Oroxin A from Oroxylum indicum improves disordered lipid metabolism by inhibiting SREBPs in oleic acid-induced HepG2 cells and high-fat diet-fed non-insulin-resistant rats.

Background: Lipid metabolism disorders have become a major global public health issue. Due to the complexity of these diseases, additional research and drugs are needed. Oroxin A, the major component of Oroxylum indicum (L.) Kurz (Bignoniaceae), can improve the lipid profiles of diabetic and insulin-resistant (IR) rats. Because insulin resistance is strongly correlated with lipid metabolism, improving insulin resistance may also constitute an effective strategy for improving lipid metabolism. Thus, additional research on the efficacy and mechanism of oroxin An under non-IR conditions is needed. Methods: In this study, we established lipid metabolism disorder model rats by high-fat diet feeding and fatty HepG2 cell lines by treatment with oleic acid and evaluated the therapeutic effect and mechanism of oroxin A in vitro and in vivo through biochemical indicator analysis, pathological staining, immunoblotting, and immunofluorescence staining. Results: Oroxin A improved disordered lipid metabolism under non-IR conditions, improved the plasma and hepatic lipid profiles, and enhanced the lipid-lowering action of atorvastatin. Additionally, oroxin A reduced the total triglyceride (TG) levels by inhibiting sterol regulatory element-binding protein 1 (SREBP1) expression and reducing the expression of acetyl coenzyme A carboxylase (ACC) and fatty acid synthase (FASN) in vivo and in vitro. Oroxin A also reduced the total cholesterol (TC) levels by inhibiting SREBP2 expression and reducing HMGCR expression in vivo and in vitro. In addition, oroxin A bound to low-density lipoprotein receptor (LDLR) and increased AMPK phosphorylation. Conclusions: Our results suggested that oroxin A may modulate the nuclear transcriptional activity of SREBPs by binding to LDLR proteins and increasing AMPK phosphorylation. Oroxin A may thus reduce lipid synthesis and could be used for the treatment and prevention of lipid metabolism disorders.

Meta-analysis of perioperative outcomes and safety of percutaneous nephrostomy versus retrograde ureteral stenting in the treatment of acute obstructive upper urinary tract infection.

Background: The debate regarding the optimal drainage method for acute obstructive upper urinary tract infection persists, focusing on the choice between percutaneous nephrostomy (PCN) and retrograde ureteral stenting (RUS). Aims: This study aims to systematically examine the perioperative outcomes and safety associated with PCN and RUS in treating acute obstructive upper urinary tract infections. Methods: A comprehensive investigation was conducted using the Medline, Embase, Web of Science, and Cochrane databases up to December 2022, following the guidelines of the Preferred Reporting Items for Systematic Review and Meta-analysis (PRISMA) statement. The utilized keywords included 'PCN', 'RUS', 'acute upper obstructive uropathy', and 'RCT'. Inclusion criteria encompassed studies providing accurate and analyzable data, which incorporated the total subject count, perioperative outcomes, and complication rates. The assessed perioperative outcomes included fluoroscopy time, normalization of temperature, normalization of serum creatinine, normalization of white blood cell (WBC) count, and operative time. Safety outcomes encompassed failure rate, intraoperative and postoperative hematuria, postoperative fever, postoperative pain, and postoperative nephrostomy tube or stent slippage rate. The study protocol was prospectively registered at PROSPERO (CRD42022352474). Results: The meta-analysis encompassed 7 trials involving 727 patients, with 412 assigned to the PCN group and 315 to the RUS group. The outcome of the meta-analysis unveiled a reduced occurrence of postoperative hematuria in the PCN group [odds ratio (OR) = 0.54, 95% confidence interval (CI) 0.30-0.99, p = 0.04], along with a decreased frequency of insertion failure (OR = 0.42, 95% CI 0.21-0.81, p = 0.01). In addition, the RUS group exhibited a shorter fluoroscopy time than the PCN group (mean difference = 0.31, 95% CI 0.14-0.48, p = 0.0004). Conclusion: Given the significant impact of hematuria and catheterization failure on postoperative quality of life, the preference for PCN appears more advantageous than RUS.

Meta-analysis of perioperative outcomes and safety of percutaneous nephrostomy vs retrograde ureteral stenting in the treatment of acute obstructive upper urinary tract infection The optimal drainage method for acute obstructive upper urinary tract infection between PCN and RUS is currently debatable. Our meta-analysis found PCN performed better than RUS in hematuria and catheterization failure rate, although PCN was associated with longer exposure time.

CD8 T cell-derived perforin regulates macrophage-mediated inflammation in a murine model of gout.

OBJECTIVES: Gout is characterized by hyperuricemia and recurrent inflammatory episodes caused by intra-articular crystal deposition of monosodium urate (MSU). There is a clear relationship between gout and metabolic syndrome. Recent evidence indicates that perforin plays a role in regulating glucose homeostasis and provides protection in diet-induced non-alcoholic steatohepatitis models. However, the impact of perforin on immune inflammation in gout remains unclear. METHODS: We induced acute gout models in both wild-type (WT) mice and Prf1null mice by administering intra-articular injections of MSU crystals. We compared the ankle joint swelling and the histological score between the two groups. Furthermore, we investigated underlying mechanisms through in vitro co-culture experiments involving CD8 T cells and macrophages. RESULTS: In this study, Prf1null mice showed significantly more pronounced ankle swelling with increased inflammatory cell infiltrations compared with WT mice 24 h after local MSU injection. Moreover, MSU-induced Prf1null mice exhibited increased accumulation of CD8 T cells but not NK cells. Perforin-deficient CD8 T cells displayed reduced cytotoxicity towards bone marrow-derived M0 and M1 macrophages and promoted TNF-α secretion from macrophage. CONCLUSIONS: Perforin from CD8 T cells limits joint inflammation in mice with acute gout by downregulating macrophage-mediated inflammation. Key Points • Perforin deficiency increased swelling in the ankle joints of mice upon MSU injection. • Perforin deficiency is associated with increased immune cell recruitment and severe joint damage in gout. • Perforin regulated CD8 T cell accumulation in gout and promoted CD8 T cell cytotoxicity towards M0 and M1 macrophages. • CD8 T cell-derived perforin regulated pro-inflammatory cytokine secretion of macrophage.

Renal Metastasis Arising From a Pulmonary Adenoid Cystic Carcinoma: A Rare Case Report and Literature Review.

Adenoid cystic carcinoma (ACC), a rare malignancy, typically originates in salivary glands and is rarely found in other locations. In this case report, we describe a 54-year-old male patient who was presented to the Urology Department of Yantai Yuhuangding hospital with right-sided waist pain. The patient underwent percutaneous ultrasound-guided biopsies of lesions in the kidney and lung, which were histologically confirmed as primary adenoid cystic carcinoma of the lung and metastatic renal adenoid cystic carcinoma, respectively. Given the presence of multiple metastases, the patient received systemic palliative chemotherapy, which was well-tolerated and effectively controlled the tumor. At the last follow-up, there was no evidence of tumor progression in the patient.

[Role of Ferroptosis in Non-small Cell Lung Cancer and Progress 
of Traditional Chinese Medicine Intervention].

Non-small cell lung cancer (NSCLC) is one of the malignant tumors with high morbidity and mortality worldwide. Ferroptosis is a new type of programmed cell death caused by abnormal accumulation of iron-dependent reactive oxygen species (ROS) leading to lipid peroxidation. It involves the balance between iron metabolism, lipid metabolism, oxygen free radical reaction and lipid peroxidation. Recent studies have found that ferroptosis is closely related to the occurrence and development of NSCLC. Due to the emergence of chemotherapy resistance and radiotherapy resistance in the treatment of NSCLC, there is an urgent need to develop new effective drugs and treatment strategies. Traditional Chinese medicine has unique advantages in the prevention and treatment of NSCLC due to its multi-targets and minimal side effects. In this review, we summarize the mechanism of ferroptosis in NSCLC, and discuss the research status of active ingredients of traditional Chinese medicine, single-herb traditional Chinese medicine and Chinese herbal compounds in the intervention of NSCLC through ferroptosis, in order to provide a new theoretical basis for the research of ferroptosis pathway and the prevention and treatment of NSCLC by targeted ferroptosis of traditional Chinese medicine.
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Protocol for evaluating mutualistic cooperative behavior in mice using a water-reward task assay.

Social cooperation is fundamentally important for group animals but rarely studied in mice because of their natural aggressiveness. Here, we present a new water-reward assay to investigate mutualistic cooperative behavior in mice. We describe the construction of the apparatus and provide details of the procedures and analysis for investigators to characterize and quantify the mutualistic cooperative behavior. This protocol has been validated in mice and can be used for investigating mechanisms of cooperation. For complete details on the use and execution of this protocol, please refer to Zhang et al. and Wang et al.1,2.

Utilizing mobile digital radiography for detection of thoracolumbar vertebrae traits in live donkeys.

It has been well-established that the number of vertebrae is associated with body size and meat productivity. In current study we utilized a digital radiography (DR) technology to detect the number of thoracolumbar vertebrae in live donkeys. For this purpose, we introduced for the first time a groundbreaking device designed by our team for assessing thoracolumbar vertebrae number traits in equids, employing a sample of 1,000 donkeys sourced from five distinct donkey farms. This assessment incorporates a range of crucial body metrics, including body height, length, and various other measurements. Subsequently, our study determined the number of thoracolumbar vertebrae in 112 donkeys, utilizing the DR system. These findings were further validated through post-mortem evaluations conducted by slaughtering the donkeys. Our findings demonstrated a remarkable resemblance between the thoracolumbar vertebrae numbers visualized through the DR system in live donkeys and those obtained via slaughter verification. In conclusion, this research underscores the accuracy and effectiveness of the DR system for the detection of thoracolumbar vertebrae in live donkeys, which might be helpful for assessing the body size and meat productivity. We also recommended the utilization of DR system for counting thoracolumbar vertebrae in other animals in live state and could be a useful addition to livestock business industry for the prediction of body size and meat productivity efficiency.

Tunable Gas Admission via a "Molecular Trapdoor" Mechanism in a Flexible Cationic Metal-Organic Framework Featuring 1D Channels.

Achieving high gas selectivity is challenging when dealing with gas pairs of similar size and physiochemical properties. The "molecular trapdoor" mechanism discovered in zeolites holds promise for highly selective gas adsorption separation but faces limitations like constrained pore volume and slow adsorption kinetics. To address these challenges, for the first time, a flexible metal-organic framework (MOF) featuring 1D channels and functioning as a "molecular trapdoor" material is intoduced. Extra-framework anions act as "gate-keeping" groups at the narrowest points of channels, permitting gas admissions via gate opening induced by thermal/pressure stimuli and guest interactions. Different guest molecules induce varied energy barriers for anion movement, enabling gas separation based on distinct threshold temperatures for gas admission. The flexible framework of Pytpy MOFs, featuring swelling structure with rotatable pyridine rings, facilitates faster gas adsorption than zeolite. Analyzing anion properties of Pytpy MOFs reveals a guiding principle for selecting anions to tailor threshold gas admission. This study not only overcomes the kinetic limitations related to gas admission in the "molecular trapdoor" zeolites but also underscores the potential of developing MOFs as molecular trapdoor adsorbents, providing valuable insights for designing ionic MOFs tailored to diverse gas separation applications.

Enhanced bacterial cancer therapy delivering therapeutic RNA interference of c-Myc.

BACKGROUND: Bacterial cancer therapy was first trialled in patients at the end of the nineteenth century. More recently, tumour-targeting bacteria have been harnessed to deliver plasmid-expressed therapeutic interfering RNA to a range of solid tumours. A major limitation to clinical translation of this is the short-term nature of RNA interference in vivo due to plasmid instability. To overcome this, we sought to develop tumour-targeting attenuated bacteria that stably express shRNA by virtue of integration of an expression cassette within the bacterial chromosome and demonstrate therapeutic efficacy in vitro and in vivo. RESULTS: The attenuated tumour targeting Salmonella typhimurium SL7207 strain was modified to carry chromosomally integrated shRNA expression cassettes at the xylA locus. The colorectal cancer cell lines SW480, HCT116 and breast cancer cell line MCF7 were used to demonstrate the ability of these modified strains to perform intracellular infection and deliver effective RNA and protein knockdown of the target gene c-Myc. In vivo therapeutic efficacy was demonstrated using the Lgr5creERT2Apcflx/flx and BlgCreBrca2flx/flp53flx/flx orthotopic immunocompetent mouse models of colorectal and breast cancer, respectively. In vitro co-cultures of breast and colorectal cancer cell lines with modified SL7207 demonstrated a significant 50-95% (P < 0.01) reduction in RNA and protein expression with SL7207/c-Myc targeted strains. In vivo, following establishment of tumour tissue, a single intra-peritoneal administration of 1 × 106 CFU of SL7207/c-Myc was sufficient to permit tumour colonisation and significantly extend survival with no overt toxicity in control animals. CONCLUSIONS: In summary we have demonstrated that tumour tropic bacteria can be modified to safely deliver therapeutic levels of gene knockdown. This technology has the potential to specifically target primary and secondary solid tumours with personalised therapeutic payloads, providing new multi-cancer detection and treatment options with minimal off-target effects. Further understanding of the tropism mechanisms and impact on host immunity and microbiome is required to progress to clinical translation.

Inhibition of UBA52 induces autophagy via EMC6 to suppress hepatocellular carcinoma tumorigenesis and progression.

Ubiquitin A-52 residue ribosomal protein fusion product 1 (UBA52) has a role in the occurrence and development of tumours. However, the mechanism by which UBA52 regulates hepatocellular carcinoma (HCC) tumorigenesis and progression remains poorly understood. By using the Cell Counting Kit (CCK-8), colony formation, wound healing and Transwell assays, we assessed the effects of UBA52 knockdown and overexpression on the proliferation and migration of HCC cells in vitro. By establishing subcutaneous and metastatic tumour models in nude mice, we evaluated the effects of UBA52 on HCC cell proliferation and migration in vivo. Through bioinformatic analysis of data from the Gene Expression Profiling Interactive Analysis (GEPIA) and The Cancer Genome Atlas (TCGA) databases, we discovered that UBA52 is associated with autophagy. In addition, we discovered that HCC tissues with high UBA52 expression had a poor prognosis in patients. Moreover, knockdown of UBA52 reduced HCC cell growth and metastasis both in vitro and in vivo. Mechanistically, knockdown of UBA52 induced autophagy through EMC6 in HCC cells. These findings suggest that UBA52 promoted the proliferation and migration of HCC cells through autophagy regulation via EMC6 and imply that UBA52 may be a viable novel treatment target for HCC patients.

In Situ Plasma Polymerization of Self-Stabilized Polythiophene Enables Dendrite-Free Lithium Metal Anodes with Ultra-Long Cycle Life.

Constructing a flexible and chemically stable multifunctional layer for the lithium (Li) metal anodes is a highly effective approach to improve the uneven deposition of Li+ and suppress the dendrite growth. Herein, an organic protecting layer of polythiophene is in situ polymerized on the Li metal via plasma polymerization. Compared with the chemically polymerized thiophene (C-PTh), the plasma polymerized thiophene layer (P-PTh), with a higher Young's modulus of 8.1 GPa, shows strong structural stability due to the chemical binding of the polythiophene and Li. Moreover, the nucleophilic C─S bond of polythiophene facilitates the decomposition of Li salts in the electrolytes, promoting the formation of LiF-rich solid electrolyte interface (SEI) layers. The synergetic effect of the rigid LiF as well as the flexible PTh-Li can effectively regulate the uniform Li deposition and suppress the growth of Li dendrites during the repeated stripping-plating, enabling the Li anodes with long-cycling lifespan over 8000 h (1 mA cm-2 , 1 mAh cm-2) and 2500 h (10 mA cm-2 , 10 mAh cm-2 ). Since the plasma polymerization is facile (5-20 min) and environmentally friendly (solvent-free), this work offers a novel and promising strategy for the construction of the forthcoming generation of high-energy-density batteries.

A comprehensive analysis and experimental validation of TK1 in uterine corpus endometrial carcinoma.

Uterine corpus endometrial carcinoma (UCEC) is becoming a main malignant cancer that threaten to women's health. Thymidine kinase 1 (TK1) is considering to be associated with tumorigenesis and development. Nevertheless, the function of TK1 in UCEC is still unclear. Herein, we analyzed the TK1 expression level in pan-cancer and found that TK1 was upregulated in a variety of cancers including UCEC. Patients of UCEC with high expression of TK1 were related to poor outcome. TK1 was also related to clinical stage, histologic grade and lymph node metastasis. Abnormal expression of TK1 in UCEC was related to promoter methylation while gene mutation was not frequent. TK1 and its associated genes appeared to be prominent in cell cycle and DNA replication, according to GO and KEGG analysis. Analysis of immune infiltration revealed a negative correlation between TK1 and CD8 + T cells, macrophages, and dendritic cells. In vitro experiments, TK1 knockdown resulted in the inhibition of proliferation, migration, invasion and EMT in UCEC cell lines.

Self-supporting multi-channel Janus carbon fibers: A new strategy to achieve an efficient bifunctional electrocatalyst for overall water splitting.

A new type of self-supporting multi-channel Janus carbon fibers with efficient water splitting has been successfully manufactured using a specially designed parallel spinneret through electrospinning technology and subsequent carbonization technique. Every single Janus fiber composes of a half side of Mo2C and the other half side of Ni components as Mo2C, Ni embedded in N-doped multi-channel Janus carbon fibers ([Mo2C/C]//[Ni/C]-NMCFs) for overall water splitting. Under optimized condition, the hydrogen evolution reaction overpotential of [Mo2C/C]//[Ni/C]-NMCFs (62 mV) is just 24 mV higher than 20 wt% Pt/C (38 mV) at a current density of 10 mA cm-2. Furthermore, it achieves current density of 10 mA cm-2 to require an overpotential of 324 mV for oxygen evolution reaction. Additionally, the cell assembled by the identical [Mo2C/C]//[Ni/C]-NMCFs catalyst as both the cathode and anode needs only 1.607 V at a current density of 10 mA cm-2, which is only 0.022 V higher than that of Pt/C-IrO2 electrodes. Moreover, [Mo2C/C]//[Ni/C]-NMCFs catalyst also exhibits a long-term stability. The synergistic effect and unique heterostructure of Mo2C and Ni enhance the catalytic activity.

Micro Lubrication and Heat Transfer in Wedge-Shaped Channel Slider with Convex Surface Texture Based on Lattice Boltzmann Method.

Hydrodynamic lubrication is widely used between two relatively moving objects, and the effect of fluid flow state and temperature distribution on lubrication performance in wedge-shaped gaps is a popular topic to study. In this paper, the incompressible double-distribution lattice Boltzmann method (LBM) is applied to study the effect of micro convex surface texture on micro lubrication and heat transfer in wedge-shaped channels. By comparing this model with the analytical solution of an infinitely wide wedge slider, the maximum pressure calculated by LBM is 0.1081 MPa, and the maximum pressure calculated by the Reynolds equation is 0.1079 MPa. The error of the maximum pressure is 1.11%, and the Reynolds equation result is slightly smaller. The reason is that the Reynolds equation ignores the influence of fluid inertia force on oil film pressure. The results indicate that the application of LBM can be used to study lubrication problems. Compared with the Reynolds equation, LBM can calculate the velocity field and pressure field in the film thickness direction, and can also observe precise flow field details such as vortices. Three micro convex texture shapes were established to study the effects of different convex textures on micro lubrication and oil film temperature distribution, and the velocity distribution, temperature distribution and oil film pressure along the oil film thickness direction were given. Under the same conditions, comparing the oil film pressure with and without surface texture, the results show that the maximum oil film pressure with surface texture 3 is increased by about 4.34% compared with that without surface texture. The slightly convex texture can increase the hydrodynamic lubrication effect and obtain greater load-bearing capacity, helping to reduce the possibility of contact friction. The results show that the convex surface texture can improve the hydrodynamic lubrication performance, increase the load carrying capacity and reduce the possibility of contact friction, and the convex surface texture can influence the temperature distribution of the oil film. At 3.6 mm in the slider length direction and 7.5 µm in the oil film thickness direction, the temperature of surface texture 1 is 402.64 K, the temperature of surface texture 2 is 403.31 K, and the temperature of surface texture 3 is 403.99 K. The presence of vortices is captured at a high convergence ratio.

Microorganisms uptake zero-valent sulfur via membrane lipid dissolution of octasulfur and intracellular solubilization as persulfide.

Zero-valent sulfur, commonly utilized as a fertilizer or fungicide, is prevalent in various environmental contexts. Its most stable and predominant form, octasulfur (S8), plays a crucial role in microbial sulfur metabolism, either through oxidation or reduction. However, the mechanism underlying its cellular uptake remains elusive. We presented evidence that zero-valent sulfur was adsorbed to the cell surface and then dissolved into the membrane lipid layer as lipid-soluble S8 molecules, which reacted with cellular low-molecular thiols to form persulfide, e.g., glutathione persulfide (GSSH), in the cytoplasm. The process brought extracellular zero-valent sulfur into the cells. When persulfide dioxygenase is present in the cells, GSSH will be oxidized. Otherwise, GSSH will react with another glutathione (GSH) to produce glutathione disulfide (GSSG) and hydrogen sulfide (H2S). The mechanism is different from simple diffusion, as insoluble S8 becomes soluble GSSH after crossing the cytoplasmic membrane. The uptake process is limited by physical contact of insoluble zero-valent sulfur with microbial cells and the regeneration of cellular thiols. Our findings elucidate the cellular uptake mechanism of zero-valent sulfur, which provides critical information for its application in agricultural practices and the bioremediation of sulfur contaminants and heavy metals.

A comparative study on the deformation behavior and mechanical properties of new lower extremity arterial stents.

BACKGROUND AND OBJECTIVE: The lower extremity movement involves a complex and large amplitude extremity movement process, and arterial stents implanted in the lower extremity are prone to complex mechanical deformation behavior. Hence, the lower extremity arterial stent is required to have favorable comprehensive mechanical properties. METHODS: In this study, a new lower extremity arterial stent (New) was proposed, and its deformation behavior and mechanical properties were analyzed by numerical simulations under different deformation modes, such as radial compression, axial compression/tension, bending, and torsion. Stents with different diameters were modeled to compare the effect of diameter size on their biomechanical properties. Additionally, a comparative analysis was conducted between this new stent and seven commercially available stents. RESULTS: The results demonstrated that the stent diameter exerted a significant effect on its deformation behavior and mechanical properties. Specifically, with the increase of the stent diameter, the radial expansion rate, radial shrinkage rate, radial support stiffness, axial compression stiffness, and axial tensile stiffness tended to decrease, and the expansion inhomogeneity, stenosis rate, bending stiffness, and torsional stiffness tended to increase. In contrast, the stent diameter exerted a small effect on the stent axial shortening rate and ellipticity. The new lower extremity arterial stent was validated to outperform other stents in terms of most performance indicators. Especially, the radial expansion rate and ellipticity of the New stent were better than those of all commercially available stents. Moreover, the New stent presented favorable mechanical properties and flexibility under the premise of ensuring the support performance. CONCLUSIONS: Based on these findings, this lower extremity arterial stent may play a better therapeutic effect in clinical application. Furthermore, these analysis results may provide reference for the clinical application and selection of the stent.

Femtosecond Laser Combined with Hydrothermal Method to Construct Three-Dimensional Spatially Distributed Wurtzite ZnO Micro/Nanostructures to Enhance Photocatalytic Properties.

Conventional approaches employing nanopowder particles or deposition photocatalytic nanofilm materials encounter challenges such as performance instability, susceptibility to detachment, and recycling complications in practical photocatalytic scenarios. In this study, a novel fabrication strategy is proposed that uses femtosecond laser direct writing of self-sourced metal to prepare a self-supporting microstructure substrate and combines the hydrothermal method to construct a three-dimensional spatially distributed metal oxide micro/nanostructure. The obtained wurtzite ZnO micro/nanostructure has excellent wetting properties while obtaining a larger specific surface area and can achieve effective adsorption of methyl orange molecules. Moreover, the tight integration of ZnO with the surface interface of the self-sourced metal microstructure substrate will facilitate efficient charge transfer. Simultaneously, it improves the efficiency of light utilization (absorption) and the number of active sites in the photocatalytic process, ultimately leading to excellent photodegradation stability. This result provides an innovative technology solution for achieving efficient semiconductor surface-interface photocatalytic performance and stability.

A novel extracellular vesicles production system harnessing matrix homeostasis and macrophage reprogramming mitigates osteoarthritis.

Osteoarthritis (OA) is a degenerative disease that significantly impairs quality of life. There is a pressing need for innovative OA therapies. While small extracellular vesicles (sEVs) show promising therapeutic effects against OA, their limited yield restricts clinical translation. Here, we devised a novel production system for sEVs that enhances both their yield and therapeutic properties. By stimulating mesenchymal stem cells (MSCs) using electromagnetic field (EMF) combined with ultrasmall superparamagnetic iron oxide (USPIO) particles, we procured an augmented yield of EMF-USPIO-sEVs. These vesicles not only activate anabolic pathways but also inhibit catabolic activities, and crucially, they promote M2 macrophage polarization, aiding cartilage regeneration. In an OA mouse model triggered by anterior cruciate ligament transection surgery, EMF-USPIO-sEVs reduced OA severity, and augmented matrix synthesis. Moreover, they decelerated OA progression through the microRNA-99b/MFG-E8/NF-κB signaling axis. Consequently, EMF-USPIO-sEVs present a potential therapeutic option for OA, acting by modulating matrix homeostasis and macrophage polarization.

Urinary Exosomal miR-17-5p Accelerates Bladder Cancer Invasion by Repressing its Target Gene ARID4B and Regulating the Immune Microenvironment.

BACKGROUND: Urothelial bladder cancer (BCa) is a common malignant tumor of the urinary system. It has been identified that exosomal miRNAs contribute to the development of BCa. However, its significance and mechanism in the malignant biological behavior of BCa remain unclear. In this study, the influence of exosomal miRNAs on BCa progression was investigated. METHODS: High-throughput sequencing was conducted to analyze the microRNA-expression profile in urinary exosomes to screen out the key miRNA of muscle-invasive bladder cancer (MIBC). Then, candidate miRNA expression was verified and validated in urinary exosomes and tissue samples. To address the potential role of the candidate miRNA, we overexpressed and knocked down the candidate miRNA and explored its activity in BCa cell lines. Furthermore, the target gene of the selected miRNA was predicted and validated. RESULTS: The expression profile of miRNAs revealed increased expression of miR-17-5p in MIBC urinary exosomes, and this was later confirmed in urinary exosomes and tissue samples. Cell function studies revealed that exosomal miR-17-5p significantly promoted the growth and invasion of BCa cells. Bioinformatics and luciferase experiments demonstrated that the ARID4B mRNA 3' UTR might be the binding site for miR-17-5p. Low ARID4B levels were linked to high-grade BCa patients and were associated with a better prognosis. CONCLUSION: Elevated miR-17-5p contributes to BCa progression by targeting ARID4B and influencing the immune system. Based on these findings, miR-17-5p has the potential to be a new therapeutic target for the treatment of BCa.