Exogenous methylglyoxal alleviates drought-induced 'plant diabetes' and leaf senescence in maize.

Drought-induced leaf senescence is associated with high sugar levels, which bears some resemblance to the syndrome of diabetes in humans; however, the underlying mechanisms of such 'plant diabetes' on carbon imbalance and the corresponding detoxification strategy are not well understood. Here, we investigated the regulatory mechanism of exogenous methylglyoxal (MG) on 'plant diabetes' in maize plants under drought stress applied via foliar spraying during the grain-filling stage. Exogenous MG delayed leaf senescence and promoted photoassimilation, thereby reducing the yield loss induced by drought by 14%. Transcriptome and metabolite analyses revealed that drought increased sugar accumulation in leaves through inhibition of sugar transporters that facilitate phloem loading. This led to disequilibrium of glycolysis and overaccumulation of endogenous MG. Application of exogenous MG up-regulated glycolytic flux and the glyoxalase system that catabolyses endogenous MG and glycation end-products, ultimately alleviating 'plant diabetes'. In addition, the expression of genes facilitating anabolism and catabolism of trehalose-6-phosphate was promoted and suppressed by drought, respectively, and exogenous MG reversed this effect, implying that trehalose-6-phosphate signaling in the mediation of 'plant diabetes'. Furthermore, exogenous MG activated the phenylpropanoid biosynthetic pathway, promoting the production of lignin and phenolic compounds, which are associated with drought tolerance. Overall, our findings indicate that exogenous MG activates defense-related pathways to alleviate the toxicity derived from 'plant diabetes', thereby helping to maintain leaf function and yield production under drought.

Yiguanjian decoction and its ingredients inhibit angiogenesis in carbon tetrachloride-induced cirrhosis mice.

BACKGROUND: Cirrhosis is associated with angiogenesis and disruption of hepatic vascular architecture. Yiguanjian (YGJ) decoction, a prescription from traditional Chinese medicine, is widely used for treating liver diseases. We studied whether YGJ or its ingredients (iYGJ) had an anti-angiogenic effect and explored possible mechanisms underlying this process. METHODS: Cirrhosis was induced with carbon tetrachloride (CCl4) (ip) in C57BL/6 mice for 6 weeks. From week 4 to week 6, cirrhotic mice were randomly divided into four groups: sorafenib-treated, YGJ-treated and iYGJ-treated mice and placebo. Serum biochemistries, hydroxyproline (Hyp) content and histopathological changes of hepatic tissues were measured as were α-smooth muscle actin (α-SMA), collagen I, CD31, vascular endothelial growth factor (VEGF), VEGF receptor (VEGFR) 2 and hypoxia-inducible factor (HIF)-1α. RESULTS: Both YGJ and iYGJ improved serum biochemistries. Changes of histopathology showed that YGJ and iYGJ reduced hepatic tissue necroinflammatory and collagen fiber deposition in cirrhosis mice. Compared to the CCl4 treated animals, Hyp, α-SMA, collagen I, CD31, VEGF, VEGFR, and HIF-1α expression decreased in YGJ and iYGJ groups. CONCLUSIONS: YGJ and iYGJ inhibited liver angiogenesis in cirrhotic mice treated with CCl4 by inhibiting the HIF-1α/VEGF signaling pathway, suggesting that anti-angiogenic effects of YGJ and iYGJ are associated with improving the hepatic hypoxic microenvironment.

Yiqi Yangjing recipe stimulates apoptosis while suppressing the energy metabolism via under-expression of PFKFB3 in A549 cells.

Background: Lung cancer is a malignant tumor associated with high morbidity and mortality. Yiqi Yangjing recipe (YYR) is a formula of traditional Chinese medicine (TCM) that is commonly used for the treatment of lung cancer with good clinical efficacy. The specific anti-cancer mechanism of YYR is still unknown. We need to embark on a more in-depth pharmacological study of YYR to determine the complex compound ingredients, which could be promoted in clinical practice to achieve efficacy in prolonging recurrent metastasis of lung cancer. Methods: The cytotoxic effects of YYR on A549 cells were evaluated by Cell Counting Kit-8 (CCK-8) assay. The PFKFB3-under-expressed and overexpressed A549 cell lines were constructed via PFK15 treatment and transfection, respectively. The effects of YYR on PFKFB3 messenger RNA (mRNA) and protein expression were detected by reverse transcription quantitative polymerase chain reaction (RT-qPCR) and western blot. The pro-apoptotic and anti-glycolytic abilities of YYR were measured using flow cytometry assay and hippocampal XF96 extracellular flux analyzer. An in vivo tumorigenicity assay was performed on nude mice to confirm the anti-cancer effects of YYR. Results: YYR has a noticeable cytotoxic activity on A549 cells, with the treatment with both YYR and PFK15 significantly inducing apoptosis. YYR and PFK15 treatment reduced the extracellular acidification rate (ECAR) and oxygen consumption rate (OCR) in A549 cells. Similar to PFK15, YYR can down-regulate PFKFB3 expression, and PFKFB3 overexpression suppressed the apoptosis, which was reversed by YYR. Animal experiments confirmed that YYR was able to inhibit tumor growth, induce tumor cell apoptosis, and down-regulate PFKFB3 in tumor tissues. Conclusions: This study demonstrated that YYR promoted lung cancer cell apoptosis and inhibited energy metabolism by targeting PFKFB3. Furthermore, we believe that YYR may be a suitable supplement or alternative drug for lung cancer treatment.

Cyberbullying and internet gaming disorder in Chinese youth: The role of positive youth development attributes.

Introduction: As digital natives, young people enjoy the convenience and benefits of the internet but also suffer from unique developmental problems of this age, such as cyberbullying and internet gaming disorder (IGD). Research suggests that these online problem behaviors enjoy high prevalence and various negative impacts. To prevent or intervene, this study attempts to explore the association between cyberbullying and IGD and the potential protectors from the positive youth development (PYD) perspective. Methods: Through the convenience sampling method, a sample of 463 Chinese adolescents was recruited and participated in the survey. They completed a questionnaire regarding PYD attributes, cyberbullying, IGD, and demographic information. Results: After controlling adolescents' sex and age, results of regression analyses indicated that cyberbullying was positively associated with IGD; PYD attributes had negative cumulative effects on cyberbullying and IGD; and cyberbullying and IGD were negatively related to PYD attributes. Moreover, the mediating effect of PYD attributes was significant in the relationship between cyberbullying and IGD. Discussion: Specifically, it is very possible for adolescents who have experienced one online problem behavior to suffer from another one. Fortunately, positive personal attributes could effectively buffer this cascading effect. These findings may provide theoretical and practical guidance for practitioners that improving PYD attributes may be a promising approach to prevent or reduce adolescent cyberbullying and IGD.

RNF115 promotes lung adenocarcinoma through Wnt/ß-catenin pathway activation by mediating APC ubiquitination.

BACKGROUND: Patients with lung adenocarcinoma (LUAD) have high mortality rate and poor prognosis. The LUAD cells display increased aerobic glycolysis, which generates energy required for their survival and proliferation. Deregulation of Wnt/ß-catenin signaling pathway induces the metabolism switching and oncogenesis in tumor cells. RING finger protein 115 (RNF115) is an E3 ligase for ubiquitin-mediated degradation. Although the oncogenic functions of RNF115 have been revealed in breast tumor cells, the effect of RNF115 on lung cancer is still not clear. METHODS: RNF115 expression and its correlation with the features of LUAD patients were analyzed by using public database and our own cohort. The functions of RNF115 in proliferation and energy metabolism in LUAD cells were explored by downregulating or upregulating RNF115 expression. RESULTS: We demonstrated that RNF115 was overexpressed in LUAD tissues and its expression was positively correlated with the poor overall survival of LUAD patients. Moreover, RNF115 overexpression inhibited LUAD cell apoptosis and promoted cellular proliferation and metabolism in LUAD cells. On the contrary, RNF115 knockdown displayed reverse effects. Furthermore, the underlying mechanism of the biological function of RNF115 in LUAD was through regulating Wnt/ß-catenin pathway via ubiquitination of adenomatous polyposis coli (APC). CONCLUSION: The current study reveals a close association between RNF115 expression and prognostic conditions in LUAD patients and the oncogenic roles of RNF115 in LUAD at the first time. These findings may help establish the foundation for the development of therapeutics strategies and clinical management for lung cancer in future.

Enhanced fluorescence of carboxymethyl chitosan via metal ion complexation in both solution and hydrogel states.

Recently, biopolymer-based non-traditional luminogens had attracted a great deal of interest because of their potential applications in biomedical field. Herein, we report for the first time that carboxymethyl chitosan (CMCh) can exhibit strong blue fluorescence at λ = 436.8 nm when brought in contact with zinc ion (Zn2+) in both solution and hydrogel states. The resultant CMCh-Zn sample exhibits a typical fluorescence lifetime of 3.68 ns and a quantum yield of 6.8%. The fluorescence behaviors of CMCh-Zn samples at different excitation wavelengths, CMCh concentrations, temperature, and pH values, are also investigated. The results clearly indicate clustering-triggered emission characteristic of the CMCh-Zn. In order to further elucidate the chemical nature of this new fluorescence system, a series of CMCh-Zn samples are characterized by using ultraviolet-visible spectrometer, Fourier-transform infrared spectrometer and X-ray diffractometer. The data suggest that the metal-ligand complexation of CMCh with Zn2+ account for the generation of such an enhanced fluorescence.

Continuous production of antibacterial carboxymethyl chitosan-zinc supramolecular hydrogel fiber using a double-syringe injection device.

Large-scale production of an antibacterial hydrogel is of critical importance for its practical application in biomedical field. In this regard, herein we report on the construction of a double-syringe injection device by using all the commercial parts and its use for continuous production of carboxymethyl chitosan-zinc (CMCh-Zn) supramolecular hydrogel fiber. The resultant CMCh-Zn hydrogel fibers exhibit good stretchability and knittability. The Zn loading into the hydrogel fibers can be easily controlled by adjusting the concentration of Zn2+ solution. Scanning electron microscope measurements indicate that the CMCh-Zn hydrogel fibers have a relatively smooth and thin skin layer, as well as, a 3-dimensional interconnected microporous interior architecture. Antibacterial activities of the CMCh-Zn hydrogel fibers against both Gram-positive Staphylococcus aureus and Gram-negative Escherichia coli are also investigated. The results show that the intrinsic blue fluorescence of the as-prepared CMCh-Zn hydrogel fibers can be employed as optical indicator of their antibacterial effectiveness.

Injectable self-healing carboxymethyl chitosan-zinc supramolecular hydrogels and their antibacterial activity.

Injectable and self-healing hydrogels have found numerous applications in drug delivery, tissue engineering and 3D cell culture. Herein, we report an injectable self-healing carboxymethyl chitosan (CMCh) supramolecular hydrogels cross-linked by zinc ions (Zn2+). Supramolecular hydrogels were obtained by simple addition of metal ions solution to CMCh solution at an appropriate pH value. The mechanical properties of these hydrogels were adjustable by the concentration of Zn2+. For example, the hydrogel with the highest concentration of Zn2+ (CMCh-Zn4) showed strongest mechanical properties (storage modulus~11,000Pa) while hydrogel with the lowest concentration of Zn2+ (CMCh-Zn1) showed weakest mechanical properties (storage modulus~220Pa). As observed visually and confirmed rheologically, the CMCh-Zn1 hydrogel with the lowest Zn2+ concentration showed thixotropic property. CMCh-Zn1 hydrogel also presented injectable property. Moreover, the antibacterial properties of the prepared supramolecular hydrogels were studied against Staphylococcus aureus (S. aureus) and Escherichia coli (E. coli) by agar well diffusion method. The results revealed Zn2+ dependent antibacterial properties against both kinds of strains. The inhibition zones were ranging from ~11-24mm and ~10-22mm against S. aureus and E. coli, respectively. We believe that the prepared supramolecular hydrogels could be used as a potential candidate in biomedical fields.

Xuefuzhuyu decoction inhibition of angiogenesis attenuates liver fibrosis induced by CCl4 in mice.

ETHNOPHARMACOLOGICAL RELEVANCE: Xuefuzhuyu decoction (XFZY) is a well-known traditional Chinese herbal formulation composed of 11 herbs. It is an effective treatment for cardiovascular and chronic liver diseases. The aim of the study is to investigate the role of XFZY on angiogensis in hepatic fibrogenesis, and identify the possible mechanism. MATERIAL AND METHODS: Liver fibrosis was induced by intraperitoneal injection of Carbon tetrachloride (CCl4) in C57BL/6 mice for 6 weeks. From week 4 to week 6, the CCl4-injected mice were randomly divided into three groups, followed by oral administration of Sorafenib, XFZY and water for 3 weeks. Biochemical parameters, hydroxyproline (Hyp) content and histological changes of the liver were determined. The expressions of alpha smooth muscle actin (α-SMA), collagen I, CD31 and vascular endothelial grow factor (VEGF) were assessed by immunohistochemistry and western blot. The protein expressions of VEGFR-2, hypoxia inducing factor (HIF)-1α, asymmetric dimethylarginine (ADMA) and dimethylarginine hydrolase (DDAH) 1 were determined by western blot. The mRNA levels of α-SMA, VEGF and HIF-1α were measured by RT-PCR. RESULTS: Both Sorafenib and XFZY improved biochemical parameters of the liver fibrosis mice. A significant reduction in Hyp content was found in the XFZY-treated mice as well as the Sorafenib-treated mice. Changes in histopathology showed that Sorafenib and XFZY decreased inflammatory and fibrotic stages of the liver in fibrosis mice. Compared to CCl4 model group, Sorafenib and XFZY decreased α-SMA, collagen I, CD31, VEGF, VEGFR-2, HIF-1α and ADMA, and increased the expression of DDAH1. CONCLUSION: XFZY inhibits liver fibrosis not only through inhibiting collagen deposition but also through an antiangiogenic effect on the fibrotic liver. Moreover, the antiangiogenic mechanism of XFZY involves alleviating hypoxia and protecting liver sinusoidal endothelial cell function.