Surface functionalization of polyurethanes: A critical review.

Synthetic polymers, particularly polyurethanes (PUs), have revolutionized bioengineering and biomedical devices due to their customizable mechanical properties and long-term stability. However, the inherent hydrophobic nature of PU surfaces arises common issues such as high friction, strong protein adsorption, and thrombosis, especially in the physiological environment of blood contact. To overcome these issues, researchers have explored various modification techniques to improve the surface biofunctionality of PUs. In this review, we have systematically summarized several typical surface modification methods including surface plasma modification, surface oxidation-induced grafting polymerization, isocyanate-based chemistry coupling, UV-induced surface grafting polymerization, adhesives-assisted attachment strategy, small molecules-bridge grafting, solvent evaporation technique, and hydrogen bonding interaction. Correspondingly, the advantages, limitations, and future prospects of these surface modification methods were discussed. This review provides an important guidance or tool for developing surface functionalized PUs in the fields of bioengineering and medical devices.

Autophagy is involved in degradation of AQP1 in response to an acute decrement in tonicity.

Renal medullary aquaporin-1 (AQP1) plays an important role in the urinary concentration. This study aimed to investigate the regulation of AQP1 by low osmotic stress and a potential role of autophagy. Low osmotic stress induced a dramatically decreased AQP1 protein expression in murine inner medullary collecting duct 3 (mIMCD3) cells, which was associated with a marked activation of autophagy. Inhibition of autophagy by 3-methyladenine (3-MA), chloroquine, or knockdown of autophagy-related protein 5 (ATG5) prevented the decrease in AQP1 protein abundance. Rapamycin-induced autophagy was associated with a decreased AQP1 protein expression and an enhanced interaction between AQP1 and ATG5 in mIMCD3 cells under low osmotic stress. In kidney inner medulla of mice given a 3% NaCl solution, activation of autophagy was associated with decreased AQP1 protein expression, which was prevented by 3-MA. In conclusion, low osmotic stress induced autophagy which contributed to the decreased AQP1 protein expression in the renal medulla.

Functional Zwitterionic Polyurethanes: State-of-the-Art Review.

Recent advancements in bioengineering and medical devices have been greatly influenced and dominated by synthetic polymers, particularly polyurethanes (PUs). PUs offer customizable mechanical properties and long-term stability, but their inherent hydrophobic nature poses challenges in practically biological application processes, such as interface high friction, strong protein adsorption, and thrombosis. To address these issues, surface modifications of PUs for generating functionally hydrophilic layers have received widespread attention, but the durability of generated surface functionality is poor due to irreversible mechanical wear or biodegradation. As a result, numerous researchers have investigated bulk modification techniques to incorporate zwitterionic polymers or groups onto the main or side chains of PUs, thereby improving their hydrophilicity and biocompatibility. This comprehensive review presents an extensive overview of notable zwitterionic PUs (ZPUs), including those based on phosphorylcholine, sulfobetaine, and carboxybetaine. The review explores their wide range of biomedical applications, from blood-contacting devices to antibacterial coatings, fouling-resistant marine coatings, separation membranes, lubricated surfaces, and shape memory and self-healing materials. Lastly, the review summarizes the challenges and future prospects of ZPUs in biological applications.

Piezo1 specific deletion in macrophage protects the progression of liver fibrosis in mice.

Background and Aims: Liver fibrosis is the common pathological pathway of chronic liver diseases and its mechanisms of which have not been fully declared. Macrophages play essential roles in progression of liver fibrosis partially by sensing abnormal mechanical signals. The aim of the study is to investigate the functions of macrophage Piezo1, a mechano-sensitive ion channel, in liver fibrosis. Approach and Results: Immunofluorescence in human and murine fibrotic liver samples revealed that expression of macrophage Piezo1 was increased. Myeloid-specific Piezo1 knockout (Piezo1ΔLysM) attenuated liver fibrosis by decreased collagen deposition and epithelial-mesenchymal transition (EMT). In Piezo1ΔLysM mice, less inflammation during development of liver fibrosis was observed by lessened macrophage infiltration, decreased M1 polarization and expression of inflammatory cytokines. RNA-seq data showed macrophage Piezo1 regulated transcription of cathepsin S (CTSS). Piezo1ΔLysM inhibited expression and activity of CTSS in vitro and in vivo and regulated T cell activity. Furthermore, inhibition of CTSS reversed macrophage inflammatory response driven by Piezo1 activation and LPS. Macrophage Piezo1 activation promoted CTSS secretion due to increased activity of Ca2+-dependent calpain protease induced by Ca2+ influx to cleave lysosome-associated membrane protein-1 (LAMP1). Pharmacological inhibition of calpain activity partially blocked Piezo1 mediated CTSS secretion. Conclusions: Macrophage Piezo1 deficiency limits the progression of liver fibrosis by inhibited inflammatory response and decreased secretion of CTSS. These findings suggest that targeting Piezo1 channel may be a potential strategy for treating hepatic fibrosis.

Electrospun fibrous membrane reinforced hydrogels with preferable mechanical and tribological performance as cartilage substitutes.

Hydrogels have attracted much attention as cartilage substitutes due to their human tissue-like characteristics. However, developing cartilage substitutes require the combination of high mechanical strength and low friction. Despite great success in tough hydrogels, this combination was hardly realized. Inspired by the natural cartilage, electrospun fibrous membrane reinforced hydrogels with superior mechanical properties and low friction coefficient were designed using electrospinning, freeze-thawing, and annealing techniques. An ordered fibrous membrane was first constructed by electrospinning, in which the tensile strength and modulus have been improved successfully. Then the PVA/PAA/GO hydrogel was modified layer-by-layer by the multilayer ordered electrospun membrane of PVA/PAA/GO. The ordered fibrous membrane significantly enhanced the mechanical strength and friction properties in a manner that mimicked the collagen fibrils in the cartilage. When the number of the membranes was 4, the mechanical properties of the fibrous membrane reinforced hydrogel is maximized, which can be compared to natural cartilage, which can achieve a tensile strength of 13.7 ± 1.5 MPa, tensile modulus of 27.5 ± 3.2 MPa, compressive strength of 12.32 ± 1.35 MPa, compressive modulus of 20.35 ± 2.50 MPa. The ordered fibrous membrane endows the hydrogel with a higher tearing energy of 39.16 ± 4.05 KJ m-2, which is the 5 times that of pure hydrogel (7.74 ± 0.86 KJ m-2). In addition, the friction coefficient of the fibrous membrane reinforced hydrogel is as low as 0.039, 2 times smaller than that of the hydrogel without addition of the fibrous membrane. Therefore, such hydrogels had excellent mechanical properties and tribological properties, which could be widely used in tissue engineering such as in cartilage replacement.

Gut-derived ß-amyloid: Likely a centerpiece of the gut-brain axis contributing to Alzheimer's pathogenesis.

Peripheral ß-amyloid (Aß), including those contained in the gut, may contribute to the formation of Aß plaques in the brain, and gut microbiota appears to exert an impact on Alzheimer's disease (AD) via the gut-brain axis, although detailed mechanisms are not clearly defined. The current study focused on uncovering the potential interactions among gut-derived Aß in aging, gut microbiota, and AD pathogenesis. To achieve this goal, the expression levels of Aß and several key proteins involved in Aß metabolism were initially assessed in mouse gut, with key results confirmed in human tissue. The results demonstrated that a high level of Aß was detected throughout the gut in both mice and human, and gut Aß42 increased with age in wild type and mutant amyloid precursor protein/presenilin 1 (APP/PS1) mice. Next, the gut microbiome of mice was characterized by 16S rRNA sequencing, and we found the gut microbiome altered significantly in aged APP/PS1 mice and fecal microbiota transplantation (FMT) of aged APP/PS1 mice increased gut BACE1 and Aß42 levels. Intra-intestinal injection of isotope or fluorescence labeled Aß combined with vagotomy was also performed to investigate the transmission of Aß from gut to brain. The data showed that, in aged mice, the gut Aß42 was transported to the brain mainly via blood rather than the vagal nerve. Furthermore, FMT of APP/PS1 mice induced neuroinflammation, a phenotype that mimics early AD pathology. Taken together, this study suggests that the gut is likely a critical source of Aß in the brain, and gut microbiota can further upregulate gut Aß production, thereby potentially contributing to AD pathogenesis.

Injectable carboxymethyl chitosan/nanosphere-based hydrogel with dynamic crosslinking network for efficient lubrication and sustained drug release.

The typical symptoms of arthritis are inflammation and lubrication deficiency in joints, which increase wear of articular cartilage along with pain of patients. In the present study, one kind of novel macromolecular/microsphere-based injectable hydrogels (CMC-ODex NPs) with dual functionalities of drug release and lubrication, was fabricated via dynamic Schiff base crosslinking network between carboxymethyl chitosan (CMC) and oxidation dextran nanoparticles (ODex NPs). The CMC-ODex NPs hydrogels exhibited typical viscosity-thinning phenomenon at wide range of shear rates and obvious gel-sol transition feature at specific strain. As a result, CMC-ODex NPs hydrogels presented low friction coefficient at the sliding interface of bovine articular cartilages, resulting from the boundary lubrication of hydrogel and the rolling friction effect of ODex NPs. Furthermore, the anti-inflammatory drug (dexamethasone, DXM) encapsulated in ODex NPs exhibited sustainable drug release behavior during the dynamic shearing process, which making CMC-ODex NPs hydrogels possessed good and stable anti-inflammatory effect. CMC-ODex NPs hydrogels was prepared without utilizing any toxic agents, thus demonstrated excellent cytocompatibility. Our experimental results reveal the CMC-ODex NPs hydrogels is promising to be used as functional lubricant for inhibiting the development of arthritis.

Biomimetic chitosan nanoparticles with simultaneous water lubricant and anti-inflammatory.

Rheumatoid arthritis (RA) is a chronic inflammatory immune and lubrication dysfunction disease that causes great damage to the joints. Herein, inspired by the unique biochemistry structure and excellent hydration of chondroitin sulfate (CHI) existing in joint system, one kind of novel polysaccharide nanoparticle lubricant, that is chitosan nanoparticles (CS NPs) grafting CHI (CS-CHI), is synthesized by one-step surface chemistry reaction. CHI with negative charges can form hydration layers on the surface of CS NPs, thus improving the lubricity of nanoparticles. Simultaneously, CS-CHI NPs have effective loading and sustained drug release ability for anti-inflammatory drug diclofenac sodium (DS), along with good biocompatibility. Finally, based on a collagen-induced rat RA model, in vitro animals experimental results indicate that the as-synthesized CS-CHI@DS NPs has obvious inhibitory effects on inflammatory factors and can effectively prevent the damaged cartilage from further destruction.

Expression Regulation and Trafficking of Aquaporins.

Aquaporins (AQPs) mediate the bidirectional water flow driven by an osmotic gradient. Either gating or trafficking allows for rapid and specific AQP regulation in a tissue-dependent manner. The regulatory mechanisms of AQP2 are discussed mainly in this chapter, as the mechanisms controlling the regulation and trafficking of AQP2 have been very well studied. The targeting of AQP2 to the apical plasma membrane of collecting duct principal cells is mainly regulated by the action of arginine vasopressin (AVP) on the type 2 AVP receptor (V2R), which cause increased intracellular cAMP or elevated intracellular calcium levels. Activation of these intracellular signaling pathways results in vesicles bearing AQP2 transport, docking and fusion with the apical membrane, which increase density of AQP2 on the membrane. The removal of AQP2 from the membrane requires dynamic cytoskeletal remodeling. AQP2 is degraded through the ubiquitin proteasome pathway and lysosomal proteolysis pathway. Finally, we review updated findings in transcriptional and epigenetic regulation of AQP2.

Biomimetic chitosan-derived bifunctional lubricant with superior antibacterial and hydration lubrication performances.

The lubrication deficiency in joints is a major cause of osteoarthritis. One of the most commonly used treatment means is to inject artificial lubricants, but there is a potential risk of infection during the injection process. Therefore, developing artificial lubricants with dual functions of friction-reduction and antibacterial is urgent. In this work, a novel polysaccharide-derived lubricant with simultaneous anti-bacteria and water-lubrication properties, called CS-MPC-N, is developed by grafting 2­methacryloyloxylethyl phosphorylcholine (MPC) and nisin peptide onto backbone of chitosan (CS). Compared to the control CS, CS-MPC-N exhibits good lubrication and friction-reduction properties because of its excellent water solubility. Especially, CS-MPC-N shows low friction coefficient (0.03 âˆ¼ 0.05) at the sliding interfaces of artificial joints materials or even natural articular cartilages. Moreover, CS-MPC-N can effectively inhibit the proliferation of Staphylococcus aureu, exhibiting excellent antibacterial effect. This kind of novel polysaccharide-derived lubricant is expected to be used in treating infectious arthritis.

Bilayer Hydrogels with Low Friction and High Load-Bearing Capacity by Mimicking the Oriented Hierarchical Structure of Cartilage.

Natural articular cartilages exhibit extraordinary lubricating properties and excellent load-bearing capacity based on their penetrated surface lubricated biomacromolecules and gradient-oriented hierarchical structure. Hydrogels are considered as the most promising cartilage replacement materials due to their excellent flexibility, good biocompatibility, and low friction coefficient. However, the construction of high-strength, low-friction hydrogels to mimic cartilage is still a great challenge. Here, inspired by the structure and functions of natural articular cartilage, anisotropic hydrogels with horizontal and vertical orientation structure were constructed layer by layer and bonded with each other, successfully developing a bilayer oriented heterogeneous hydrogel with a high load-bearing capacity, low friction, and excellent fatigue resistance. The bilayer hydrogel exhibited a high compressive strength of 5.21 ± 0.45 MPa and a compressive modulus of 4.06 ± 0.31 MPa due to the enhancement mechanism of the anisotropic structure within the bottom anisotropic hydrogel. Moreover, based on the synergistic effect of the high load-bearing capacity of the bottom layer and the lubrication of the surface layer, the bilayer hydrogel possesses excellent biotribological properties in hard/soft (0.032) and soft/soft (0.028) contact, which is close to that of natural cartilage. It is worth noting that the bilayer oriented heterogeneous hydrogel is able to withstand repeated loading without fatigue crack. Therefore, this work could open up a new avenue for constructing cartilage-like materials with both high strength and low friction.

Genetic parameters and genome-wide association for milk production traits and somatic cell score in different lactation stages of Shanghai Holstein population.

The aim of this study was to investigate the genetic parameters and genetic architectures of six milk production traits in the Shanghai Holstein population. The data used to estimate the genetic parameters consisted of 1,968,589 test-day records for 305,031 primiparous cows. Among the cows with phenotypes, 3,016 cows were genotyped with Illumina Bovine SNP50K BeadChip, GeneSeek Bovine 50K BeadChip, GeneSeek Bovine LD BeadChip v4, GeneSeek Bovine 150K BeadChip, or low-depth whole-genome sequencing. A genome-wide association study was performed to identify quantitative trait loci and genes associated with milk production traits in the Shanghai Holstein population using genotypes imputed to whole-genome sequences and both fixed and random model circulating probability unification and a mixed linear model with rMVP software. Estimated heritabilities (h2) varied from 0.04 to 0.14 for somatic cell score (SCS), 0.07 to 0.22 for fat percentage (FP), 0.09 to 0.27 for milk yield (MY), 0.06 to 0.23 for fat yield (FY), 0.09 to 0.26 for protein yield (PY), and 0.07 to 0.35 for protein percentage (PP), respectively. Within lactation, genetic correlations for SCS, FP, MY, FY, PY, and PP at different stages of lactation estimated in random regression model were ranged from -0.02 to 0.99, 0.18 to 0.99, 0.04 to 0.99, 0.04 to 0.99, 0.01 to 0.99, and 0.33 to 0.99, respectively. The genetic correlations were highest between adjacent DIM but decreased as DIM got further apart. Candidate genes included those related to production traits (DGAT1, MGST1, PTK2, and SCRIB), disease-related (LY6K, COL22A1, TECPR2, and PLCB1), heat stress-related (ITGA9, NDST4, TECPR2, and HSF1), and reproduction-related (7SK and DOCK2) genes. This study has shown that there are differences in the genetic mechanisms of milk production traits at different stages of lactation. Therefore, it is necessary to conduct research on milk production traits at different stages of lactation as different traits. Our results can also provide a theoretical basis for subsequent molecular breeding, especially for the novel genetic loci.

Bioinspired Polysaccharide Derivative with Efficient and Stable Lubrication for Silicon-Based Devices.

It is becoming increasingly important to synthesize efficient biomacromolecule lubricants suitable for medical devices. Even though the development of biomimetic lubricants has made great progress, the current system suitable for hydrophobic silicone-based medical devices is highly limited. In this work, we synthesize one kind of novel polysaccharide-derived macromolecule lubricant of chitosan (CS) grafted polyethylene glycol (PEG) chains and catechol groups (CT) (CS-g-PEG-g-CT). CS-g-PEG-g-CT shows good adsorption ability by applying quantitative analysis of quartz crystal microbalance (QCM), attenuated total reflectance-Fourier transform infrared spectroscopy (ATR-FTIR), and confocal fluorescence imaging technique, as well as the typical shear-thinning feature. CS-g-PEG-g-CT exhibits low and stable coefficients of friction (COFs) (0.01-0.02) on polydimethylsiloxane (PDMS) surfaces at a wide range of mass concentrations in diverse media including pure water, physiological saline, and PBS buffer solution and is even tolerant to various normal loads and sliding frequencies for complex pressurizing or shearing environments. Subsequently, systematic surface characterizations are used to verify the dynamic attachment ability of the CS-g-PEG-g-CT lubricant on the loading/shearing process. The lubrication mechanism of CS-g-PEG-g-CT can be attributed to the synergy of strong adsorption from catechol groups to form a uniform assembly layer, excellent hydration effect from PEG chains, and typical shear-thinning feature to dissipate viscous resistance. Surprisingly, CS-g-PEG-g-CT exhibits efficient lubricity on silicone-based commercial contact lenses and catheters. The current macromolecule lubricant demonstrates great real application potential in the fields of medical devices and disease treatments.

Successive Redox-Reaction-Triggered Interface Radical Polymerization for Growing Hydrogel Coatings on Diverse Substrates.

Growing lubricating hydrogel coatings in controllable manners on diverse material surfaces demonstrates promising applications. Here, a surface modification method is reported for in situ growing hydrogel coatings onto surfaces of diverse substrates in the absence of UV assistance. It is performed by decorating substrates with a universal mussel-inspired synthetic adhesive with catechol groups. Upon being immersed in reaction solution, these groups can assist substrate bonding and in situ capture and reduce Fe3+ into Fe2+ for decomposing S2 O8 2- into SO4 - ⋅ catalytically at the interface to initiate interface polymerization of monomers. As a result, hydrogel coatings with controllable thickness could be grown on surfaces of arbitrary substrates to change their surface characteristics regardless of materials size, category, geometry and transparency, implying considerable potential in surface engineering.

Statins attenuate cholesterol-induced ROS via inhibiting NOX2/NOX4 and mitochondrial pathway in collecting ducts of the kidney.

BACKGROUND: Statins therapy has been primarily recommended for the prevention of cardiovascular risk in patients with chronic kidney diseases. Statins has also been proved some benefits in lipid-induced kidney diseases. The current study aims to investigate the protection and underlying mechanisms of statins on renal tubular injuries induced by cholesterol overloaded. METHODS: We used tubular suspensions of inner medullary collecting duct (IMCD) cells from rat kidneys and mouse collecting duct cell line mpkCCD cells to investigate the effect of statins on reactive oxygen species (ROS) production induced by cholesterol. Protein and mRNA expression of NADPH oxidase 2 (NOX2) /NOX4 was examined by Western blot and RT-PCR in vitro studies and in rats with 5/6 nephrectomy and high-fat diet. Mitochondrial morphology and membrane potential was observed by Mito-tracker and JC-1. RESULTS: Statins treatment was associated with decreased NOX2 and NOX4 protein expression and mRNA levels in 5/6Nx rats with high-fat diet. Statins treatment markedly reduced the ROS production in IMCD suspensions and mpkCCD cells. Also, statins reduced NOX2 and NOX4 protein expression and mRNA levels in cholesterol overload mpkCCD cells and improved mitochondrial morphology and function. CONCLUSION: Statins prevented ROS production induced by cholesterol in the kidney, likely through inhibiting NOXs protein expression and improving mitochondrial function. Statins may be a therapeutic option in treating obesity-associated kidney diseases.

Bioinspired Polysaccharide-Derived Zwitterionic Brush-like Copolymer as an Injectable Biolubricant for Arthritis Treatment.

Developing highly efficient and biocompatible biolubricants for arthritis treatment is extraordinarily demanded. Herein, inspired by the efficient lubrication of synovial joints, a paradigm that combines natural polysaccharide (chitosan) with zwitterionic poly[2-(methacryloyloxy) ethyl phosphorylcholine] (PMPC), to design a series of brush-like Chitosan-g-PMPC copolymers with highly efficient biological lubrication and good biocompatibility is presented. The Chitosan-g-PMPC copolymers are prepared via facile one-step graft polymerization in aqueous medium without using any toxic catalysts and organic solvents. The as-prepared Chitosan-g-PMPC copolymers exhibit very low coefficient of friction (µ < 0.01) on Ti6 Al4 V alloy substrate in both pure water and biological fluids. The superior lubrication is attributed primarily to the hydrated feature of PMPC side chains, interface adsorption of copolymer as well as to the hydrodynamic effect. In vivo experiments confirm that Chitosan-g-PMPC can alleviate the swelling symptom of arthritis and protect the bone and cartilage from destruction. Due to their facile preparation, distinctive lubrication properties, and good biocompatibility, Chitosan-g-PMPC copolymers represent a new type of biomimetic lubricants derived from natural biopolymer for promising arthritis treatment and artificial joint lubrication.

Mechanosensitive Piezo1 channels mediate renal fibrosis.

Kidney fibrosis is the final common pathway of progressive kidney diseases, the underlying mechanisms of which are not fully understood. The purpose of the current study is to investigate a role of Piezo1, a mechanosensitive nonselective cation channel, in kidney fibrosis. In human fibrotic kidneys, Piezo1 protein expression was markedly upregulated. The abundance of Piezo1 protein in kidneys of mice with unilateral ureter obstruction (UUO) or with folic acid treatment was significantly increased. Inhibition of Piezo1 with nonspecific inhibitor GsMTx4 markedly ameliorated UUO- or folic acid-induced kidney fibrosis. Mechanical stretch, compression, or stiffness induced Piezo1 activation and profibrotic responses in human HK2 cells and primary cultured mouse proximal tubular cells (mPTCs), which were greatly prevented by inhibition or silence of Piezo1. TGF-ß1 induced increased Piezo1 expression and profibrotic phenotypic alterations in HK2 cells and mPTCs, which were again markedly prevented by inhibition of Piezo1. Activation of Piezo1 by Yoda1, a Piezo1 agonist, caused calcium influx and profibrotic responses in HK2 cells and induced calcium-dependent protease calpain2 activation, followed by adhesion complex protein talin1 cleavage and upregulation of integrin ß1. Also, Yoda1 promoted the link between ECM and integrin ß1. In conclusion, Piezo1 is involved in the progression of kidney fibrosis and profibrotic alterations in renal proximal tubular cells, likely through activating calcium/calpain2/integrin ß1 pathway.

Molecular Engineering Super-Robust Dry/Wet Adhesive with Strong Interface Bonding and Excellent Mechanical Tolerance.

Despite the fact that synthetic adhesives have achieved great progress, achieving robust dry/wet adhesion under harsh operating environments is still challenging. Herein, inspired from the extraordinary adhesion mechanism of nature mussel protein adhesive, the balanced design concept of co-adhesion and interfacial adhesion is proposed to prepare one kind of novel copolymer adhesive of [poly(dopamine methacrylamide-co-methoxethyl acrylate-co-adamantane-1-carboxylic acid 2-(2-methyl-acryloyloxy)-ethyl ester)] [p(DMA-co-MEA-co-AD)], named as super-robust adhesive (SRAD). The SRAD exhibits ultra-high interface bonding strengths in air (∼7.66 MPa) and underwater (∼2.78 MPa) against an iron substrate. Especially, a greatly tough and stable adhesion strength (∼2.11 MPa) can be achieved after immersing the bonded sample in water for half a year. Furthermore, the SRAD demonstrates surprising wet bonding robustness/tolerance even encountering harsh conditions such as fluid shearing, dynamic loading, and cyclic mechanical fretting. The great advantages of SRAD, such as strong interface bonding, stable wet adhesion underwater, and good mechanical tolerance, makes it demonstrate huge application potential in engineering sealants and underwater adhesion.

Bioinspired Design of a Cartilage-like Lubricated Composite with Mechanical Robustness.

Natural articular cartilages show extraordinary tribological performance based on their penetrated surface lubricated biomacromolecules and good mechanical tolerance. Hydrogels are considered to be potential alternatives to cartilages due to their low surface friction and good biocompatibility, although the poor mechanical properties limited their applications. Inspired by the excellent mechanical properties and the remarkable surface lubrication mechanism of natural articular cartilages, one kind of cartilage-like composite material with a lubrication phase (Composite-LP) was developed by chemically grafting a thick hydrophilic polyelectrolyte brush layer onto the subsurface of a three-dimensional manufactured elastomer scaffold-hydrogel composite architecture. The Composite-LP exhibited good load-bearing capacities because of the nondissipation strategy and the stress dispersion mechanism resulting from the elastomer scaffold enhancement. In the presence of the top lubrication layer, the Composite-LP showed superior friction reduction functionality and wear resistance under a dynamic shearing process. This design concept of coupling the non-dissipative mechanism and interface lubrication provides a new avenue for developing cartilage-like hydrogels and soft robots.

HDAC3 inhibition improves urinary-concentrating defect in hypokalaemia by promoting AQP2 transcription.

AIM: This study investigated whether enhanced histone acetylation, achieved by inhibiting histone deacetylases (HDACs), could prevent decreased aquaporin-2 (AQP2) expression during hypokalaemia. METHODS: Male Wistar rats were fed a potassium-free diet with or without 4-phenylbutyric acid (4-PBA) or the selective HDAC3 inhibitor RGFP966 for 4 days. Primary renal inner medullary collecting duct (IMCD) cells and immortalized mouse cortical collecting duct (mpkCCD) cells were cultured in potassium-deprivation medium with or without HDAC inhibitors. RESULTS: 4-PBA increased the levels of AQP2 mRNA and protein in the kidney inner medullae in hypokalaemic (HK) rats, which was associated with decreased urine output and increased urinary osmolality. The level of acetylated H3K27 (H3K27ac) protein was decreased in the inner medullae of HK rat kidneys; this decrease was mitigated by 4-PBA. The H3K27ac levels were decreased in IMCD and mpkCCD cells cultured in potassium-deprivation medium. Decreased H3K27ac in the Aqp2 promoter region was associated with reduced Aqp2 mRNA levels. HDAC3 protein expression was upregulated in mpkCCD and IMCD cells in response to potassium deprivation, and the binding of HDAC3 to the Aqp2 promoter was also increased. RGFP966 increased the levels of H3K27ac and AQP2 proteins and enhanced binding between H3K27ac and AQP2 in mpkCCD cells. Furthermore, RGFP966 reversed the hypokalaemia-induced downregulation of AQP2 and H3K27ac and alleviated polyuria in rats. RGFP966 increased interstitial osmolality in the kidney inner medullae of HK rats but did not affect urinary cAMP levels. CONCLUSION: HDAC inhibitors prevented the downregulation of AQP2 induced by potassium deprivation, probably by enhancing H3K27 acetylation.