Extracellular vesicles derived from mesenchymal stem cells mediate extracellular matrix remodeling in osteoarthritis through the transport of microRNA-29a.

BACKGROUND: Knee osteoarthritis (KOA) is a common orthopedic condition with an uncertain etiology, possibly involving genetics and biomechanics. Factors like changes in chondrocyte microenvironment, oxidative stress, inflammation, and immune responses affect KOA development. Early-stage treatment options primarily target symptom relief. Mesenchymal stem cells (MSCs) show promise for treatment, despite challenges. Recent research highlights microRNAs (miRNAs) within MSC-released extracellular vesicles that can potentially promote cartilage regeneration and hinder KOA progression. This suggests exosomes (Exos) as a promising avenue for future treatment. While these findings emphasize the need for effective KOA progression management, further safety and efficacy validation for Exos is essential. AIM: To explore miR-29a's role in KOA, we'll create miR-29a-loaded vesicles, testing for early treatment in rat models. METHODS: Extraction of bone marrow MSC-derived extracellular vesicles, preparation of engineered vesicles loaded with miR-29a using ultrasonication, and identification using quantitative reverse transcription polymerase chain reaction; after establishing a rat model of KOA, rats were randomly divided into three groups: Blank control group injected with saline, normal extracellular vesicle group injected with normal extracellular vesicle suspension, and engineered extracellular vesicle group injected with engineered extracellular vesicle suspension. The three groups were subjected to general behavioral observation analysis, imaging evaluation, gross histological observation evaluation, histological detection, and immunohistochemical detection to compare and evaluate the progress of various forms of arthritis. RESULTS: General behavioral observation results showed that the extracellular vesicle group and engineered extracellular vesicle group had better performance in all four indicators of pain, gait, joint mobility, and swelling compared to the blank control group. Additionally, the engineered extracellular vesicle group had better pain relief at 4 wk and better knee joint mobility at 8 wk compared to the normal extracellular vesicle group. Imaging examination results showed that the blank control group had the fastest progression of arthritis, the normal extracellular vesicle group had a relatively slower progression, and the engineered extracellular vesicle group had the slowest progression. Gross histological observation results showed that the blank control group had the most obvious signs of arthritis, the normal extracellular vesicle group showed signs of arthritis, and the engineered extracellular vesicle group showed no significant signs of arthritis. Using the Pelletier gross score evaluation, the engineered extracellular vesicle group had the slowest progression of arthritis. Results from two types of staining showed that the articular cartilage of rats in the normal extracellular vesicle and engineered extracellular vesicle groups was significantly better than that of the blank control group, and the engineered extracellular vesicle group had the best cartilage cell and joint surface condition. Immunohistochemical detection of type II collagen and proteoglycan showed that the extracellular matrix of cartilage cells in the normal extracellular vesicle and engineered extracellular vesicle groups was better than that of the blank control group. Compared to the normal extracellular vesicle group, the engineered extracellular vesicle group had a better regulatory effect on the extracellular matrix of cartilage cells. CONCLUSION: Engineered Exos loaded with miR-29a can exert anti-inflammatory effects and maintain extracellular matrix stability, thereby protecting articular cartilage, and slowing the progression of KOA.

Polymer-acid-metal quasi-ohmic contact for stable perovskite solar cells beyond a 20,000-hour extrapolated lifetime.

The development of a robust quasi-ohmic contact with minimal resistance, good stability and cost-effectiveness is crucial for perovskite solar cells. We introduce a generic approach featuring a Lewis-acid layer sandwiched between dopant-free semicrystalline polymer and metal electrode in perovskite solar cells, resulting in an ideal quasi-ohmic contact even at elevated temperature up to 85 °C. The solubility of Lewis acid in alcohol facilitates nondestructive solution processing on top of polymer, which boosts hole injection from polymer into metal by two orders of magnitude. By integrating the polymer-acid-metal structure into solar cells, devices exhibit remarkable resilience, retaining 96% ± 3%, 96% ± 2% and 75% ± 7% of their initial efficiencies after continuous operation in nitrogen at 35 °C for 2212 h, 55 °C for 1650 h and 85 °C for 937 h, respectively. Leveraging the Arrhenius relation, we project an impressive T80 lifetime of 26,126 h at 30 °C.

Advances in the Application of Bone Transport Techniques in the Treatment of Bone Nonunion and Bone Defects.

Bone nonunion and bone defects frequently occur following high-energy open injuries or debridement surgeries, presenting complex challenges to treatment and significantly affecting patients' quality of life. At present, there are three primary treatment options available for addressing bone nonunion and bone defects: vascularized bone grafts, the Masquelet technique, and the Ilizarov technique. The Ilizarov technique, also known as distraction osteogenesis, is widely favored by orthopedic surgeons because of several advantages, including minimal soft tissue requirements, low infection risk, and short consolidation time. However, in recent years, the application of the Masquelet technique has resulted in novel treatment methods for managing post-traumatic bone infections when bone defects are present. Although these new techniques do not constitute a panacea, they continue to be the most commonly employed options for treating complex large bone nonunion and bone defects. This review evaluates the currently available research on the Ilizarov and Masquelet bone transport techniques applied at various anatomical sites. Additionally, it explores treatment durations and associated complications to establish a theoretical foundation that can guide clinical treatment decisions and surgical procedures for the management of bone nonunion and bone defects.

Synergistic Combination of Reductive Covalent Functionalization and Atomic Layer Deposition-Towards Spatially Defined Graphene-Organic-Inorganic Heterostructures.

Three-dimensionally (3D) well-ordered and highly integrated graphene hybrid architectures are considered to be next-generation multifunctional graphene materials but still remain elusive. Here, we report the first realization of unprecedented 3D-patterned graphene nano-ensembles composed of a graphene monolayer, a tailor-made structured organophenyl layer, and three metal oxide films, providing the first example of such a hybrid nano-architecture. These spatially resolved and hierarchically structured quinary hybrids are generated via a two-dimensional (2D)-functionalization-mediated atomic layer deposition growth process, involving an initial lateral molecular programming of the graphene lattice via lithography-assisted 2D functionalization and a subsequent stepwise molecular assembly in these regions in the z-direction. Our breakthrough lays the foundation for the construction of emerging 3D-patterned graphene heterostructures.

A pyroptosis-related gene signature that predicts immune infiltration and prognosis in colon cancer.

Background: Colon cancer (CC) is a highly heterogeneous malignancy associated with high morbidity and mortality. Pyroptosis is a type of programmed cell death characterized by an inflammatory response that can affect the tumor immune microenvironment and has potential prognostic and therapeutic value. The aim of this study was to evaluate the association between pyroptosis-related gene (PRG) expression and CC. Methods: Based on the expression profiles of PRGs, we classified CC samples from The Cancer Gene Atlas and Gene Expression Omnibus databases into different clusters by unsupervised clustering analysis. The best prognostic signature was screened and established using least absolute shrinkage and selection operator (LASSO) and multivariate COX regression analyses. Subsequently, a nomogram was established based on multivariate COX regression analysis. Next, gene set enrichment analysis (GSEA) and gene set variation analysis (GSVA) were performed to explore the potential molecular mechanisms between the high- and low-risk groups and to explore the differences in clinicopathological characteristics, gene mutation characteristics, abundance of infiltrating immune cells, and immune microenvironment between the two groups. We also evaluated the association between common immune checkpoints and drug sensitivity using risk scores. The immunohistochemistry staining was utilized to confirm the expression of the selected genes in the prognostic model in CC. Results: The 1163 CC samples were divided into two clusters (clusters A and B) based on the expression profiles of the 33 PRGs. Genes with prognostic value were screened from the DEGs between the two clusters, and an eight PRGs prognostic model was constructed. GSEA and GSVA of the high- and low-risk groups revealed that they were mainly enriched in inflammatory response-related pathways. Compared to those in the low-risk group, patients in the high-risk group had worse overall survival, an immunosuppressive microenvironment, and worse sensitivity to immunotherapy and drug treatment. Conclusion: Our findings provide a foundation for future research targeting pyroptosis and new insights into prognosis and immunotherapy from the perspective of pyroptosis in CC.

Highly Localized Optical Field Enhancement at Neon Ion Sputtered Tungsten Nanotips.

We present laser-driven rescattering of electrons at a nanometric protrusion (nanotip), which is fabricated with an in situ neon ion sputtering technique applied to a tungsten needle tip. Electron energy spectra obtained before and after the sputtering show rescattering features, such as a plateau and high-energy cutoff. Extracting the optical near-field enhancement in both cases, we observe a strong increase of more than 2-fold for the nanotip. Accompanying finite-difference time-domain (FDTD) simulations show a good match with the experimentally extracted near-field strengths. Additionally, high electric field localization for the nanotip is found. The combination of transmission electron microscope imaging of such nanotips and the determination of the near-field enhancement by electron rescattering represent a full characterization of the electric near-field of these intriguing electron emitters. Ultimately, nanotips as small as single nanometers can be produced, which is of utmost interest for electron diffraction experiments and low-emittance electron sources.

Hexagonal Hybrid Bismuthene by Molecular Interface Engineering.

High-quality devices based on layered heterostructures are typically built from materials obtained by complex solid-state physical approaches or laborious mechanical exfoliation and transfer. Meanwhile, wet-chemically synthesized materials commonly suffer from surface residuals and intrinsic defects. Here, we synthesize using an unprecedented colloidal photocatalyzed, one-pot redox reaction a few-layers bismuth hybrid of "electronic grade" structural quality. Intriguingly, the material presents a sulfur-alkyl-functionalized reconstructed surface that prevents it from oxidation and leads to a tuned electronic structure that results from the altered arrangement of the surface. The metallic behavior of the hybrid is supported by ab initio predictions and room temperature transport measurements of individual nanoflakes. Our findings indicate how surface reconstructions in two-dimensional (2D) systems can promote unexpected properties that can pave the way to new functionalities and devices. Moreover, this scalable synthetic process opens new avenues for applications in plasmonics or electronic (and spintronic) device fabrication. Beyond electronics, this 2D hybrid material may be of interest in organic catalysis, biomedicine, or energy storage and conversion.

Tetra-Nuclear Cluster-Based Lanthanide Metal-Organic Frameworks as White Phosphor, Information Encryption, Self-Calibrating Thermometers, and Fe2+ Sensors.

The application of one kind of metal-organic framework (MOF) material used in multiple fields is one of the most interesting research topics. In this work, four new tetra-nuclear cluster-based lanthanide metal-organic frameworks (LnMOFs) [Ln2(BTDB)3(DMA)(phen)]n (Ln = Tb TbMOF, Eu EuMOF, Gd GdMOF, Tb1.830Eu0.170 Tb,EuMOF, 3,5-bis(trifluoromethyl)-4',4″-dicarboxytriphenylamine = H2BTDB, 1,10-phenanthroline = phen) are obtained based on the ligand of H2BTDB that is synthesized in our laboratory, and the precise single-crystal structure of H2BTDB is obtained for the first time. The white phosphor was obtained by facilely hybridizing two components of the orange-yellow emission phosphor of Tb,EuMOF and the blue luminescence material of triphenylamine according to the trichromatic theory. At the same time, TbMOF, EuMOF, Tb,EuMOF, and the white phosphor can be used for information encryption, demonstrating their potential application in the field of anti-counterfeiting. Tb,EuMOF is also a multi-mode and self-calibrating thermometer within a broad temperature range of 110-300 K. Further studies show that EuMOF is a rapid response sensor for Fe2+, with a very low limit of detection of 2.0 nM, which is much lower than the national standards for Fe2+ (GB 5749-2005, 5.357 µM). It can achieve strong anti-interference detection of Fe2+ in actual samples of tap water and lake water. In addition, EuMOF can also be made into an easy-to-use sensing device of test paper for real-time and visual sensing of Fe2+.

Combination therapy with BMSCs­exosomes and porous tantalum for the repair of femur supracondylar defects.

In the field of orthopedics, defects in large bones have proven challenging to resolve. The aim of the present study was to address this problem through the combination of tantalum metal (pTa) with exosomes derived from bone marrow mesenchymal stem cells (BMSCs), which have the potential to enhance regeneration of full thickness femoral bone defects in rats. Cell culture results demonstrated that exosomes improved the proliferation and differentiation of BMSCs. Following establishment of a supracondylar femoral bone defect, exosomes and pTa were implanted into the defect area. Results demonstrated that pTa acts as a core scaffold for cell adhesion and exhibits good biocompatibility. Moreover, micro­CT scan results as well as histological examination demonstrated that pTa had a significant effect on osteogenesis, with the addition of exosomes further promoting bone tissue regeneration and repair. In conclusion, this novel composite scaffold can effectively promote bone regeneration in large bone defect areas, providing a new approach for the treatment of large bone defects.

Isolated Rh atoms in dehydrogenation catalysis.

Isolated active sites have great potential to be highly efficient and stable in heterogeneous catalysis, while enabling low costs due to the low transition metal content. Herein, we present results on the synthesis, first catalytic trials, and characterization of the Ga9Rh2 phase and the hitherto not-studied Ga3Rh phase. We used XRD and TEM for structural characterization, and with XPS, EDX we accessed the chemical composition and electronic structure of the intermetallic compounds. In combination with catalytic tests of these phases in the challenging propane dehydrogenation and by DFT calculations, we obtain a comprehensive picture of these novel catalyst materials. Their specific crystallographic structure leads to isolated Rhodium sites, which is proposed to be the decisive factor for the catalytic properties of the systems.

Influence of tin oxide decoration on the junction conductivity of silver nanowires.

Flexible electrodes using nanowires (NWs) suffer from challenges of long-term stability and high junction resistance which limit their fields of applications. Welding via thermal annealing is a common strategy to enhance the conductivity of percolated NW networks, however, it affects the structural and mechanical integrity of the NWs. In this study we show that the decoration of NWs with an ultrathin metal oxide is a potential alternative procedure which not only enhances the thermal and chemical stability but, moreover, provides a totally different mechanism to reduce the junction resistance upon heat treatment. Here, we analyze the effect of SnOxdecoration on the conductance of silver NWs and NW junctions by using a four-probe measurement setup inside a scanning electron microscope. Dedicated transmission electron microscopy analysis in plan-view and cross-section geometry are carried out to characterize the nanowires and the microstructure of the junctions. Upon heat treatment the junction resistance of both plain silver NWs and SnOx-decorated NWs is reduced by around 80%. While plain silver NWs show characteristic junction welding during annealing, the SnOx-decoration reduces junction resistance by a solder-like process which does not affect the mechanical integrity of the NW junction and is therefore expected to be superior for applications.

Effects of angiotensin II combined with asparaginase and dexamethasone on the femoral head in mice: A model of steroid-induced femoral head osteonecrosis.

Background: To study the pathogenesis of steroid-induced femoral head osteonecrosis, an ideal animal model is very important. As experimental animals, mice are beneficial for studying the pathogenesis of disease. However, there are currently few mouse models of steroid-induced femoral head osteonecrosis, and there are many questions that require further exploration and research. Purposes: The purpose of this study was to establish a new model of osteonecrosis in mice using angiotensin II (Ang II) combined with asparaginase (ASP) and dexamethasone (DEX) and to study the effects of this drug combination on femoral head osteonecrosis in mice. Methods: Male BALB/c mice (n = 60) were randomly divided into three groups. Group A (normal control, NC) was treated with physiological saline and given a normal diet. Group B (DEX + ASP, DA) was given free access to food and water (containing 2 mg/L DEX) and subjected to intraperitoneal injection of ASP (1200 IU/kg twice/week for 8 weeks). Group C (DEX + ASP + Ang II, DAA) was treated the same as group B, it was also given free access to food and water (containing 2 mg/L DEX) and subjected to intraperitoneal injection of ASP (1200 IU/kg twice/week for 8 weeks), but in the 4th and 8th weeks, subcutaneous implantation of a capsule osmotic pump (0.28 mg/kg/day Ang II) was performed. The mice were sacrificed in the 4th and 8th weeks, and the model success rate, mouse mortality rate, body weight, blood lipids, coagulation factors, histopathology, and number of local vessels in the femoral head were evaluated. Results: DAA increased the model success rate [4th week, 30% (DA) vs. 40% (DAA) vs. 0% (NC); 8th week, 40% (DA) vs. 70% (DAA) vs. 0% (NC)]. There was no significant difference in mortality rate between the groups [4th week, 0% (DA) vs. 0% (DAA) vs. 0% (NC); 8th week, 5% (DA) vs. 10% (DAA) vs. 0% (NC)]. DAA affected mouse body weight and significantly affected blood lipids and blood coagulation factors. DAA reduces the number of blood vessels in the femoral head and destroys the local blood supply. Conclusion: Angiotensin II combined with asparaginase and dexamethasone can obviously promote the necrosis of femoral head and provide a new idea for the model and treatment of osteonecrosis.

sp-Carbon Incorporated Conductive Metal-Organic Framework as Photocathode for Photoelectrochemical Hydrogen Generation.

Metal-organic frameworks (MOFs) have attracted increasing interest for broad applications in catalysis and gas separation due to their high porosity. However, the insulating feature and the limited active sites hindered MOFs as photocathode active materials for application in photoelectrocatalytic hydrogen generation. Herein, we develop a layered conductive two-dimensional conjugated MOF (2D c-MOF) comprising sp-carbon active sites based on arylene-ethynylene macrocycle ligand via CuO4 linking, named as Cu3 HHAE2 . This sp-carbon 2D c-MOF displays apparent semiconducting behavior and broad light absorption till the near-infrared band (1600 nm). Due to the abundant acetylene units, the Cu3 HHAE2 could act as the first case of MOF photocathode for photoelectrochemical (PEC) hydrogen generation and presents a record hydrogen-evolution photocurrent density of ≈260 µA cm-2 at 0 V vs. reversible hydrogen electrode among the structurally-defined cocatalyst-free organic photocathodes.

Radiolysis-Driven Evolution of Gold Nanostructures - Model Verification by Scale Bridging In Situ Liquid-Phase Transmission Electron Microscopy and X-Ray Diffraction.

Utilizing ionizing radiation for in situ studies in liquid media enables unique insights into nanostructure formation dynamics. As radiolysis interferes with observations, kinetic simulations are employed to understand and exploit beam-liquid interactions. By introducing an intuitive tool to simulate arbitrary kinetic models for radiation chemistry, it is demonstrated that these models provide a holistic understanding of reaction mechanisms. This is shown for irradiated HAuCl4 solutions allowing for quantitative prediction and tailoring of redox processes in liquid-phase transmission electron microscopy (LP-TEM). Moreover, it is demonstrated that kinetic modeling of radiation chemistry is applicable to investigations utilizing X-rays such as X-ray diffraction (XRD). This emphasizes that beam-sample interactions must be considered during XRD in liquid media and shows that reaction kinetics do not provide a threshold dose rate for gold nucleation relevant to LP-TEM and XRD. Furthermore, it is unveiled that oxidative etching of gold nanoparticles depends on both, precursor concentration, and dose rate. This dependency is exploited to probe the electron beam-induced shift in Gibbs free energy landscape by analyzing critical radii of gold nanoparticles.

Seeing structural evolution of organic molecular nano-crystallites using 4D scanning confocal electron diffraction (4D-SCED).

Direct observation of organic molecular nanocrystals and their evolution using electron microscopy is extremely challenging, due to their radiation sensitivity and complex structure. Here, we introduce 4D-scanning confocal electron diffraction (4D-SCED), which enables direct in situ observation of bulk heterojunction (BHJ) thin films. 4D-SCED combines confocal electron optic setup with a pixelated detector to record focused spot-like diffraction patterns with high angular resolution, using an order of magnitude lower dose than previous methods. We apply it to study an active layer in organic solar cells, namely DRCN5T:PC71BM BHJ thin films. Structural details of DRCN5T nano-crystallites oriented both in- and out-of-plane are imaged at ~5 nm resolution and dose budget of ~5 e-/Å2. We use in situ annealing to observe the growth of the donor crystals, evolution of the crystal orientation, and progressive enrichment of PC71BM at interfaces. This highly dose-efficient method opens more possibilities for studying beam sensitive soft materials.

Identification and Comprehensive Analysis of FREM2 Mutation as a Potential Prognostic Biomarker in Colorectal Cancer.

Gene mutations play an important role in tumor progression. This study aimed to identify genes that were mutated in colorectal cancer (CRC) and to explore their biological effects and prognostic value in CRC patients. We performed somatic mutation analysis using data sets from The Cancer Genome Atlas and International Cancer Genome Consortium, and identified that FREM2 had the highest mutation frequency in patients with colon adenocarcinoma (COAD). COAD patients were divided into FREM2-mutated type (n = 36) and FREM2-wild type (n = 278), and a Kaplan-Meier survival curve was generated to perform prognostic analysis. A FREM2-mutation prognosis model was constructed using random forest method, and the performance of the model was evaluated using receiver operating characteristic curve. Next, the random forest method and Cox regression analysis were used to construct a prognostic model based on the gene expression data of 36 FREM2-mutant COAD patients. The model showed a high prediction accuracy (83.9%), and 13 prognostic model characteristic genes related to overall survival were identified. Then, the results of tumor mutation burden (TMB) and microsatellite instability (MSI) analyses revealed significant differences in TMB and MSI among the risk scores of different prognostic models. Differentially expressed genes were identified and analyzed for functional enrichment and immune infiltration. Finally, 30 samples of CRC patients were collected for immunohistochemical staining to analyze the FREM2 expression levels, which showed that FREM2 was highly expressed in tumor tissues. In conclusion, CRC patients had a high level of FREM2 mutations associated with a worse prognosis, which indicated that FREM2 mutations may be potential prognostic markers in CRC.

Exploring the Preparation Dependence of Crystalline 2D-Extended Ultrathin C8-BTBT-C8 Films.

Crystalline organic semiconducting thin films from the benchmark molecule C8-BTBT-C8 were obtained using physical vapor deposition and various solution-based methods. Utilizing atomic force microscopy and X-ray spectromicroscopy, we illustrate the influence of the underlying growth mechanism and determine the highly preparation-dependent orientation of the thiophene backbone. We observe a continuous trend for crystalline C8-BTBT-C8 thin film domains to extend into the square millimeter-range under near-equilibrium growth conditions. For such well-defined systems, electron diffraction tomography allows us to precisely determine the unit cell directly after film deposition and to reveal an 8° molecular tilt angle with respect to the surface normal. This finding is in almost perfect accordance with the values derived from near-edge X-ray absorption fine structure linear dichroism. Within this work, we shine a light on both the successes and challenges connected to the realization of potent, thiophene-based semiconducting films, paving the way toward square centimeter-sized ultrathin organic crystals and their application in organic circuitry.