Ginkgo Leaf-Derived Carbon Supports for the Immobilization of Iron/Iron Phosphide Nanospheres for Electrocatalytic Hydrogen Evolution.

Iron/iron phosphide nanospheres supported on ginkgo leaf-derived carbon (Fe&FeP@gl-C) are prepared using a post-phosphidation approach, with varying amounts of iron (Fe). The activity of the catalysts in the hydrogen evolution reaction (HER) outperforms iron/iron carbide nanospheres supported on ginkgo leaf-derived carbon (Fe&FexC@gl-C), due to enhanced work function, electron transfer, and Volmer processes. The d-band centers of Fe&FeP@gl-C-15 move away from the Fermi level, lowering the H2 desorption energy and accelerating the Heyrovsky reaction. Density functional theory (DFT) calculations reveal that the hydrogen-binding free energy |ΔGH*| value is close to zero for the Fe&FeP@gl-C-15 catalyst, showing a good balance between Volmer and Heyrovsky processes. The Fe&FeP@gl-C-15 catalyst shows excellent hydrogen evolution performance in 0.5 m H2SO4, driving a current density of 10 mA cm-2 at an overpotential of 92 mV. Notably, the Fe&FeP@gl-C-15 catalyst outperforms a 20 wt% Pt/C catalyst, with a smaller overpotential required to drive a higher current density above 375 mA cm-2.

Omeprazole and risk of osteoarthritis: insights from a mendelian randomization study in the UK Biobank.

BACKGROUND: A former cohort study has raised concern regarding the unanticipated hazard of omeprazole in expediting osteoarthritis (OA) advancement. The precise nature of their causal evidence, however, remains undetermined. The present research endeavors to investigate the underlying causal link between omeprazole and OA through the application of mendelian randomization (MR) analysis. METHODS: The study incorporated the ukb-a-106 and ukb-b-14,486 datasets. The investigation of causal effects employed methodologies such as MR-Egger, Weighted median, Inverse variance weighted (IVW) with multiplicative random effects, and IVW (fixed effects). The IVW approach was predominantly considered for result interpretation. Sensitivity analysis was conducted, encompassing assessments for heterogeneity, horizontal pleiotropy, and the Leave-one-out techniques. RESULTS: The outcomes of the MR analysis indicated a causal relationship between omeprazole and OA, with omeprazole identified as a contributing risk factor for OA development (IVW model: OR = 1.2473, P < 0.01 in ukb-a-106; OR = 1.1288, P < 0.05 in ukb-b-14,486). The sensitivity analysis underscored the robustness and dependability of the above-mentioned analytical findings. CONCLUSION: This study, employing MR, reveals that omeprazole, as an exposure factor, elevates the risk of OA. Considering the drug's efficacy and associated adverse events, clinical practitioners should exercise caution regarding prolonged omeprazole use, particularly in populations with heightened OA risks. Further robust and high-quality research is warranted to validate our findings and guide clinical practice.

A Novel Curcumin-Loaded Nanoplatform Alleviates Osteoarthritis by Inhibiting Chondrocyte Ferroptosis.

Osteoarthritis (OA) is a chronic degenerative joint disease characterized by the degradation of articular cartilage. Recent studies have demonstrated that chondrocyte ferroptosis plays a crucial role in the progression of OA. Consequently, developing nanomedicines that suppress chondrocyte ferroptosis is a promising strategy for OA treatment. However, there are few reports on nanomedicines specifically targeting chondrocyte ferroptosis for OA therapy. In this study, Curcumin-loaded nanoparticles (Cur-NPs) are fabricated to suppress chondrocyte ferroptosis by regulating reactive oxygen species (ROS), ferrous ion (Fe2⁺), and Acyl-CoA Synthetase Long-Chain Family Member 4 (ACSL4) levels of chondrocyte. This is achieved by combining the functions of curcumin and an amphiphilic block copolymer with ROS scavenging and iron-chelating properties. The in vitro anti-ferroptotic effects of Cur-NPs are thoroughly investigated. The findings indicate that Cur-NPs decrease the expression of ferroptosis markers such as ROS, Fe2⁺, and ACSL4, while protecting the mitochondrial membrane potential of chondrocytes. Additionally, Cur-NPs attenuated lipid peroxidation in chondrocytes. Furthermore, Cur-NPs significantly reduced the expression of the catabolic factor Matrix Metallopeptidase 13 (MMP13) and increased the expression of the anabolic factor Collagen type II (Col II) in vitro. This study demonstrates that Cur-NPs exhibit enhanced chondroprotective effects through anti-ferroptotic actions, presenting a promising approach for inhibiting chondrocyte ferroptosis using bioactive nanomaterials in OA treatment.

Osteoarthritis: Role of Peroxisome Proliferator-Activated Receptors.

Osteoarthritis (OA) represents the foremost degenerative joint disease observed in a clinical context. The escalating issue of population aging significantly exacerbates the prevalence of OA, thereby imposing an immense annual economic burden on societies worldwide. The current therapeutic landscape falls short in offering reliable pharmaceutical interventions and efficient treatment methodologies to tackle this growing problem. However, the scientific community continues to dedicate significant efforts towards advancing OA treatment research. Contemporary studies have discovered that the progression of OA may be slowed through the strategic influence on peroxisome proliferator-activated receptors (PPARs). PPARs are ligand-activated receptors within the nuclear hormone receptor family. The three distinctive subtypes-PPARα, PPARß/δ, and PPARγ-find expression across a broad range of cellular terminals, thus managing a multitude of intracellular metabolic operations. The activation of PPARγ and PPARα has been shown to efficaciously modulate the NF-κB signaling pathway, AP-1, and other oxidative stress-responsive signaling conduits, leading to the inhibition of inflammatory responses. Furthermore, the activation of PPARγ and PPARα may confer protection to chondrocytes by exerting control over its autophagic behavior. In summation, both PPARγ and PPARα have emerged as promising potential targets for the development of effective OA treatments.

Retrobulbarly injecting nerve growth factor attenuates visual impairment in streptozotocin-induced diabetes rats.

PURPOSE: To explore whether retrobulbar administration of nerve growth factor (NGF) can restore visual function of streptozotocin-induced diabetes rats. METHODS: A high-sucrose/high-fat diet and single injection of streptozotocin (STZ) were used in modeling diabetes. During week 13-15 after STZ injection, diabetic rats were received retrobulbar ßNGF injection. On week 17 after STZ injection, the rats were tested with flash visual evoked potential (FVEP) to reflect visual function and with both optical coherence tomography (OCT) and hematoxylin and eosin (H&E) staining to show retinal morphological changes. Furthermore, periodic acid-Schiff (PAS) staining for retinal vascular digest preparations was performed to investigate retinal microvascular alterations, and immunofluorescences for slides of the optic nerve or retina were checked to assess astrocyte activation, autophagy level, and the unfolded protein response (UPR). RESULTS: Retrobulbar ßNGF injection significantly improved FVEP of diabetic rats. It also significantly alleviated retinal ganglion cell (RGC) loss and scarcely elicited other retinal/microvascular morphological changes, in OCT, H&E staining, and microvascular preparation. Moreover when diabetes rats treated with NGF, immunostaining of the optic nerve showed downregulation of complement 3d (C3d) and upregulations of glial fibrillary acidic protein (GFAP), S100-A10, microtubule-associated proteins 1A/1B light chain 3b (LC3b), and activating transcription factor 4 (ATF-4), while immunostaining of the retina showed upregulation of LC3b and no expression of ATF-4. CONCLUSION: Our findings demonstrate that retrobulbar administration of ßNGF reduces visual impairment with RGC-loss attenuation and without retinal-microvascular morphological alteration in diabetic rats. Furthermore, enhancements of A2 astrocyte activation, autophagy-protein expression, and ATF-4-mediated UPR may play crucial roles in the protective mechanism of NGF in diabetic visual-pathway neurodegeneration.

Integrative analysis of anoikis-related genes prognostic signature with immunotherapy and identification of CDKN3 as a key oncogene in lung adenocarcinoma.

Anoikis, a form of programmed cell death induced by loss of cell contact, is closely associated with tumor invasion and metastasis, making it highly significant in lung cancer research. We examined the expression patterns and prognostic relevance of Anoikis-related genes (ARGs) in lung adenocarcinoma (LUAD) using the TCGA-LUAD database. This study identified molecular subtypes associated with Anoikis in LUAD and conducted functional enrichment analyses. We constructed an ARG risk score using univariate least absolute shrinkage and selection operator (LASSO) Cox regression, validated externally with GEO datasets and clinical samples. The clinical applicability of the prognostic model was evaluated using nomograms, calibration curves, decision curve analysis (DCA), and time-dependent AUC assessments. We identified four prognostically significant genes (PLK1, SLC2A1, CDKN3, PHLDA2) and two ARG-related molecular subtypes. ARGs were generally upregulated in LUAD and correlated with multiple pathways including the cell cycle and DNA replication. The prognostic model indicated that the low-risk group had better outcomes and significant correlations with clinicopathological features, tumor microenvironment, immune therapy responses, drug sensitivity, and pan-RNA epigenetic modification-related genes. Patients with low-risk LUAD were potential beneficiaries of immune checkpoint inhibitor (ICI) therapy. Prognostic ARGs' distribution and expression across various immune cell types were further analyzed using single-cell RNA sequencing. The pivotal role of CDKN3 in LUAD was confirmed through qRT-PCR and gene knockout experiments, demonstrating that CDKN3 knockdown inhibits tumor cell proliferation, migration, and invasion. Additionally, we constructed a ceRNA network involving CDKN3/hsa-miR-26a-5p/SNHG6, LINC00665, DUXAP8, and SLC2A1/hsa-miR-218-5p/RNASEH1-AS1, providing new insights for personalized and immune therapy decisions in LUAD patients.

Tuning the electronic metal-carbon interactions in Lignin-based carbon-supported ruthenium-based electrocatalysts for enhanced hydrogen evolution reactions.

Ruthenium (Ru) nanoparticles dispersed on carbon support are promising electrocatalysts for hydrogen evolution reaction (HER) due to strong electronic metal-carbon interactions (EMCIs). Defects engineering in carbon supports is an effective strategy to adjust EMCIs. We prepared nitrogen/sulfur co-doped carbon supported Ru nanoparticles (Ru@N/S-LC) using sodium lignosulfonate and urea as feedstocks. Intrinsic S dopants from sodium lignosulfonate create rich S defects, thus enhancing the EMCIs within Ru@N/S-LC, leading a faster electron transfer between Ru nanoparticles and N/S-LC compared with N-doped carbon supported Ru nanoparticles (Ru@N-CC). The resulting Ru@N/S-LC exhibits an enhanced work function and a down-shifted d-band center, inducing stronger electron capturing ability and weaker hydrogen desorption energy than Ru@N-CC. Ru@N/S-LC requires only 7 and 94 mV overpotential in acidic medium and alkaline medium to achieve a current density of 10 mA cm-2. Density Functional Theory (DFT) calculations were utilized to clarify the impact of sulfur (S) doping and the mechanism underlying the notable catalytic activity of Ru@N/S-LC. This study offers a perspective for utilizing the natural dopants of biomass to adjust the EMCIs for electrocatalysts.

Enhanced osteogenic and ROS-scavenging MXene nanosheets incorporated gelatin-based nanocomposite hydrogels for critical-sized calvarial defect repair.

The healing of critical-sized bone defects is a major challenge in the field of bone tissue engineering. Gelatin-related hydrogels have emerged as a potential solution due to their desirable properties. However, their limited osteogenic, mechanical, and reactive oxygen species (ROS)-scavenging capabilities have hindered their clinical application. To overcome this issue, we developed a biofunctional gelatin-Mxene nanocomposite hydrogel. Firstly, we prepared two-dimensional (2D) Ti3C2 MXene nanosheets using a layer delamination method. Secondly, these nanosheets were incorporated into a transglutaminase (TG) enzyme-containing gallic acid-imbedded gelatin (GGA) pre-gel solution to create an injectable GGA-MXene (GM) nanocomposite hydrogel. The GM hydrogels exhibited superior compressive strength (44-75.6 kPa) and modulus (24-44.5 kPa) compared to the GGA hydrogels. Additionally, the GM hydrogel demonstrated the ability to scavenge reactive oxygen species (OH- and DPPH radicals), protecting MC3T3-E1 cells from oxidative stress. GM hydrogels were non-toxic to MC3T3-E1 cells, increased alkaline phosphatase secretion, calcium nodule formation, and upregulated osteogenic gene expressions (ALP, OCN, and RUNX2). The GM400 hydrogel was implanted in critical-sized calvarial defects in rats. Remarkably, it exhibited significant potential for promoting new bone formation. These findings indicated that GM hydrogel could be a viable candidate for future clinical applications in the treatment of critical-sized bone defects.

Microstructure Characteristics and Hydrogen Storage Kinetics of Mg77+xNi20-xLa3 (x = 0, 5, 10, 15) Alloys.

Mg77+xNi20-xLa3 (x = 0, 5, 10, 15) alloys were successfully prepared by the vacuum induction melting method. The structural characterizations of the alloys were performed by using X-ray diffraction and scanning electron microscope. The effects of nickel content on the microstructure and hydrogen storage kinetic of the as-cast alloys were investigated. The results showed that the alloys are composed of a primary phase of Mg2Ni, lamella eutectic composites of Mg + Mg2Ni, and some amount of LaMg12 and La2Mg17. Nickel addition significantly improved the hydrogen-absorption kinetic performance of the alloy. At 683 K, Mg77Ni20La3 alloy and Mg82Ni15La3 alloy underwent hydrogen absorption and desorption reactions for 2 h, respectively, and their hydrogen absorption and desorption capacities were 4.16 wt.% and 4.1 wt.%, and 4.92 wt.% and 4.69 wt.%, respectively. Using the Kissinger equation, it was calculated that the activation energy values of Mg77Ni20La3, Mg82Ni15La3, Mg87Ni10La3 and Mg92Ni5La3 alloys were in the range of 68.5~75.2 kJ/mol, much lower than 150~160 kJ/mol of MgH2.

Research Progress in Calcitonin Gene-Related Peptide and Bone Repair.

Calcitonin gene-related peptide (CGRP) has 37 amino acids. Initially, CGRP had vasodilatory and nociceptive effects. As research progressed, evidence revealed that the peripheral nervous system is closely associated with bone metabolism, osteogenesis, and bone remodeling. Thus, CGRP is the bridge between the nervous system and the skeletal muscle system. CGRP can promote osteogenesis, inhibit bone resorption, promote vascular growth, and regulate the immune microenvironment. The G protein-coupled pathway is vital for its effects, while MAPK, Hippo, NF-κB, and other pathways have signal crosstalk, affecting cell proliferation and differentiation. The current review provides a detailed description of the bone repair effects of CGRP, subjected to several therapeutic studies, such as drug injection, gene editing, and novel bone repair materials.

Identification and verification of m7G-Related genes as biomarkers for prognosis of sarcoma.

Background: Increasing evidence indicates a crucial role for N7-methylguanosine (m7G) methylation modification in human disease development, particularly cancer, and aberrant m7G levels are closely associated with tumorigenesis and progression via regulation of the expression of multiple oncogenes and tumor suppressor genes. However, the role of m7G in sarcomas (SARC) has not been adequately evaluated. Materials and methods: Transcriptome and clinical data were gathered from the TCGA database for this study. Normal and SARC groups were compared for the expression of m7G-related genes (m7GRGs). The expression of m7GRGs was verified using real-time quantitative PCR (RT-qPCR) in SARC cell lines. Then, differentially expressed genes (DEGs) were identified between high and low m7GRGs expression groups in SARC samples, and GO enrichment and KEGG pathways were evaluated. Next, prognostic values of m7GRGs were evaluated by Cox regression analysis. Subsequently, a prognostic model was constructed using m7GRGs with good prognostic values by Lasso regression analysis. Besides, the relationships between prognostic m7GRGs and immune infiltration, clinical features, cuproptosis-related genes, and antitumor drugs were investigated in patients with SARC. Finally, a ceRNA regulatory network based on m7GRGs was constructed. Results: The expression of ten m7GRGs was higher in the SARC group than in the control group. DEGs across groups with high and low m7GRGs expression were enriched for adhesion sites and cGMP-PKG. Besides, we constructed a prognostic model that consists of EIF4A1, EIF4G3, NCBP1, and WDR4 m7GRGs for predicting the survival likelihood of sarcoma patients. And the elevated expression of these four prognostic m7GRGs was substantially associated with poor prognosis and elevated expression in SARC cell lines. Moreover, we discovered that these four m7GRGs expressions were negatively correlated with CD4+ T cell levels, dendritic cell level and tumor purity, and positively correlated with tumor mutational burden, microsatellite instability, drug sensitivity and cuproptosis-related genes in patients with sarcomas. Then, a triple regulatory network of mRNA, miRNA, and lncRNA was established. Conclusion: The current study identified EIF4A1, EIF4G3, NCBP1, and WDR4 as prognostic genes for SARC that are associated with m7G.These findings extend our knowledge of m7G methylation in SARC and may guide the development of innovative treatment options.

"Cross-talk" between gut microbiome dysbiosis and osteoarthritis progression: a systematic review.

Objectives: The aim of this systematic review was to summarize the available literature on gut microbiome (GMB) and osteoarthritis (OA), analyze the correlation between GMB and OA, and explore potential underlying mechanisms. Methods: A systematic search of the PubMed, Embase, Cochrane, and Web of Science with the keywords "Gut Microbiome" and "Osteoarthritis" was conducted to identify the human and animal studies exploring the association between GMB and OA. The retrieval time range was from the database inception to July 31, 2022. Studies reported the other arthritic diseases without OA, reviews, and studies focused on the microbiome in other parts of the body with OA, such as oral or skin, were excluded. The included studies were mainly reviewed for GMB composition, OA severity, inflammatory factors, and intestinal permeability. Results: There were 31 studies published met the inclusion criteria and were analyzed, including 10 human studies and 21 animal studies. Human and animal studies have reached a consistent conclusion that GMB dysbiosis could aggravate OA. In addition, several studies have found that alterations of GMB composition can increase intestinal permeability and serum levels of inflammatory factors, while regulating GMB can alleviate the changes. Owing to the susceptibility of GMB to internal and external environments, genetics, and geography, the included studies were not consistent in GMB composition analysis. Conclusion: There is a lack of high-quality studies evaluating the effects of GMB on OA. Available evidence indicated that GMB dysbiosis aggravated OA through activating the immune response and subsequent induction of inflammation. Future studies should focus on more prospective, cohort studies combined with multi-omics to further clarify the correlation.

A Systematic Study of Anti-Osteosarcoma Mechanism of pH-Sensitive Charge-Conversion Cinnamaldehyde Polymeric Prodrug Micelles In Vitro.

Osteosarcoma is an aggressive malignant neoplasm, and it is of great significance to the fabrication and investigation of the anti-tumor mechanism of nanomedicine in the treatment of osteosarcoma. Herein, a cinnamaldehyde polymeric prodrug micelle with pH-sensitive charge-conversion ability (mPEG-b-P(C7-co-CA)) was fabricated, and the anti-osteosarcoma mechanism of mPEG-b-P(C7-co-CA) micelle was investigated. mPEG-b-P(C7-co-CA) micelles were prepared by self-assembly method, and their diameter was 227 nm. mPEG-b-P(C7-co-CA) micelles could regulate the cell cycle and inhibit the proliferation of 143B cells, which was demonstrated by flow cytometry analysis, CCK-8 assay and 5-Ethynyl-2'-deoxyuridine (EdU) staining. The wound-healing assay and transwell assay showed that mPEG-b-P(C7-co-CA) micelles effectively inhibited the migration and invasion of 143B cells. It was proven that mPEG-b-P(C7-co-CA) micelles downregulated the levels of proliferation and apoptosis-related proteins and affected osteosarcoma migration and invasion by inhibiting the epithelial-mesenchymal transition (EMT). In addition, mPEG-b-P(C7-co-CA) micelles can also inhibit the transcriptional activity of the PI3K/Akt signaling pathway. Therefore, these findings provide new evidence for the pharmacological effects of mPEG-b-P(C7-co-CA) micelles.

Comprehensive analysis of cuproptosis-related prognostic gene signature and tumor immune microenvironment in HCC.

Background: Copper is an indispensable mineral element involved in many physiological metabolic processes. Cuproptosis is associated with a variety of cancer such as hepatocellular carcinoma (HCC). The objective of this study was to examine the relationships between the expression of cuproptosis-related genes (CRGs) and tumor characteristics, including prognosis and microenvironment of HCC. Methods: The differentially expressed genes (DEGs) between high and low CRGs expression groups in HCC samples were identified, and further were analyzed for functional enrichment analysis. Then, CRGs signature of HCC was constructed and analyzed utilizing LASSO and univariate and multivariate Cox regression analysis. Prognostic values of CRGs signature were evaluated by Kaplan-Meier analysis, independent prognostic analysis and nomograph. The expression of prognostic CRGs was verified by Real-time quantitative PCR (RT-qPCR) in HCC cell lines. In addition, the relationships between prognostic CRGs expression and the immune infiltration, tumor microenvironment, antitumor drugs response and m6A modifications were further explored using a series of algorithms in HCC. Finally, ceRNA regulatory network based on prognostic CRGs was constructed. Results: The DEGs between high and low CRG expression groups in HCC were mainly enriched in focal adhesion and extracellular matrix organization. Besides, we constructed a prognostic model that consists of CDKN2A, DLAT, DLST, GLS, and PDHA1 CRGs for predicting the survival likelihood of HCC patients. And the elevated expression of these five prognostic CRGs was substantially in HCC cell lines and associated with poor prognosis. Moreover, immune score and m6A gene expression were higher in the high CRG expression group of HCC patients. Furthermore, prognostic CRGs have higher mutation rates in HCC, and are significantly correlated with immune cell infiltration, tumor mutational burden, microsatellite instability, and anti-tumor drug sensitivity. Then, eight lncRNA-miRNA-mRNA regulatory axes that affected the progression of HCC were predicted. Conclusion: This study demonstrated that the CRGs signature could effectively evaluate prognosis, tumor immune microenvironment, immunotherapy response and predict lncRNA-miRNA-mRNA regulatory axes in HCC. These findings extend our knowledge of cuproptosis in HCC and may inform novel therapeutic strategies for HCC.

[Analysis of misdiagnostic causes of Coats disease].

OBJECTIVE: To analyze the clinical features and misdiagnostic causes of Coats disease. METHODS: The clinical data were retrospectively analyzed in 69 eyes of 68 patients with Coats disease. RESULTS: Misdiagnostic histories to a varying degree occurred in 11 of the 68 cases with a misdiagnosis rate of 16.18% and misdiagnostic mean time of 7.5 months. CONCLUSION: Lack of knowledge on pathogenic characteristics of Coats disease, lack of typical manifestations, no timely accessory examinations, and advanced cases are the main causes of misdiagnosis.