evolution rate of Co3S4/CNNS-900 is 20,536.4 µmol g-1 h-1, which is 555 times than CNNS. The excellent photocatalytic performance is due to the highly dispersed Co3S4 quantum dots on 2D CNNS, which facilitate the formation of more active sites, Co3S4/CNNS promotes the separation and migration of photogenerated carriers, shortens the migration distance of photogenerated carriers, and eventually leads to an increase of the photocatalytic performance.

Uniform P doped Co-Ni-S nanostructures for asymmetric supercapacitors with ultra-high energy densities.

Uniform P doped Co-Ni-S nanosheet arrays were directly grown on Ni foams by an efficient and cost-effective process. The binder-free electrode of P doped Co-Ni-S nanosheet arrays possesses an ultra-high specific capacitance of ∼3677 F g-1 at 1 A g-1 with an excellent rate capability (∼63% capacitance retention at 20 A g-1) and considerable cycling performance (∼84% capacitance retention after 10 000 cycles). Correspondingly, the asymmetric supercapacitors assembled with P doped Co-Ni-S as the positive electrode and AC as the negative electrode display an ultra-high energy density of ∼68.7 W h kg-1 at a power density of ∼0.8 kW kg-1. In view of these features, this work provides a simple and scalable strategy for designing electrodes and devices with superior electrochemical performance in next generation energy storage applications.

Hedgehog-inspired nanostructures for hydrogel-based all-solid-state hybrid supercapacitors with excellent flexibility and electrochemical performance.

High-security deformable energy-storage devices that are mechanically robust, with considerable energy and power densities are becoming desirable for smart wearable electronics. Here, a highly flexible hydrogel-based all-solid-state hybrid supercapacitor was rationally designed and assembled, with unique NiCo2O4@NixCoyMoO4 (x : y = 3 : 1) nanostructures as the electrode, which was bio-inspired by the curling up and relaxation of hedgehogs. The hybrid supercapacitor shows no obvious decay in capacitance during bending to different states, indicating its outstanding flexibility and mechanical stability. The capacitance was still maintained at 92.0% of the initial value, even after continuous bending for 3000 cycles. The highly monodisperse NiCo2O4@NixCoyMoO4 nanostructures releasing stress during bending is responsible for the favorable stability and flexibility. Furthermore, the hybrid supercapacitor displayed outstanding electrochemical performance, with a high specific capacitance of 207 F g-1 at 1 A g-1, a high energy density of 64.7 W h kg-1 at 749.6 W kg-1, and favorable cycling stability (nearly 100% after 10 000 cycles). The flexible hybrid supercapacitor could be charged with a solar cell and served as the power source to light up LEDs. This simple and reliable hybrid supercapacitor, with extraordinary mechanical stability and electrochemical performance, is a promising power source for smart wearable electronics.

Atomic View of Filament Growth in Electrochemical Memristive Elements.

Memristive devices, with a fusion of memory and logic functions, provide good opportunities for configuring new concepts computing. However, progress towards paradigm evolution has been delayed due to the limited understanding of the underlying operating mechanism. The stochastic nature and fast growth of localized conductive filament bring difficulties to capture the detailed information on its growth kinetics. In this work, refined programming scheme with real-time current regulation was proposed to study the detailed information on the filament growth. By such, discrete tunneling and quantized conduction were observed. The filament was found to grow with a unit length, matching with the hopping conduction of Cu ions between interstitial sites of HfO2 lattice. The physical nature of the formed filament was characterized by high resolution transmission electron microscopy. Copper rich conical filament with decreasing concentration from center to edge was identified. Based on these results, a clear picture of filament growth from atomic view could be drawn to account for the resistance modulation of oxide electrolyte based electrochemical memristive elements.

Thermal crosstalk in 3-dimensional RRAM crossbar array.

High density 3-dimensional (3D) crossbar resistive random access memory (RRAM) is one of the major focus of the new age technologies. To compete with the ultra-high density NAND and NOR memories, understanding of reliability mechanisms and scaling potential of 3D RRAM crossbar array is needed. Thermal crosstalk is one of the most critical effects that should be considered in 3D crossbar array application. The Joule heat generated inside the RRAM device will determine the switching behavior itself, and for dense memory arrays, the temperature surrounding may lead to a consequent resistance degradation of neighboring devices. In this work, thermal crosstalk effect and scaling potential under thermal effect in 3D RRAM crossbar array are systematically investigated. It is revealed that the reset process is dominated by transient thermal effect in 3D RRAM array. More importantly, thermal crosstalk phenomena could deteriorate device retention performance and even lead to data storage state failure from LRS (low resistance state) to HRS (high resistance state) of the disturbed RRAM cell. In addition, the resistance state degradation will be more serious with continuously scaling down the feature size. Possible methods for alleviating thermal crosstalk effect while further advancing the scaling potential are also provided and verified by numerical simulation.

High uniformity and improved nonlinearity by embedding nanocrystals in selector-less resistive random access memory.

The sneak path problem is one of the major hindrances for the application of high density 3D crossbar resistive random access memory (RRAM). For the selector-less RRAM devices, nonlinear (NL) current-voltage (I-V) characteristics are an alternative approach to minimize the sneak paths. In this work we have demonstrated metallic IrOx nanocrystal (IrOx-NC) based selector-less crossbar RRAM devices in an IrOx/AlOx/IrOx-NC/AlOx/W structure with very reliable hysteresis resistive switching of >10 000 cycles, stable multiple levels, and high temperature (HT) data retention. Moreover, an improvement in the NL behavior has been reported as compared to a pure high-κ AlOx RRAM. The origin of the NL nature has been discussed using the hopping model and Luittenger's 1D metal theory. The nonlinearity can be further improved by structure engineering and will improve the sensing margin of the devices, which is rewarding for crossbar array integration.

Thermoelectric Seebeck effect in oxide-based resistive switching memory.

Reversible resistive switching induced by an electric field in oxide-based resistive switching memory shows a promising application in future information storage and processing. It is believed that there are some local conductive filaments formed and ruptured in the resistive switching process. However, as a fundamental question, how electron transports in the formed conductive filament is still under debate due to the difficulty to directly characterize its physical and electrical properties. Here we investigate the intrinsic electronic transport mechanism in such conductive filament by measuring thermoelectric Seebeck effects. We show that the small-polaron hopping model can well describe the electronic transport process for all resistance states, although the corresponding temperature-dependent resistance behaviours are contrary. Moreover, at low resistance states, we observe a clear semiconductor-metal transition around 150 K. These results provide insight in understanding resistive switching process and establish a basic framework for modelling resistive switching behaviour.

Increased levels of calcitonin gene-related peptide in serum accelerate fracture healing following traumatic brain injury.

The mechanisms responsible for the phenomenon of an accelerated speed of fracture healing in patients with traumatic brain injury (TBI) remain unclear. The present study was performed to test the hypothesis that TBI causes changes in calcitonin gene-related peptide (CGRP) levels in sera that enhance fracture healing. A standard closed femoral fracture was produced in rats, which were subjected to additional closed head trauma. The fracture healing was assessed 4 and 8 weeks later using micro-CT. Sera, brain tissues and muscles surrounding the fracture sites collected at 24, 48, 72 and 168 h after injury were used to detect the expression of CGRP using ELISA, immunohistochemistry and RT-PCR. Micro-CT demonstrated that fracture healing and mineralization in the TBI-fracture group occurred earlier compared to the fracture-only group. ELISA analysis revealed a high concentration of CGRP in the TBI-fracture group (P<0.05), and immunohistochemistry assay and RT-PCR analysis revealed a significant increase in CGRP in the brain and muscle of the TBI-fracture group at 168 h after fracture (P<0.001). Our results indicate that the mechanism for the enhancement of fracture-healing secondary to traumatic brain injury is correlated to the high levels of CGRP, which may be released from the brain tissue into the serum.