Diabetic retinopathy (DR) accounts for ~80% of legal blindness in persons aged 20-74 years and is associated with enormous social and health burdens. Current therapies are invasive, non-curative, and in-effective in 15-25% of DR patients. This review outlines the potential utility of microRNAs (miRNAs) as biomarkers and potential therapy for diabetic retinopathy. miRNAs are small noncoding forms of RNA that may play a role in the pathogenesis of DR by altering the level of expression of genes via single nucleotide polymorphism and regulatory loops. A majority of miRNAs are intracellular and specific intracellular microRNAs have been associated with cellular changes associated with DR. Some microRNAs are extracellular and called circulatory microRNAs. Circulatory miRNAs have been found to be differentially expressed in serum and bodily fluid in patients with diabetes mellitus (DM) with and without retinopathy. Some miRNAs have been associated with the severity of DR, and future studies may reveal whether circulatory miRNAs could serve as novel reliable biomarkers to detect or predict retinopathy progression. Therapeutic strategies can be developed utilizing the natural miRNA/long noncoding RNA (lncRNA) regulatory loops. miRNAs and lncRNAs are two major families of the non-protein-coding transcripts. They are regulatory molecules for fundamental cellular processes via a variety of mechanisms, and their expression and function are tightly regulated. The recent evidence indicates a cross-talk between miRNAs and lncRNAs. Therefore, dysregulation of miRNAs and lncRNAs is critical to human disease pathogenesis, such as diabetic retinopathy. miRNAs are long-distance communicators and reprogramming agents, and they embody an entirely novel paradigm in cellular and tissue signaling and interaction. By targeting specific miRNAs, whole pathways implicated in the pathogenesis of DR may potentially be altered. Understanding the endogenous roles of miRNAs in the pathogenesis of diabetic retinopathy could lead to novel diagnostic and therapeutic approaches to managing this frequently blinding retinal condition.

/pdf/microrna-and-diabetic-retinopathy-biomarkers-and-novel-2zipmqmghl.pdf

MicroRNA and diabetic retinopathy-biomarkers and novel therapeutics.

The complicated flow behaviors of multiphase fluids in shale reservoirs are significantly influenced by fluid-fluid and fluid-rock interactions due to the non-negligible intermolecular forces at the nanoscale, which is crucial for the effective development and efficient extraction of shale oil. The complexity of multiphase fluid distribution and flow behaviors in shale reservoirs is further increased by low porosity, low permeability, poor connectivity, high inhomogeneity, and multi-component minerals, making the development process more challenging. Molecular dynamics simulation is widely to precisely capture the intermolecular forces and effectively explain the complex distribution and flow behaviors of these fluids under fluid-fluid and fluid-rock interaction forces. In this review, the characteristics of mineral composition, pore structure, porosity, permeability, and fluid types are first elaborated to illustrate the particularity of shale reservoirs and fluids compared to conventional scale reservoirs. The results show that shale minerals are composed of inorganic and organic matter with extremely low porosity and permeability, and nanoscale pore size, in which the complicated oil-water-CO2 multiphase fluid types are caused by the primary underground water, fracturing water and injected CO2. The research progress of molecular simulation on the fluid-fluid and fluid-rock interaction mechanisms and on multiphase shale fluids flow behaviors are then reviewed in detail. The strong intermolecular interaction forces can result in the different occurrence states of fluids, the fluid-fluid interfacial slip, the fluid-rock boundary slip and heterogeneous fluid viscosity/density, significantly exacerbating the complexity of fluids flow. Meanwhile, the injected CO2 in the formation becomes a supercritical state with high diffusivity and strong solubility, and causes oil expansion, density and viscosity reduction, interfacial tension reduction, wettability alteration and molecular diffusion, which effectively replaces adsorbed hydrocarbon components by competitive adsorption behaviors, and promotes oil flow. The challenges and outlook of molecular simulation research and upscaling applications are finally discussed. This review aims to provide a microscopic understanding of the distribution characteristics and flow behaviors of multiphase shale fluids in nanoconfined space for both unconventional oil and gas researchers and industry professionals. 

Multiphase fluid-rock interactions and flow behaviors in shale nanopores: A comprehensive review

Micro ribonucleic acids (miRNAs), as a category of post-transcriptional gene inhibitors, have a wide range of biological functions, are involved in many pathological processes, and are attractive therapeutic targets. Considerable evidence in ophthalmology indicates that miRNAs play an important role in diabetic retinopathy (DR), especially in inflammation, oxidative stress, and neurodegeneration. Targeting specific miRNAs for the treatment of DR has attracted much attention. This is a review focusing on the pathophysiological roles of miRNAs in DR, diabetic macular edema, and proliferative DR complex multifactorial retinal diseases, with particular emphasis on how miRNAs regulate complex molecular pathways and underlying pathomechanisms. Moreover, the future development potential and application limitations of therapy that targets specific miRNAs for DR are discussed.

The Correlation Between MicroRNAs and Diabetic Retinopathy

Diabetic retinopathy (DR) is the leakage and obstruction of retinal microvessels caused by chronic progressive diabetes that leads to a series of fundus lesions. If not treated or controlled, it will affect vision and even cause blindness. DR is caused by a variety of factors, and its pathogenesis is complex. Pericyte-related diseases are considered to be an important factor for DR in many pathogeneses, which can lead to DR development through direct or indirect mechanisms, but the specific mechanism remains unclear. Exosomes are small vesicles of 40–100 nm. Most cells can produce exosomes. They mediate intercellular communication by transporting microRNAs (miRNAs), proteins, mRNAs, DNA, or lipids to target cells. In humans, intermittent hypoxia has been reported to alter circulating excretory carriers, increase endothelial cell permeability, and promote dysfunction in vivo. Therefore, we believe that the changes in circulating exocrine secretion caused by hypoxia in DR may be involved in its progress. This article examines the possible roles of miRNAs, proteins, and DNA in DR occurrence and development and discusses their possible mechanisms and therapy. This may help to provide basic proof for the use of exocrine hormones to cure DR.

Research progress on exosomes/microRNAs in the treatment of diabetic retinopathy

Role of the JAK/STAT pathway in a streptozotocin-induced diabetic retinopathy mouse model

microRNA-216a protects against human retinal microvascular endothelial cell injury in diabetic retinopathy by suppressing the NOS2/JAK/STAT axis

Exploring the occurrence of shale oil is of guiding significance to the exploration and recovery of shale oil. However, most studies focus on adsorption and neglect absorption or study it independently, which weakens the understanding of the coupling relationship between adsorption and absorption and the occurrence mechanism of shale oil in kerogen and its associated pores. Based on molecular dynamics (MD) simulation, the kerogen matrix with a smooth surface is constructed, and the general amber force field is adopted to calculate the adsorption and absorption of shale oil in a type II kerogen slit, and the influences of temperature, pressure, and pore diameter on the occurrence of shale oil are also discussed. Molecules absorbed in the kerogen matrix are mainly retained in the free space formed by the accumulation of aliphatic carbon. The effects of temperature on the distribution of shale oil in adsorption and absorption are opposite. High temperature improves the desorption of molecules from the adsorption sites and causes a lower adsorption and greater absorption. In contrast, pressure and pore diameter only slightly influence the distribution of shale oil. Unexpectedly, the result under aqueous conditions shows that the shale oil was absorbed quickly before the formation of water clusters. Once the water clusters are formed due to the strong hydrogen bonding and adsorbed near the N-, S-, and O-containing groups on the kerogen surface, the matrix gaps are blocked due to the size exclusion, and the absorption is suppressed. Additionally, we established the evolution of the ratio of free-adsorbed–absorbed oil at different temperatures and pressures, which provides a new idea and a new method for detecting the occurrence and mobility evaluation of shale oil under reservoir conditions. 

Molecular Dynamics Simulation of Adsorption and Absorption Behavior of Shale Oil in Realistic Kerogen Slits

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microRNA-216a protects against human retinal microvascular endothelial cell injury in diabetic retinopathy by suppressing the NOS2/JAK/STAT axis

Molecular Dynamics Simulation of Adsorption and Absorption Behavior of Shale Oil in Realistic Kerogen Slits