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Background: Osteopenia and fragile fractures are diabetes-associated complications. Many hypoglycemic drugs have effects on bone metabolism. Metformin, as is a prescribed medication for type 2 diabetes mellitus (T2DM), had been reported to have osteoprotective effects beyond its hypoglycemic effect, however the potential mechanism behind these effects remains unclear. In this study, we aimed to investigate the comprehensive effects of metformin on bone metabolism in T2DM rat model and elucidate the potential mechanism. Methods: Goto-Kakizaki spontaneous T2DM rats with significant hyperglycemia were treated with/without metformin for 20 weeks. Glucose tolerance was tested and all rats were weighed every two weeks. The osteoprotective effects of metformin in diabetic rats were determined by quantifying serum bone biomarkers, μ-CT imaging, histological staining, bone histomorphometry, and biomechanical properties analyses. Potential targets of metformin in the treatment of T2DM and osteoporosis were predicted using network pharmacology. The effects of metformin on mesenchymal stem cells (C3H10) cultured in high glucose medium were evaluated by CCK-8 assay, alkaline phosphatase (ALP) staining, qPCR and western blotting. Results: This study demonstrated that metformin significantly attenuated osteopenia, decreased serum glucose and glycated serum protein (GSP) levels, improved bone microarchitecture, and biomechanical properties in GK rats with T2DM. Metformin significantly increased biomarkers of bone formation, and significantly decreased muscle ubiquitin C (Ubc) expression. Network pharmacology analysis found that signal transducer and activator of transcription1 (STAT1) would be a potential target of metformin for regulating bone metabolism. Metformin increased C3H10 ​cell viability in vitro, alleviated ALP inhibition caused by hyperglycemia, increased the osteogenic gene expression of runt-related transcription factor 2 (RUNX2), collagen type I alpha 1 (Col1a1), osteocalcin (OCN), and ALP, while suppressing RAGE and STAT1 expression. Metformin also increased the protein expression of Osterix and decreased that of RAGE, p-JAK2, and p-STAT1. Conclusions: Our results demonstrate that metformin attenuated osteopenia and improved bone microarchitecture in GK rats with T2DM and significantly promoted stem cell osteogenic differentiation under high glucose condition. The effects of metformin on bone metabolism are closely associated with the suppression of RAGE-JAK2-STAT1 signaling axis. The translational potential of this article: Our research provides experiment evidence and potential mechanistic rationale for the use of metformin as an effective candidate for diabetes-induced osteopenia treatment.

Embedding fiber optic sensors in critical components is a key step for real-time monitoring of structural conditions during service and supporting autonomous system operations. Successful integration of these sensors necessitates effective interfacial bonding between the fiber and matrix, good integrity and functionality of the embedded sensors, robust mechanical strength of the matrix materials, and the ability to retain these properties during transient thermal and stress events. This study demonstrates the encapsulation of fused silica optical fibers in stainless steel and nickel through the electric field-assisted sintering (EFAS) process. Copper-coated and gold-coated single mode optical fibers were embedded under different EFAS conditions. The resulting components with embedded sensors were evaluated using advanced microscopy and optical frequency domain reflectometry (OFDR) to assess the aforementioned critical aspects of embedding. The results indicate that both copper- and gold-coated fibers can be successfully embedded in stainless steel and nickel with good fiber integrity and fiber-matrix bonding. Samples fabricated under optimal conditions passed helium leak testing, confirming effective interfacial bonding. Microstructural characterization revealed excellent fiber-matrix adhesion and interdiffusion of elements across the interface. The functionality of the embedded fibers was evaluated through OFDR scans, which revealed signal insertion loss of 0.43–0.52 dB for nickel samples and 0–0.75 dB for stainless steel samples at the embedding sites. Additionally, the embedded fibers underwent cyclic thermal treatment between 500 °C and 700 °C. The fibers maintained good integrity and interfacial characteristics, demonstrating their ability to survive cyclic thermal events for sensing in harsh environments.

Balanophora dioica R.Br.ex Royle, belongs to the the Balanophoraceae family, has been documented as Chinese folk medicine in Lahu nationality in China for millennia. Myocardial injury is the main manifestation of cardiovascular disease. However, the role of Balanophora dioica ethanol extract (BDEE) in improving myocardial injury is unclear. The main purpose of this study is to clarify the pharmacological effect and molecular mechanisms of BDEE on myocardial injury. The major compounds of BDEE were analyzed by GC-MS and HPLC-FT-ICR-MS. The male C57BL/6 mice were randomly divided into 6 groups (n = 10), the control group, the isoproterenol (ISO) model group, ISO + 100, 200, and 400 mg/kg/d of BDEE groups, and the BDEE group (400 mg/kg/d). The heart weight/body weight was calculated, serum biochemistry markers CK, LDH, and myocardial enzyme indexes MDA, SOD, CAT, GSH-Px were measured by corresponding kits. Heart tissue histopathology was detected by hematoxylin-eosin and Sirius Red staining. Immunohistochemistry and western blotting were used to determine the protein expression associated with myocardial fibrosis, inflammation and apoptosis. TUNEL staining was used to evaluate the apoptosis level. The results demonstrated that BDEE can restore cardiac morphology and serum biochemical level, and restrain ISO-induced myocardial fibrosis by regulating TGF-β1/Smad3 pathway. Additionally, BDEE can reduce inflammation-related TLR4, MyD88, IRAK-1, TRAF-6, and NF-κB expression, and also inhibit cardiomyocyte apoptosis by regulating the expression of Bcl-2, Bax, Caspase-9 and Caspase-3. The above results indicated that BDEE improved ISO-induced myocardial injury by regulating myocardial fibrosis, inflammation and apoptosis, and it may be developed as a potential drug to prevent cardiovascular diseases.

Objective: To explore the current status and trends of disease-modifying therapies (DMTs) for multiple sclerosis through bibliometric and visual analyses of the related literature. Methods: Relevant literature from the Web of Science Core Collection from 2017 to 2022 was retrieved, and a bibliometric analysis was performed using CiteSpace 6.1. R2. Thesoftware was used to generate visual graphs of the author, institution, country, keyword co-occurrence, and literature co-citation network. Results: A total of 1719 manuscripts were retrieved, including 1397 original studies and 322 reviews. In the past five years, Patti F and the University of London were the authors and institutions generating the largest number of publications, respectively, and there was active collaboration between authors and institutions. The United States was the largest contributor to the relevant literature, and the high-frequency keywords in the field of multiple sclerosis disease-modifying therapies in the past five years mainly included multiple sclerosis, disease-modifying therapy, double-blind, disability, natalizumab, effectiveness, fingolimod, glatiramer acetate, and dimethyl fumarate. Conclusions: Current research hotspots and trends in DMTs in multiple sclerosis focus on the effectiveness of different DMTs drugs in treating patients with MS and how to optimise treatment strategies. In the context of the COVID-19 pandemic, the correlation between MS and COVID-19 infection and the method to manage and address the adverse effects of DMTs on multiple sclerosis patients is also future research trends.

TRistructural ISOtropic (TRISO) fuel is a leading-edge nuclear fuel form representing a departure from the more traditional nuclear fuel forms utilized in the reactor fleet of today. Rather than a monolithic fuel pellet of uranium dioxide, integral fuel forms containing TRISO fuel are composed of thousands of microencapsulated uranium-bearing fuel kernels and individually coated with multiple layers of pyrolytic carbon and silicon carbide. These multilayered ceramic coatings serve as an environmental barrier to ensure radioactive and chemically reactive fission products are contained within the reactor fuel elements, but also participate in the transfer of heat generated in the nuclear fuel to the coolant – the primary purpose of a nuclear reactor. Since traditional thermal property measurement techniques, such as laser flash analysis, would be unable to resolve the thermal properties of the individual TRISO coating layers, a simplified frequency-domain thermoreflectance technique has been developed to rapidly map the thermal properties of TRISO particles. Using this technique, the thermal properties of TRISO particles have been mapped from room temperature up to 1000 °C to examine the spatial variation and temperature-dependency of the thermal properties within each layer. Additionally, spatial-domain thermoreflectance was used to examine the anisotropy of the thermal properties for each layer at different locations within a single TRISO particle, and across multiple TRISO particles to assess the intra- and inter-particle uniformity of thermal properties, respectively. To elucidate the underlying causes for the measured variations in thermal properties, scanning electron microscopy and Raman spectroscopy were used to examine variations in microstructure and chemical bonding within the different coating layers. Results from this work are then compared with previous examinations of TRISO fuel particles and microstructurally driven mechanisms for the variations in the measured thermal properties of the different carbonaceous layers are discussed.

Non-invasive fast imaging of grain microstructure of polycrystalline ceria with sub-micrometric spatial resolution is performed via time-domain Brillouin scattering. The propagation of a nanoacoustic pulse is monitored down to 8 μm deep in a 30 × 30 μm2 area. Grains boundaries are reconstructed in three-dimensions via a two-step processing method, relying on the wavelet synchro-squeezed transform and the alphashape algorithm. Imaging contrast is improved by taking advantage of stronger sensitivity to anisotropy of transverse acoustic waves, compared with longitudinal waves. Utilization of transverse waves in the image processing reveals additional boundaries, confirmed by an electron backscattering diffraction pattern but not discerned using longitudinal waves. A buried inclined interface between differently oriented grains is identified by monitoring changes in amplitude (phase) of the portion of the signal associated with transverse (longitudinal) waves. Estimates of the inclination angle of this interface prove the sensitivity of our laser ultrasonic method to image inclined boundaries.