Yinhuang granule alleviates carbon tetrachloride-induced liver fibrosis in mice and its mechanism.

BACKGROUND: Liver fibrosis is a formidable global medical challenge, with no effective clinical treatment currently available. Yinhuang granule (YHG) is a proprietary Chinese medicine comprising Scutellariae Radix and Lonicerae Japonicae Flos. It is frequently used for upper respiratory tract infections, pharyngitis, as well as acute and chronic tonsillitis. AIM: To investigate the potential of YHG in alleviating carbon tetrachloride (CCl4)-induced liver fibrosis in mice. METHODS: To induce a hepatic fibrosis model in mice, this study involved intraperitoneal injections of 2 mL/kg of CCl4 twice a week for 4 wk. Meanwhile, liver fibrosis mice in the low dose of YHG (0.4 g/kg) and high dose of YHG (0.8 g/kg) groups were orally administered YHG once a day for 4 wk. Serum alanine/aspartate aminotransferase (ALT/AST) activity and liver hydroxyproline content were detected. Sirius red and Masson's trichrome staining assay were conducted. Real-time polymerase chain reaction, western-blot and enzyme-linked immunosorbent assay were conducted. Liver glutathione content, superoxide dismutase activity level, reactive oxygen species and protein carbonylation amount were detected. RESULTS: The administration of YHG ameliorated hepatocellular injury in CCl4-treated mice, as reflected by decreased serum ALT/AST activity and improved liver histological evaluation. YHG also attenuated liver fibrosis, evident through reduced liver hydroxyproline content, improvements in Sirius red and Masson's trichrome staining, and lowered serum hyaluronic acid levels. Furthermore, YHG hindered the activation of hepatic stellate cells (HSCs) and ameliorated oxidative stress injury and inflammation in liver from CCl4-treated mice. YHG prompted the nuclear accumulation of nuclear factor erythroid 2-related factor 2 (Nrf2) and upregulated the expression of Nrf2-dependent downstream antioxidant genes. In addition, YHG promoted mitochondrial biogenesis in liver from CCl4-treated mice, as demonstrated by increased liver adenosine triphosphate content, mitochondrial DNA levels, and the expression of peroxisome proliferator-activated receptor gamma coactivator 1 alpha and nuclear respiratory factor 1. CONCLUSION: YHG effectively attenuates CCl4-induced liver fibrosis in mice by inhibiting the activation of HSCs, reducing inflammation, alleviating liver oxidative stress damage through Nrf2 activation, and promoting liver mitochondrial biogenesis.

Parallel edge extraction operators on chip speed up photonic convolutional neural networks.

We experimentally establish a 3 × 3 cross-shaped micro-ring resonator (MRR) array-based photonic multiplexing architecture relying on silicon photonics to achieve parallel edge extraction operations in images for photonic convolution neural networks. The main mathematical operations involved are convolution. Precisely, a faster convolutional calculation speed of up to four times is achieved by extracting four feature maps simultaneously with the same photonic hardware's structure and power consumption, where a maximum computility of 0.742 TOPS at an energy cost of 48.6 mW and a convolution accuracy of 95.1% is achieved in an MRR array chip. In particular, our experimental results reveal that this system using parallel edge extraction operators instead of universal operators can improve the imaging recognition accuracy for CIFAR-10 dataset by 6.2% within the same computing time, reaching a maximum of 78.7%. This work presents high scalability and efficiency of parallel edge extraction chips, furnishing a novel, to the best of our knowledge, approach to boost photonic computing speed.

Helix-to-sheet transition of the Aß42 peptide revealed using an enhanced sampling strategy and Markov state model.

The self-assembly of Aß peptides into toxic oligomers and fibrils is the primary cause of Alzheimer's disease. Moreover, the conformational transition from helix to sheet is considered a crucial step in the aggregation of Aß peptides. However, the structural details of this process still remain unclear due to the heterogeneity and transient nature of the Aß peptides. In this study, we developed an enhanced sampling strategy that combines artificial neural networks (ANN) with metadynamics to explore the conformational space of the Aß42 peptides. The strategy consists of two parts: applying ANN to optimize CVs and conducting metadynamics based on the resulting CVs to sample conformations. The results showed that this strategy achieved better sampling performance in terms of the distribution of sampled conformations. The sampling efficiency is increased by 10-fold compared to our previous Hamiltonian Exchange Molecular Dynamics (MD) and by 1000-fold compared to ordinary MD. Based on the sampled conformations, we constructed a Markov state model to understand the detailed transition process. The intermediate states in this process are identified, and the connecting paths are analyzed. The conformational transitions in D23-K28 and M35-V40 are proven to be crucial for aggregation. These results are helpful in clarifying the mechanism and process of Aß42 peptide aggregation. D23-K28 and M35-V40 can be identified as potential targets for screening and designing inhibitors of Aß peptide aggregation.

Exploring the efficacy and mechanism of Glycyrrhizae Radix et Rhizoma in improving collagen-induced arthritis in mice.

ETHNOPHARMACOLOGICAL RELEVANCE: Rheumatoid arthritis (RA), a chronic auto-immune disease, will cause serious joint damage and disability. Glycyrrhizae Radix et Rhizoma (GRR) is commonly included in many anti-RA formulas used in the clinical practice in China. AIM OF THE STUDY: To elucidate the alleviation of GRR and its active compounds on RA and the possible engaged mechanism. MATERIALS AND METHODS: The clinical score, paw swelling degree and pain threshold were detected in the collagen-induced arthritis (CIA) in DBA/1 mice. The ankle joints of mice were observed by using X-Ray, hematoxylin-eosin (H&E), masson's trichrome (Masson), and safranin O and fast green (Safranin O) staining. The potential targets of GRR were predicted by network pharmacology and further verified by using enzyme-linked immunosorbent assay (ELISA) and western-blot. Real-time polymerase chain reaction (Real-time PCR) and wound healing assay were conducted in synovial MH7A cells. The interaction between active compounds and potential targets predicted by molecular docking was confirmed by using cellular thermal shift assay (CETSA). RESULTS: GRR (615 mg/kg) obviously alleviated CIA in mice. Network pharmacology implied that GRR might affect angiogenesis and inflammation, among which vascular endothelial growth factor-A (VEGF-A), tumor necrosis factor-α (TNFα), interleukin-1ß (IL-1ß), IL-6 and phosphorylated protein kinase B (AKT) might be the key targets involved in this process. GRR decreased AKT phosphorylation and reduced the elevated levels of TNFα, VEGF-A, IL-1ß and IL-6. Next, in vitro results demonstrated that glycyrrhetinic acid (GA) and isoliquiritigenin (ISL) were two active compounds that inhibited TNFα-induced synovial cell angiogenesis and inflammation. Moreover, GA and ISL actually improved RA in CIA mice. The results of molecular docking and CETSA displayed that ISL and GA might interact with TNF receptor-1 (TNFR1), toll-like receptor-4 (TLR4) and VEGF receptor-2 (VEGFR2), thereby contributing to their inhibition on angiogenesis and inflammation. CONCLUSION: GRR and two active compounds, including ISL and GA, alleviated RA via inhibiting angiogenesis and inflammation.

Research progress of traditional Chinese medicine in improving hepatic fibrosis based on inhibiting pathological angiogenesis.

Hepatic fibrosis is the formation of scar tissue in the liver. This scar tissue replaces healthy liver tissue and can lead to liver dysfunction and failure if left untreated. It is usually caused by chronic liver disease, such as hepatitis B or C, alcohol abuse, or non-alcoholic fatty liver disease. Pathological angiogenesis plays a crucial role in the development of hepatic fibrosis by promoting the growth of new blood vessels in the liver. These new vessels increase blood flow to the damaged areas of the liver, which triggers the activation of hepatic stellate cells (HSCs). HSCs are responsible for producing excess collagen and other extracellular matrix proteins that contribute to the development of fibrosis. Pathological angiogenesis plays a crucial role in the development of hepatic fibrosis by promoting the growth of new blood vessels in the liver. These new vessels increase blood flow to the damaged areas of the liver, which triggers the activation of HSCs. HSCs are responsible for producing excess collagen and other extracellular matrix proteins that contribute to the development of fibrosis. Traditional Chinese medicine (TCM) has been found to target pathological angiogenesis, thereby providing a potential treatment option for hepatic fibrosis. Several studies have demonstrated that TCM exhibits anti-angiogenic effects by inhibiting the production of pro-angiogenic factors, such as vascular endothelial growth factor and angiopoietin-2, and by reducing the proliferation of endothelial cells. Reviewing and highlighting the unique TCM recognition of treating hepatic fibrosis by targeting pathological angiogenesis may shed light on future hepatic fibrosis research.

Progress on traditional Chinese medicine in improving hepatic fibrosis through inhibiting oxidative stress.

Hepatic fibrosis is a common pathological process that occurs in the development of various chronic liver diseases into cirrhosis and liver cancer, characterized by excessive deposition of the extracellular matrix. In the past, hepatic fibrosis was thought to be a static and irreversible pathological process. In recent years, with the rapid development of molecular biology and the continuous in-depth study of the liver at the microscopic level, more and more evidence has shown that hepatic fibrosis is a dynamic and reversible process. Therefore, it is particularly important to find an effective, simple, and inexpensive method for its prevention and treatment. Traditional Chinese medicine (TCM) occupies an important position in the treatment of hepatic fibrosis due to its advantages of low adverse reactions, low cost, and multi-target effectiveness. A large number of research results have shown that TCM monomers, single herbal extracts, and TCM formulas play important roles in the prevention and treatment of hepatic fibrosis. Oxidative stress (OS) is one of the key factors in the occurrence and development of hepatic fibrosis. Therefore, this article reviews the progress in the understanding of the mechanisms of TCM monomers, single herbal extracts, and TCM formulas in preventing and treating hepatic fibrosis by inhibiting OS in recent years, in order to provide a reference and basis for drug therapy of hepatic fibrosis.

Scutellarin suppresses the metastasis of triple-negative breast cancer via targeting TNFα/TNFR2-RUNX1-triggered G-CSF expression in endothelial cells.

Triple-negative breast cancer (TNBC) is heterogeneous and aggressive, with high vascularity and frequent metastasis. We have already found natural flavonoid scutellarin (SC) suppressed spontaneous TNBC metastasis via normalizing tumor vasculature in vivo. In this study, supernatant from tumor necrosis factorα (TNFα)-treated human mammary microvascular endothelial cell (HMMEC) promoted cell migration and pseudopod formation in TNBC cells, but these phenomena were disappeared in SC-co-treated HMMEC. TNFα enhanced the expression of granulocyte colony-stimulating factor (G-CSF) and granulocyte-macrophage colony-stimulating factor (GM-CSF) in both HMMEC and human umbilical vein endothelial cell (HUVEC). G-CSF promoted TNBC migration and invasion in vitro, while G-CSF neutralization antibody and SC both inhibited TNBC metastasis in Balb/c mice. SC had no inhibition on the G-CSF-induced TNBC cell migration, but reduced G-CSF content in TNBC tumor tissues and TNFα-stimulated endothelial cells (ECs). SC restricted the nuclear translocation of runt-related transcription factor 1 (RUNX1) in TNBC tumor vessels and TNFα-treated ECs. RUNX1 was found to directly bind to the promoter of G-CSF in TNBC tumor vessels and regulated G-CSF expression. TNF receptor 2 (TNFR2) was crucial for regulating the TNFα-induced RUNX1 activation and G-CSF expression. Notably, SC hindered the interaction between TNFα and TNFR2 via binding to TNFR2. This work demonstrated that SC reduced TNBC metastasis by targeting TNFα/TNFR2-initiated RUNX1 activation and subsequent G-CSF production in TNBC-associated ECs.

A triphenylamine-based fluorescent probe with phenylboronic acid for highly selective detection of Hg2+ and CH3Hg+ in groundwater.

Mercury is a highly toxic heavy metal and it poses a serious threat to the natural environment and human health. Thus, selective detection of trace mercury (e.g. inorganic mercury and methylmercury) in the environment is critical yet challenging. Herein, we describe the rational design and facile synthesis of a new triphenylamine-based phenylboronic acid fluorescent probe (TPA-PBA) for selective detection of Hg2+ and CH3Hg+. Due to the inherent specificity of the displacement reaction between phenylboronic acid and mercury, this probe exhibits exceptionally high selectivity towards Hg2+/CH3Hg+ against other tested ions with ppb-level sensitivity. More importantly, the probe TPA-PBA is effective and selective in detecting Hg2+/CH3Hg+ in tap water and real-world groundwater, indicating its potential practical applications in in situ and online mercury detection in real-world scenarios. With TPA-PBA based test strips Hg2+ can be distinguished from CH3Hg+ by the naked eye. This study could accelerate the development of low-cost, highly efficient and selective fluorescent probes for rapid trace mercury detection.

Traditional Chinese medicines and natural products targeting immune cells in the treatment of metabolic-related fatty liver disease.

MAFLD stands for metabolic-related fatty liver disease, which is a prevalent liver disease affecting one-third of adults worldwide, and is strongly associated with obesity, hyperlipidemia, and type 2 diabetes. It encompasses a broad spectrum of conditions ranging from simple liver fat accumulation to advanced stages like chronic inflammation, tissue damage, fibrosis, cirrhosis, and even hepatocellular carcinoma. With limited approved drugs for MAFLD, identifying promising drug targets and developing effective treatment strategies is essential. The liver plays a critical role in regulating human immunity, and enriching innate and adaptive immune cells in the liver can significantly improve the pathological state of MAFLD. In the modern era of drug discovery, there is increasing evidence that traditional Chinese medicine prescriptions, natural products and herb components can effectively treat MAFLD. Our study aims to review the current evidence supporting the potential benefits of such treatments, specifically targeting immune cells that are responsible for the pathogenesis of MAFLD. By providing new insights into the development of traditional drugs for the treatment of MAFLD, our findings may pave the way for more effective and targeted therapeutic approaches.

Erianin alleviated liver steatosis by enhancing Nrf2-mediated VE-cadherin expression in vascular endothelium.

Non-alcoholic fatty liver disease (NAFLD) is emerging as the most common chronic liver disease and is closely associated with metabolic syndrome. Endothelial dysfunction was involved in many metabolic diseases, but the concrete participation of hepatic vascular endothelial dysfunction in liver steatosis that is an early stage of NAFLD is still unclear. In this study, the formation of liver steatosis and the elevation of serum insulin content were observed accompanying with the decreased vascular endothelial cadherin (VE-cadherin) expression in hepatic vessels from db/db mice, Goto-Kakizaki (GK) and high-fat diet (HFD)-fed rats. Liver steatosis was obviously enhanced in mice after the application of VE-cadherin neutralizing antibody. In vitro results showed that insulin decreased VE-cadherin expression and caused endothelial barrier breakdown. Furthermore, the alteration of VE-cadherin expression was found to be positively related with the transcriptional activation of nuclear erythroid 2-related factor 2 (Nrf2), and chromatin immunoprecipitation (ChIP) assay displayed that Nrf2 could directly regulate VE-cadherin expression. Insulin reduced Nrf2 activation by decreasing sequestosome-1 (p62/SQSTM1) expression downstream of insulin receptor. Moreover, the p300-mediated Nrf2 acetylation was weakened by enhancing the competitive binding of transcription factor GATA-binding protein 4 (GATA4) to p300. Finally, we found that erianin, a natural compound, could promote VE-cadherin expression by inducing Nrf2 activation, thereby alleviating liver steatosis in GK rats. Our results suggest that hepatic vascular endothelial dysfunction owing to the VE-cadherin deficiency dependent on the reduced Nrf2 activation promoted liver steatosis, and erianin alleviated liver steatosis through enhancing Nrf2-mediated VE-cadherin expression.

Oligo[2]catenane That Is Robust at Both the Microscopic and Macroscopic Scales.

Polycatenanes are extremely attractive topological architectures on account of their high degrees of conformational freedom and multiple motion patterns of the mechanically interlocked macrocycles. However, exploitation of these peculiar structural and dynamic characteristics to develop robust catenane materials is still a challenging goal. Herein, we synthesize an oligo[2]catenane that showcases mechanically robust properties at both the microscopic and macroscopic scales. The key feature of the structural design is controlling the force-bearing points on the metal-coordinated core of the [2]catenane moiety that is able to maximize the energy dissipation of the oligo[2]catenane via dissociation of metal-coordination bonds and then activation of sequential intramolecular motions of circumrotation, translation, and elongation under an external force. As such, at the microscopic level, the single-molecule force spectroscopy measurement exhibits that the force to rupture dynamic bonds in the oligo[2]catenane reaches a record high of 588 ± 233 pN. At the macroscopic level, our oligo[2]catenane manifests itself as the toughest catenane material ever reported (15.2 vs 2.43 MJ/m3). These fundamental findings not only deepen the understanding of the structure-property relationship of poly[2]catenanes with a full set of dynamic features but also provide a guiding principle to fabricate high-performance mechanically interlocked catenane materials.

Chlorogenic acid ameliorated non-alcoholic steatohepatitis via alleviating hepatic inflammation initiated by LPS/TLR4/MyD88 signaling pathway.

Non-alcoholic steatohepatitis (NASH) is a severe pathological stage in non-alcoholic fatty liver disease (NAFLD) and is generally recognized to be induced by chronic inflammation. Natural compound chlorogenic acid (CGA) is well-known for its anti-inflammatory capacity. This study aimed at evaluating the alleviation of CGA on NASH and further exploring its engaged mechanism via focusing on abrogating hepatic inflammation. Our results showed that CGA had a good amelioration on NASH in vivo. CGA alleviated liver oxidative injury by inducing nuclear factor erythroid 2-related factor 2 (Nrf2) activation and reduced liver steatosis via up-regulating peroxisome proliferator-activated receptor-alpha (PPARα). CGA attenuated hepatic inflammation in vivo, but didn't decrease the elevated lipopolysaccharide (LPS) content. CGA blocked the activation of nuclear factor kappa-B (NFκB) or inflammasome both in MCDD-fed mice and in LPS-stimulated macrophages. CGA was found to directly bind to myeloid differentiation primary response 88 (MyD88), and thus competitively blocked the interaction between toll-like receptor 4 (TLR4) and MyD88, thereby abrogating hepatic inflammation initiated by LPS-TLR4-MyD88. Moreover, the CGA-provided anti-inflammatory effect was obviously disappeared in macrophages overexpressed MyD88. Hence, CGA has an excellent efficacy in improving NASH. CGA alleviated liver inflammation during NASH progression through blocking LPS-TLR4-MyD88 signaling pathway via directly binding to MyD88.

A Novel Prognostic Pyroptosis-Related Gene Signature Correlates to Oxidative Stress and Immune-Related Features in Gliomas.

Gliomas are highly invasive and aggressive tumors having the highest incidence rate of brain cancer. Identifying effective prognostic and potential therapeutic targets is necessitated. The relationship of pyroptosis, a form of programmed cellular death, with gliomas remains elusive. We constructed and validated a prognostic model for gliomas using pyroptosis-related genes. Differentially expressed pyroptosis-related genes were screened using the "limma" package. Based on LASSO-Cox regression, nine significant genes including CASP1, CASP3, CASP6, IL32, MKI67, MYD88, PRTN3, NOS1, and VIM were employed to construct a prognostic model in the TCGA cohort; the results were validated in the CGGA cohort. According to the median risk score, the patients were classified into two risk groups, namely, high- and low-risk groups. Patients at high risk had worse prognoses relative to those at low risk evidenced by the Kaplan-Meier curve analysis. The two groups exhibited differences in immune cell infiltration and TMB scores, with high immune checkpoint levels, TMB scores, and immune cell infiltration levels in the high-risk group. KEGG and GO analyses suggested enrichment in immune-related pathways. Furthermore, we found that the genes in our signature strongly correlated with oxidative stress-related pathways and the subgroups exhibited different ssGSEA scores. Some small molecules targeted the genes in the model, and we verified their drug sensitivities between the risk groups. The scRNA-seq dataset, GSE138794, was processed using the "Seurat" package to assess the level of risk gene expression in specific cell types. Finally, the MYD88 level was lowered in the U87 glioma cell line using si-RNA constructs. Cellular proliferation was impaired, and fewer pyroptosis-related cytokines were released upon exposure to LPS. In summary, we built a pyroptosis-related gene model that accurately classified glioma patients into high- and low-risk groups. The findings suggest that the signature may be an effective prognostic predictive tool for gliomas.

Deep Video Prior for Video Consistency and Propagation.

Applying an image processing algorithm independently to each video frame often leads to temporal inconsistency in the resulting video. To address this issue, we present a novel and general approach for blind video temporal consistency. Our method is only trained on a pair of original and processed videos directly instead of a large dataset. Unlike most previous methods that enforce temporal consistency with optical flow, we show that temporal consistency can be achieved by training a convolutional network on a video with Deep Video Prior (DVP). Moreover, a carefully designed iteratively reweighted training strategy is proposed to address the challenging multimodal inconsistency problem. We demonstrate the effectiveness of our approach on 7 computer vision tasks on videos. Extensive quantitative and perceptual experiments show that our approach obtains superior performance than state-of-the-art methods on blind video temporal consistency. We further extend DVP to video propagation and demonstrate its effectiveness in propagating three different types of information (color, artistic style, and object segmentation). A progressive propagation strategy with pseudo labels is also proposed to enhance DVP's performance on video propagation. Our source codes are publicly available at https://github.com/ChenyangLEI/deep-video-prior.

New insight of Mn(III) in δ-MnO2 for peroxymonosulfate activation reaction: Via direct electron transfer or via free radical reactions.

Due to the increasing of industrial plastic waste and its refractory characteristics, it is extremely urgent to develop new degradation technology and environmentally friendly catalyst for industrial plastic waste. Manganese oxides are one of the most promising candidates for the catalytic degradation of plastic wastes. However, an improved understanding of the structural properties affecting their catalytic activity is required for high-efficient wastewater treatment. We herein report the surface reactivity effects of δ-MnO2 structural defects with regards to Bisphenol A (BPA) degradation/probe in the presence of peroxymonosulfate (PMS). Four δ-MnOx samples with different Mn(III) contents (different Mn(III)-deficient sample) were prepared and their structural properties as well as surface reactivity were characterized by batch test, ESR and XAFS analysis. For the Mn(III)-deficient sample, BPA removal was principally affected by direct electron transfer, with the adsorbed BPA degraded following hydroxylation. In contrast, a small fraction of Mn(III) substitution in δ-MnO2 could significantly encouraged the activation of PMS to produce SO4-☐and ☐OH, and a BPA degradation via beta scission. Moreover, the Mn(III)-rich δ-MnO2 demonstrate a high BPA removal rate even with a low sample load, which performed well following a reuse of five times. Our results provide a new way for the improvement of δ-MnO2 activity for the use of industrial plastic wastes treatment.

Thermo-Mechanical and Creep Behaviour of Polylactic Acid/Thermoplastic Polyurethane Blends.

There is a great need to develop biodegradable thermoplastics for a variety of applications in a wide range of temperatures. In this work, we prepare polymer blends from polylactic acid (PLA) and thermoplastic polyurethane (TPU) via a melting blend method at 200 °C and study the creep deformation of the PLA/TPU blends in a temperature range of 10 to 40 °C with the focus on transient and steady-state creep. The stress exponent for the power law description of the steady state creep of PLA/TPU blends decreases linearly with the increase of the mass fraction of TPU from 1.73 for the PLA to 1.17 for the TPU. The activation energies of the rate processes for the steady-state creep and transient creep decrease linearly with the increase of the mass fraction of TPU from 97.7 ± 3.9 kJ/mol and 59.4 ± 2.9 kJ/mol for the PLA to 26.3 ± 1.3 kJ/mol and 25.4 ± 1.7 kJ/mol for the TPU, respectively. These linearly decreasing trends can be attributed to the weak interaction between the PLA and the TPU. The creep deformation of the PLA/TPU blends consists of the contributions of individual PLA and TPU.

Integrated Design for Regulating the Interface of a Solid-State Lithium-Oxygen Battery with an Improved Electrochemical Performance.

A composite solid-state electrolyte (SSE) with acceptable safety and durability is considered as a potential candidate for high-performance lithium-oxygen (Li-O2) batteries. Herein, to address the safety issues and improve the electrochemical performance of Li-O2 batteries, a solvent-free composite SSE is prepared based on the thermal initiation of poly(ethylene glycol) diacrylate radical polymerization, and an integrated battery is achieved by injecting an electrolyte precursor between electrodes during the assembly process through a simple heat treatment. The Li-metal symmetric cells based on this composite SSE achieve a critical current density of 0.8 mA cm-2 and a stable cycle life of over 900 h at a current density of 0.2 mA cm-2. This composite SSE effectively inhibits the erosion of O2 on the Li metal anode, optimizes the interface between the electrolyte and cathode, and provides abundant reaction sites for the electrochemical reactions during cycling. The integrated solid-state Li-O2 battery prepared in this work achieves stable long cycling (118 cycles) at a current density of 500 mA g-1 at room temperature, showing the promising future application prospects.

Stress Relaxation Behavior of Poly(Methyl Methacrylate)/Graphene Composites: Ultraviolet Irradiation.

The graphene/poly (methyl methacrylate) (PMMA) composites are a promising candidate for electronic, optoelectrical, and environmental applications. Understanding the mechanical degradation of PMMA-based materials is of practical importance in improving the reliability and lifespan of the associated structures and systems. In this study, we investigate the effects of functionalized graphene (FG) and UV irradiation on the stress-relaxation of PMMA. Uniaxial tensile and stress -relaxation tests are performed to evaluate the mechanical properties of the composites. The mechanical strength and elongation at the break increase with the graphene concentration but decrease with the increase of the irradiation dose. Raman spectroscopy and intrinsic viscosity measurement are applied to examine the root cause of the degradation in the composites. UV irradiation leads to polymer chain scission and loss of molecular weight. The Kelvin representation of the standard linear solid model (SLSM) is used to describe the stress-relaxation curves of the composites. The value of the elastic modulus in the Kelvin element decreases with the increase in temperature. The viscosity follows the Arrhenius equation. The activation energy of viscosity increases with the increasing FGs concentration because the FGs hinder the chain motion of PMMA. However, UV irradiation makes chain scission of PMMA/FGs composite so that the polymer chain moves more easily and the activation energy of stress relaxation lowers. The steady-state stress follows the van 't Hoff equation that stress relaxation is an exothermal deformation process. Although Maxwell's representation of SLSM is mathematically identical to the Kelvin representation of SLSM, the former cannot interpret the stress-relaxation behavior of PMMA/FGs composite, which is against the concept of Young's modulus as a decreasing temperature function.

Chlorogenic acid alleviated liver fibrosis in methionine and choline deficient diet-induced nonalcoholic steatohepatitis in mice and its mechanism.

Nonalcoholic steatohepatitis, one of the most common chronic liver diseases, is a progressive form of nonalcoholic fatty liver disease accompanied by the development of liver fibrosis. Chlorogenic acid (CGA) is a natural polyphenolic compound. This study aims to observe the CGA-provided alleviation on liver fibrosis in methionine and choline deficient (MCD) diet-induced nonalcoholic steatohepatitis in mice and to elucidate its engaged mechanism. CGA attenuated hepatocellular injury, decreased the elevated hepatic lipids accumulation and attenuated liver fibrosis by reducing hepatic collagen deposition in mice fed with MCD diet. CGA abrogated the activation of hepatic stellate cells (HSCs) and promoted mitochondrial biogenesis both in vivo and in vitro. Moreover, the CGA-provided inhibition on HSCs activation in vitro was obviously disappeared after the application of peroxisome proliferator-activated receptor gamma, coactivator 1alpha (PGC1α) siRNA. CGA reduced the enhanced hepatic extracellular matrix (ECM) expression and the elevated serum high-mobility group box 1 (HMGB1) content in mice fed with MCD diet. CGA decreased the HMGB1-induced ECM production in both human liver sinusoidal endothelial cells and human umbilical vein endothelial cells. CGA also weakly promoted mitochondrial biogenesis in both liver sinusoidal endothelial cells and human umbilical vein endothelial cells incubated with HMGB1. Hence, CGA ameliorated hepatic fibrosis in mice fed with MCD diet through inhibiting HSCs activation via promoting mitochondrial biogenesis and reducing the HMGB1-initiated ECM production in hepatic vascular endothelial cells.

Chlorogenic acid improves diabetic retinopathy by alleviating blood-retinal-barrier dysfunction via inducing Nrf2 activation.

As one of the major diabetic microvascular complications, diabetic retinopathy (DR) is mainly initiated by the blood-retinal barrier (BRB) dysfunction. Chlorogenic acid (CGA) is a natural polyphenolic compound in Lonicerae Japonicae Flos, which traditionally has the beneficial function for eyes and is commonly included in many anti-diabetic formulas. In this study, the potential protective mechanism of CGA against DR was investigated. Streptozotocin (STZ) was used to induce diabetes in mice. CGA attenuated BRB dysfunction and reversed endothelial-mesenchymal transition (EndoMT) and epithelial-mesenchymal transition (EMT) in retinas in vivo. CGA inhibited microglia activation and reduced tumor necrosis factor (TNF)α release both in vivo and in vitro. CGA promoted nuclear factor erythroid 2-related factor 2 (Nrf2) activation and prevented EndoMT/EMT in TNFα-treated human retinal endothelial cells (HRECs) or retinal pigment epithelial APRE19 cells. CGA alleviated endothelial/epithelial barrier oxidative injury in HRECs or APRE19 cells stimulated with TNFα, but this effect was disappeared in cells co-incubated with Nrf2 inhibitor. Additionally, the CGA-supplied alleviation on BRB damage and EndoMT/EMT was markedly weakened in retinas from STZ-treated Nrf2 knock-out mice. All results suggest that CGA improves DR through attenuating BRB injury by reducing microglia-initiated inflammation and preventing TNFα-induced EndoMT/EMT and oxidative injury via inducing Nrf2 activation.