Intracellular and extracellular Cyclophilin a promote cardiac fibrosis through TGF-ß signaling in response to angiotensin â ¡.

Cardiac fibrosis is characterized by abnormal proliferation of cardiac fibroblasts (CFs) and ventricular remodeling, which finally leads to heart failure. Inflammation and oxidative stress play a central role in the development of cardiac fibrosis. CyPA (Cyclophilin A) is a main proinflammatory cytokine secreted under the conditions of oxidative stress. The mechanisms by which intracellular and extracellular CyPA interact with CFs are unclear. Male C57BL/6 J mice received angiotensin Ⅱ (Ang Ⅱ) or vehicle for 4 weeks. Inhibition of CyPA significantly reversed Ang Ⅱ-induced cardiac hypertrophy and fibrosis. Mechanically, TGF-ß (Transforming growth factor-ß) signaling was found to be an indispensable downstream factor of CyPA-mediated myofibroblast differentiation and proliferation. Furthermore, intracellular CyPA and extracellular CyPA activate TGF-ß signaling through NOD-like receptor protein 3 (NLRP3) inflammasome and nicotinamide-adenine dinucleotide phosphate (NADPH) oxidase, respectively. Pharmacological inhibition of CyPA and its receptor CD147 implemented by Triptolide also attenuated the expression of TGF-ß signaling and cardiac fibrosis in Ang Ⅱ-model. These studies elucidate a novel mechanism by which CyPA promotes TGF-ß and its downstream signaling in CFs and identify CyPA (both intracellular and extracellular) as plausible therapeutic targets for preventing or treating cardiac fibrosis induced by chronic Ang Ⅱ stimulation.

Search progress of pyruvate kinase M2 (PKM2) in organ fibrosis.

Fibrosis is characterized by abnormal deposition of the extracellular matrix (ECM), leading to organ structural remodeling and loss of function. The principal cellular effector in fibrosis is activated myofibroblasts, which serve as the main source of matrix proteins. Metabolic reprogramming, transitioning from mitochondrial oxidative phosphorylation to aerobic glycolysis, is widely observed in rapidly dividing cells such as tumor cells and activated myofibroblasts and is increasingly recognized as a fundamental pathogenic basis in organ fibrosis. Targeting metabolism represents a promising strategy to mitigate fibrosis. PKM2, a key enzyme in glycolysis, plays a pivotal role in metabolic reprogramming through allosteric regulation, impacting both metabolic and non-metabolic pathways. Therefore, metabolic reprogramming induced by PKM2 activation is involved in the occurrence and development of fibrosis in various organs. A comprehensive understanding of the role of PKM2 in fibrotic diseases is crucial for seeking new anti-fibrotic therapeutic targets. In this context, we summarize PKM2's role in glycolysis, mediating the intricate mechanisms underlying fibrosis in multiple organs, and discuss the potential value of PKM2 inhibitors and allosteric activators in future clinical treatments, aiming to identify novel therapeutic targets for proliferative fibrotic diseases.

Regulating Underwater Oil Adhesion on Superoleophobic Copper Films through Assembling n-Alkanoic Acids.

Controlling liquid adhesion on special wetting surface is significant in many practical applications. In this paper, an easy self-assembled monolayer technique was advanced to modify nanostructured copper substrates, and tunable adhesive underwater superoleophobic surfaces were prepared. The surface adhesion can be regulated by simply varying the chain length of the n-alkanoic acids, and the tunable adhesive properties can be ascribed to the combined action of surfaces nanostructures and related variation in surface chemistry. Meanwhile, the tunable ability is universal, and the oil-adhesion controllability is suitable to various oils including silicon oil, n-hexane, and chloroform. Finally, on the basis of the special tunable adhesive properties, some applications of our surfaces including droplet storage, transfer, mixing, and so on are also discussed. The paper offers a novel and simple method to prepare underwater superoleophobic surfaces with regulated adhesion, which can potentially be applied in numerous fields, for instance, biodetection, microreactors, and microfluidic devices.

pH-induced reversible wetting transition between the underwater superoleophilicity and superoleophobicity.

Surfaces with controlled oil wettability in water have great potential for numerous underwater applications. In this work, we report a smart surface with pH-responsive oil wettability. The surface shows superoleophilicity in acidic water and superoleophobicity in basic water. Reversible transition between the two states can be achieved through alteration of the water pH. Such smart ability of the surface is due to the cooperation between the surface chemistry variation and hierarchical structures on the surface. Furthermore, we also extended this strategy to the copper mesh substrate and realized the selective oil/water separation on the as-prepared film. This paper reports a new surface with excellently controllable underwater oil wettability, and we believe such a surface has a lot of applications, for instance, microfluidic devices, bioadhesion, and antifouling materials.

Underwater superoleophilic to superoleophobic wetting control on the nanostructured copper substrates.

Surfaces with controlled underwater oil wettability would offer great promise in the design and fabrication of novel materials for advanced applications. Herein, we propose a new approach based on self-assembly of mixed thiols (containing both HS(CH2)9CH3 and HS(CH2)11OH) on nanostructured copper substrates for the fabrication of surfaces with controlled underwater oil wettability. By simply changing the concentration of HS(CH2)11OH in the solution, surfaces with controlled oil wettability from the underwater superoleophilicity to superoleophobicity can be achieved. The tunable effect can be due to the synergistic effect of the surface chemistry variation and the nanostructures on the surfaces. Noticeably, the amplified effect of the nanostructures can provide better control of the underwater oil wettability between the two extremes: superoleophilicity and superoleophobicity. Moreover, we also extended the strategy to the copper mesh substrates and realized the selective oil/water separation on the as-prepared copper mesh films. This report offers a flexible approach of fabricating surfaces with controlled oil wettability, which can be further applied to other ordinary materials, and open up new perspectives in manipulation of the surface oil wettability in water.

Designing heterogeneous chemical composition on hierarchical structured copper substrates for the fabrication of superhydrophobic surfaces with controlled adhesion.

Controlling water adhesion is important for superhydrophobic surfaces in many applications. Compared with numerous researches about the effect of microstructures on the surface adhesion, research relating to the influence of surface chemical composition on the surface adhesion is extremely rare. Herein, a new strategy for preparation of tunable adhesive superhydrophobic surfaces through designing heterogeneous chemical composition (hydrophobic/hydrophilic) on the rough substrate is reported, and the influence of surface chemical composition on the surface adhesion are examined. The surfaces were prepared through self-assembling of mixed thiol (containing both HS(CH2)9CH3 and HS(CH2)11OH) on the hierarchical structured copper substrates. By simply controlling the concentration of HS(CH2)11OH in the modified solution, tunable adhesive superhydrophobic surfaces can be obtained. The adhesive force of the surfaces can be increased from extreme low (about 8 µN) to very high (about 65 µN). The following two reasons can be used to explain the tunable effect: one is the number of hydrogen bond for the variation of surface chemical composition; and the other is the variation of contact area between the water droplet and surface because of the capillary effect that results from the combined effect of hydrophilic hydroxyl groups and microstructures on the surface. Noticeably, water droplets with different pH (2-12) have similar contact angles and adhesive forces on the surfaces, indicating that these surfaces are chemical resistant to acid and alkali. Moreover, the as-prepared surfaces were also used as the reaction substrates and applied in the droplet-based microreactor for the detection of vitamin C. This report provides a new method for preparation of superhydrophobic surfaces with tunable adhesion, which could not only help us further understand the principle for the fabrication of tunable adhesive superhydrophobic surfaces, but also potentially be used in many important applications, such as microfluidic devices and chemical microreactors.

pH-controllable water permeation through a nanostructured copper mesh film.

Water permeation is an important issue in both fundamental research and industrial applications. In this work, we report a novel strategy to realize the controllable water permeation on the mixed thiol (containing both alkyl and carboxylic acid groups) modified nanostructured copper mesh films. For acidic and neutral water, the film is superhydrophobic, and the water cannot permeate the film because of the large negative capillary effect resulting from the nanostructures. For basic water, the film shows superhydrophilic property, and thus the water can permeate the film easily. The permeation process of water can be controlled just by simply altering the water pH. A detailed investigation indicates that nanostructures on the substrate and the appropriate size of the microscale mesh pores can enhance not only the static wettability but also the dynamic properties. The excellent controllability of water permeation is ascribed to the combined effect of the chemical variation of the carboxylic acid group and the microstructures on the substrate. This work may provide interesting insight into the new applications that are relevant to the surface wettability, such as filtration, microfluidic device, and some separation systems.