Structural impacts on the degradation behaviors of Ir-based electrocatalysts during water oxidation in acid.

Large-scale hydrogen production by electrocatalytic water splitting still remains as a critical challenge due to the severe catalyst degradation during the oxygen evolution reaction (OER) in acidic media. In this study, we investigate the structural impacts on catalyst degradation behaviors using three iridium-based oxides, namely SrIrO3, Sr2IrO4, and Sr4IrO6 as model catalysts. These Ir oxides possess different connection configurations of [IrO6] octahedra units in their structure. Stable OER performance is observed on SrIrO3 and attributed to the edge-linked [IrO6] structure and rapid formation of a continuous IrOx layer on its surface, which functions not only as the "real" catalyst but also a shield preventing continuous cation leaching (with <1.0 at.% of Ir leaching). In comparison, both Sr2IrO4 and Sr4IrO6 catalysts demonstrate quick current fading with structure transformation to rutile IrO2 and formation of inconducive SrSO4 precipitates on surface, blocking the reactive sites. Nevertheless, over 60 at.% of Ir leaching is detected from the Sr4IrO6 catalyst due to its isolated [IrO6] structure configuration. Results of this work highlight the structural impacts on the catalyst stability in acidic OER conditions.

Active immunization with recombinant GnRH6-CRM197 inhibits reproductive function of male rats.

Gonadotropin-releasing hormone (GnRH) vaccines have been successfully used for the inhibition of gonadal development and function, but current GnRH-based vaccines often present variability in the response. Cross-reactive material 197 (CRM197) has been used as carrier molecules to enhance an immune response to associated antigens. So, the synthetic mammalian tandem-repeated GnRH hexamer (GnRH6) gene was integrated into the expression plasmid pET-21a. Recombinant GnRH6-CRM197 protein was subsequently overexpressed in Escherichia coli strain BL21 and purified through Nickel column affinity chromatography and the antigenicity and biological effects of GnRH6-CRM197 were evaluated in rats. Sixteen 4-month-old adult male rats were randomly divided into two groups: the GnRH6-CRM197 group (n = 8) and the control group (n = 8). The GnRH6-CRM197 group rats were subcutaneously immunized with 100 µg of GnRH6-CRM197, administered thrice at 2-week intervals with GnRH6-CRM197.The control group received only a white oil adjuvant. Following the initial immunization, the weights of animals were recorded, and blood samples were collected from the orbital sinus at 4, 4.5, 5, 5.5, 6, 6.5, and 7 months. Serum antibody titers and testosterone concentrations were quantified using ELISA and CLIA, respectively. Additionally, testicular tissues were collected for morphological examination. The results revealed a significant increase in serum GnRH antibody titers (p < 0.05), but a significant decrease in serum testosterone concentrations (p < 0.05), and the weight, length, width, and girth of the testis, and the number of spermatogonia cells, spermatocytes, and sperm cells in the immunized rats. Furthermore, seminiferous tubules revealed significant atrophy and no sperm were observed in the immunized animals. Thus, GnRH6-CRM197 may be an effective antigen and a potential immunocastration vaccine.

Research progress of intra-aortic balloon counterpulsation in the treatment of acute myocardial infarction with cardiogenic shock: A review.

The mortality rate of patients with acute myocardial infarction complicated with cardiogenic shock is very high, and in recent years, intra-aortic balloon counterpulsation has been used more and more. It plays a very important role in improving left ventricular ejection, increasing coronary artery perfusion pressure and reducing myocardial oxygen consumption. This article reviews the development of intra-aortic balloon counterpulsation in the treatment of acute myocardial infarction with cardiogenic shock in recent years.

Exploring the conformational dynamics and thermodynamics of EGFR S768I and G719X + S768I mutations in non-small cell lung cancer: An in silico approaches.

Non-small cell lung cancer (NSCLC) is often driven by mutations in the epidermal growth factor receptor (EGFR) gene. However, rare mutations such as G719X and S768I lack standard anti-EGFR targeted therapies. Understanding the structural differences between wild-type EGFR and these rare mutants is crucial for developing EGFR-targeted drugs. We performed a systematic analysis using molecular dynamics simulations, essential dynamics (ED), molecular mechanics Poisson-Boltzmann surface area, and free energy calculation methods to compare the kinetic properties, molecular motion, and free energy distribution between wild-type EGFR and the rare mutants' structures G719X-EGFR, S768I-EGFR, and G719X + S768I-EGFR. Our results showed that S768I-EGFR and G719X + S768I-EGFR have higher global and local conformational flexibility and lower thermal and global structural stability than WT-EGFR. ED analysis revealed different molecular motion patterns between S768I-EGFR, G719X + S768I-EGFR, and WT-EGFR. The A-loop and αC-helix, crucial structural elements related to the active state, showed a tendency toward active state development, providing a molecular mechanism explanation for NSCLC caused by EGFR S768I and EGFR G719C + S768I mutations. The present study may be helpful in the development of new EGFR-targeted drugs based on the structure of rare mutations. Our findings may aid in developing new targeted treatments for patients with EGFR S768I and EGFR G719X + S768I mutations.

Analysis of protein phosphorylation sites in the hypothalamus tissues of pubescent goats.

Protein phosphorylation plays an important role in animal reproduction. However, its role in the onset of puberty in goats remains largely unexplored. Accordingly, in the present study, the molecular changes controlling the onset of puberty in goats were investigated by identifying the differentially phosphorylated proteins (DPPs) and phosphorylation sites (DPSs) in the hypothalami of prepubertal and pubertal female goats using LC-MS/MS and tandem mass tag labelling. A total of 3265 phosphopeptides corresponding to 1628 phosphoproteins were identified, including 234 upregulated and 342 downregulated phosphopeptides. The DPSs HTT, MAP1B, CAMKK1, MAP2, DNAJC5, and GAP43 were identified. These DPPs are enriched in the endocytosis, cAMP signaling, Rap1 signaling, melanogenesis, and insulin secretion pathways. These pathways are related to gonadotropin-releasing hormone and puberty. In particular, glucose-6-phosphate isomerase, fructose-bisphosphate aldolase C, and fructose-bisphosphate aldolase A occupy important locations in the protein-protein interaction network. These data provide evidence for a complex interaction network in goat hypothalamus proteins that affects puberty. Furthermore, they may help identify new puberty-regulating candidates and/or serve as an important resource for exploring the physiological mechanism of puberty onset in mammals. SIGNIFICANCE: This study provides evidence for a complex interaction network in goat hypothalamus proteins that affects puberty. Furthermore, our data may help identify new puberty-regulating candidates and/or serve as an important resource for exploring the physiological mechanism of puberty onset in mammals.

Boron, nitrogen co-doped biomass-derived carbon aerogel embedded nickel-cobalt-iron nanoparticles as a promising electrocatalyst for oxygen evolution reaction.

The electrocatalytic performance of oxygen evolution reaction (OER) electrocatalysts is highly reliant on the activity of its catalytic active site, which may be augmented by raising the number of active sites. In this study, nanoscaled nickel-cobalt-iron (NiCoFe) alloy was embedded on conductive boron(B), nitrogen(N) co-doped/biomass-derived carbon aerogel as an OER electrocatalyst. The synthesized electrocatalysts were calcined under different temperatures and with variable dopants. The optimal electrocatalyst (BN/CA-NiCoFe-600) demonstrated a low overpotential of 321 mV (at current density of 10 mA cm-2) and a minute Tafel slope of 42 mV dec-1, which was even smaller than that of IrO2 and RuO2. Its mass activity and specific activity were calculated to be 201.7 A g-1, and 34.1 cm-2ECSA, respectively. Furthermore, the electrocatalyst showed excellent stability and durability. This work provides an easy and practical synthetic strategy for acquiring very active and durable electrocatalysts for OER.

The Antioxidation of Different Fractions of Dill (Anethum graveolens) and Their Influences on Cytokines in Macrophages RAW264.7.

Dill (Anethum graveolens L.) has been shown strong antioxidative and immune propertise, but the precise potency and action mechanisms remain largely elusive. This study is to dissect the different fractions' antioxidant power and antiinflammatory function. We extracted 4 fractions from China original dill with ether (DI-E), ethyl acetate (DI-EA), n-butanol (DI-B) and water (DI-W), and performed 4 different kinds of antioxidative analysis together with vitamine C (Vc): DPPH, ABTS, reducing power and TPTZ-FRAP. For correlated compounds in antioxidant assays Folin-Ciocalteu's analysis was performed. For antiinflammation, cell proliferation by MTT, NO molecules and interleukin-1 and 6 in supernatant were detected by Griess reaction and Elisa, respectively, and gene expression of inducible nitric oxide synthase (iNOS) was analyzed by RT-PCR. The strength of antioxidant activity was Vc > DI-EA > DI-B > DI-W > DI-E. Folin-Ciocalteu's analysis showed that antioxidant power was correlated to phenolic compounds. However, in antiinflammatory assays DI-E was most active one by cell proliferation, iNOS's gene expression, and secretion of interleukin IL-1 and 6 in macrophage RAW264.7. The antioxidant fraction and antiinflammatory fraction of the dill were determined. The certain fractions of dill may be strong at antioxidation, but weak at antiinflammation, vice versa. Thus dill has anti-ageing and anticancer potential, a good resource for functional food and ancillary drugs of rehabilitation.

Mining spatial information to investigate the evolution of karst rocky desertification and its human driving forces in Changshun, China.

The processes of karst rocky desertification (KRD) have been found to cause the most severe environmental degradation in southwestern China. Understanding the driving forces that cause KRD is essential for managing and restoring the areas that it impacts. Studies of the human driving forces of KRD are limited to the county level, a specific administrative unit in China; census data are acquired at this scale, which can lead to scale biases. Changshun County is studied here as a representative area and anthropogenic influences in the county are accounted for by using Euclidean distances for the proximity to roads and settlements. We propose a standard coefficient of human influence (SOI) that standardizes the Euclidean distances for different KRD transformations to compare the effects of human activities in different areas. In Changshun County, the individual influences of roads and settlements share similar characteristics. The SOIs of improved KRD transformation types are almost negative, but the SOIs of deteriorated types are nearly positive except for one form of KRD turning to the extremely severe KRD. The results indicated that the distribution and evolution of the KRD areas from 2000 to 2010 in Changshun were affected positively by human activities (e.g., KRD restoration projects) and also negatively (e.g., by intense and irrational land use). Our results demonstrate that the spatial techniques and SOI used in this study can effectively incorporate information concerning human influences and internal KRD transformations. This provides a suitable approach for studying the relationships between human activities and KRD processes at fine scales.

Nitric oxide and interleukins are involved in cell proliferation of RAW264.7 macrophages activated by viili exopolysaccharides.

Viili has been traditionally regarded as healthy food; viili exopolysaccharides (VEPS) function as antioxidants, but the molecular and cellular mechanisms, especially its immune functions, remain largely unclear. To assess VEPS's immunological roles, VEPS were separated by Sevage's method and purified by anion exchange chromatography. Cell proliferation, phagocytosis, releases of nitric oxide (NO), interleukin (IL)-1ß, and IL-6, the inducible nitric oxide synthase (iNOS) gene expression by reverse transcription polymerase chain reaction (RT-PCR) and iNOS protein by Western blotting, and morphology by scanning electron microscopy in lipopolysaccharides (LPS)/VEPS-stimulated and non-stimulated RAW264.7 macrophages were analyzed. VEPS increased cell proliferation at 50-200 µg/mL. The uptake of neutral red for the indication of phagocytosis and releases of NO, IL-6, and IL-1ß were enhanced after exposure to LPS and VEPS. Gene expressions of iNOS, IL-6, and IL-1ß and protein expressions of iNOS were increased with VEPS. The RAW264.7 cell treated with VEPS became flattened, a strong indication of the activation of macrophages. We concluded that VEPS promoted the activation of macrophages in which NO, IL-6, and IL-1ß were involved; the release of NO and other cytokines may eventually activate lymphocytes, increasing nonspecific (innate) and specific immunity in humans.

Cytosolic protection against ultraviolet induced DNA damage by blueberry anthocyanins and anthocyanidins in hepatocarcinoma HepG2 cells.

UV-induced DNA damage plays a key role in the etiology of certain diseases. The ability of blueberry anthocyanins and anthocyanidins (BA) to protect cellular DNA from UV-induced damage was investigated. BA were extracted by water (BAW), ethanol (BAE) or methanol (BAM). These extracts partially restored proliferation of UV-irradiated HepG2 cells as shown by MTT assay. Treatment with BA extracts at 75 µg/ml decreased reactive oxygen species and decreased DNA damage by tail moment of comet assay and expression of γH2AX in situ. BAM significantly decreased gene and protein expression of p53, phospho-p53 (Ser15), and p21 in UV-irradiated HepG2 cells. BA thus efficiently protects cells from DNA damage in vitro. Blueberry may potentially be used as a good source of naturally radioprotective agents.

A polysaccharide fraction of adlay seed (Coixlachryma-jobi L.) induces apoptosis in human non-small cell lung cancer A549 cells.

Different seed extracts from Coix lachryma-jobi (adlay seed) have been used for the treatment of various cancers in China, and clinical data support the use of these extracts for cancer therapy; however, their underlying molecular mechanisms have not been well defined. A polysaccharide fraction, designated as CP-1, was extracted from the C.lachryma-jobi L. var. using the ethanol subsiding method. CP-1 induced apoptosis in A549 cells in a dose-dependent manner, as determined by MTT assay. Apoptotic bodies were observed in the cells by scanning electronic microscopy. Apoptosis and DNA accumulation during S-phase of the cell cycle were determined by annexin V-FITC and PI staining, respectively, and measured by flow cytometry. CP-1 also extended the comet tail length on single cell gel electrophoresis, and disrupted the mitochondrial membrane potential. Further analysis by western blotting showed that the expression of caspase-3 and caspase-9 proteins was increased. Taken together, our results demonstrate that CP-1 is capable of inhibiting A549 cell proliferation and inducing apoptosis via a mechanism primarily involving the activation of the intrinsic mitochondrial pathway. The assay data suggest that in addition to its nutritional properties, CP-1 is a very promising candidate polysaccharide for the development of anti-cancer medicines.

[Progresses and perspectives in the study on citrin deficiency].

Citrin deficiency causes autosomal recessive disorders including adult-onset type II citrullinemia (CTLN2) and neonatal intrahepatic cholestasis caused by citrin deficiency (NICCD). The responsive gene of citrin deficiency, SLC25A13, locates on chromosome 7q21.3 and encodes citrin as a liver-type mitochondrial aspartate/glutamate carrier (AGC). The mutations on SLC25A13 will result in deficiency of citrin and CTLN2 or NICCD. Citrin deficiency was found at first in Japan. However, recently, some of cases were identified in China, Korea, Vietnam, Israel, Czech, United States and England, and racial differences of the SLC25A13 mutations were found, suggesting the patients with citrin deficiency maybe exist worldwide. In this article, authors reviewed the progresses in the study on citrin deficiency up to now and put forward authors' considerations for further research on it.

Increased insulin sensitivity despite lipodystrophy in Crebbp heterozygous mice.

The CBP protein (cAMP response element binding protein (CREB) binding protein) is a co-activator for several transcription factors with a wide range of important biological functions, such as sterol regulatory element binding proteins (SREBPs), CCAAT/enhancer-binding proteins (C/EBPs), nuclear receptors (including peroxisome proliferator-activated receptors, PPARs), and signal transducers and activators of transcription (STATs). In contrast to these individual transcription factors, the biological roles of CBP are poorly understood. CBP enhances transcriptional activities via histone acetylation and the recruitment of additional co-activators such as SRC (steroid coactivator)-1 (ref. 9). To identify its physiological functions using a loss-of-function mutant, we analyzed CBP-deficient mice. As Crebbp null mice (Crebbp-/-) died during embryogenesis, we used Crebbp+/- mice. Unexpectedly, Crebbp+/- mice showed markedly reduced weight of white adipose tissue (WAT) but not of other tissues. Despite this lipodystrophy, Crebbp+/- mice showed increased insulin sensitivity and glucose tolerance and were completely protected from body weight gain induced by a high-fat (HF) diet. We observed increased leptin sensitivity and increased serum adiponectin levels in Crebbp+/- mice. These increased effects of insulin-sensitizing hormones secreted from WAT may explain, at least in part, the phenotypes of Crebbp+/- mice. This study demonstrates that CBP may function as a 'master-switch' between energy storage and expenditure.