Bacteroid cerium oxide particles promote macrophage polarization to achieve early vascularization and subsequent osseointegration around implants.

The establishment of an osseointegration is crucial for the long-term stability and functionality of implant materials, and early angiogenesis is the key to successful osseointegration. However, the bioinertness of titanium implants affects osseointegration, limiting their clinical application. In this study, inspired by the rapid polarization of macrophages following the phagocytosis of bacteria, we developed bacteroid cerium oxide particles; these particles were composed of CeO2 and had a size similar to that of Bacillus (0.5 µ m). These particles were constructed on the implant surfaces using a hydrothermal method. In vitro experiments demonstrated that the particles effectively decreased the reactive oxygen species (ROS) levels in macrophages (RAW264.7). Furthermore, these particles exerted effects on M1 macrophage polarization, enhanced nitric oxide (NO) secretion to promote vascular regeneration, and facilitated rapid macrophage transition to the M2 phenotype. Subsequently, the particles facilitated human umbilical vein endothelial cell (HUVEC) migration. In vivo studies showed that these particles rapidly stimulated innate immune responses in animal models, leading to enhanced angiogenesis around the implant and improved osseointegration. In summary, the presence of bacteroid cerium oxide particles on the implant surface regulated and accelerated macrophage polarization, thereby enhancing angiogenesis during the immune response and improving peri-implant osseointegration.

Association between triglyceride glucose index and arterial stiffness and coronary artery calcification: a systematic review and exposure-effect meta-analysis.

BACKGROUND: The triglyceride and glucose (TyG) index has been linked to various cardiovascular diseases. However, it's still unclear whether the TyG index is associated with arterial stiffness and coronary artery calcification (CAC). METHODS: We conducted a systematic review and meta-analysis of relevant studies until September 2022 in the PubMed, Cochrane Library, and Embase databases. We used a random-effects model to calculate the pooled effect estimate and the robust error meta-regression method to summarize the exposure-effect relationship. RESULTS: Twenty-six observational studies involving 87,307 participants were included. In the category analysis, the TyG index was associated with the risk of arterial stiffness (odds ratio [OR]: 1.83; 95% CI 1.55-2.17, I2 = 68%) and CAC (OR: 1.66; 95% CI 1.51-1.82, I2 = 0). The per 1-unit increment in the TyG index was also associated with an increased risk of arterial stiffness (OR: 1.51, 95% CI 1.35-1.69, I2 = 82%) and CAC (OR: 1.73, 95% CI 1.36-2.20, I2 = 51%). Moreover, a higher TyG index was shown to be a risk factor for the progression of CAC (OR = 1.66, 95% CI 1.21-2.27, I2 = 0, in category analysis, OR = 1.47, 95% CI 1.29-1.68, I2 = 41% in continuity analysis). There was a positive nonlinear association between the TyG index and the risk of arterial stiffness (Pnonlinearity < 0.001). CONCLUSION: An elevated TyG index is associated with an increased risk of arterial stiffness and CAC. Prospective studies are needed to assess causality.

Interfacial engineered PANI/carbon nanotube electrode for 1.8 V ultrahigh voltage aqueous supercapacitors.

Flexible three-dimensional interconnected carbon nanotubes on the carbon cloth (3D-CNTs/CC) were obtained through simple magnesium reduction reactions. According to the Nernst equation, the cell voltage based on these pure carbon electrodes without any additives could reach 1.5 V due to the higher di-hydrogen evolution over potential in neutral 3.5 M LiCl electrolytes. In order to improve the electrochemical performance of the electrodes, 3D-CNTs/CC electrodes covered with polyaniline barrier layer (3D-PANI/CNTs/CC) were prepared byin situelectropolymerization using interfacial engineering method. The assembled symmetric supercapacitors display a broadened voltage of 1.8 V, high areal capacitance of 380 mF cm-2, outstanding areal energy density of 85.5µWh cm-2and 84% of its initial capacitance after 20 000 charge-discharge cycles. This work demonstrated that the interface engineering strategy provides a promising way to improve the energy density of carbon-based aqueous supercapacitors by widening the voltage and boosting the capacitance simultaneously.

RNA interference-based osteoanabolic therapy for osteoporosis by a bone-formation surface targeting delivery system.

RNA interference (RNAi)-based gene therapy that promotes anabolic bone formation is an effective approach for addressing osteoporosis. However, the selection of target gene and tissue-specific delivery systems has hindered the progression of this strategy. In this study, we identified casein kinase-2 interacting protein-1 encoding gene (Ckip-1), a negative regulator of bone formation, as an effective target of small interfering RNAs (siRNAs) for improving bone mass. Moreover, an impressive (DSS)6-Liposome (Lipos) nanoparticle system that could target the bone formation surface was synthesized to enhance the delivery of Ckip-1 siRNA to osteogenic lineage cells. The in vitro results confirmed that the (DSS)6-Lipos system could efficaciously improve the intracellular delivery of Ckip-1 siRNA without obvious cell toxicity. The in vivo application of the delivery system showed specific accumulation of siRNA in osteogenic cells located around the bone formation surface. Bone-related analysis indicated increased bone mass and improved bone microarchitecture in mice with ovariectomy-induced osteoporosis. Moreover, the biomechanical characteristics of the tibia were enhanced significantly, indicating increased resistance to fragile fracture induced by osteoporosis. Thus, (DSS)6-Lipos-Ckip-1 siRNA-based osteoanabolic therapy may be a promising option for the treatment of osteoporosis.

Prevalence of NSAID use among people with COVID-19 and the association with COVID-19-related outcomes: Systematic review and meta-analysis.

AIM: Recent reports of potential harmful effects of nonsteroidal anti-inflammatory drugs (NSAIDs) in treating patients with coronavirus disease 2019 (COVID-19) have raised great concern. METHODS: We searched the PubMed, EMBASE, Cochrane Library and MedRxiv databases to examine the prevalence of NSAID use and associated COVID-19 risk, outcomes and safety. RESULTS: Twenty-five studies with a total of 101 215 COVID-19 patients were included. Prevalence of NSAID use among COVID-19 patients was 19% (95% confidence interval [CI] 14-23%, no. of studies [n] = 22) and NSAID use prior to admission or diagnosis of COVID-19 was not associated with an increased risk of COVID-19 (adjusted odds ratio [aOR] = 0.93, 95% CI 0.82-1.06, I2  = 34%, n = 3), hospitalization (aOR = 1.06, 95% CI 0.76-1.48, I2  = 81%, n = 5), mechanical ventilation (aOR = 0.71, 95% CI 0.47-1.06, I2  = 38%, n = 4) or length of hospital stay. Moreover, prior use of NSAIDs was associated with a decreased risk of severe COVID-19 (aOR = 0.79, 95% CI 0.71-0.89, I2  = 0%, n = 7) and death (aOR = 0.68, 95% CI 0.52-0.89, I2 = 85%, n = 10). Prior NSAID administration might also be associated with an increased risk of stroke (aOR = 2.32, 95% CI 1.04-5.2, I2  = 0%, n = 2), but not myocardial infarction (aOR = 1.49, 95% CI 0.25-8.92, I2  = 0, n = 2) and composite thrombotic events (aOR = 1.56, 95% CI 0.66-3.69, I2  = 52%, n = 2). CONCLUSION: Based on current evidence, NSAID use prior to admission or diagnosis of COVID-19 was not linked with increased odds or exacerbation of COVID-19. NSAIDs might provide a survival benefit, although they might potentially increase the risk of stroke. Controlled trials are still required to further assess the clinical benefit and safety (e.g., stroke and acute renal failure) of NSAIDs in treating patients with COVID-19.

The role of mitochondrial dynamics in the TiO2 nanotube-accelerated osteogenic differentiation of MC3T3-E1 cells.

Nano titanium implants induce osteogenesis, but how osteoblasts respond to this physical stimulation remains unclear. In this study, we tried to reveal the role of the mitochondrial fission-fusion of osteoblasts in response to a nano titanium surface during the process of osteogenesis, which is important for the design of the surface structure of titanium implants. A TiO2 nanotube array (nano titanium, NT) was fabricated by anodization, and a smooth surface (smooth titanium, ST) was used as a control. We investigated changes in the mitochondrial fission-fusion (MFF) dynamics in MC3T3-E1 cells on the NT surface with those on the ST surface by performing transmission electron microscopy (TEM), confocal laser scanning microscope (CLSM) and real-time PCR. At the same time, we also detected changes in the MFF and osteogenic differentiation of MC3T3-E1 cells after DRP1 downregulation with RNA interference. Cells on the NT surface exhibited more mitochondrial fusion than those on the ST surface, and DRP1 was the key regulatory molecule. Interestingly, DRP1 increased for only a short time at the early stage on the NT surface, and when DRP1 was inhibited by siRNA at the early stage, the osteogenic differentiation of MC3T3-E1 cells significantly decreased. In conclusion, DRP1-regulated mitochondrial dynamics played a key role in the nanotopography-accelerated osteogenic differentiation of MC3T3-E1 cells.

Real-World Relationship Between Proton Pump Inhibitors and Cerebro-Cardiovascular Outcomes Independent of Clopidogrel.

Previous studies have provided established evidence on adverse outcomes of the coadministration of proton pump inhibitors (PPIs) and clopidogrel, whereas cerebro-cardiovascular outcomes of PPI use in the absence of clopidogrel therapy remain controversial.In this study, we aimed to assess the association between PPIs and cerebro-cardiovascular outcomes independent of clopidogrel.Systematic searches were conducted in the Cochrane Library, PubMed, and Embase databases for all relevant studies up to August 2018. Odds ratios (ORs) with its 95% confidence intervals (CIs) were abstracted and pooled using the random-effects model.A total of 14 observational studies (13 cohort studies and 1 case-control study) were identified. Compared with non-PPI users, PPI users experienced higher risks of stroke (OR: 1.22, 95% CI: 1.08-1.36), myocardial infarction (MI; OR: 1.23, 95% CI: 1.14-1.32), cardiovascular death (OR: 1.83, 95% CI: 1.69-1.98), and major adverse cardiovascular events (MACEs; OR: 1.22, 95% CI: 1.05-1.40) independent of clopidogrel use, but not all-cause death (OR: 1.50, 95% CI: 0.99-2.25). In the subgroup analysis, PPI alone was associated with significant risks of new-onset MI (OR: 1.23, 95% CI: 1.13-1.35) and stroke (OR: 1.17, 95% CI: 1.05-1.30) in patients without previous MI or stoke and recurrent MI (OR: 1.24, 95% CI: 1.02-1.51) and stroke (OR: 1.36, 95% CI: 1.19-1.55) risks in patients with a previous MI.Based on current publications, PPI use seems to be associated with increased risks of stroke, MI, cardiovascular death, and MACEs independent of clopidogrel. Greater caution should be therefore exercised while considering its clinical benefits and further investigate any causal relationships.

Short-term effect of ultrasound-guided low-molecular-weight hyaluronic acid injection on clinical outcomes and imaging changes in patients with rheumatoid arthritis of the ankle and foot joints. A randomized controlled pilot trial.

To determine whether hyaluronic acid (HA) injection into rheumatoid arthritis ankles and feet can achieve improvement in foot function and reduce synovial hyper-vascularization. Forty-four patients with RA having unilateral or bilateral painful ankle and foot involvement (N = 75) were studied. All the patients were randomized to receive HA (N = 40) or lidocaine (LI) (N = 35) injection at 2-week intervals; Clinical assessments were performed using a visual analog scale (VAS) and foot function index (FFItotal) including subscales of pain (FFIpain) before injection at baseline, 4 weeks (first evaluation) and 12 weeks (secondary evaluation). Imaging evaluation based on color Doppler ultrasound (CDUS) and synovitis scores was performed simultaneously. HA injection improved the VAS score (p = .009), FFIpain (p = .041), and FFItotal (p = .032) considerably more than LI injections did at the first evaluation. The CDUS values at first evaluation (p = .005) and secondary evaluation (p < .001) decreased significantly compared with the base line values. HA injections reduced the CDUS values of more than half of the joints (54%, p = .042) while the control group exhibited no change (20%, p = .56). However, HA injection did not reduce the CDUS values more than LI injection did. Regarding the evaluation of synovial hypertrophy, no significant difference was observed between or within the groups in the synovitis scores. HA injection improved short-term foot function and pain reduction. HA injection may have a modest effect in reducing synovial hyper-vascularization. Further large-scale study is warranted to confirm this result.

Association of living alone with clinical outcomes in patients with heart failure: A systematic review and meta-analysis.

Living alone is an objective sign of social isolation. It is uncertain whether living alone worsens clinical outcomes in heart failure (HF) patients. We aimed to assess how living alone affected clinical outcomes in individuals with HF. We searched the electronic databases of PubMed, Embase, and Cochrane from 1990 to April 2022 for studies comparing living alone with HF. A random-effects model with inverse variance was used to pool adjusted hazard ratios (HRs) and 95% confidence intervals (CIs). Seven studies were deemed to meet the standards. In patients with HF, compared with living with others, living alone was associated with an elevated risk of any hospitalization at the 30-day (HR: 1.78, 95% CI: 1.09-2.89), 90-day (HR: 1.24, 95% CI: 1.02-1.51), or ≥1-year (HR: 1.14, 95% CI: 1.04-1.26) follow-up periods. HF patients living alone also had a greater risk of any hospitalization or death at the 30-day (HR: 1.56, 95% CI: 1.15-2.11), 90-day (HR: 1.26, 95% CI: 1.05-1.50), and ≥1-year (HR: 1.18, 95% CI: 1.09-1.28) follow-up periods. However, patients living alone had no increased risk of all-cause death at the 30-day (HR: 1.0, 95% CI: 0.19-5.36), 90-day (HR: 0.46, 95% CI: 0.03-7.42), or ≥ 1-year (HR: 1.10, 95% CI: 0.73-1.67) follow-up periods. In comparison to living with others, living alone was associated with an increased risk of any hospitalization but not all-cause death in HF patients.

Reduced corrosion of Zn alloy by HA nanorods for enhancing early bone regeneration.

Zinc alloys have emerged as promising materials for bone regeneration due to their moderate biodegradation rates. However, the blast release of Zn2+ from Zn alloy substrates affects cell behaviors and the subsequent osseointegration quality, retarding their early service performance. To address this issue, extracellular matrix-like hydroxyapatite (HA) nanorods were prepared on Zn-1Ca (ZN) by a combined hydrothermal treatment (HT). HA nanoclusters nucleate on the presetting ZnO layer and grow into nanorods with prolonged HT. HA nanorods protect the ZN substrate from serious corrosion and the corrosion rate is reduced by dozens of times compared with the bare ZN, resulting in a significantly decreased release of Zn2+ ions. The synergistic effect of HA nanorods and appropriate Zn2+ endow ZN implants with obviously improved behaviors of osteoblasts and endothelial cells (e.g. adhesion, proliferation and differentiation) in vitro and new bone formation in vivo. Our work opens up a promising avenue for Zn-based alloys to improve bone regeneration in clinics.

Living alone increases the risk of developing type 2 diabetes mellitus: A systematic review and meta-analysis based on longitudinal studies.

BACKGROUND: Living alone is a prevalent psychological issue that has been found to have significant implications for lifestyle and health status. While considerable research has been conducted to explore the relationship between living alone and the risk of developing type 2 diabetes mellitus (T2DM), the majority of studies have been cross-sectional, leaving direct correlations elusive. Therefore, this study aims to analyze data from longitudinal studies to determine whether living alone increases the risk of T2DM. METHODS: A comprehensive search was conducted in the PubMed, Cochrane, and Embase databases to identify studies examining the association between living alone and T2DM risk. The search encompassed studies published until September 2023. Pooled analysis utilized the random-effects model with inverse variance and included adjusted hazard ratios (HRs) and their corresponding 95% confidence intervals (CIs). RESULTS: The meta-analysis comprised a total of 8 studies, which consisted of 5 prospective cohort studies and 3 retrospective cohort studies. The total population under consideration included 11,686,677 individuals without T2DM, of whom 54.3% were female. Among this population, 396,368 individuals developed T2DM. To account for heterogeneity, a random-effects model was employed. Overall, the pooled data demonstrated a significant association between living alone and an increased risk of T2DM when compared to living with others (HR 1.24, 95% CI 1.06-1.46). Subgroup analysis revealed that this risk was not statistically significant for either males (HR 1.28, 95% CI 0.93-1.76) or females (HR 1.06, 95% CI 0.84-1.33), nor in prospective cohort studies (HR 1.26, 95% CI 0.91-1.74) or retrospective cohort studies (HR 1.26, 95% CI 0.91-1.74). CONCLUSION: Individuals living alone faced a significantly higher risk of developing diabetes compared to those who did not live alone. However, no significant difference in this risk was observed between genders and study types. Further high-quality studies are necessary in the future to elucidate this causal association.

USP18 Curbs the Progression of Metabolic Hypertension by Suppressing JAK/STAT Pathway.

Hypertension is a pathological state of the metabolic syndrome that increases the risk of cardiovascular disease. Managing hypertension is challenging, and we aimed to identify the pathogenic factors and discern therapeutic targets for metabolic hypertension (MHR). An MHR rat model was established with the combined treatment of a high-sugar, high-fat diet and ethanol. Histopathological observations were performed using hematoxylin-eosin and Sirius Red staining. Transcriptome sequencing was performed to screen differentially expressed genes. The role of ubiquitin-specific protease 18 (USP18) in the proliferation, apoptosis, and oxidative stress of HUVECs was explored using Cell Counting Kit-8, flow cytometry, and enzyme-linked immunosorbent assays. Moreover, USP18 downstream signaling pathways in MHR were screened, and the effects of USP18 on these signaling pathways were investigated by western blotting. In the MHR model, total cholesterol and low-density lipoprotein levels increased, while high-density lipoprotein levels decreased. Moreover, high vessel thickness and percentage of collagen were noted along with increased malondialdehyde, decreased superoxide dismutase and catalase levels. The staining results showed that the MHR model exhibited an irregular aortic intima and disordered smooth muscle cells. There were 78 differentially expressed genes in the MHR model, and seven hub genes, including USP18, were identified. USP18 overexpression facilitated proliferation and reduced apoptosis and oxidative stress in HUVECs treated with Ang in vitro. In addition, the JAK/STAT pathway was identified as a USP18 downstream signaling pathway, and USP18 overexpression inhibited the expression of JAK/STAT pathway-related proteins. Conclusively, USP18 restrained MHR progression by promoting cell proliferation, reversing apoptosis and oxidative stress, and suppressing the JAK/STAT pathway.

Developing Air-Stable n-Type SWCNT-Based Composites with High Thermoelectric and Robust Mechanical Properties for Wearable Electronics.

Flexible organic thermoelectric generators are gaining prominence in wearable electronics, leveraging body heat as an energy source. Their advancement is hindered by the scarcity of air-stable n-type organic materials with robust mechanical properties. This study introduces two new polymers (HDCN4 and HDCN8), created through polycondensation of paraformaldehyde and diamine-terminated poly(ethylene glycol) (PEGDA) with molecular weights of 4000 and 8000 g/mol into single-walled carbon nanotubes (SWCNTs). The resulting HDCN4/SWCNT and HDCN8/SWCNT composites show impressive power factors of 225.9 and 108.2 µW m-1 K-2, respectively, and maintain over 90% in air for over four months without encapsulation. The HDCN4/SWCNT composite also demonstrates significant tensile strength (33.2 MPa) and flexibility (up to 10% strain), which is currently the best mechanically n-type thermoelectric material with such a high power factor reported in the literature. A thermoelectric device based on HDCN4/SWCNT generates 4.2 µW of power with a 50 K temperature difference. Additionally, when used in wearable temperature sensors, these devices exhibit high mechanical reliability and a temperature resolution of 0.1 K. This research presents a viable method to produce air-stable n-type thermoelectric materials with excellent performance and mechanical properties.

A Novel and Green Method for Preparing Highly Conductive PEDOT:PSS Films for Thermoelectric Energy Harvesting.

As a π-conjugated conductive polymer, poly(3,4-ethylenedioxythiophene):poly(styrene sulfonate) (PEDOT:PSS) is recognized as a promising environmentally friendly thermoelectric material. However, its low conductivity has limited applications in the thermoelectric field. Although thermoelectric efficiency can be significantly enhanced through post-treatment doping, these processes often involve environmentally harmful organic solvents or reagents. In this study, a novel and environmentally benign method using purified water (including room temperature water and subsequent warm water) to treat PEDOT:PSS film has been developed, resulting in improved thermoelectric performance. The morphology data, chemical composition, molecular structure, and thermoelectric performance of the films before and after treatment were characterized and analyzed using a scanning electron microscope (SEM), Raman spectrum, XRD pattern, X-ray photoelectron spectroscopy (XPS), and a thin film thermoelectric measurement system. The results demonstrate that the water treatment effectively removes nonconductive PSS from PEDOT:PSS composites, significantly enhancing their conductivity. Treated films exhibit improved thermoelectric properties, particularly those treated only 15 times with room temperature water, achieving a high electrical conductivity of 62.91 S/cm, a Seebeck coefficient of 14.53 µV K-1, and an optimal power factor of 1.3282 µW·m-1·K-2. In addition, the subsequent warm water treatment can further enhance the thermoelectric properties of the film sample. The underlying mechanism of these improvements is also discussed.

The Construction of Three-Layered Biomimetic Arterial Graft Balances Biomechanics and Biocompatibility for Dynamic Biological Reconstruction.

The process of reconstructing an arterial graft is a complex and dynamic process that is subject to the influence of various mechanical factors, including tissue regeneration and blood pressure. The attainment of favorable remodeling outcomes is contingent upon the biocompatibility and biomechanical properties of the arterial graft. A promising strategy involves the emulation of the three-layer structure of the native artery, wherein the inner layer is composed of polycaprolactone (PCL) fibers aligned with blood flow, exhibiting excellent biocompatibility that fosters endothelial cell growth and effectively prevents platelet adhesion. The middle layer, consisting of PCL and polyurethane (PU), offers mechanical support and stability by forming a contractile smooth muscle ring and antiexpansion PU network. The outer layer, composed of PCL fibers with an irregular arrangement, promotes the growth of nerves and pericytes for long-term vascular function. Prioritizing the reconstruction of the inner and outer layers establishes a stable environment for intermediate smooth muscle growth. Our three-layer arterial graft is designed to provide the blood vessel with mechanical support and stability through nondegradable PU, while the incorporation of degradable PCL generates potential spaces for tissue ingrowth, thereby transforming our graft into a living implant.

Comprehensive repair of the alveolar cleft using cortical and cancellous bone layers: A retrospective study.

To retrospectively review the clinical effect of comprehensive treatment of alveolar cleft (CTAC) using the mandible as the bone source. Patients with alveolar clefts who met the inclusion criteria were subjected to a CTAC protocol that included the following: (1) preoperative orthodontic treatment for creating good soft-tissue conditions; (2) 'area-like grafting' with subperiosteal osteogenic chin bone instead of cartilaginous osteogenic iliac bone; (3) simulation of normal bone anatomy via a sandwich-like bone graft consisting of 'cortical bone + cancellous bone + cortical bone'; and (4) strong internal fixation to ensure initial bone block stability. At 6 months postoperatively, the titanium plate was removed and cone-beam computed tomography was performed to evaluate the surgical results. A total of 54 patients underwent treatment with the CTAC protocol. The average age at the initial operation was 10.3 ± 2.1 years, and the average hospital stay was 2.8 ± 0.6 days. At 6 months postoperatively, 49 patients (90.7%) showed good clinical results. The transplanted bone block formed a 'cortical bone + cancellous bone + cortical bone' structure similar to that of the normal jawbone. A mature bone bridge formed, and the impacted permanent teeth continued to erupt and enter the bone graft area. CTAC is a comprehensive restorative solution for alveolar cleft repair that integrates multiple concepts, including orthodontics, embryology, anatomy, and improvements to surgical methods. The method is easy to perform, causes little surgical trauma, and shows a stable success rate, and is thus worth promoting.

CKIP-1-Loaded Cartilage-Affinitive Nanoliposomes Reverse Osteoarthritis by Restoring Chondrocyte Homeostasis.

Osteoarthritis (OA) is a chronic joint disease characterized by cartilage imbalance and disruption of cartilage extracellular matrix secretion. Identifying key genes that regulate cartilage differentiation and developing effective therapeutic strategies to restore their expression is crucial. In a previous study, we observed a significant correlation between the expression of the gene encoding casein kinase-2 interacting protein-1 (CKIP-1) in the cartilage of OA patients and OA severity scores, suggesting its potential involvement in OA development. To test this hypothesis, we synthesized a chondrocyte affinity plasmid, liposomes CKIP-1, to enhance CKIP-1 expression in chondrocytes. Our results demonstrated that injection of CAP-Lipos-CKIP-1 plasmid significantly improved OA joint destruction and restored joint motor function by enhancing cartilage extracellular matrix (ECM) secretion. Histological and cytological analyses confirmed that CKIP-1 maintains altered the phosphorylation of the signal transduction molecule SMAD2/3 of the transforming growth factor-ß (TGF-ß) pathway by promoting the phosphorylation of the 8T, 416S sit. Taken together, this work highlights a novel approach for the precise modulation of chondrocyte phenotype from an inflammatory to a noninflammatory state for the treatment of OA and may be broadly applicable to patients suffering from other arthritic diseases.

RNA Coating Promotes Peri-Implant Osseointegration.

In addition to transmitting and carrying genetic information, RNA plays an important abiotic role in the world of nanomaterials. RNA is a natural polyanionic biomacromolecule, and its ability to promote osteogenesis by binding with other inorganic materials as an osteogenic induction agent was discovered only recently. However, whether it can promote osseointegration on implants has not been reported. Here, we investigated the effect of the RNA-containing coating materials on peri-implant osseointegration. Total RNA extracted from rat muscle tissue was used as an osteogenic induction agent, and hyaluronic acid (HA) was used to maintain its negative charge. In simulated body fluids (SBF), in vitro studies demonstrated that the resulting material encouraged calcium salt deposition. Cytological experiments showed that the RNA-containing coating induced greater cell adhesion and osteogenic differentiation in comparison to the control. The results of animal experiments showed that the RNA-containing coating had osteoinductive and bone conduction activities, which are beneficial for bone formation and osseointegration. Therefore, the RNA-containing coatings are useful for the surface modification of titanium implants to promote osseointegration.

An updated meta-analysis of cardiac resynchronization therapy with or without defibrillation in patients with nonischemic cardiomyopathy.

Background: Cardiac resynchronization therapy (CRT) is a major device therapy used to treat patients suffering from heart failure (HF) and electrical asynchrony. It can improve HF symptoms, reduce HF hospitalization time, and improve long-term survival in HF with and without implantable cardioverter (ICD) therapy. However, the benefit of defibrillator therapy in CRT-eligible patients with nonischemic cardiomyopathy (NICM) remains unknown. As a result, we conducted a systematic review and meta-analysis to compare clinical outcomes in patients with NICM and HF who were treated with implantable CRT defibrillators (CRT-D) vs. a CRT pacemaker (CRT-P) alone. Methods: We searched the electronic databases PubMed, Embase, and Cochrane for all studies comparing CRT-D vs. CRT-P treatment in patients with NICM. The time frame was from 1990 to September 2022. All-cause mortality and cardiovascular mortality were the primary clinical outcomes of interest to us. To pool adjusted hazard ratios (HRs) and 95% confidence intervals (CIs), a random-effects model with inverse variance was used. Results: A pooled meta-analysis included two randomized controlled trials (RCTs), each with 1,200 CRT-eligible patients with NICM (592 with CRT-D and 608 with CRT-P) and nine cohort studies representing 27,568 CRT-eligible patients with NICM (16,196 with CRT-D and 11,372 with CRT-P). The adjusted HR for all-cause mortality for CRT-D vs. CRT-P was 0.90 (95% CI, 0.81-0.99). In a subgroup analysis of two RCTs and nine cohort studies, the adjusted HR for all-cause mortality was 0.72 (95% CI, 0.43-1.19) and HR 0.92 (95% CI, 0.83-1.03) for CRT-D vs. CRT-P, respectively. Conclusion: With the addition of defibrillation leads, we found a significantly lower risk of all-cause mortality in patients with NICM, but this association was not found in subgroup analyses of RCTs and observational studies.

Damage evolution law and failure mechanism of rock impacted by high-pressure water jet under in-situ stress condition.

To investigate the real physical mechanism of rock fragmentation subjected to water jet under in-situ stress condition, a numerical model based on the SPH algorithm was established using the rate-dependent constitutive model to simulate the rock-breaking process. First, the damage evolution law of rock impacted by high-pressure water jet under in-situ stress conditions was studied by analyzing the distribution characteristics of the damage field in the dynamic process of water jet impinging. The results showed that the damage field, widths of surface damage, maximum widths of damage and mean depths of damage of rock decreased with the increase of in-situ stress, indicating that the existence of initial in-situ stress had a strong inhibitory effect on rock fragmentation. The attenuation of the maximum widths of damage could be divided into two stages. The mean depths of damage of rock played a leading role in the number of damage elements. Furthermore, on this basis, the real physical mechanism of rock fragmentation subjected to water jet under in-situ stress condition was revealed by analyzing the stress states and damage history variables of the particles in the selected five typical regions. The study showed that the failure type of the upper rock elements in the crushing zone was brittle failure caused by a combination of compressive stress and shear stress with or without in-situ stress. However, the failure mechanisms of rock elements in crack zone were completely different with or without in-situ stress. In the absence of in-situ stress, the failure type of rock impacted by water jet was the coexistence of damage caused by compressive-shear stress and tensile stress, while in the presence of in-situ stress, the failure type of rock impacted by water jet was mainly the damage caused by compressive-shear stress.