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Cancer-derived exosomes are considered a major driver of cancer-induced pre-metastatic niche formation at foreign sites, but the mechanisms remain unclear. Here, we show that miR-25-3p, a metastasis-promoting miRNA of colorectal cancer (CRC), can be transferred from CRC cells to endothelial cells via exosomes. Exosomal miR-25-3p regulates the expression of VEGFR2, ZO-1, occludin and Claudin5 in endothelial cells by targeting KLF2 and KLF4, consequently promotes vascular permeability and angiogenesis. In addition, exosomal miR-25-3p from CRC cells dramatically induces vascular leakiness and enhances CRC metastasis in liver and lung of mice. Moreover, the expression level of miR-25-3p from circulating exosomes is significantly higher in CRC patients with metastasis than those without metastasis. Our work suggests that exosomal miR-25-3p is involved in pre-metastatic niche formation and may be used as a blood-based biomarker for CRC metastasis. The mechanisms underlying pre-metastatic niche formation by cancer derived exosomes is unclear. Here they show that colorectal cancer (CRC) derived exosomal miR-25-3p promotes vascular leakiness and angiogenesis, CRC metastasis, and is upregulated in CRC pateints with metastasis, and suggest miR-25-3p as a biomarker for CRC metastasis.

Oxidative stress plays an important role in the development of aging-related diseases by accelerating the lipid peroxidation of polyunsaturated fatty acids in the cell membrane, resulting in the production of aldehydes, such as malondialdehyde and 4-hydroxy-2-nonenal (4-HNE) and other toxic substances. The compound 4-HNE forms adducts with DNA or proteins, disrupting many cell signaling pathways including the regulation of apoptosis signal transduction pathways. The binding of proteins to 4-HNE (4-HNE-protein) acts as an important marker of lipid peroxidation, and its increasing concentration in brain tissues and fluids because of aging, ultimately gives rise to some hallmark disorders, such as neurodegenerative diseases (Alzheimer’s and Parkinson’s diseases), ophthalmic diseases (dry eye, macular degeneration), hearing loss, and cancer. This review aims to describe the physiological origin of 4-HNE, elucidate its toxicity in aging-related diseases, and discuss the detoxifying effect of aldehyde dehydrogenase and glutathione in 4-HNE-driven aging-related diseases.

Uterine corpus endometrial carcinoma (UCEC) is a significant cause of cancer-related mortality among women worldwide. Prior research has demonstrated an association between cyclin-dependent kinase inhibitor 2 A (CDKN2A) and various tumors. As a member of the INK4 family, CDKN2A is involved in cell cycle regulation by controlling CDKs. In the present study, bioinformatics was used to analyze public datasets. The expression levels, signaling pathways, and copy number variations of CDKN2A in UCEC were explored, along with its immune cell subset associations. CDKN2A expression was found to be elevated in UCEC, particularly in the signaling pathways involved in cell proliferation and inflammation. Analysis of somatic copy number alterations in the TCGA (The Cancer Genome Atlas)-UCEC dataset revealed a connection between CDKN2A and drug metabolism in UCEC. Assessment of the relationship between CDKN2A and genes involved in immunotherapy for UCEC patients showed a negative correlation between CDKN2A and CD8 + T cell activity, as well as IL-2 and TP53. Collectively, these insights suggest that CDKN2A may be a potential biomarker for prognosis and treatment strategies in UCEC.

Homogeneous earth-abundant metal catalysis based on well-defined molecular complexes has achieved great advance in synthetic methodologies. However, sophisticated ligand, hazardous activator and multistep synthesis starting from base metal salts are generally required for the generation of active molecular catalysts, which may hinder their broad application in large scale organic synthesis. Therefore, the development of metal cluster catalysts formed in situ from simple earth-abundant metal salts is of importance for the practical utilization of base metal resource, yet it is still in its infancy. Herein, a mixture of catalytic amounts of cobalt (II) iodide and potassium tert-butoxide is discovered to be highly active for selective hydroboration of vinylarenes and dihydroboration of nitriles, affording a good yield of diversified hydroboration products that without isolation can readily undergo further one pot transformations. It should be highlighted that the alkoxide-pinacolborane combination acts as an efficient activation strategy to activate cobalt (II) iodide for the generation of metastable heterotopic cobalt catalysts in situ, which is proposed to be catalytically active species. Homogeneous earth-abundant metal catalysis based on well-defined metal complexes is of interest for organic synthesis, but typically employs expensive catalysts, air sensitive or synthetically challenging chemicals. Here, the authors report an efficient and regio-selective catalytic system for hydroboration of vinylarenes and organic nitriles with HBPin, using commercially available CoI 2 and KO t Bu under ligand-free conditions.

Recent findings suggest that tumor microenvironment (TME) plays an important regulatory role in the occurrence, proliferation, and metastasis of tumors. Different from normal tissue, the condition around tumor significantly altered, including immune infiltration, compact extracellular matrix, new vasculatures, abundant enzyme, acidic pH value, and hypoxia. Increasingly, researchers focused on targeting TME to prevent tumor development and metastasis. With the development of nanotechnology and the deep research on the tumor environment, stimulation-responsive intelligent nanostructures designed based on TME have attracted much attention in the anti-tumor drug delivery system. TME-targeted nano therapeutics can regulate the distribution of drugs in the body, specifically increase the concentration of drugs in the tumor site, so as to enhance the efficacy and reduce adverse reactions, can utilize particular conditions of TME to improve the effect of tumor therapy. This paper summarizes the major components and characteristics of TME, discusses the principles and strategies of relevant nano-architectures targeting TME for the treatment and diagnosis systematically.

Ophiocordyceps sinensis is globally recognized for its exceptional nutritional and medicinal properties. Variations in the edible qualities and tonic values of O. sinensis at different harvesting stages remain poorly understood in terms of compositional changes and regulatory mechanisms. Utilizing UPLC-MS/MS and transcriptome sequencing (RNA-seq), this study unveiled discrepancies in metabolite accumulation and gene expression of O. sinensis across various harvesting stages. Metabolomics analysis identified 596 differentially accumulated metabolites (DAMs), primarily enriched in amino acid-related metabolic pathways such as tyrosine, tryptophan, cysteine, and methionine metabolism. The up accumulation of organic acids and derivatives with delayed harvesting led to distinct abundances and compositions of amino acids, peptides, analogs, and fatty acids and conjugates, ultimately influencing the quality of O. sinensis . Transcriptomic analysis revealed 2550 differentially expressed genes (DEGs) at different harvesting stages, with KEGG-based enrichment analysis highlighting their involvement in amino acid-related activities like tyrosine metabolism and fatty acid degradation. The upregulation of these DEGs in amino acid-related pathways presents a promising target for studying O. sinensis quality. Integrative metabolomic and transcriptomic analyses indicated potential roles for DDC ( G6O67_000335 ), TYR ( G6O67_005660 ), AOC ( G6O67_005457 ), and fahA ( G6O67_004634 ) in the synthesis pathways of amino acids, peptides, and their analogs, suggesting a possible indirect association with O. sinensis quality. These findings offer novel insights into the molecular mechanisms underlying the quality formation and metabolic evolution of O. sinensis .

Cancer-secreted exosomes are critical mediators of cancer-host crosstalk. In the present study, we showed the delivery of miR-21-5p from colorectal cancer (CRC) cells to endothelial cells via exosomes increased the amount of miR-21-5p in recipient cells. MiR-21-5p suppressed Krev interaction trapped protein 1 (KRIT1) in recipient HUVECs and subsequently activated β-catenin signaling pathway and increased their downstream targets VEGFa and Ccnd1, which consequently promoted angiogenesis and vascular permeability in CRC. A strong inverse correlation between miR-21-5p and KRIT1 expression levels was observed in CRC-adjacent vessels. Furthermore, miR-21-5p expression in circulating exosomes was markedly higher in CRC patients than in healthy donors. Thus, our data suggest that exosomal miR-21-5p is involved in angiogenesis and vascular permeability in CRC and may be used as a potential new therapeutic target.

This paper investigates resilient consensus control for teleoperation systems under denial-of-service (DoS) attacks. We design resilient controllers with auxiliary systems based on sampled positions of both master and slave robots, enhancing robustness during DoS attacks. Additionally, we establish stability conditions on DoS attack duration and frequency by applying multivariate small-gain methods to ensure closed-loop stability without the need to solve linear matrix inequalities. Finally, the effectiveness of the controllers is validated through the simulation results, demonstrating that the master-slave synchronization is achieved.

Intervertebral disc degeneration (IVDD) is rising worldwide and leading to significant health issues and financial strain for patients. Traditional treatments for IVDD can alleviate pain but do not reverse disease progression, and surgical removal of the damaged disc may be required for advanced disease. The inflammatory microenvironment is a key driver in the development of disc degeneration. Suitable anti-inflammatory substances are critical for controlling inflammation in IVDD. Several treatment options, including glucocorticoids, non-steroidal anti-inflammatory drugs, and biotherapy, are being studied for their potential to reduce inflammation. However, anti-inflammatories often have a short half-life when applied directly and are quickly excreted, thus limiting their therapeutic effects. Biomaterial-based platforms are being explored as anti-inflammation therapeutic strategies for IVDD treatment. This review introduces the pathophysiology of IVDD and discusses anti-inflammatory therapeutics and the components of these unique biomaterial platforms as comprehensive treatment systems. We discuss the strengths, shortcomings, and development prospects for various biomaterials platforms used to modulate the inflammatory microenvironment, thus providing guidance for future breakthroughs in IVDD treatment. The inflammatory response is crucial to the onset and progression of intervertebral disc degeneration. This review provides a comprehensive understanding of the role of inflammation in intervertebral disc degeneration. It introduces the development of anti-inflammatory biomaterial platforms from hydrogels, microspheres, and nanoparticles to electrospun nanofibers. [Display omitted] •The inflammatory response is crucial to the onset and progression of IVDD, and modulation of the inflammatory environment can be effective in the treatment of IVDD.•Anti-Inflammatory biomaterials are recognized as promising strategies in intervertebral disc degeneration, and the current anti-inflammatory biomaterials are introduced.•The challenges and future research direction of multifunctional biomaterials to ameliorate IVDD inflammation are presented.

The two-dimensional electron gas (2DEG) in BaSnO 3 -based heterostructure (HS) has received tremendous attention in the electronic applications because of its excellent electron migration characteristic. We modeled the n -type (LaO) + /(SnO 2 ) 0 interface by depositing LaGaO 3 film on the BaSnO 3 substrate and explored strain effects on the critical thickness for forming 2DEG and electrical properties of LaGaO 3 /BaSnO 3 HS system using first-principles electronic structure calculations. The results indicate that to form 2DEG in the unstrained LaGaO 3 /BaSnO 3 HS system, a minimum thickness of approximately 4 unit cells of LaGaO 3 film is necessary. An increased film thickness of LaGaO 3 is required to form the 2DEG for -3%-biaxially-strained HS system and the critical thickness is 3 unit cells for 3%-baxially-strained HS system, which is caused by the strain-induced change of the electrostatic potential in LaGaO 3 film. In addition, the biaxial strain plays an important role in tailoring the electrical properties of 2DEG in LaGaO 3 /BaSnO 3 HS syestem. The interfacial charge carrier density, electron mobility and electrical conductivity can be optimized when a moderate tensile strain is applied on the BaSnO 3 substrate in the ab -plane.