Effect of Oxygen-Glucose Deprivation of Microglia-Derived Exosomes on Hippocampal Neurons: A Study on miR-124 and Inflammatory Cytokines.

Stroke is a cerebrovascular disease that threatens human health. Developing safe and effective drugs and finding therapeutic targets has become an urgent scientific problem. The aim of this study was to investigate the effect of oxygen-glucose deprivation of the microglia-derived exosome on hippocampal neurons and its relationship to miR-124 in the exosome. We incubated hippocampal neurons with exosomes secreted by oxygen-glucose deprivation/ reoxygenation (OGD/R) microglia. The levels of glutamic acid (GLU) and gamma-aminobutyric acid (GABA) in the culture supernatant were detected by ELISA. CCK-8 was used to measure neuronal survival rates. The mRNA levels of TNF-α and IL-6 were detected by RT-qPCR to evaluate the effect of exosomes on neurons. RT-qPCR was then used to detect miR-124 in microglia and their secreted exosomes. Finally, potential targets of miR-124 were analyzed through database retrieval, gene detection with dual luciferase reporters, and western blotting experiments. The results showed that the contents of GLU, TNF-α and IL-6 mRNA increased in the supernatant of cultured hippocampal neurons, the content of GABA decreased, and the survival rate of neurons decreased. Oxygen-glucose deprivation increases miR-124 levels in microglia and their released exosomes. miR-124 acts as a target gene on cytokine signaling suppressor molecule 1(SOCS1), while miR-124 inhibitors reduce the expression of TNF-α and IL-6 mRNA in neurons. These results suggest that oxygen- and glucose-deprived microglia regulate inflammatory cytokines leading to reduced neuronal survival, which may be achieved by miR-124 using SOCS1 as a potential target.

VEGF overexpression in transplanted NSCs promote recovery of neurological function in rats with cerebral ischemia by modulating the Wnt signal transduction pathway.

Neural stem cell transplantation is a good method to treat stroke, but the mechanism is still unclear. Therefore, this study aims to explore the regulatory mechanism of VEGF overexpression in transplanted NSCs to promote the recovery of neural function in ischemic rats by regulating Wnt signal transduction pathways. We amplified VEGF gene fragments by PCR and transfected them into NSCs with Ad5 adenovirus. Rat brain IRI model was established by MCAO method, and VEGF transfected NSCs (VEGF-NSCs) were transplanted 24 h after successful IRI model. One week after the transplant, cognitive function was assessed using a neurological deficit score; Brain injury was assessed by histopathology; Photochemical and ELISA methods were used to detect oxidative stress markers and inflammatory factors, respectively. Western blotting has been detected in molecules of the Wnt signaling pathway. The results showed that the transduced NSCs express VEGF at least for 14 days. VEGF-NSCs transplantation (VNT) improved spatial learning and memory in rats, and inhibited oxidative stress injury, inflammatory response, and histopathological injury. VNT also resulted in significant changes in the phosphorylation levels of ß-catenin and GSK-3ß proteins, ultimately triggering activation of the Wnt signal transduction pathway. These results suggest that the neuroprotective effects of VNT may be related to the regulation of the Wnt signal transduction pathway.

Natural products in osteoarthritis treatment: bridging basic research to clinical applications.

Osteoarthritis (OA) is the most prevalent degenerative musculoskeletal disease, severely impacting the function of patients and potentially leading to disability, especially among the elderly population. Natural products (NPs), obtained from components or metabolites of plants, animals, microorganisms etc., have gained significant attention as important conservative treatments for various diseases. Recently, NPs have been well studied in preclinical and clinical researches, showing promising potential in the treatment of OA. In this review, we summed up the main signaling pathways affected by NPs in OA treatment, including NF-κB, MAPKs, PI3K/AKT, SIRT1, and other pathways, which are related to inflammation, anabolism and catabolism, and cell death. In addition, we described the therapeutic effects of NPs in different OA animal models and the current clinical studies in OA patients. At last, we discussed the potential research directions including in-depth analysis of the mechanisms and new application strategies of NPs for the OA treatment, so as to promote the basic research and clinical transformation in the future. We hope that this review may allow us to get a better understanding about the potential bioeffects and mechanisms of NPs in OA therapy, and ultimately improve the effectiveness of NPs-based clinical conservative treatment for OA patients.

Characterization of PEDOT:PSS Nanofilms Printed via Electrically Assisted Direct Ink Deposition with Ultrasonic Vibrations.

Poly(3,4-ethylenedioxythiophene):poly(styrenesulfonate) (PEDOT:PSS) has emerged as a promising conductive polymer for constructing efficient hole-transport layers (HTLs) in perovskite solar cells (PSCs). However, conventional fabrication methods, such as spin coating, spray coating, and slot-die coating, have resulted in PEDOT:PSS nanofilms with limited performance, characterized by a low density and non-uniform nanostructures. We introduce a novel 3D-printing approach called electrically assisted direct ink deposition with ultrasonic vibrations (EF-DID-UV) to overcome these challenges. This innovative printing method combines programmable acoustic field modulation with electrohydrodynamic spraying, providing a powerful tool for controlling the PEDOT:PSS nanofilm's morphology precisely. The experimental findings indicate that when PEDOT:PSS nanofilms are crafted using horizontal ultrasonic vibrations, they demonstrate a uniform dispersion of PEDOT:PSS nanoparticles, setting them apart from instances involving vertical ultrasonic vibrations, both prior to and after the printing process. In particular, when horizontal ultrasonic vibrations are applied at a low amplitude (0.15 A) during printing, these nanofilms showcase exceptional wettability performance, with a contact angle of 16.24°, and impressive electrical conductivity of 2092 Ω/square. Given its ability to yield high-performance PEDOT:PSS nanofilms with precisely controlled nanostructures, this approach holds great promise for a wide range of nanotechnological applications, including the production of solar cells, wearable sensors, and actuators.

Ultrafast and Large-Scale Fabrication of PEDOT:PSS Nanofilms Using Electrical-Field-Assisted Direct Ink Deposition.

The importance of conductive polymers has significantly increased over the decade due to their various applications, such as in electronic devices, sensors, and photovoltaics. Poly(3,4-ethylene dioxythiophene) polystyrene sulfonate (PEDOT:PSS) is one of the most successfully and widely used polymers in practical applications. Spin coating is extensively used to fabricate these conductive films; however, it has disadvantages. It is inherently a batch process with relatively low output and high solution wastage. To address these issues, we developed a novel printing process called electrical-field-assisted direct ink deposition (EF-DID), which yields a continuous, homogenous film with high electrical conductivity. In this process, we studied the formation of nanodroplets under an electrical field and their effects on film characteristics. Furthermore, dimethyl sulfoxide (DMSO) was considered as an additive solvent to increase the conductivity and wettability of the films. We then compared EF-DID-printed PEDOT:PSS films with spin-coated films to better understand the film properties. Finally, inverted perovskite solar cell devices were fabricated and compared, where the PEDOT:PSS layers were prepared by EF-DID printing and spin coating. Based on the experimental results, a solution of 20% PEDOT:PSS in DMSO (vol/vol) printed by EF-DID for 15 s provided optimal morphology.

Simple and compact high-power continuous-wave deep ultraviolet source at 261†nm based on diode-pumped intra-cavity frequency doubled Pr:LiYF4 green laser.

We report the recent progress on diode-pumped high-power continuous-wave Pr:LiYF4 (YLF) green laser and deep ultraviolet (DUV) laser generation via intracavity frequency doubling. Using two InGaN blue diode lasers as pump source to form a double-end pumping geometry, in this work, we have demonstrated a green laser at 522 nm with a maximum output power of 3.42 W, which is believed to be the highest power ever achieved in all-solid-state Pr3+ lasers in this specific spectral region. Moreover, by intracavity frequency doubling of the achieved green laser, we have further obtained a DUV laser at about 261 nm with a maximum output power of 1.42 W, which is far higher than previous results. The watt-level 261-nm laser paves the way towards the realization of simple and compact DUV source for a variety of applications.

In-situ transfer vat photopolymerization for transparent microfluidic device fabrication.

While vat photopolymerization has many advantages over soft lithography in fabricating microfluidic devices, including efficiency and shape complexity, it has difficulty achieving well-controlled micrometer-sized (smaller than 100 µm) channels in the layer building direction. The considerable light penetration depth of transparent resin leads to over-curing that inevitably cures the residual resin inside flow channels, causing clogs. In this paper, a 3D printing process - in-situ transfer vat photopolymerization is reported to solve this critical over-curing issue in fabricating microfluidic devices. We demonstrate microchannels with high Z-resolution (within 10 µm level) and high accuracy (within 2 µm level) using a general method with no requirements on liquid resins such as reduced transparency nor leads to a reduced fabrication speed. Compared with all other vat photopolymerization-based techniques specialized for microfluidic channel fabrication, our universal approach is compatible with commonly used 405 nm light sources and commercial photocurable resins. The process has been verified by multifunctional devices, including 3D serpentine microfluidic channels, microfluidic valves, and particle sorting devices. This work solves a critical barrier in 3D printing microfluidic channels using the high-speed vat photopolymerization process and broadens the material options. It also significantly advances vat photopolymerization's use in applications requiring small gaps with high accuracy in the Z-direction.

3D Printing of Nacre-Inspired Structures with Exceptional Mechanical and Flame-Retardant Properties.

Flame-retardant and thermal management structures have attracted great attention due to the requirement of high-temperature exposure in industrial, aerospace, and thermal power fields, but the development of protective fire-retardant structures with complex shapes to fit arbitrary surfaces is still challenging. Herein, we reported a rotation-blade casting-assisted 3D printing process to fabricate nacre-inspired structures with exceptional mechanical and flame-retardant properties, and the related fundamental mechanisms are studied. 3-(Trimethoxysilyl)propyl methacrylate (TMSPMA) modified boron nitride nanoplatelets (BNs) were aligned by rotation-blade casting during the 3D printing process to build the "brick and mortar" architecture. The 3D printed structures are more lightweight, while having higher fracture toughness than the natural nacre, which is attributed to the crack deflection, aligned BN (a-BNs) bridging, and pull-outs reinforced structures by the covalent bonding between TMSPMA grafted a-BNs and polymer matrix. Thermal conductivity is enhanced by 25.5 times compared with pure polymer and 5.8 times of anisotropy due to the interconnection of a-BNs. 3D printed heat-exchange structures with vertically aligned BNs in complex shapes were demonstrated for efficient thermal control of high-power light-emitting diodes. 3D printed helmet and armor with a-BNs show exceptional mechanical and fire-retardant properties, demonstrating integrated mechanical and thermal protection.