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Micro-cracks inevitably form in cement concrete structures, presenting substantial risks to safety, service life, and eco-efficiency. Developing high-intrinsic self-healing concrete offers a promising approach to promptly alleviate issues caused by microcracks. These issues include rapid matrix degradation and frequent maintenance requirements. This paper reviews recent advancements in autogenous self-healing concrete technologies. It discusses their classification, efficiency, and mechanisms based on concrete component categorisation, normalisation methods, and statistical analyses. Results indicate that intrinsic self-healing relies heavily on the physical and chemical properties of the concrete, external water, and crack dimensions. Several methods for adjusting concrete component parameters, types, and proportions enhance self-healing capability. In addition, minimising crack width proves beneficial. Enhancement mechanisms of each technology demonstrate significant diversity and complexity due to the intricate self-healing process. They primarily fall into three categories: mechanical mechanisms (microparticle accumulation, fibre bridging), physical mechanisms (swelling, ion adsorption, matrix porosity, roughness, crack width), and chemical mechanisms (improved hydration reaction, expansion product generation, precipitation reaction mechanisms, complexation-precipitation and chelation reactions). [ABSTRACT FROM AUTHOR]

Pulmonary fibrosis is a progressive and fatal fibrotic lung disease and associated with a high mortality rate. In the study, the prevention and treatment effects of fibroblast growth factor-21 (FGF-21) in bleomycin (BLM)-induced pulmonary fibrosis were investigated in vivo and vitro. In the prevention of pulmonary fibrosis studies, the results showed that interdict of FGF-21 could reduce the related gene and protein expression levels of pulmonary fibrosis. In addition, FGF-21 significantly reduced both the aggregation of inflammatory cells and deposition of collagen in the lung by histopathology. In therapy of pulmonary fibrosis studies, the results indicated that treatment with FGF-21 resulted in an amelioration of the pulmonary fibrosis in mice with reductions of the pathological score, collagen deposition and transforming growth factor (TGF)-β and α-smooth muscle actin (α-SMA) expressions in the lung tissues at fibrotic stage, and late administration was also able to reduce the degree of pulmonary fibrosis and even better than these in the prevention group. Furthermore, BLM-induced THP-1 macrophage model was verified using FGF-21; the result showed that FGF-21 decreased the related gene expression level of pulmonary fibrosis. FGF-21 may have preventive and therapeutic effects on BLM-induced pulmonary fibrosis via inhibiting myofibroblast differentiation and inflammatory. Thus, FGF-21 represents a potential drug for the prevention and treatment of pulmonary fibrosis. [ABSTRACT FROM AUTHOR]

Ultra-high-performance concrete (UHPC) has gained significant attention as a construction material owing to its exceptional mechanical properties and durability. Steel fibers are widely utilized as a reinforcement material for UHPC. Achieving excellent bond and tensile performances is considered to be a predominant issue for the utilization of steel fiber reinforcement. This comprehensive review presents recent research progress on the bond and tensile properties of steel-fiber-reinforced UHPC. First, an overview of the experimental methods for evaluating pullout and tensile performance is provided. Subsequently, the factors influencing these properties are discussed in detail. The review then comprehensively examines several analytical models for steel-fiber-reinforced UHPC, ranging from traditional approaches to innovative methods such as artificial neural network models, genetic algorithms, deep learning methods, inverse analysis, and micromechanical damage models. Furthermore, the correlations between pullout behavior, tensile performance, and flexural strength are explored in detail. Finally, the review addresses essential considerations and summarizes various modification techniques for improving the pullout and tensile performances, including physical and chemical methods of modifying the steel fiber surface and UHPC matrix. This review serves as a valuable reference for researchers and engineers in relevant fields, promoting further research and application of steel fiber-reinforced UHPC. [ABSTRACT FROM AUTHOR]

Microbial-mineral interaction has a broad application prospect in the field of environmental remediation of organic pollutants. However, the disadvantages of long repair cycle and low repair rate limit its industrial application. In this study, natural hematite was used as an auxiliary material for soil remediation in a bio-electrochemical system. It was found that the power density of soil microbial fuel cell (SMFC) system composed of 2.0 mm hematite was 2.889 mW/m2, which is 2.7 times compared with the blank group (1.068 mW/m2) in the particle size optimization experiment. A similarly increased power density (1.068 to 2.467 mW/m2) was observed when the hematite content changed from 0 to 20% in the concentration optimization experiment. Under 20% and 2.0-mm hematite condition, the phenol removal rate was closed to 99% after 7 days, which is 1.9-folds compared with blank control (53%). These results suggest that addition of hematite enhances soil porosity and conductivity, and increases the number of electron acceptors in soil. These findings inspire that this economic and abundant natural mineral is expected to be a potential auxiliary material in the field of soil organic pollutant purification, and expand the understanding of interactions between hematite and microorganisms in nature. [ABSTRACT FROM AUTHOR]

The soil microbial fuel cell (SMFC) has been widely used for soil remediation for its low cost and being eco-friendly. But low degradation efficiency and high mass transfer resistance limit its performance. This study constructed a solar cell-soil microbial fuel cell (SC-SMFC) with different voltages, which use clean energy to improve system performance. At different voltages, 2.0-V system showed the best performance and the maximum output power increased by 330% compared with SMFC. Moreover, 2.0-V SC-SMFC showed the fastest phenol degradation rate of 14 μg·mL−1·d−1 at the concentration of 80 μg/mL, which was twice of SMFC. Further increasing the concentration to 320 μg/mL, the system showed extremely high concentration limit and degraded 90% within 19 days. Under this condition, SC-SMFC still showed excellent cycle stability, with the third-round degrading 90% phenol in 13 days. Finally, electrochemical impedance spectroscopy (EIS) mechanism study showed that solar cells can accelerate microbial metabolic process and reduce the internal resistance, in which the 2.0-V system was only 87% of SMFC. In conclusion, SC-SMFC provides a green, low-cost, and convenient method for in situ soil remediation in the future. [ABSTRACT FROM AUTHOR]

As a novel technique with a wide range of applications, microbial fuel cell (MFC) could simultaneously remove organic contaminants and heavy metals in complex wastewater, despite striking differences in physicochemical properties of these contaminant. But its wastewater treatment efficiency is restricted by its lower generation performance. However, approaches for the modification of MFCs' cathode with appropriate catalyst could effectively overcome this limitation. Herein, a new-type efficient cathode catalyst was invented through modifying natural molybdenite via one-step oxidation method. In this case, molybdenite had many changes in morphology (wave-shaped bending, fragmentation and decrescent diameter) during oxidation modification process, and oxidation-modified molybdenite could provide much more active sites for the cathode. After applying this novel cathode catalyst, the electric generation capacity of MFC system increased by 5.08 times, and its simultaneous degradation efficiency of methyl blue (MB) and Cr (VI) increased by 3.35 times (compared with graphite cathode MFC). This study provides a novel low-carbon and environmentally friendly way to prepare high efficiency cathode catalyst materials and provides a new idea of simultaneous purification for organic and metallic pollutants from complex wastewater. [ABSTRACT FROM AUTHOR]

Fibroblast growth factor-21 (FGF-21) performs a wide range of biological functions in organisms. Here, we report for the first time that FGF-21 suppresses thrombus formation with no notable risk of bleeding. Prophylactic and therapeutic administration of FGF-21 significantly improved the degree of vascular stenosis and reduced the thrombus area, volume and burden. We determined the antithrombotic mechanism of FGF-21, demonstrating that FGF-21 exhibits an anticoagulant effect by inhibiting the expression and activity of factor VII (FVII). FGF-21 exerts an antiplatelet effect by inhibiting platelet activation. FGF-21 enhances fibrinolysis by promoting tissue plasminogen activator (tPA) expression and activation, while inhibiting plasminogen activator inhibitor 1 (PAI-1) expression and activation. We further found that FGF-21 mediated the expression and activation of tPA and PAI-1 by regulating the ERK1/2 and TGF-β/Smad2 pathways, respectively. In addition, we found that FGF-21 inhibits the expression of inflammatory factors in thrombosis by regulating the NF-κB pathway. [ABSTRACT FROM AUTHOR]

In recent decades when biological agents have flourished, a part of patients suffering from inflammatory bowel disease (IBD) have received the treatment of tumor necrosis factor inhibitors or IL-1 antibodies. This study aims to investigate the anti-colitis effects of bispecific antibody (FL-BsAb1/17) targeting IL-1β and IL-17A comparing with TNF-α soluble receptor medicine etanercept. IBD model in mice was established by drinking 3% DSS (dextran sulfate sodium salt). On the first day of drinking DSS, treatments with etanercept (5 mg/kg) or different doses of FL-BsAb1/17 (1 mg/kg, 5 mg/kg, and 10 mg/kg) were started by intraperitoneal injection every other day. The results demonstrated that FL-BsAb1/17 treatment was more effective than etanercept at the same dose (5 mg/kg) in relieving the typical symptom of ulcerative colitis induced by DSS (such as the severity score and intestinal shortening), and down-regulating the expression of inflammatory factors (IL-17A, IL-6, IL-12, IL-22, IL-1β, IL-23, TNF-α) in the serum and colon. FL-BsAb1/17 could also reduce the degree of intestinal fibrosis. The same dose of FL-BsAb1/17 (5 mg/kg) performed better than etanercept in down-regulating MDA and up-regulating SOD (superoxide dismutase), CAT (catalase), and T-AOC (total antioxidant capacity) in serum. Both FL-BsAb1/17 and etanercept could reduce the transcription of Bax and increase the transcription of Bcl-2 and slow down apoptosis in colitis colon tissue. We conclude that the blocking of IL-1β and IL-17A can inhibit DSS-induced ulcerative colitis and FL-BsAb1/17 may have potential to become a new dual-target candidate for colitis treatment. [ABSTRACT FROM AUTHOR]

Currently, insulin is commonly used in the clinical management of canine diabetes. However, it must be injected preprandially causing much inconvenience to the owners. Therefore, the development of long-acting hypoglycemic agents has attracted much attention in the scientific community. This study aimed to investigate the long-acting hypoglycemic effect of canine fibroblast growth factor 21 (cFGF-21) in diabetic dogs. Diabetic dogs were administered with cFGF-21, polyethylene glycol-modified cFGF-21 (PEG-cFGF-21), or insulin once a day, once every 2, 3, or 4 days subcutaneously. The results showed that cFGF-21 and PEG-cFGF-21 maintained blood glucose comparable to normal levels for 2 and 3 days respectively while insulin maintained the blood glucose for only 2 h after a single injection. After treatment with cFGF-21, oral glucose tolerance test (OGTT) was significantly improved with glycosylated hemoglobin (HbA1c) close to the normal levels. In addition, cFGF-21 significantly repaired islet β cells, increased insulin content, and protected the pancreas from streptozotocin-induced injury. Furthermore, cFGF-21 exhibited both antioxidant and anti-inflammatory properties in the pancreas. We conclude, therefore, that cFGF-21 and PEG-cFGF-21 can maintain blood glucose comparable to normal levels for 2 and 3 days respectively after a single dose. The long-acting efficacy of cFGF-21 can be attributed to improvement in oxidative stress and the reduction of inflammation in the pancreas. [ABSTRACT FROM AUTHOR]

Rheumatoid arthritis, a chronic degenerative autoimmune disease is hallmarked by tenacious inflammation of synovial membranes causing cartilage destruction and bone erosion. The search for effective therapies to mitigate its degenerative conditions remains partly elusive. Fibroblast growth factor 21 (FGF21) is known to modulate inflammation, playing a significant role in immune-mediated diseases such as rheumatoid arthritis. Here, we histopathologically evaluate the therapeutic efficacy of FGF21 in collagen-induced arthritis (CIA) mice. CIA mice were subcutaneously treated with FGF21 (3 mg/kg) for three consecutive weeks. Arthritic severity was scored followed by histopathological evaluation of the joints and immunohistochemistry using rabbit ant-cathepsin K, IL-10, MMP1, and 3 antibodies. Our data revealed that FGF21 significantly mitigated the severity of arthritis. Histopathologically, the articular structure was considerably enhanced by FGF21 through the reduction in the expression of cathepsin K and MMP3 whiles upregulating the expression of IL-10. Taken together, our findings suggest that FGF21 preserves the integrity of the articular structure thereby preventing cartilage and bone destruction in CIA mice. FGF21, therefore, has therapeutic prospects in the treatment of RA. [ABSTRACT FROM AUTHOR]

Fibroblast growth factor-21 (FGF21) is a member of the family of fibroblast growth factors (FGFs). FGF21 (synthesized by many organs) has been studied extensively for its role in the regulation of energy homeostasis. FGF21 came into the spotlight after its beneficial metabolic effects in reducing blood glucose, and weight in obesity were identified. Since then, FGF21 has been extensively exploited for therapeutic purposes and clinical applications with significant achievements. Its therapeutic roles in diabetes, obesity, cardiovascular diseases, fibrosis, cancer and aging among others have been studied over the last decade with significant strides making it a promising candidate for the management of chronic diseases. Here we review the therapeutic prospects of FGF21 with emphasis on the management of chronic diseases, and breakthroughs in its shortfalls. The future of FGF21 as a therapeutic agent is auspicious and will help revolutionize the world of medicine. [ABSTRACT FROM AUTHOR]

βKlotho as the major role is a necessary auxiliary protein when fibroblast growth factor 21 (FGF21) binds FGF21 receptors (FGFR) for activating intracellular signaling pathways that ultimately generate biological effects. To achieve the aim of high throughput screening of FGF21 analogues, we established 3T3-L1-βKlotho cells that could stably express βklotho protein. The glucose uptake, expression of GLUT1 mRNA and activation of FGF signaling molecules ERK1/2 phosphorylation were detected by GOD-POD assay, real-time PCR analysis and western blotting assay in 3T3-L1-βKlotho cells and 3T3-L1 adipocytes, respectively. The results showed that FGF21 increased glucose uptake significantly in a dose-dependent and time-dependent manner in 3T3-L1-βKlotho cells. 3T3-L1-βKlotho cells stimulated with FGF21 up-regulated the transcriptional levels of GLUT1 mRNA obviously. FGF21 activated the FGF signaling molecules ERK1/2 in 3T3-L1-βKlotho cells. In addition, the same results were obtained in 3T3-L1 adipocytes. Furthermore, FGF21-stimulated elevation of glucose uptake, GLUT1 mRNA transcription and the phosphorylation of ERK1/2 were dramatically attenuated by pretreatment of cells with FGFR specific inhibitor SU5402 in 3T3-L1-βKlotho cells. This study demonstrated that the cell model could be applied to high throughput screen FGF21 analogues. [ABSTRACT FROM AUTHOR]

The aim of this study is to evaluate the role of fibroblast growth factor 21 (FGF21) in nonalcoholic fatty liver disease (NAFLD) and seek to determine if its therapeutic effect is through induction of autophagy. In this research, Monosodium L-glutamate (MSG)-induced obese mice or normal lean mice were treated with vehicle, Fenofibrate, and recombinant murine FGF21, respectively. After 5 weeks of treatment, metabolic parameters including body weight, blood glucose and lipid levels, hepatic and fat gene expression levels were monitored and analyzed. Also, fat-loaded HepG2 cells were treated with vehicle or recombinant murine FGF21. The expression levels of proteins associated with autophagy were detected by western blot, real-time PCR, and transmission electron microscopy (TEM). Autophagic flux was monitored by laser confocal microscopy and western blot. Results showed that FGF21 significantly reduced body weight ( P < 0.01) and serum triglyceride, improved insulin sensitivity, and reversed hepatic steatosis in the MSG model mice. In addition, FGF21 significantly increased the expression of several proteins related to autophagy both in MSG mice and fat-loaded HepG2 cells, such as microtubule associated protein 1 light chain 3, Bcl-2-interacting myosin-like coiled-coil protein-1 (Beclin-1), and autophagy-related gene 5. Furthermore, the evidence of TEM revealed an increased number of autophagosomes and lysosomes in the model cells treated with FGF21. In vitro experimental results also showed that FGF21 remarkably increased autophagic flux. Taken together, FGF21 corrects multiple metabolic parameters on NAFLD in vitro and in vivo by inducing autophagy. [ABSTRACT FROM AUTHOR]

Purpose: In this study, we explored whether treatment with FGF-21 could prevent diethylnitrosamine (DEN) induced hepatocarcinogenesis in mice.Methods& Results: Hepatoma was induced by injection of DEN every three days for 18 weeks. For the prophylactic experiment, mice were firstly injected with FGF-21 for 2 weeks, then FGF-21 was administered to the mice once daily in association with DEN injection till the end of the experiment. The hepatoma incidence of mice treated with FGF-21 was 13.3%, while the incidence of mice treated with saline was 61.5%. To understand the mechanisms, we compared the expression of βklotho (KLB) and oxidative stress level in the livers between the mice treated with FGF-21 and saline. We found that FGF-21 could suppress DEN-induced oxidative stress and up-regulate the expression of KLB in the livers. To confirm these results, we compared the expression of KLB in L02 cells stimulated with or without FGF-21. Besides, we established DEN-induced oxidative stress cell model to affirm the relationship between FGF-21 and DEN-induced oxidative stress in vitro. Results showed that FGF-21 increased the expression of KLB and diminished the DEN-induced oxidative stress in vitro in a dose dependent manner.Conclusion: Systemic administration of FGF-21 can prevent DEN-induced hepatocarcinogenesis via suppressing oxidative stress and increasing the expression of KLB. [ABSTRACT FROM AUTHOR]

FGF21 is recently discovered with pleiotropic effects on glucose and lipid metabolism. However, the potential protective effect of FGF21 against d-gal-induced injury in the liver has not been demonstrated. The aim of this study is to investigate the pathophysiological role of FGF21 on hepatic oxidative injury and apoptosis in mice induced by d-gal. The 3-month-old Kunming mice were subcutaneously injected with d-gal (180 mg kg d) for 8 weeks and administered simultaneously with FGF21 (5 or 1 mg kg d). Our results showed that the administration of FGF21 significantly alleviated histological lesion including structure damage, degeneration, and necrosis of hepatocytes induced by d-gal, and attenuated the elevation of liver injury markers, serum AST, and ALP in a dose-dependent manner. FGF21 treatment also suppressed d-gal-induced profound elevation of ROS production and oxidative stress, as evidenced by an increase of the MDA level and depletion of the intracellular GSH level in the liver, and restored the activities of antioxidant enzymes SOD, CAT, GSH-Px, and T-AOC. Moreover, FGF21 treatment increased the nuclear abundance of Nrf2 and subsequent up regulation of several antioxidant genes. Furthermore, a TUNEL assay showed that d-gal-induced apoptosis in the mouse liver was significantly inhibited by FGF21. The expression of caspase-3 was markedly inhibited by the treatment of FGF21 in the liver of d-gal-treated mice. The levels of PI3K and PBK/Akt were also largely enhanced, which in turn inactivated pro-apoptotic signaling events, restoring the balance between pro- and anti-apoptotic Bcl-2 and Bax proteins in the liver of d-gal-treated mice. In conclusion, these results suggest that FGF21 protects the mouse liver against d-gal-induced hepatocyte oxidative stress via enhancing Nrf2-mediated antioxidant capacity and apoptosis via activating PI3K/Akt pathway. [ABSTRACT FROM AUTHOR]

Fibroblast growth factor (FGF)-21 is a member of the FGF superfamily based on sequence homology. However, unlike most members of this family it does not show any mitogenic activity in all cell types tested. The objective of this study is to identify and characterize receptors for this molecule. Sequencing of the cDNA clones from 3T3-L1 adipocytes indicates that the only isoforms for FGFR-1 and 2 expressed in 3T3-L1 cells are 1IIIc and 2IIIc, respectively, suggesting that FGF-21 regulates glucose metabolism in 3T3-L1 adipocytes through FGFR-1IIIc and FGFR-2IIIc. [ABSTRACT FROM AUTHOR]