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With growing interest in flexible and wearable devices, the demand for nature-inspired soft smart materials, especially intelligent hydrogels with multiple perceptions toward external strain and temperatures to mimic the human skin, is on the rise. However, simultaneous achievement of intelligent hydrogels with skin-compatible performances, including good transparency, appropriate mechanical properties, autonomous self-healing ability, multiple mechanical/ thermoresponsiveness, and retaining flexibility at subzero temperatures, is still challenging and thus limits their application as skinlike devices.Here, conductive nanocomposite hydrogels (NC gels) were delicately designed and prepared via gelation of oligo(ethylene glycol) methacrylate (OEGMA)-based monomers in a glycerol−water cosolvent, where inorganic clay served as the physical cross-linker and provided conductive ions. The resultant NC gels exhibited good conductivity (∼3.32 × 10 −4 S cm −1 , akin to biological muscle tissue) and an autonomously self-healing capacity (healing efficiency reached 84.8%). Additionally, such NC gels displayed excellent flexibility and responded well to multiple strain/temperature external stimuli and subtle human motions in a wide temperature range (from −20 to 45 °C). These distinguished properties would endow such NC gels significant applications in fields of biosensors, human−machine interfaces, and soft robotics.

The podocyte functions as a glomerular filtration barrier. Autophagy of postmitotic cells is an important protective mechanism that is essential for maintaining the homeostasis of podocytes. Exploring an in vivo rat model of passive Heymann nephritis and an in vitro model of puromycin amino nucleotide (PAN)-cultured podocytes, we examined the specific mechanisms underlying changing autophagy levels and podocyte injury. In the passive Heymann nephritis model rats, the mammalian target-of-rapamycin (mTOR) levels were upregulated in injured podocytes while autophagy was inhibited. In PAN-treated podocytes, mTOR lowered the level of autophagy through the mTOR-ULK1 pathway resulting in damaged podocytes. Rapamycin treatment of these cells reduced podocyte injury by raising the levels of autophagy. These in vivo and in vitro experiments demonstrate that podocyte injury is associated with changes in autophagy levels, and that rapamycin can reduce podocyte injury by increasing autophagy levels via inhibition of the mTOR-ULK1 pathway. These results provide an important theoretical basis for future treatment of diseases involving podocyte injury.

Hydrogels are an important class of soft materials with high water retention that exhibit intelligent and elastic properties and have promising applications in the fields of biomaterials, soft machines, and artificial tissue. However, the low mechanical strength and limited functions of traditional chemically cross-linked hydrogels restrict their further applications. Natural materials that consist of stiff and soft components exhibit high mechanical strength and functionality. Among artificial soft materials, nanocomposite hydrogels are analogous to these natural materials because of the synergistic effects of nanoparticle (NP) polymers in hydrogels construction. In this article, the structural design and properties of nanocomposite hydrogels are summarized. Furthermore, along with the development of nanocomposite hydrogel-based devices, the shaping and potential applications of hydrogel devices in recent years are highlighted. The influence of the interactions between NPs and polymers on the dispersion as well as the structural stability of nanocomposite hydrogels is discussed, and the novel stimuli-responsive properties induced by the synergies between functional NPs and polymeric networks are reviewed. Finally, recent progress in the preparation and applications of nanocomposite hydrogels is highlighted. Interest in this field is growing, and the future and prospects of nanocomposite hydrogels are also reviewed.

The miRNAs in urinary sediment are easy to obtain, which provides a new approach to searching for non-invasive biomarkers of IgA nephropathy (IgAN). Compared with normal controls (n = 3), 214 different miRNAs in the urinary sediment of IgAN (n = 9) were found by miRNA chip assay. By quantitative PCR analysis, miR-25-3p, miR-144-3p and miR-486-5p were confirmed to be significantly higher in IgAN (n = 93) than in the normal group (n = 82) or disease control (n = 40). These three miRNAs had good specificity and sensitivity for the diagnosis of IgAN by receiver operating characteristic curve analysis, in which the AUC value of miR-486-5p was the largest at 0.935. Urinary sediment miR-25-3p, miR-144-3p and miR-486-5p were demonstrated to be mainly derived from urinary erythrocytes, which were separated by CD235a magnetic beads. The increased expression of urinary erythrocyte miRNAs in IgAN patients was not associated with those in the blood erythrocytes. In addition, urinary supernatant microvesicles of miR-144-3p and miR-486-5p in the IgAN group were also significantly increased. This study showed that the miR-25-3p, miR-144-3p and miR-486-5p in urinary sediment were mainly derived from urinary erythrocytes, which could be non-invasive candidate biomarkers for IgA nephropathy.

Keloid, a common dermal fibroproliferative disorder, is benign skin tumors characterized by the aggressive fibroblasts proliferation and excessive accumulation of extracellular matrix. However, common therapeutic approaches of keloid have limited effectiveness, emphasizing the momentousness of developing innovative mechanisms and therapeutic strategies. Epigenetics, representing the potential link of complex interactions between genetics and external risk factors, is currently under intense scrutiny. Accumulating evidence has demonstrated that multiple diverse and reversible epigenetic modifications, represented by DNA methylation, histone modification, and non-coding RNAs (ncRNAs), play a critical role in gene regulation and downstream fibroblastic function in keloid. Importantly, abnormal epigenetic modification manipulates multiple behaviors of keloid-derived fibroblasts, which served as the main cellular components in keloid skin tissue, including proliferation, migration, apoptosis, and differentiation. Here, we have reviewed and summarized the present available clinical and experimental studies to deeply investigate the expression profiles and clarify the mechanisms of epigenetic modification in the progression of keloid, mainly including DNA methylation, histone modification, and ncRNAs (miRNA, lncRNA, and circRNA). Besides, we also provide the challenges and future perspectives associated with epigenetics modification in keloid. Deciphering the complicated epigenetic modification in keloid is hopeful to bring novel insights into the pathogenesis etiology and diagnostic/therapeutic targets in keloid, laying a foundation for optimal keloid ending.

Sodium-dependent dicarboxylate transporters (NaDC) include low-affinity NaDC1 and high-affinity NaDC3. Despite high similarities structurally and functionally, both are localized to opposite surfaces of renal tubular cells. The molecular mechanisms and localization signals leading to this polarized distribution remain unknown. In this study, distribution of NaDC3 in human kidney tissue was firstly observed by immunohistochemistry and immunofluorescence. Then, EGFP-fused wild-type, NH2- and COOH-terminal deletion and point mutants of NaDC3, and chimera between NaDC3 and NaDC1, were generated and transfected into polarized renal cells lines, LLC-PK1 and MDCK. Their subcellular localizations were analyzed by laser confocal microscopy. Immunolocalization results revealed that NaDC3 was expressed at basolateral membrane of human renal proximal tubular epithelia. Confocal examinations showed that wild-type NaDC3 was targeted to the basolateral membrane of MDCK and LLC-PK1. Deletion mutations indicated that the basolateral targeting signal of NaDC3 located within a short sequence AKKVWSARR of its amino-terminal cytoplasmic domain. Addition of this sequence could redirect apical NaDC1 to the basolateral membrane of LLC-PK1. Point mutagenesis revealed that mutation of either of two hydrophobic amino acids V and W in this short sequence largely redirected NaDC3 to both apical and basolateral surfaces of LLC-PK, indicating that the two hydrophobic amino acids are critical for the basolateral targeting of NaDC3. Our studies provide direct evidence of the localization of NaDC3 at the basolateral membrane of human renal proximal tubule cells and identify a di-hydrophobic amino acid motif VW as basolateral localization signal in the N-terminal cytoplasmic domain of NaDC3.

Hydrogel optical light-guides have received substantial interest for applications such as deep-tissue biosensors, optogenetic stimulation and photomedicine due to their biocompatibility, (micro)structure control and tissue-like Young's modulus. However, despite recent developments, the large-scale fabrication with a continuous synthetic methodology, which could produce core-sheath hydrogel fibers with the desired optical and mechanical properties suitable for deep-tissue applications has yet to be achieved. In this study, we report a versatile concept of integrated light-triggered dynamic wet spinning (ILDWS), which capable of continuously producing core-sheath hydrogel optical fibers with tunable fiber diameters, mechanical and optical-propagation properties. Furthermore, this concept also exhibited versatility for various kinds of core-sheath functional fibers. The wet spinning synthetic procedure and fabrication process were optimized with the rational design of the core/sheath material interface compatibility [core = poly(ethylene glycol diacrylate-co-acrylamide); sheath = Ca-alginate], optical transparency, refractive index and spinning solution viscosity. The resulting hydrogel optical fibers exhibited desirable low optical attenuation (0.18 ± 0.01 dB cm−1 with 650 nm laser light), excellent biocompatibility and tissue-like Young's modulus (< 2.60 MPa). The optical-waveguide hydrogel fibers (OWHFs) were successfully employed for deep-tissue cancer therapy and brain optogenetic stimulation, confirming that they could serve as an efficient versatile tool for diverse deep-tissue therapy and brain optogenetic applications.