Tough hydrogels that are capable of efficient mechanical energy dissipation and withstanding large strains have potential applications in diverse areas. However, most reported fabrication strategies are performed in multiple steps with long-time UV irradiation or heating at high temperatures, limiting their biological and industrial applications. Hydrogels formed with a single pair of mechanisms are unstable in harsh conditions. Here we report a one-step, biocompatible, straightforward and general strategy to prepare tough soft hydrogels in a few tens of seconds under mild conditions. With a multimechanism design, the network structures remarkably improve the mechanical properties of hydrogels and maintain their high toughness in various environments. The broad compatibility of the proposed method with a spectrum of printing technologies makes it suitable for potential applications requiring high-resolution patterns/structures. This strategy opens horizons to inspire the design and application of high-performance hydrogels in fields of material chemistry, tissue engineering, and flexible electronics.Determining nanoscale protein distribution via Photoactivated Localization Microscopy (PALM) mandates precise knowledge of the applied fluorophore's blinking properties to counteract overcounting artifacts that distort the resulting biomolecular distributions. Here, we present a readily applicable methodology to determine, optimize and quantitatively account for the blinking behavior of any PALM-compatible fluorophore. Using a custom-designed platform, we reveal complex blinking of two photoswitchable fluorescence proteins (PS-CFP2 and mEOS3.2) and two photoactivatable organic fluorophores (PA Janelia Fluor 549 and Abberior CAGE 635) with blinking cycles on time scales of several seconds. TI17 cell line Incorporating such detailed information in our simulation-based analysis package allows for robust evaluation of molecular clustering based on individually recorded single molecule localization maps.Antagonism or agonism of the glucose-dependent insulinotropic polypeptide (GIP) receptor (GIPR) prevents weight gain and leads to dramatic weight loss in combination with glucagon-like peptide-1 receptor agonists in preclinical models. Based on the genetic evidence supporting GIPR antagonism, we previously developed a mouse anti-murine GIPR antibody (muGIPR-Ab) that protected diet-induced obese (DIO) mice against body weight gain and improved multiple metabolic parameters. This work reconciles the similar preclinical body weight effects of GIPR antagonists and agonists in vivo, and here we show that chronic GIPR agonism desensitizes GIPR activity in primary adipocytes, both differentiated in vitro and adipose tissue in vivo, and functions like a GIPR antagonist. Additionally, GIPR activity in adipocytes is partially responsible for muGIPR-Ab to prevent weight gain in DIO mice, demonstrating a role of adipocyte GIPR in the regulation of adiposity in vivo.Cellular senescence is a known driver of carcinogenesis and age-related diseases, yet senescence is required for various physiological processes. However, the mechanisms and factors that control the negative effects of senescence while retaining its benefits are still elusive. Here, we show that the rasGAP SH3-binding protein 1 (G3BP1) is required for the activation of the senescent-associated secretory phenotype (SASP). During senescence, G3BP1 achieves this effect by promoting the association of the cyclic GMP-AMP synthase (cGAS) with cytosolic chromatin fragments. In turn, G3BP1, through cGAS, activates the NF-κB and STAT3 pathways, promoting SASP expression and secretion. G3BP1 depletion or pharmacological inhibition impairs the cGAS-pathway preventing the expression of SASP factors without affecting cell commitment to senescence. These SASPless senescent cells impair senescence-mediated growth of cancer cells in vitro and tumor growth in vivo. Our data reveal that G3BP1 is required for SASP expression and that SASP secretion is a primary mediator of senescence-associated tumor growth.BACKGROUND As one of the crucial causes leading to cardiovascular disease, atherosclerosis (AS) develops in association with the dysfunction of vascular smooth muscle cells (VSMCs). However, the associated mechanism of the proliferation and migration in VSMCs requires further elucidation. MATERIAL AND METHODS Human VSMCs and ApoE-knockout (ApoE-/-) mice were used to establish AS cell and animal models, respectively. Expression levels of miR-188-3p and fibroblast growth factor 1 (FGF1) mRNA were detected using quantitative reverse transcription-polymerase chain reaction (qRT-PCR). Western blot was used to assess FGF1 protein expression. The proliferation, migration, and apoptosis of the cells were determined using MTT, BrdU, and Transwell assays, as well as flow cytometry analysis. The interaction between miR-188-3p and FGF1 was validated using dual-luciferase reporter gene assay, qRT-PCR, and Western blot analysis. RESULTS MiR-188-3p was found to be significantly decreased in the serum of AS patients and ApoE-/- mice as well as VSMCs of ApoE-/- mice and human VSMCs treated with oxidized low-density lipoprotein. MiR-188-3p repressed the proliferation and migration of VSMCs but promoted apoptosis of VSMCs. The binding site between miR-188-3p and 3' untranslated region (3'-UTR) of FGF1 was identified, and FGF1 was verified as a target gene of miR-188-3p. Restoration of FGF1 reversed the effects of miR-188-3p on VSMCs. CONCLUSIONS MiR-188-3p suppresses the proliferation and migration of VSMCs and induces their apoptosis through targeting FGF1.BACKGROUND We present the possibility of successful peritoneal dialysis (PD) treatment in acute kidney injury (AKI) patients with multiple comorbidities. CASE REPORT A 60-year-old woman with chronic kidney disease (CKD, stage G3b), liver cirrhosis (Child-Pugh class A score), and thrombocytopenia developed AKI due to urosepsis. Laboratory tests showed serum creatinine 430.5 µmol/L, urea 44.0 mmol/L, potassium 5.7 mmol/L, C-reactive protein 208 mg/L, procalcitonin 8 ng/mL, platelets 14×10⁹/L, hemoglobin 5.83 mmol/L, and albumin 30 g/L. Due to hemodynamic instability with profound hypotension and the potentially high bleeding risk when doing central venous catheter insertion or using anticoagulants, PD was selected as the AKI treatment. The PD catheter was implanted by the surgical method after the transfusion of platelet concentrate. Automated PD in tidal mode was implemented using 1.5% and 2.3% glucose basic inflow volume 1200 mL and a tidal volume of 700 mL. Effective dialysis with ultrafiltration up to 1200 mL/day was achieved.