AIM:Renal fibrosis is a major contributor to chronic kidney disease (CKD) progression and eventual organ failure. G protein-coupled bile acid receptor 1 (TGR5) was previously shown to have beneficial effects on kidney diseases. The current study aimed to investigate whether TGR5 activation prevents kidney fibrosis and to clarify the underlying mechanism. METHODS:TGR5 expression was examined in human fibrotic kidneys. Two animal models of renal fibrosis were used: unilateral ureteral obstruction (UUO) and unilateral ischemia-reperfusion injury with contralateral nephrectomy (uIRIx) in wild-type and TGR5 knockout mice. Renal histology, extracellular matrix (ECM) deposition, and renal function were examined. In vitro studies were performed on human proximal tubular HK2 cells by treating them with transforming growth factor-β1 and TGR5 agonists/antagonists. RESULTS:TGR5 was significantly downregulated in fibrotic human kidneys. In both UUO and uIRIx models, TGR5 activation by lithocholic acid alleviated renal fibrosis, reduced ECM deposition, and improved kidney function. Conversely, Tgr5 knockout in mice exacerbated fibrotic injury. Mechanistically, TGR5 activation prevented fibrosis development, probably by enhancing NEDD4L-mediated ubiquitination and degradation of phosphorylated Smad2/3 by inhibiting the upstream PI3K-SGK1 pathway. CONCLUSION:TGR5 activation protects against renal fibrosis by inhibiting the PI3K-SGK1-NEDD4L axis and promoting p-Smad2/3 degradation.

The manufacture of biocompatible multifunctional medical metal materials constitutes a frontier challenge. Meanwhile, surface modification offers substantial potential for enhancing their functionality and broadening their application scope. Nevertheless, it remains crucial to customize and modify the surface of medical metal materials to endow them with multiple functionalities, including anticorrosive, antibacterial, and wear-resistance properties. In this study, we designed a new concept and realized the successful manufacture of a multifunctional composite coating with a hierarchical structure on diverse medical metal substrates, including CoCrMo, Ti6Al4V, and 316L. This composite coating system consists of a hard diamond-like carbon (DLC) layer serving as a corrosion barrier, an intermediate silica sol layer incorporating both reactive initiators and antibacterial agents for load-bearing, and a top-soft hydration layer composed of polysulfobetaine methacrylate (PSPMA) brush for friction reduction. The as-manufactured composite coating exhibits superior hydrophilicity, excellent corrosion resistance, as well as durable super-lubrication properties in diverse media. This manufacture concept has been validated on curved 316L artificial hip joint femoral head. Notably, the composite coating can even maintain a stable and super-low coefficient of friction (COF: ∼0.0035) on the surface of three kinds of metal substrates after encountering 50,000 friction sliding cycles, as well as ignorable wear. Furthermore, the composite coating demonstrates outstanding antibacterial performance against Gram-positive Staphylococcus aureus (S. aureus). This work presents a novel manufacture strategy for the design and development of multifunctional implantable/interventional metallic materials and devices, holding great promise for biomedical engineering applications.

Medical catheters play an extremely important role in clinical interventional diagnosis and treatment. However, their hydrophobic surface may lead to unfavorable outcomes such as tissue damage and infection, making a firm and stable lubrication modification essential. This goal is challenged by an inherent trade-off between coating lubricity and interfacial stability, as well as the critical prerequisite of manufacturability. This review initially examines this core challenge, and systematically outlines corresponding strategies in terms of materials, coating strategies, and manufacturability. Subsequently, existing performance evaluation techniques for coatings are summarized. Finally, future research directions in the field of catheter lubrication modification are discussed. This review aims to provide a reference for the material design, manufacture, and evaluation of lubrication modifications for catheters, so as to promote the development and clinical translation of innovative high-performance catheter coatings.

Uncontrolled hemorrhage, particularly from deep, irregular, and noncompressible wounds, remains a critical challenge in emergency medicine. Conventional hemostatic agents are frequently limited by poor sprayability, inadequate conformability to complex wound geometries, insufficient mechanical robustness, and lack of asymmetric adhesion properties. To address these limitations, we engineered a novel powder (CS-PSBMA@OHA) composed of zwitterionic poly(sulfobetaine methacrylate)-grafted chitosan (CS-PSBMA) and oxidized hyaluronic acid (OHA). Upon contact with moist tissue, the powder undergoes rapid liquid-triggered gelation, forming a stable, dual-network hydrogel. This architecture integrates a dense physical network, formed by strong intra- and interchain electrostatic interactions of zwitterionic PSBMA, with a dynamic chemical network established via Schiff base bonds with OHA. The resultant hydrogel adheres firmly to tissues by combining the rapid interfacial dehydration driven by zwitterionic PSBMA with the dynamic cross-linking enabled by OHA. This synergistic mechanism confers exceptional mechanical stability and sustained adhesion, even under dynamic fluid conditions. In both rat liver laceration and femoral artery transection models, CS-PSBMA@OHA demonstrated superior hemostatic efficacy, significantly reducing blood loss and hemostasis time compared to gauze and Yunnan Baiyao. Furthermore, the hydrogel exhibits a gradient adhesive interface: the tissue-contacting surface maintains strong adhesion, while the opposing side forms a hydrated lubrication layer. This asymmetric design effectively mitigates postoperative adhesions, as evidenced in a rat intestinal adhesion model. Collectively, this self-gelling powder-based platform represents a promising strategy for the development of multifunctional biomaterials that integrate rapid hemostasis with antiadhesive properties, offering potential clinical advantages in trauma and surgical settings.

ABSTRACT The fabrication of biohydrogel coatings faces a trilemma in balancing gelation speed, functional fidelity, and scalability. Rapid reactions often lead to heterogeneous networks due to kinetic trapping, whereas precise methods tend to be slow and difficult to scale. To address this challenge, we propose an Interfacial confined Mutual Catalysis (ICMC) strategy. This approach constructs a cyclic catalytic cascade in which the MXene surface catalyzes monomer polymerization, while the sulfonate groups on the monomer reciprocally enhance the catalytic activity of MXene, resulting in a self‐accelerating polymerization process. This method enables sub‐minute gelation at low temperatures, yielding self‐growing hydrogel coatings with tunable thickness (20–430 µm) and intrinsic multi‐functionalities, including ultra‐low friction (µ < 0.03), strong antibacterial activity (>99.2%), photothermal effect, and excellent biocompatibility. As a proof of concept, MXene‐hydrogel coated surgical sutures reduce surface friction by 83% relative to commercial sutures and significantly mitigate inflammation and epithelial hyperplasia in a rat wound model. Notably, the ICMC approach is compatible with roll‐to‐roll (R2R) processing, enabling continuous and programmable fabrication of multifunctional hydrogel coatings. This work opens a door for easy and scalable manufacture of hydrogels‐based functional biomaterials and medical devices.

Renal fibrosis is the terminal pathological manifestation of most chronic kidney diseases. The phosphodiesterase type 5 (PDE5) inhibitors have shown therapeutic potentials in a wide array of chronic conditions. LW1646 is a newly identified inhibitor with high specificity and potency against PDE5. The current study aims to investigate the therapeutic effects of LW1646 on renal fibrosis and its underlying mechanisms. mRNA and protein expression level of PDE5 was elevated in renal cortex of mice with unilateral ureter obstruction for seven days (7UUO). LW1646 effectively suppressed pro-fibrotic responses in TGF-β1-stimulated HK-2 cells as well as in mice with 7UUO-induced renal fibrosis. Genetic deletion or knockdown of Pde5a produced similar antifibrotic benefits. Mechanistically, both PDE5 inhibition with LW1646 and Pde5a knockout alleviated ER stress and mitigated mitochondrial dysfunction, as evidenced by restored mitochondrial biogenesis, suppression of excessive fragmentation, preservation of membrane potential, and reduction of oxidative stress. Further investigation revealed that ER stress-driven mitochondrial injury involved augmented mitochondria associated membrane (MAM) formation, characterized by increased expression of the hallmark IP3R1-GRP75-VDAC1 complex. This enhanced interaction facilitated excessive calcium transfer from the ER to mitochondria, culminating in mitochondrial calcium overload. PDE5 inhibition effectively suppressed MAM formation and reduced mitochondrial calcium accumulation, thereby maintaining mitochondrial homeostasis under fibrotic stress. Collectively, these findings identify activation of cGMP-PKG signaling by LW1646 as a promising therapeutic pathway for renal fibrosis through suppression of ER stress and stabilization of mitochondrial homeostasis.

Solvent-based antifouling coatings, widely used in marine environments, not only posed health risks to construction workers but also threatened the sustainability of marine ecosystems. To develop antifouling coatings with low volatile organic compound (VOC) content was urgent needed consequently. In this study, waterborne zinc acrylate self-polishing emulsions (WZSEs) were synthesized via free-radical polymerization, and corresponding waterborne antifouling coatings were developed. Infrared spectroscopy, thermogravimetric analysis, gel permeation chromatography, rheometer, dynamic light scattering, scanning electron microscopy, and threedimensional profilometry were employed to character the physicochemical properties of the coatings. The wetting behavior, mechanical properties, and antifouling component release kinetics were evaluated through contact angle measurements, adhesion testing, and atomic absorption spectroscopy. Importantly, the relationship between the content of self-polishing component and the antifouling performance of coatings in both laboratory and marine field was investigated. Experimental results revealed that the coatings achieved more than 98 % antifouling efficiency against typical fouling organisms, such as diatom Diplophora and green algae Chlorella. When the self-polishing component content exceeded 20 wt%, the coatings exhibited quasi-static antifouling effect for up to 180 days and dynamic antifouling effect for up to 8 cycles (320 days) under real marine conditions. Meanwhile, the coatings demonstrated a substrate adhesion strength of 4.8 MPa, a release rate of antifoulants below 1.0 mu g/cm2.day-1, and an abrasion rate of approximately 11.25 mu m/month. Finally, the practical antifouling performance was validated through a 12 months field test on a ship in marine conditions, confirming their considerable potential to replace conventional solvent-based antifouling technologies. This study therefore offers an alternative prototype for the development of waterborne, environmentally friendly marine antifouling coatings.

Abstract Background The blood-brain barrier (BBB) is increasingly recognized as an active immunoregulatory interface that responds dynamically to systemic inflammation. As intestinal inflammation can influence brain homeostasis through the gut-brain axis, the endogenous mechanisms that preserve BBB integrity during gut-derived inflammatory stress remain poorly understood. Methods and Results We combined dextran sulfate sodium-induced colitis, fecal microbiota transplantation, aged mice, APP/PS1 mice, human Alzheimer’s disease (AD) brain tissue, single-cell RNA sequencing, in vivo BBB permeability assays, and gain- and loss-of- function approaches to investigate adaptive neurovascular responses to gut inflammation and their mechanism in maintaining BBB integrity. Intestinal inflammation induced a region- specific adaptive response characterized by increased hippocampal vascular remodeling and partial restoration of BBB integrity following the initial inflammatory insult. Single-cell transcriptomic analysis identified a transthyretin (TTR)-enriched vascular-associated microglial state accompanying these neurovascular changes. Functional studies demonstrated that TTR contributes to maintaining BBB integrity by promoting endothelial homeostasis and limiting endothelial endocytosis, consistent with modulation of FcRn-associated transport pathways. This adaptive neurovascular response was progressively attenuated in aged mice and APP/PS1 mice and was accompanied by reduced vascular TTR expression in human AD brains. Conclusion These findings identify TTR as a contributor of adaptive neurovascular homeostasis during gut-derived neuroinflammation. Impairment of this homeostatic response with aging and AD may contribute to persistent BBB dysfunction and chronic neuroinflammation, highlighting neurovascular resilience as a potential therapeutic target.

Achieving nanoscale superlubricity with ionic liquids (ILs) in the absence of external fields or additives remains a major challenge in tribology. Here, we investigate the nanoscale friction of a homologous series of three borate-based ILs (denoted A4, A8, and A12) with a varying anion alkyl-chain length [A4BMB]-, [A8BMB]-, [A12BMB]-, and a common cation trioctyldodecylammonium ([N88812] +) on graphite surfaces, using AFM, in situ AFM-IR, angle-resolved XPS (AR-XPS), and nonequilibrium molecular dynamics (NEMD) simulations. Both A4 and A8 show stable superlow friction across the load range (mu approximate to 0.0032 and 0.0068, respectively). A12, however, demonstrates a frictional transition triggered by an increasing load. The friction mu approximate to 0.023, obtained at a low load, drops drastically to mu approximate to 0.0013 once the normal load exceeds similar to 30 nN (approximate to 2.4 GPa) and enters a clear superlubric state. As neither AFM-IR nor AR-XPS reveals any tribochemical transformation during this transition, it appears to be a purely physical, load-induced structural reorganization of the interfacial ion layers. Further studies show near-homogeneous cation/anion distributions in A12 at the interface, while NEMD simulations can identify load-dependent reorientation of the long anion alkyl chains that reduces interfacial locking and shear resistance. Our results show a purely mechanical unlocking pathway to nanoscale superlubricity in ILs and suggest that long-chain borate anions can be used for extreme-pressure lubrication in micro/nano electromechanical systems.

Friction control plays a vital role in soft interfacial engineering. However, surface-based regulation strategies are often limited by their modulation depth and range, while bulk regulation is constrained by the efficiency of mass and energy transfer. Achieving extremely large-span friction switching in a soft contact system throughout the entire material remains a formidable challenge. Inspired by Sphagnum moss's through-pore structures, we present a water-triggered, adaptive, and penetrative friction-switching prototype (APFP) that integrates penetrative hydration to simultaneously achieve mechanical switching and interfacial lubrication. APFP features biomimetic surface pores constructed by hydrophilic polymer brushes and lithium-stabilized interconnected channels under phase separation, enabling rapid water penetration and throughout bulk modulus switching (>1000 times), along with a significant reduction in molecular chain damping (similar to 18 times). Unlike conventional surface regulation strategies, the APFP's penetrative mechanism allows for throughout property modulation, achieving over 100 times the coefficient of friction (CoF) switch (from similar to 2.6 to similar to 0.02). As proof of concept, APFP can be fabricated into intelligent medical devices with adaptive lubrication and self-supporting mechanics, serving as sutures that reduce tissue-piercing friction, while maintaining wound shape to prevent deformation. This work establishes a paradigm for constructing novel intelligent friction-control systems and soft robotics.

Polyelectrolyte brushes (PEBs) are effective biomimetic lubricating interfaces that maintain low friction under varying loads, primarily through counterion osmotic pressure and hydration around charged polymer segments. However, the dynamic rearrangement of interfacial water in such systems remains insufficiently explored. In this work, three representative PEBs, anionic poly(3-sulfopropyl methacrylate potassium salt) (pSPMA), cationic poly([2-(methacryloyloxy)ethyl]trimethylammonium chloride) (pMETAC) and zwitterionic poly([2-(methacryloyloxy)ethyl]dimethyl-(3-sulfopropyl)ammonium hydroxide) (pSBMA), were investigated to correlate interfacial water organization with polymer conformational evolution. Progressive screening of electrostatic interactions driven by counterion association facilitated chain collapse within the anionic and cationic brushes in the presence of NaCl, accompanied by distinct changes in hydration and friction. At high ionic strength (1000mM NaCl), pSPMA showed weak dehydration while maintaining a low coefficient of friction of 0.08-0.09 over a normal load range of 10-40 nN, whereas pronounced dehydration in pMETAC coincided with a higher coefficient of friction of 0.19-0.27. Conversely, ion penetration disrupted inter- and intrachain dipole-dipole interactions within the zwitterionic brushes while strengthening the association between charged moieties and surrounding water. The resulting enhanced interfacial hydration stabilized an extended chain conformation, enabling pSBMA to achieve a low coefficient of friction of 0.09-0.10 over the same load range. These findings highlight the critical role of ion-mediated hydration evolution in coupling polymer conformation with lubrication at PEB interfaces.

Conventional homogeneous hydrogels typically face an inherent trade-off between mechanical strength and lubrication performance. Achieving high load-bearing capacity requires dense crosslinking and tight chain entanglement, which inevitably restrict water uptake and suppress the formation of effective hydration layers. Herein, inspired by the anisotropic architecture of natural ligaments, we developed a robust lubricious hydrogel material (STOC-D) through synergistic spontaneous tensile orientation under confinement (STOC) processing and surface dissociation modification. The STOC process generates highly aligned polymer chains and densely packed microcrystalline domains that serve as robust physical crosslinks, effectively restricting chain slippage and crack propagation. This yields exceptional mechanical properties, including a tensile strength of 54.5 MPa, an elastic modulus of 62.7 MPa, and a tear energy of 25.7 kJ m-2. Subsequent surface dissociation creates a modulus gradient featuring a soft, highly hydrated outer layer rich in dangling chains, which enables rapid water infiltration and the formation of a stable hydration lubrication layer. As a result, the STOC-D hydrogel achieves ultralow coefficients of friction against both metallic and biological surfaces. Furthermore, in vitro cytotoxicity and in vivo subcutaneous implantation studies confirm its excellent biocompatibility. By successfully decoupling bulk mechanical reinforcement from surface hydration, this strategy overcomes the longstanding strength-lubrication trade-off in hydrogels, offering a promising method for load-bearing biomedical applications.

The nanoscale organization of ionic liquids (ILs) on graphitic electrodes governs interfacial transport and stability, yet whether ion mobility can drive extended interfacial layering remains insufficiently understood. Here, a structurally related series of ILs spanning approximate ion lengths from 0.64 to 2.9 nm was studied on highly oriented pyrolytic graphite to test whether chain-length-tuned mobility dictates interfacial ordering. Shortening the ions increases interfacial mobility, evidenced by a monotonic decrease in the nanoscale friction coefficient (≈0.0036 to ≈0.0019) measured by atomic force microscopy (AFM) using a sharp silicon probe, together with a reduced diffusion resistance reflected by a smaller Warburg contribution. This mobility increase transforms the interfacial morphology from thicker, less laterally coherent films to thinner, more ordered layered architectures. Notably, the shortest-chain IL forms terraces epitaxially registered with the graphite lattice and remains essentially unchanged under biased voltages. Consistently, colloid probe AFM force-distance plateaus and simulation-derived density oscillations indicate compact near-surface layers for the high-mobility system, whereas longer-chain ILs exhibit weaker early layering. These results support a mobility-mediated assembly mechanism in which faster interfacial reorganization enables surface-guided packing into robust layered structures, offering a practical molecular design rule for tuning IL-carbon interfaces in electrochemical systems.

Polyelectrolyte brushes (PEBs) are effective biomimetic lubricating interfaces that maintain low friction under varying loads, primarily through counterion osmotic pressure and hydration around charged polymer segments. However, the dynamic rearrangement of interfacial water in such systems remains insufficiently explored. In this work, three representative PEBs, anionic poly(3-sulfopropyl methacrylate potassium salt) (pSPMA), cationic poly([2-(methacryloyloxy)ethyl]trimethylammonium chloride) (pMETAC) and zwitterionic poly([2-(methacryloyloxy)ethyl]dimethyl-(3-sulfopropyl)ammonium hydroxide) (pSBMA), were investigated to correlate interfacial water organization with polymer conformational evolution. Progressive screening of electrostatic interactions driven by counterion association facilitated chain collapse within the anionic and cationic brushes at high ionic strength, accompanied by weakened hydration and increased coefficients of friction (0.08 and 0.19 for pSPMA and pMETAC respectively). Conversely, ion penetration disrupted inter- and intrachain dipole-dipole interactions within zwitterionic brushes while strengthening the association between charged moieties and surrounding water. The enhanced interfacial hydration stabilized extended chain conformations, allowing pSBMA to maintain a low coefficient of friction of 0.09 under the same conditions. These findings reveal that ion-mediated hydration dynamics govern the coupling between polymer conformation and lubrication at PEB interfaces.

Polyether ether ketone (PEEK) is a high-performance biomaterial valued for its bone-comparable hardness and chemical stability, yet its inherent hydrophobicity and high coefficient of friction restrict its broader clinical application. Herein, inspired by the superior mechanics and surface lubrication of natural articular cartilage, a biomimetic gradient modulus-matched PEEK composite material (SPEH) was successfully fabricated. Specifically, an interconnected porous structure was first created on the PEEK surface through sulfonation treatment, and the hydrogel precursor solution was then infused into the pores and crosslinked under ultraviolet irradiation, forming a highly entangled hydrogel layer that was tightly anchored to the substrate via covalent chemical bonding. The resulting SPEH composite demonstrated strong interfacial adhesion, as evidenced by the 90 degrees peel test. Meanwhile, it exhibited significantly enhanced surface hydrophilicity, a cartilage-mimetic elastic modulus, and superior tribological performance. The ultralow friction coefficient (COF < 0.080) and outstanding wear resistance of the composite could be attributed to the formation of a stable hydration film at the sliding interface, which effectively reduced direct solid-solid contact and frictional dissipation through hydration lubrication. This strategy offers a promising pathway to broaden the application scope of PEEK in high-performance orthopedic implants.

With growing demands for multifunctional biomaterials in biomedicine and medical devices, developing novel biolubricants that combine outstanding lubricity with antibacterial properties poses a significant challenge. In this work, a ternary copolymer P(PEGMA-co-DMA-co-METAC) was molecularly engineered by integrating three functional monomers: poly(ethylene glycol) methyl ether methacrylate (PEGMA) for improved rheology, dopamine methacrylamide (DMA) for strong interfacial adhesion, and [2-(methacryloyloxy)ethyl]trimethy-lammonium chloride (METAC) to confer antibacterial activity and hydration lubrication. The copolymer exhibited macroscopic superlubricity with an ultralow friction coefficient of similar to 0.0056 and negligible wear-in period, along with potent antibacterial efficacy against Staphylococcus aureus. Molecular dynamics simulations combined with experimental analyses revealed that the synergistic interactions among these components underpin its superior performance. This molecular design overcomes the single-function limitation of conventional biolubricants and provides a promising strategy for biomedical applications such as medical devices and artificial joints by simultaneously reducing friction and preventing infection, demonstrating both theoretical significance and clinical relevance.

Renal ischemia-reperfusion (IR) injury is a major cause of acute kidney injury (AKI), with limited specific therapies. Recombinant human brain natriuretic peptide (rhBNP) shows potential renal protective effects, but its role and mechanism in IR-induced AKI is unclear. The present study showed rhBNP improved renal function recovery and reduced AKI progression in ICU patients. In rat IR models, rhBNP alleviated tubular injury and enhanced kidney function. Selenocysteine lyase (SCLY), an enzyme critical for selenium recycling and selenoprotein synthesis, was identified as the hub gene associated with rhBNP treatment by transcriptome sequencing. rhBNP treatment markedly upregulated the expression of SCLY in rat kidneys with elevated selenium levels. rhBNP also inhibited ferroptosis and apoptosis in the kidney, which was significantly reversed by the knockdown of SCLY. SCLY silencing blocked the protective effect of rhBNP on human HK2 cells subjected to CCCP-R (carbonyl cyanide 3-chlorophenylhydrazone induced ATP depletion-repletion), while SCLY overexpression enhanced it. rhBNP modulated SCLY expression likely through inhibiting the binding of active GTPase RhoA to SCLY protein. In conclusion, rhBNP prevented IR-induced AKI through inhibiting ferroptosis by upregulating SCLY level and promoting selenium recycling, presenting a potentially new target for AKI treatment.

Renal fibrosis is the terminal pathological manifestation of most chronic kidney diseases (CKDs). Inhibitors targeting phosphodiesterase 5 (PDE5) have been used to treat erectile dysfunction and pulmonary arterial hypertension by increasing cGMP levels and activating the cGMP/PKG signaling pathway. Studies have shown that PDE5 inhibitors can attenuate the progression of CKD, although the underlying mechanisms remain unclear. LW1646 is a newly identified inhibitor with higher specificity and potency against PDE5. This study aims to investigate the therapeutic effects of LW1646 on renal fibrosis and its underlying mechanisms. In vitro, pro-fibrotic response in HK2 cells was induced by TGF-β1 and intervened with LW1646. In vivo, renal interstitial fibrosis model was established by unilateral ureteral obstruction for 7 days (7UUO) in Pde5a-/- mice. mRNA expression level of Pde5a was analyzed by qPCR. Western blot was used to assess changes in fibrosis markers, endoplasmic reticulum stress indicators, mitochondrial homeostasis metrics, and components of mitochondrial-associated membranes (MAM). Mitochondrial membrane potential (MMP) and reactive oxygen species were evaluated using flow cytometry, fluorescent imaging was employed to visualize mitochondrial networks, accumulation of mitochondrial calcium (mtCa2+) and formation of MAM. Histological assessments of renal fibrosis were performed using H&E staining and Masson's trichrome staining. Morphology of mitochondria and ER and mitochondria-ER contact in kidney cortex were investigated by transmission electron microscope (TEM). mRNA expression level of Pde5a was elevated in renal cortex in 7UUO-induced kidney fibrosis mice. Expression of fibrosis markers and endoplasmic reticulum stress indicators were markedly upregulated both in vitro and in vivo. Meanwhile, mitochondrial biogenesis was inhibited, which was accompanied by increased oxidative stress, decreased MMP and augmented mitochondrial fission. MAMs formation and mtCa2+ level were enhanced. LW1646 significantly prevented development of fibrosis in mice with 7UUO and exhibited a more pronounced effect than sildenafil. Pde5a knockout was associated with alleviated fibrosis in mice. LW1646 or Pde5a knockout attenuated ER stress and altered mitochondrial homeostasis in fibrotic kidneys and HK2 cells exhibiting pro-fibrotic responses. Our data demonstrated that LW1646 ameliorated renal fibrosis likely through inhibiting ER stress and maintaining mitochondrial homeostasis. Mechanistically, activation of cGPM/PKG pathway by LW1646 or Pde5a knockout conferred mitochondrial protection by inhibiting the formation of MAMs, thereby reducing mtCa2+ overload and alleviating renal fibrosis.

To minimize friction when silicone-based medical devices interact with soft tissues, coating their hydrophobic surfaces with lubricants has become a widely adopted method. In this study, a vesicle-like polysaccharide derivative biolubricant (HPC-PSBMA) is synthesized by combining hydrophilic monomers with hydroxypropyl cellulose (HPC) as the main chain. HPC-PSBMA exhibits good dispersibility in water, and it can be adsorbed onto the surface of silicone rubber. By integrating molecular dynamics simulations with experimental data, the adsorption and film-forming mechanisms are uncovered. Furthermore, HPC-PSBMA showed a lower coefficient of friction (COF similar to 0.02) on the surface of urinary catheters when compared with commercially available lubricants (COF similar to 0.05). Consequently, this work offers a novel approach to improving surface lubrication of hydrophobic medical devices with broad potential applications.