Integrative analysis of a novel super-enhancer-associated lncRNA prognostic signature and identifying LINC00945 in aggravating glioma progression.

BACKGROUND: Super-enhancers (SEs), driving high-level expression of genes with tumor-promoting functions, have been investigated recently. However, the roles of super-enhancer-associated lncRNAs (SE-lncRNAs) in tumors remain undetermined, especially in gliomas. We here established a SE-lncRNAs expression-based prognostic signature to choose the effective treatment of glioma and identify a novel therapeutic target. METHODS: Combined analysis of RNA sequencing (RNA-seq) data and ChIP sequencing (ChIP-seq) data of glioma patient-derived glioma stem cells (GSCs) screened SE-lncRNAs. Chinese Glioma Genome Atlas (CGGA) and The Cancer Genome Atlas (TCGA) datasets served to construct and validate SE-lncRNA prognostic signature. The immune profiles and potential immuno- and chemotherapies response prediction value of the signature were also explored. Moreover, we verified the epigenetic activation mechanism of LINC00945 via the ChIP assay, and its effect on glioma was determined by performing the functional assay and a mouse xenograft model. RESULTS: 6 SE-lncRNAs were obtained and identified three subgroups of glioma patients with different prognostic and clinical features. A risk signature was further constructed and demonstrated to be an independent prognostic factor. The high-risk group exhibited an immunosuppressive microenvironment and was higher enrichment of M2 macrophage, regulatory T cells (Tregs), and Cancer-associated fibroblasts (CAFs). Patients in the high-risk group were better candidates for immunotherapy and chemotherapeutics. The SE of LINC00945 was further verified via ChIP assay. Mechanistically, BRD4 may mediate epigenetic activation of LINC00945. Additionally, overexpression of LINC00945 promoted glioma cell proliferation, EMT, migration, and invasion in vitro and xenograft tumor formation in vivo. CONCLUSION: Our study constructed the first prognostic SE-lncRNA signature with the ability to optimize the choice of patients receiving immuno- and chemotherapies and provided a potential therapeutic target for glioma.

Fluoride disrupts intestinal epithelial tight junction integrity through intracellular calcium-mediated RhoA/ROCK signaling and myosin light chain kinase.

Fluoride is a common contaminant of groundwater and agricultural commodity, which poses challenges to animal and human health. A wealth of research has demonstrated its detrimental effects on intestinal mucosal integrity; however, the underlying mechanisms remain obscure. This study aimed to investigate the role of the cytoskeleton in fluoride-induced barrier dysfunction. After sodium fluoride (NaF) treatment of the cultured Caco-2 cells, both cytotoxicity and cytomorphological changes (internal vacuoles or massive ablation) were observed. NaF lowered transepithelial electrical resistance (TEER) and enhanced paracellular permeation of fluorescein isothiocyanate dextran 4 (FD-4), indicating Caco-2 monolayers hyperpermeability. In the meantime, NaF treatment altered both the expression and distribution of the tight junction protein ZO-1. Fluoride exposure increased myosin light chain II (MLC2) phosphorylation and triggered actin filament (F-actin) remodeling. While inhibition of myosin II by Blebbistatin blocked NaF-induced barrier failure and ZO-1 discontinuity, the corresponding agonist Ionomycin had effects comparable to those of fluoride, suggesting that MLC2 serves as an effector. Given the mechanisms upstream of p-MLC2 regulation, further studies demonstrated that NaF activated RhoA/ROCK signaling pathway and myosin light chain kinase (MLCK), strikingly increasing the expression of both. Pharmacological inhibitors (Rhosin, Y-27632 and ML-7) reversed NaF-induced barrier breakdown and stress fiber formation. The role of intracellular calcium ions ([Ca2+]i) in NaF effects on Rho/ROCK pathway and MLCK was investigated. We found that NaF elevated [Ca2+]i, whereas chelator BAPTA-AM attenuated increased RhoA and MLCK expression as well as ZO-1 rupture, thus, restoring barrier function. Collectively, abovementioned results suggest that NaF induces barrier impairment via Ca2+-dependent RhoA/ROCK pathway and MLCK, which in turn triggers MLC2 phosphorylation and rearrangement of ZO-1 and F-actin. These results provide potential therapeutic targets for fluoride-induced intestinal injury.

4-octyl Itaconate inhibits lipopolysaccharide (LPS)-induced osteoarthritis via activating Nrf2 signalling pathway.

Small molecule drug intervention for chondrocytes is a valuable method for the treatment of osteoarthritis (OA). The 4-octyl itaconate (OI) is a cellular derivative of itaconate with sound cell permeability and transformation rate. We attempted to confirm the protective role of OI in chondrocytes and its regulatory mechanism. We used lipopolysaccharide (LPS) to induce chondrocyte inflammation injury. After the OI treatment, the secretion and mRNA expression of Il-6, Il-10, Mcp-1 and Tnf-α were detected by ELISA and qPCR. The protective effect of OI on articular cartilage was further verified in surgical destabilization of the medial meniscus model of OA. Cell death and apoptosis were evaluated based on CCK8, LDH, Typan blue staining, Annexin V and TUNEL analyses. The small interfering RNAs were used to knockout the Nrf2 gene of chondrocytes to verify the OI-mediated Nrf2 signalling pathway. The results revealed that OI protects cells from LPS-induced inflammatory injury and attenuates cell death and apoptosis induced by LPS. Similar protective effects were also observed on articular cartilage in mice. The OI activated Nrf2 signalling pathway and promoted the stable expression and translocation of Nrf2 into the nucleus. When the Nrf2 signalling pathway was blocked, the protective effect of OI was significantly counteracted in chondrocytes and a mouse arthritis model. Both itaconate and its derivative (i.e., OI) showed important medical effects in the treatment of OA.

Identification of an endoplasmic reticulum stress-related signature associated with clinical prognosis and immune therapy in glioma.

BACKGROUND: Glioma is the most common brain tumor in adults and is characterized by a short survival time and high resistance to chemotherapy. It is imperative to determine the prognosis and therapy-related targets for glioma. Endoplasmic reticulum stress (ERS), as an adaptive protective mechanism, indicates the unfolded protein response (UPR) to determine cell survival and affects chemotherapy sensitivity, which is related to the prognosis of glioma. METHODS: Our research used the TCGA database as the training group and the CGGA database as the testing group. Lasso regression and Cox analysis were performed to construct an ERS signature-based risk score model in glioma. Three methods (time-dependent receiver operating characteristic analysis and multivariate and univariate Cox regression analysis) were applied to assess the independent prognostic effect of texture parameters. Consensus clustering was used to classify the two clusters. In addition, functional and immune analyses were performed to assess the malignant process and immune microenvironment. Immunotherapy and anticancer drug response prediction were adopted to evaluate immune checkpoint and chemotherapy sensitivity. RESULTS: The results revealed that the 7-gene signature strongly predicts glioma prognosis. The two clusters have markedly distinct molecular and prognostic features. The validation group result revealed that the signature has exceptional repeatability and certainty. Functional analysis showed that the ERS-related gene signature was closely associated with the malignant process and prognosis of tumors. Immune analysis indicated that the ERS-related gene signature is strongly related to immune infiltration. Immunotherapy and anticancer drug response prediction indicated that the ERS-related gene signature is positively correlated with immune checkpoint and chemotherapy sensitivity. CONCLUSIONS: Collectively, the ERS-related risk model can provide a novel signature to predict glioma prognosis and treatment.

Preventive effects of Lactobacillus johnsonii on the renal injury of mice induced by high fluoride exposure: Insights from colonic microbiota and co-occurrence network analysis.

Fluoride (F) exposure was widely reported to be associated with renal diseases. Since absorbed F enters the organism from drinking water mostly through the gastrointestinal tract, investigating changes of gut microbes may have profound implications for the prevention of chronic F exposure because increasing evidence supported the existence of the gut-kidney axis. In the present study, we aimed to explore the potential positive effects of probiotics on high F exposure-induced renal lesions and dysfunction in mice by the modulation of the colonic microbiota. Mice were fed with normal (Ctrl group) or sodium-fluoride (F and Prob groups; 100 mg/L sodium fluoride (NaF)) drinking water with or without Lactobaillus johnsonii BS15, a probiotic strain proven to be preventive for F exposure. Mice fed with sodium-fluoride drinking water alone exhibited renal tissue damages, decreased the renal antioxidant capability and dysfunction. In contrast, L. johnsonii BS15 reversed these F-induced renal changes. 16S rRNA gene sequencing shows that L. johnsonii BS15 alleviated the increased community diversity (Shannon diversity) and richness index (number of observed features) as well as the distured structure of colon microbiota in F-exposed mice. A total of 13 OTUs with increased relative abundance were identified as the keystone OTUs in F-exposed mice based on the analysis of degree of co-occurrence and abundance of OTUs. Moreover, Spearman's rank correlation shows that the 13 keystone OTUs had negative effect on renal health and intestinal integrity. L. johnsonii BS15 reversed four of keystone OTUs (OTU 5, OTU 794, OTU 1035, and OTU 868) changes which might be related to the underlying protected mechanism of L. johnsonii BS15 against F-induced renal damages.

Probiotic alleviate fluoride-induced memory impairment by reconstructing gut microbiota in mice.

Fluoride which is widespread in our environment and food due to its geological origin and industrial pollution has been identified as a developmental neurotoxicant. Gut-brain axis provides new insight into brain-derived injury. We previously found the psychoactive effects of a probiotic strain, Lactobacillus johnsonii BS15 against fluoride-induced memory dysfunction in mice by modulating the gut-brain axis. In this study, we aimed to detect the link between the reconstruction of gut microbiota and gut-brain axis through which probiotic alleviate fluoride-induced memory impairment. We also added an hour of water avoidance stress (WAS) before behavioral tests and sampling, aiming to demonstrate the preventive effects of the probiotic on fluoride-induced memory impairment after psychological stress. Mice were given fluoridated drinking water (sodium fluoride 100 ppm, corresponding to 37.8 ± 2.4 ppm F¯) for 70 days and administered with PBS or a probiotic strain, Lactobacillus johnsonii BS15 for 28 days prior to and throughout a 70 day exposure to sodium fluoride. Results showed that fluoride increases the hyperactivity of hypothalamic-pituitary-adrenal (HPA) axis and reduces the exploration ratio in novel object recognition (NOR) test and the spontaneous exploration during the T-maze test in mice following WAS, which were significantly improved by the probiotic. 16S rRNA sequencing showed a significant separation in ileal microbiota between the fluoride-treated mice and control mice. Lactobacillus was the main targeting bacteria and significantly reduced in fluoride-treated mice. BS15 reconstructed the fluoride-post microbiota and increased the relative abundance of Lactobacillus. D-lactate content and diamine oxidase (DAO) activity, two biomarkers of gut permeability were reduced in the serum of probiotic-inoculated mice. ZO-1, an intestinal tight junction protein was reduced by fluoride in mRNA, and its protein levels were increased by the probiotic treatment. Moreover, the hippocampus which is essential to learning and memory, down-regulated mRNA level of both the myelin-associated glycoprotein (MAG), and protein levels of brain-derived neurotrophic factor (BDNF), including the improvement of cAMP response element-binding protein (CREB) by BS15 in fluoride-exposed mice after WAS. Via spearman correlation analysis, Lactobacillus displayed significantly positive associations with the behavioral tests, levels of nerve development related factors, and intestinal tight junction proteins ZO-1, and negative association with TNF-α of the hippocampus, highlighting regulatory effects of gut bacteria on memory potential and gut barrier. These results suggested the psychoactive effects of BS15 on fluoride-induced memory dysfunction after psychological stress. In addition, there may be some correlations between fluoride-induced memory dysfunction and reconstruction of gut microbiota. AVAILABILITY OF DATA AND MATERIALS: 16S rRNA sequencing reads have uploaded to NCBI. The accession code of 16S rRNA sequencing reads in the National Center for Biotechnology Information (NCBI) BioProject database: PRJNA660154.

Temporary Balloon Occlusion of the Abdominal Aorta in Treatment of Complex Acetabular Fracture.

BACKGROUND The aim of this study was to explore the efficacy of temporary balloon occlusion of the abdominal aorta assisting open reduction and internal fixation (ORIF) in the treatment of complex acetabular fracture. MATERIAL AND METHODS From August 2000 to October 2011, a total of 48 patients with complex acetabular fracture were enrolled in this study. Average operative time, intraoperative blood loss volume, blood transfusion volume, satisfactory reduction, and postoperative functional recovery rate were recorded and compared between the 2 groups. RESULTS A significant difference was observed between the 2 groups in operative time (P=0.003). For intraoperative blood loss and blood transfusion, ORIF combined with temporary balloon occlusion of abdominal aorta techniques appeared to be superior to normal ORIF (blood loss: P=0.007; and blood transfusion: P=0.019, respectively). However, no differences were observed in postoperative blood loss or transfusion (P>0.05). Patients in group A showed better hip function than those in group B (group A: a good-to-excellent rate of 77.8%; group B: a good-to-excellent rate of 78.3%; P>0.05). With regard to the incidence of postoperative complications, there were no significant differences between the 2 groups (group A: 9/18; group B: 11/23; P=0.890). CONCLUSIONS In the treatment of complex acetabular fracture, temporary balloon occlusion of the abdominal aorta is a reliable technique to assist ORIF surgery to staunch the flow of blood.

Isocentric C-arm three-dimensional navigation versus conventional C-arm assisted C1-C2 transarticular screw fixation for atlantoaxial instability.

OBJECTIVE: The Isocentric C-arm 3D navigation has been widely used in superior cervical surgeries in recent years. Several clinical researches reported that navigation system was an effective support device for treatment of atlantoaxial instability. But there were few studies about the advantages of navigation system compared to conventional C-arm fluoroscopy in C1-C2 transarticular screw fixation for atlantoaxial instability. The aim of the study was to evaluate the precision of computer-assisted C1-C2 transarticular screw fixation (Magerl's technique) for atlantoaxial instability and compare the clinical results with conventional C-arm fluoroscopy. METHODS: Forty-two patients diagnosed as atlantoaxial instability who underwent C1-C2 transarticular screw fixation under two different fluoroscopy methods were studied. The Iso-C 3D navigation group included 18 patients and the other 24 patients were in the conventional C-arm group. The clinical and radiographic results were recorded and compared between the two groups. Patients were followed up with clinical examination and radiographs at a mean of 18.4 months. RESULTS: There were no significant differences between two groups in the mean age, gender, and causes of atlantoaxial instability. The mean blood loss in the navigation group was 236.1 ± 28.5 mL versus 308.3 ± 21.2 mL in the conventional C-arm group. The radiation time was significantly reduced using 3D navigation (48.8 ± 1.05 s versus 60.3 ± 2.23 s). Overall, 97.2 % (35/36) of 3D navigated screws and 91.7 % (44/48) of fluoroscopy screws were placed into the C1-C2 transarticular passages. Thirty-nine of forty patients showed evidence of solid fusion after 12 months on cervical plain radiographies or CT scans. CONCLUSIONS: On comparing the two imaging techniques, it was found that using Iso-C 3D navigation can improve accuracy of the C1-C2 transarticular screws, decrease intra-operative fluoroscopic time and blood loss, and not prolong the operative time. This study demonstrates that Iso-C 3D navigation is a safe and effective means of guiding C1-C2 transarticular screw fixation for atlantoaxial instability.

Macrophage Membrane-Modified MoS2 Quantum Dots as a Nanodrug for Combined Multi-Targeting of Alzheimer's Disease.

The complex pathological mechanism of Alzheimer's disease (AD) limits the efficacy of simple drug therapy, and drugs are difficult to penetrate the blood-brain barrier (BBB). Therefore, it is a breakthrough to enhance the therapeutic effect of AD by rationally using multiple therapeutic strategies to inhibit multiple pathological targets. In this study, macrophage membrane (MM) with active targeting inflammation function is used to functionalize molybdenum disulfide quantum dots (MoS2 QDs) with the properties of elimination of reactive oxygen species (ROS) and anti-Aß1-42 deposition to form the nano drug (MoS2 QDs/MM), and play the role of multi-target combined therapy with NIR. The results show that MoS2 QDs/MM has a targeted therapeutic effect on ROS elimination and anti-deposition of Aß1-42 . In addition, the combined therapy group effectively reduced Aß1-42 mediated cytotoxicity. The modification of MM could effectively target the brain, and NIR irradiation could actively increase the cross of BBB of materials. In vivo behavioral study also show that APP/PS1 mice in the combined treatment group showed the similar exploration desire and learning ability to mice in the group of WT. MoS2 QDs/MM is an excellent nano drug with multiple effects, which has advantages in the field of neurological diseases with crisscross pathogenesis.

Three-dimensional sonography has satisfied accuracy for detecting rotator cuff tears.

Background: Rotator cuff injuries and tears are common causes of shoulder pain and dysfunction, necessitating accurate diagnostic methods to guide clinical decision-making. This study evaluates the diagnostic utility of three-dimensional (3D) shoulder sonography in identifying rotator cuff injury and tear patterns. Methods: A comprehensive search across seven electronic databases, which included Cochrane Library, Embase, PubMed, Cochrane Library, China Biology Medicine (CBM) database, CNKI, Wanfang, and VIP database. These databases were utilized to retrieve articles that assess the diagnostic value of 3D shoulder sonography for identifying rotator cuff injuries and tear patterns. The effectiveness of 3D shoulder sonography was assessed in terms of sensitivity, specificity, positive likelihood ratio (PLR), negative likelihood ratio (NLR), and diagnostic odds ratio (DOR). For each parameter, the 95% confidence intervals were calculated. Additionally, summary receiver operating characteristic curves (SROCs) were constructed, allowing for a comprehensive evaluation of diagnostic accuracy, which is reflected in the area under the SROC curve (AUC). Results: Screening of 8,508 identified nine literatures eligible for inclusion in the meta-analysis, encompassing a total of 366 patients. The analysis of detecting any rotator cuff tear revealed a sensitivity of 0.97 and specificity of 0.87, yielding a DOR of 90.03 and an AUC of 0.98. Furthermore, 3D shoulder sonography demonstrated satisfactory accuracy in detecting both full and partial-thickness rotator cuff tears (Sensitivity: 0.92 vs. 0.83, specificity: 0.94 vs. 097, and AUC: 0.96 vs. 0.95). Conclusion: This study indicates that three-dimensional sonography has satisfied accuracy for detecting rotator cuff tears.

In-situ growth of CeO2 on biofilms: Innovative nanoparticles for photothermal therapy & multi-pronged attack on Alzheimer's disease.

Alzheimer's disease (AD) is complex and multifactorial, and its pathogenesis involves multiple factors and processes. This study pioneered the in situ growth of cerium oxide nanoparticles on macrophage membranes (Ce-RAW). Further, carbon quantum dots (CQD) were biomimetically modified by Ce-RAW, leading to the synthesis of a multifunctional nanocomposite (CQD-Ce-RAW). Within the framework of this research, CQD-Ce-RAW was strategically combined with photothermal therapy (PTT), aiming to achieve a more significant therapeutic effect. The macrophage membrane confers the system with anti-phagocytic and anti-inflammatory biological functions. More importantly, the ultra-small size of cerium oxide grown on the membrane acts as a reactive oxygen species (ROS) scavenger and alleviates the degree of oxidative stress. Meanwhile, CQD as a photosensitizer helps dissociate amyloid-ß (Aß) aggregates and chelates excess copper ions, thus further inhibiting Aß aggregation. Cell experiments showed that CQD-Ce-RAW combined with PTT could effectively degrade and inhibit the aggregation of Aß, remove ROS, and improve cell survival rate. The results of in vivo photothermal experiments demonstrated that near-infrared light enhanced the efficiency of drug penetration through the blood-brain barrier and facilitated its accumulation in brain tissue. This comprehensive therapeutic approach can intervene in the disease progression from multiple pathways, providing a new prospect for treating AD.

CeO2 In Situ Growth on Red Blood Cell Membranes: CQD Coating and Multipathway Alzheimer's Disease Therapy under NIR.

Alzheimer's disease (AD) has a complex etiology and diverse pathological processes. The therapeutic effect of single-target drugs is limited, so simultaneous intervention of multiple targets is gradually becoming a new research trend. Critical stages in AD progression involve amyloid-ß (Aß) self-aggregation, metal-ion-triggered fibril formation, and elevated reactive oxygen species (ROS). Herein, red blood cell membranes (RBC) are used as templates for the in situ growth of cerium oxide (CeO2) nanocrystals. Then, carbon quantum dots (CQDs) are encapsulated to form nanocomposites (CQD-Ce-RBC). This strategy is combined with photothermal therapy (PTT) for AD therapy. The application of RBC enhances the materials' biocompatibility and improves immune evasion. RBC-grown CeO2, the first application in the field of AD, demonstrates outstanding antioxidant properties. CQD acts as a chelating agent for copper ions, which prevents the aggregation of Aß. In addition, the thermal effect induced by near-infrared laser-induced CQD can break down Aß fibers and improve the permeability of the blood-brain barrier. In vivo experiments on APP/PS1 mice demonstrate that CQD-Ce-RBC combined with PTT effectively clears cerebral amyloid deposits and significantly enhances learning and cognitive abilities, thereby retarding disease progression. This innovative multipathway approach under light-induced conditions holds promise for AD treatment.

3D-printed PCL@BG scaffold integrated with SDF-1α-loaded hydrogel for enhancing local treatment of bone defects.

BACKGROUND: The long-term nonunion of bone defects is always a difficult problem in orthopaedics treatment. Artificial bone implants made of polymeric materials are expected to solve this problem due to their suitable degradation rate and good biocompatibility. However, the lack of mechanical strength, low osteogenic induction ability and poor hydrophilicity of these synthetic polymeric materials limit their large-scale clinical application. RESULTS: In this study, we used bioactive glass (BG) (20%, W/W) and polycaprolactone (PCL, 80%, W/W) as raw materials to prepare a bone repair scaffold (PCL@BG20) using fused deposition modelling (FDM) three-dimensional (3D) printing technology. Subsequently, stromal cell-derived factor-1α (SDF-1α) chemokines were loaded into the PCL@BG20 scaffold pores with gelatine methacryloyl (GelMA) hydrogel. The experimental results showed that the prepared scaffold had a porous biomimetic structure mimicking that of cancellous bone, and the compressive strength (44.89 ± 3.45 MPa) of the scaffold was similar to that of cancellous bone. Transwell experiments showed that scaffolds loaded with SDF-1α could promote the recruitment of bone marrow stromal cells (BMSCs). In vivo data showed that treatment with scaffolds containing SDF-1α and BG (PCL@BG-GelMA/SDF-1α) had the best effect on bone defect repair compared to the other groups, with a large amount of new bone and mature collagen forming at the bone defect site. No significant organ toxicity or inflammatory reactions were observed in any of the experimental groups. CONCLUSIONS: The results show that this kind of scaffold containing BG and SDF-1α serves the dual functions of recruiting stem cell migration in vivo and promoting bone repair in situ. We envision that this scaffold may become a new strategy for the clinical treatment of bone defects.

The Function and Mechanism of Anti-Inflammatory Factor Metrnl Prevents the Progression of Inflammatory-Mediated Pathological Bone Osteolytic Diseases.

Metrnl, recently identified as an adipokine, is a secreted protein notably expressed in white adipose tissue, barrier tissues, and activated macrophages. This adipokine plays a pivotal role in counteracting obesity-induced insulin resistance. It enhances adipose tissue functionality by promoting adipocyte differentiation, activating metabolic pathways, and exerting anti-inflammatory effects. Extensive research has identified Metrnl as a key player in modulating inflammatory responses and as an integral regulator of muscle regeneration. These findings position Metrnl as a promising biomarker and potential therapeutic target in treating inflammation-associated pathologies. Despite this, the specific anti-inflammatory mechanisms of Metrnl in immune-mediated osteolysis and arthritis remain elusive, warranting further investigation. In this review, we will briefly elaborate on the role of Metrnl in anti-inflammation function in inflammation-related osteolysis, arthritis, and pathological bone resorption, which could facilitate Metrnl's clinical application as a novel therapeutic strategy to prevent bone loss. While the pathogenesis of elbow stiffness remains elusive, current literature suggests that Metrnl likely exerts a pivotal role in its development.

Erythrocyte membrane coated with nitrogen-doped quantum dots and polydopamine composite nano-system combined with photothermal treatment of Alzheimer's disease.

Mitochondrial dysfunction and metal ion imbalance are recognized as pathological hallmarks of Alzheimer's Disease (AD), leading to deposition of ß-amyloid (Aß) thereby and inducing neurotoxicity, activating apoptosis, eliciting oxidative stress, and ultimately leading to cognitive impairment. In this study, the red blood cell membrane (RBC) was used as a vehicle for encapsulating carbon quantum dots (CQD) and polydopamine (PDA), creating a nanocomposite (PDA-CQD/RBC). This nanocomposite was combined with near-infrared light (NIR) for AD treatment. The RBC offers anti-immunorecognition properties to evade immune clearance, PDA exhibits enzyme-mimicking activity to mitigate oxidative stress damage, and CQD acts as a chelating agent for metal ions (Cu2+), effectively preventing Cu2+-mediated aggregation of Aß. Furthermore, the local heating induced by near-infrared laser irradiation can dismantle the formed Aß fibers and enhance the blood-brain barrier's permeability. Both in vitro and animal experiments have shown that PDA-CQD/RBC, in combination with NIR, mitigates neuroinflammation, and ameliorates behavioral deficits in mice. This approach targets multiple pathological pathways, surpassing the limitations of single-target treatments and enhancing therapeutic efficacy while decelerating disease progression.

Presenting dual-functional peptides on implant surface to direct in vitro osteogenesis and in vivo osteointegration.

The complex biological process of osseointegration and the bio-inertness of bone implants are the major reasons for the high failure rate of long-term implants, and have also promoted the rapid development of multifunctional implant coatings in recent years. Herein, through the special design of peptides, we use layer-by-layer assembly technology to simultaneously display two peptides with different biological functions on the implant surface to address this issue. A variety of surface characterization techniques (ellipsometry, atomic force microscopy, photoelectron spectroscopy, dissipation-quartz crystal microbalance) were used to study in detail the preparation process of the dual peptide functional coating and the physical and chemical properties, such as the composition, mechanical modulus, stability, and roughness of the coating. Compared with single peptide functional coatings, dual-peptide functionalized coatings had much better performances on antioxidant, cellular adhesion in early stage, proliferation and osteogenic differentiation in long term, as well as in vivo osteogenesis and osseointegration capabilities. These findings will promote the development of multifunctional designs in bone implant coatings, as a coping strategy for the complexity of biological process during osteointegration.

Enhanced vascularization and osseointegration under osteoporotic conditions through functional peptide coating on implant surfaces.

Patients with osteoporosis face challenges such as decreased bone density, a sparse trabecular structure, weakened osteogenic ability, and impaired angiogenesis, leading to poor osseointegration and implant failure. Surface modification of implants with biologically active molecules possessing various functions is an effective strategy to improve osseointegration. In this study, we constructed a simple multifunctional coating interface that significantly improves osseointegration. In brief, a multifunctional coating interface was constructed by coupling the Rgd adhesive peptide, Ogp osteogenic peptide, and Ang angiogenic peptide to Lys6 (k6), which self-assembled layer by layer with TA to form the (TA-Rgd@ogp@ang)n composite membrane. This study characterized the surface morphology and biomechanical properties of the coating under both gas and liquid phases and monitored the deposition process and reaction rate of the two peptides with TA using a quartz crystal microbalance. Moreover, (TA-Rgd@ogp@ang)n exhibited a triple synergistic effect on cell migration and adhesion, osteogenic differentiation, and angiogenesis. It also ameliorated the high ROS environment characteristic of osteoporosis pathology, promoted angiogenic bone defect regeneration in osteoporosis, thereby avoiding poor osseointegration. This work provides a new approach for the prevention of implant failure in pathological environments by constructing multifunctional coatings on implants, with tremendous potential applications in the fields of orthopedics and dentistry.

Osteoimmune Interactions and Therapeutic Potential of Macrophage-Derived Small Extracellular Vesicles in Bone-Related Diseases.

Due to the aging of the global population, the burden of bone-related diseases has increased sharply. Macrophage, as indispensable components of both innate immune responses and adaptive immunity, plays a considerable role in maintaining bone homeostasis and promoting bone establishment. Small extracellular vesicles (sEVs) have attracted increasing attention because they participate in cell cross-talk in pathological environments and can serve as drug delivery systems. In recent years, an increasing number of studies have expanded our knowledge about the effects of macrophage-derived sEVs (M-sEVs) in bone diseases via different forms of polarization and their biological functions. In this review, we comprehensively describe on the application and mechanisms of M-sEVs in various bone diseases and drug delivery, which may provide new perspectives for treating and diagnosing human bone disorders, especially osteoporosis, arthritis, osteolysis, and bone defects.

Prevalence of gastroparesis in diabetic patients: a systematic review and meta-analysis.

Although there was no significant heterogeneity in the meta-publication, sensitivity analyses revealed significant heterogeneity. Overall, the prevalence was higher in women (N = 6, R = 4.6%, 95% CI 3.1%, 6.0%, and I2 = 99.8%) than in men (N = 6, R = 3.4%, 95% CI 2.0%, 4.7%, and I2 = 99.6the %); prevalence of type 2 diabetes (N = 9, R = 12.5%, 95% CI 7.7%, 17.3%, and I2 = 95.4%) was higher than type 1 diabetes (N = 7, R = 8.3%, 95% CI 6.4%, 10.2%, and I2 = 93.6%); the prevalence of DGP was slightly lower in DM patients aged over 60 years (N = 6, R = 5.5%, 95% CI 3.3%, 7.7%, and I2 = 99.9%) compared to patients under 60 years of age (N = 12, R = 15.8%, 95% CI 11 15.8%, 95% CI 11.4%, 20.2%, and I2 = 88.3%). In conclusion, our findings indicate that the combined estimated prevalence of gastroparesis in diabetic patients is 9.3%. However, the sensitivity of the results is high, the robustness is low, and there are significant bias factors. The subgroup analysis revealed that the prevalence of DM-DGP is associated with factors such as gender, diabetes staging, age, and study method.

Biomechanical study of different fixation constructs for anterior column and posterior hemi-transverse acetabular fractures: a finite element analysis.

BACKGROUND: To compare the biomechanical properties and stability, using a finite element model, of four fixation constructs used for the treatment of anterior column and posterior hemi-transverse (ACPHT) acetabular fractures under two physiological loading conditions (standing and sitting). METHODS: A finite element model simulating ACPHT acetabular fractures was created for four different scenarios: a suprapectineal plate combined with posterior column and infra-acetabular screws (SP-PS-IS); an infrapectineal plate combined with posterior column and infra-acetabular screws (IP-PS-IS); a special infrapectineal quadrilateral surface buttress plate (IQP); and a suprapectineal plate combined with a posterior column plate (SP-PP). Three-dimensional finite element stress analysis was performed on these models with a load of 700 N in standing and sitting positions. Biomechanical stress distributions and fracture displacements were analysed and compared between these fixation techniques. RESULTS: In models simulating the standing position, high displacements and stress distributions were observed at the infra-acetabulum regions. The degree of these fracture displacements was low in the IQP (0.078 mm), as compared to either the IP-PS-IS (0.079 mm) or the SP & PP (0.413 mm) fixation constructs. However, the IP-PS-IS fixation construct had the highest effective stiffness. In models simulating the sitting position, high fracture displacements and stress distributions were observed at the regions of the anterior and posterior columns. The degree of these fracture displacements was low in the SP-PS-IS (0.101 mm), as compared to the IP-PS-IS (0.109 mm) and the SP-PP (0.196 mm) fixation constructs. CONCLUSION: In both standing and sitting positions, the stability and stiffness index were comparable between the IQP, SP-PS-IS, and IP-PS-IS. These 3 fixation constructs had smaller fracture displacements than the SP-PP construct. The stress concentrations at the regions of quadrilateral surface and infra-acetabulum suggest that the buttressing fixation of quadrilateral plate was required for ACPHT fractures.