Exosomes From Human Umbilical Cord Stem Cells Suppress Macrophage-to-myofibroblast Transition, Alleviating Renal Fibrosis.

Renal fibrosis, a progressive scarring of the kidney, lacks effective treatment. Human umbilical cord mesenchymal stem cell-derived exosomes (HucMSC-Exos) hold promise for treating kidney diseases due to their anti-inflammatory properties. This study investigates their potential to lessen renal fibrosis by targeting macrophage-to-myofibroblast transformation (MMT), a key driver of fibrosis. We employed a mouse model of unilateral ureteral obstruction (UUO) and cultured cells exposed to transforming growth factor-ß (TGF-ß) to mimic MMT. HucMSC-Exos were administered to UUO mice, and their effects on kidney function and fibrosis were assessed. Additionally, RNA sequencing and cellular analysis were performed to elucidate the mechanisms by which HucMSC-Exos inhibit MMT. HucMSC-Exos treatment significantly reduced kidney damage and fibrosis in UUO mice. They downregulated markers of fibrosis (Collagen I, vimentin, alpha-smooth muscle actin) and suppressed MMT (α-SMA + F4/80 + cells). Furthermore, ARNTL, a specific molecule, emerged as a potential target of HucMSC-Exos in hindering MMT and consequently preventing fibrosis. HucMSC-Exos effectively lessen renal fibrosis by suppressing MMT, suggesting a novel therapeutic strategy for managing kidney damage and fibrosis.

Human umbilical cord mesenchymal stem cell exosome-derived miR-874-3p targeting RIPK1/PGAM5 attenuates kidney tubular epithelial cell damage.

BACKGROUND: Kidney insults due to various pathogenic factors, such as trauma, infection, and inflammation, can cause tubular epithelial cell injury and death, leading to acute kidney injury and the transformation of acute kidney injury to chronic kidney disease. There is no definitive treatment available. In previous studies, human umbilical cord mesenchymal stem cells have been shown to promote kidney injury. In this preclinical study, we investigate the role and mechanism of human umbilical cord mesenchymal stem cell exosomes (HucMSC-Exos) on the repair of renal tubular epithelial cells after injury. METHODS: C57BL/6 mice underwent unilateral ureteral obstruction, and epithelial cell injury was induced in HK-2 cells by cisplatin. HucMSC-Exos were assessed in vivo and in vitro. The extent of renal cell injury, activation of necroptosis pathway, and mitochondrial quality-control-related factors were determined in different groups. We also analyzed the possible regulatory effector molecules in HucMSC-Exos by transcriptomics. RESULTS: HucMSC-Exo inhibited necroptosis after renal tubular epithelial cell injury and promoted the dephosphorylation of the S637 site of the Drp1 gene by reducing the expression of PGAM5. This subsequently inhibited mitochondrial fission and maintained mitochondrial functional homeostasis, mitigating renal injury and promoting repair. In addition, HucMSC-Exo displayed a regulatory role by targeting RIPK1 through miR-874-3p. CONCLUSION: The collective findings of the present study demonstrate that HucMSC-Exos can regulate necroptosis through miR-874-3p to attenuate renal tubular epithelial cell injury and enhance repair, providing new therapeutic modalities and ideas for the treatment of AKI and the process of AKI to CKD transformation to mitigate renal damage.

Lifetime visualization of femtosecond laser-induced plasma on GaP crystal.

Gallium phosphide (GaP) is a widely used and promising semiconductor material for photonics devices and we suppose the ultrafast laser can be a competitive tool for GaP processing. We used an 800 nm centered femtosecond (fs) laser with a pulse duration of 50 fs to irradiate the GaP crystal. The ablation threshold was first determined, and then the ultrafast dynamics including plasma expansion, shockwave formation and propagation, and spectral evolution were acquired and analyzed. The evolution of ejected plasma in the initial stage changed from cylindrical to planar propagation with the augment of laser fluence. The study on the propagation properties of shockwaves showed that the energy of propelling shockwaves accounted for 12% to 18% of the laser pulse energy at all fluences above the ablation threshold. A prominent plasma splitting was observed at a fluence slightly higher than the threshold, and a phenomenon that the plasma protruded out of the shockwaves was also found. Finally, the transient temperature and density of electron at different fluences were calculated. The temperature difference between the plasma and the shockwave proved the heating effect of the plasma during ablation.

MK-2206 Alleviates Renal Fibrosis by Suppressing the Akt/mTOR Signaling Pathway In Vivo and In Vitro.

Renal fibrosis is a common pathological feature of various kidney diseases, leading to irreversible renal failure and end-stage renal disease. However, there are still no effective treatments to reverse renal fibrosis. This study aimed to explore the potential mechanism of a targeted drug for fibrosis. Here, unilateral ureteral obstruction (UUO)-treated mice and a TGF-ß1-treated human renal tubular epithelial cell line (HK-2 cells) were used as models of renal fibrosis. Based on the changes of mRNA in UUO kidneys detected by transcriptome sequencing, MK-2206, an Akt inhibitor, was predicted as a potential drug to alleviate renal fibrosis through bioinformatics. We dissolved UUO mice with MK-2206 by gastric gavage and cultured TGF-ß-induced HK-2 cells with MK-2206. Histopathological examinations were performed after MK-2206 intervention, and the degree of renal fibrosis, as well as the expression of Akt/mTOR pathway-related proteins, were evaluated by immunohistochemical staining, immunofluorescence staining, and Western blot. The results showed that MK-2206 significantly improved the pathological structure of the kidney. Furthermore, MK-2206 intervention effectively inhibited UUO- and TGF-ß1-induced epithelial-mesenchymal transition, fibroblast activation, and extracellular matrix deposition. Mechanistically, MK-2206 treatment attenuated the activation of the Akt/mTOR signaling pathway. Taken together, our study revealed for the first time that MK-2206 is a promising drug for the improvement of renal fibrosis.

Nanopatterning of silicon via the near-field enhancement effect upon double-pulse femtosecond laser exposure.

Utilizing the near-field enhancement effect of a polystyrene microsphere, direct ablation of nanohole arrays by a temporal-shaping femtosecond (fs) laser pulse is presented. The nanohole arrays, which are circular, regular, and free of cracks, were processed without extra post-processing, and their average diameter decreased gradually, as the double-pulse delay increased until 2500 fs. The simulated results by a plasma model and finite difference time domain solution demonstrate that the size decrease of the structure is attributed to the increase of the ablation threshold of silicon. Through fs laser near-field fabrication, the FWHM of nanoholes can be reduced to approximately 50 nm (λ/16) and even to 23 nm when using the second harmonic laser at a wavelength of 400 nm.

Nonlinear Optical Imaging, Precise Layer Thinning, and Phase Engineering in MoTe2 with Femtosecond Laser.

The control of layer thickness and phase structure in two-dimensional transition metal dichalcogenides (2D TMDCs) like MoTe2 has recently gained much attention due to their broad applications in nanoelectronics and nanophotonics. Continuous-wave laser-based thermal treatment has been demonstrated to realize layer thinning and phase engineering in MoTe2, but requires long heating time and is largely influenced by the thermal dissipation of the substrate. The ultrafast laser produces a different response but is yet to be explored. In this work, we report the nonlinear optical interactions between MoTe2 crystals and femtosecond (fs) laser, where we have realized the nonlinear optical characterization, precise layer thinning, and phase transition in MoTe2 using a single fs laser platform. By using the fs laser with a low fluence as an excitation light source, we observe the strong nonlinear optical signals of second-harmonic generation and four-wave mixing in MoTe2, which can be used to identify the odd-even layers and layer numbers, respectively. With increasing the laser fluence to the ablation threshold (Fth), we achieve layer-by-layer removal of MoTe2, while 2H-to-1T' phase transition occurs with a higher laser fluence (2Fth to 3Fth). Moreover, we obtain highly ordered subwavelength nanoripples on both the thick and few-layer MoTe2 with a controlled fluence, which can be attributed to the fs laser-induced reorganization of the molten plasma. Our study provides a simple and efficient ultrafast laser-based approach capable of characterizing the structures and modifying the physical properties of 2D TMDCs.

Interference femtosecond laser stamping of micro-grating structures and time-resolved observation of its dynamics.

Selective slicing on a 100 nm thick ZnO film deposited on a Si substrate is achieved by an interference femtosecond (fs) laser stamping. A micro-grating structure with a period of ∼5 µm is completely ablated by an energy-optimized single pulse in one step. The elemental mappings demonstrate complete slice removals of the irradiated areas from the substrate without impurities mixed into the thin film. A calculation of the energy transmitted to the substrate and the characterization of the ablated Si channels infer that the irradiated slices are detached from the substrate by the selective ablation of the thin film and the counterforce of the Si substrate. The temporal and spatial evolution of the grating formation is investigated through a pump-probe microscope using the white light continuum (WLC) as the illumination probe. It is found that the extinctive constructive fringes occur at a delay of 8 picosecond (ps) caused by the increase of electron density. The irradiated slices initially bulge at the delay of 10-12 ps, then subsequently swell until strong material ejections at 800 ps. This study provides an opportunity to advance the understanding of micro-grating fabrications and thin film removals on heterostructures using fs lasers.

Multiscale Visualization of Colloidal Particle Lens Array Mediated Plasma Dynamics for Dielectric Nanoparticle Enhanced Femtosecond Laser-Induced Breakdown Spectroscopy.

A multiscale visualization of silica colloidal particle lens array (CPLA) assisted laser ablation of copper is investigated. The distributed holes on a crater of CPLA-deposited Cu (CPLA-Cu) show a near-field effect by the silica nanoparticles (NPs), and the plasma emission signal of CPLA-Cu is 3-5 times as strong as that of Cu. Time-resolved plasma expansion, shockwave propagation, plasma plume emission, and nanoparticle distribution are observed and analyzed for ablations on both Cu and CPLA-Cu substrates. The initial expansion of plasma generated on CPLA-Cu is faster than that of pristine Cu. The shockwave of CPLA-Cu is rounder and its plasma plume is wider than those of Cu. The nanoparticle distribution shows a strong lateral collision during plume ejection for CPLA-Cu. Plasma characterization shows the increased plasma temperature is the key reason for femtosecond laser-induced breakdown spectroscopy (fs-LIBS) signal enhancement. This work demonstrates the signal enhancement effect of dielectric NPs on fs-LIBS and provides insights into hydrodynamics of the fs laser-induced plasma generated on CPLA-deposited substrate.