Background and Purpose: Minimal hepatic encephalopathy (MHE) is implicated in the impairment of memory function. Fibroblast growth factor-2 (FGF2) is involved in modulating synaptic and neuronal formation. Experimental Approach: The aim of this study is to examined the impacts of FGF2 on MHE pathology. Our study addressed whether FGF2 could trigger neuregulin 1 (NRG1) release to ameliorate synaptic impairment in MHE rats and in primary cultured neurons. Key Results: The results showed the decreased FGF2 expression in MHE brains. After treatment with FGF2, secreted neuregulin 1 (NRG1) and ErbB4 were increased, and the interaction of the 2 proteins was enhanced. Additionally, treatment with FGF2 or NRG1 induced synaptic formation, with increase in the activity of synapse and the density of dendritic spine, through Sirt1. NRG1 signaling was prevented by administration of FGF2, which acts through the FGFR1 in MHE rats. Finally, intracerebroventricular injection with FGF2 or NRG1 mitigated the impairment of synaptogenesis. Conclusions and Implications: The data suggest that FGF2 may be a promising latent therapeutic reagent for MHE pathogenesis.

There is not any medicine during the emergency of 2019-nCov has been an outbreak and we have already found antiviral phytomedicine Chinese elderberry will be inhibition of 2019-nCoV.This commentary used to be presented in June of 2013 at the first international symposium for the elderberry, the conference, held in the USA, many scientists were surprised to learn of the 9 native species of elderberry in China. This paper aims to publish our comment on the elderberry, as, since our initial presentation in 2013, no English literature references are present in China. Most Chinese horticulturists and farmers consider the elderberry a wild plant. It is regarded as a plant of little value due to its abundance and ease of harvest. This article contains details of the Sambucus species groups, including the botanical names, Chinese common names, geographic distributions, economic uses and full descriptions of the elderberry. In southwest China, where the climate is mildly warm, there are 2 species of elderberries; one, Sambucus adnata, is termed the “blood-red herb-elderberry” by local residents as the roots, rhizomes, and branches exude red-juice when broken. The second, named S. javanica or S. chinensis, is commonly called the “herb-elderberry”. In northeast China where the climate is cold, there are 7 species of elderberry, however, most scientists recognize only 2 main species: Sambucus. williamsii, commonly called the “woody-elderberry”, and Sambucus sibirica, commonly called the “Siberian woody-elderberry”. The other 5 species of elderberry in northern-east of China.

L-lysine amino acid is cocrystallized with L-mandelic acid by the slow evaporation method. Single crystal X-ray analysis reveals that lysine-mandelic acid crystallized as a dihydrate form. In the crystalline state, the lysine molecule exists in the cationic form in which the backbone and side chain amino groups are protonated and the carboxylic acid is deprotonated. The carboxylic acid proton of the mandelic acid is transferred to the lysine side chain and thus carries a negatively charged ion. The lattice water molecules are located near the amino groups of the lysine. Intermolecular interactions formed between lysinium, mandelate and lattice water molecules are qualitatively analyzed using Hirshfeld surfaces and 2D-fingerprint plots. The energetics of different dimeric complexes is quantitatively analyzed using PIXEL energy analysis. Topological parameters derived from QTAIM framework are used to delineate the nature of different intermolecular interactions formed in the title complex.

1. Global warming is rapidly emerging as a universal threat that could alter the distribution of many animal species and change their morphology, physiology, behavior and life history. The heat dissipation limitation (HDL) hypothesis proposes that females’ reproductive performance is limited by their capacity to dissipate heat. Although exposure to wind is known to increase heat exchange, its effect on reproductive performance is unknown. 2. In this study, the effect of simulated wind on the energy budget and milk energy output of female striped hamsters (Cricetulus barabensis) was measured under cool (21°C) and hot (32.5°C) ambient temperatures and the preference of hamsters for windy conditions in lactating females was tested both in the laboratory and the wild. 3. Females lactating at 32.5°C significantly decreased their energy intake and milk output, and raised lighter offspring than those lactating at 21°C. Exposure to wind significantly increased both energy intake during lactation and heat loss at both temperatures. Females lactating at 32.5°C considerably increased their reproductive output when exposed to wind. Moreover, females kept at an ambient temperature of 21°C preferred sheltered conditions whereas those kept at 32.5°C preferred exposure to simulated wind. We captured significantly more lactating female hamsters on windy days in summer and on calm days in spring. Wrapping a glass vessel in the fresh pelt of a striped hamster significantly reduced the rate of both water loss and cooling. 4. These findings support the HDL hypothesis; high ambient temperatures do appear to limit the energy intake and reproductive output of lactating hamsters. Small mammals lactating under hot conditions may be able to utilize the cooling properties of wind to increase their energy intake and milk production, and thereby their reproductive output and fitness.

his study describes the response of Arthrospira platensis to a variety of temperature conditions as reflected in variations of photosynthetic parameters, pigmentation, and biomass productivity in indoor photobioreactor (PBR) cultivations. These experiments are designed to better understand the impact of temperature, seasonal variations, and acclimation effects on outdoor biomass production. The irradiance levels and temperature range (20 – 39°C) are chosen to enable modeling of semi-continuous operation of large-scale outdoor PBR deployments. Overall, the cultivations were quite stable with some pigment-related instabilities after prolonged high temperature exposure. Changes in productivity with temperature, as reflected in measured photosynthetic parameters, are immediate and mainly attributable to the temperature dependence of the photosaturation parameter, a secondary factor being variation in pigment content. This study confirms that temperature is critical for optimal performance of Arthospira platensis for both biomass and pigment production and provides a basis for risk assessments related to temperature mitigation for large-scale outdoor cultivations. Finally, the biomass productivities in a semi-continuous operation mode are quantitatively reproduced with a productivity model incorporating the photosynthetic parameters measured herein. Those productivities are in good agreement with extensive outdoor testing in PBR arrays at large scale (24,000 L) and over long time periods (up to 18 months).

This DFT study treats thermal metal-catalyzed alkene aziridination by azides, where the catalysts are copper(II) triflate, cobalt(II) porphin and ruthenium(II) porphin. Three azides RN3 (R = H, Me, Ac) react with alkene substrates in the presence of these catalysts leading to aziridine formation by a two-step catalysed mechanism. In Step I, the azide reacts with the catalyst to first form a metal nitrenoid via transition state TS1. The Ru(porph) catalyst is particularly effective for Step I. In Step II, the metal nitrenoid adds to the alkene via TS2 giving the aziridine product. Cu(trfl)2 is most effective as a catalyst for Step II. The facility order H > Me > Ac (with respect to the azide R group) holds for Step I, and the reverse order for Step II. Transition states TS1 and TS2 are described as “early” and “late”, respectively, in good accord with Hammond’s postulate.

Single-nucleotide polymorphisms (SNPs) have numerous advantages over microsatellites, including greater power to infer population structure and history and to detect loci undergoing selection. Here, we conduct the first continental-level SNP study of polar bears (Ursus maritimus) using genotypes from an array of 5441 SNP loci genotyped in 16–30 polar bears sampled in each of 16 geographic regions in Canada and West Greenland. Our study aimed to assess population history and genetic structure and to identify evidence of adaptive loci. Using these data, we confirmed the existence of four broad-scale genetic clusters in North America (FCT = 0.035) and identified nine fine-scale subclusters using more powerful spatial methods. An assessment of historical patterns of migration suggests that polar bears migrated into North America from the Beaufort Sea after the last glacial maximum. Using a conservative approach, we identified 17 loci that may represent adaptive variation, including one SNP in the 3’ untranslated region of PDLIM5 (PDZ And LIM Domain 5), a gene involved in cardiovascular function, which has undergone substantial selection in polar bears since their divergence from brown bears. Outlier loci differentiated the Norwegian Bay genetic cluster more strongly from remaining clusters than did our complete dataset, suggesting possible adaptive differences in the High Arctic. Through careful consideration of SNP loci, sample inclusion, and analytical approaches, we provide a comprehensive picture of polar bear population structure at a continental level. This study provides a model for the analysis of wide-ranging species that can contribute to their conservation and management.

Although photodynamic therapy (PDT) is an effective, minimally-invasive therapeutic modality with advantages in highly localized and specific tumor treatments, large and deep-seated cancers within the body cannot be successfully treated due to low transparency to visible light. To improve the therapeutic efficiency of tumor treatment in deep tissue and reduce the side effects in normal tissue, this study developed a near-infrared (NIR)-triggered upconversion nanoparticle (UCNP)-based photosensitizer (PS) carrier as a novel theranostics system. The NaYF4:Yb/Er UCNPs were synthesized by a hydrothermal method, producing uniformly small size (≈20 nm) nanoparticles and crystalline morphology of the hexagonal phase. These UCNPs were modified with folic acid-conjugated biocompatible block copolymers through a bidentate dihydrolipoic acid linker. The polymer modified hexagonal phase UCNPs (FA-PEAH-UCNPs) showed an improved dispersibility in the aqueous solution and strong NIR-to-vis upconversion fluorescence. The hydrophobic PS, pheophorbide a (Pha), was then conjugated to the stable vectors through a pH-sensitive linkage. Moreover, these UCNP-based Pha carriers containing tumor targeting folic acid ligands exhibited the significantly enhanced cellular uptake efficiency as well as PDT treatment efficiency. These results suggested that this system could extend the excitation wavelength of PDT to the NIR region and effectively improve therapeutic efficiency of PSs.

The biodiverse Neotropical ecoregion remains insufficiently assessed, poorly managed, and threatened by unregulated human activities. Novel, rapid and cost-effective DNA-based approaches are valuable to improve understanding of the biological communities and for biomonitoring in remote areas. Here, we evaluate the potential of environmental DNA (eDNA) metabarcoding for assessing the structure and distribution of fish communities by analysing sediments and water from 11 locations along the Jequitinhonha River catchment (Brazil). Each site was sampled twice, before and after a major rain event in a five-week period and fish diversity was estimated using high-through-put sequencing of 12S rRNA amplicons. In total, 252 Molecular Operational Taxonomic Units (MOTUs) and 34 fish species were recovered, including endemic, introduced, and previously unrecorded species for this basin. Spatio-temporal variation of fish assemblages was detected, richness during the first campaign was nearly twice as high as in the second sampling round; though peaks of diversity were primarily associated with only four locations. No correlation between β-diversity and longitudinal distance or presence of dams was detected, but low species richness observed at sites located near dams indicates that these anthropogenic barriers might have an impact on local fish diversity. Unexpectedly high α-diversity levels recorded at the river mouth suggest that these sections should be further evaluated as putative “eDNA reservoirs” for rapid monitoring. By uncovering spatio-temporal changes, unrecorded biodiversity components, and putative anthropogenic impacts on fish assemblages, we further strengthen the potential of eDNA metabarcoding as a biomonitoring tool, especially in regions often neglected or difficult to access.

Primary biliary cholangitis (PBC) is an immune-mediated chronic cholestasis. The disruption of T cell homeostasis plays an important role in PBC pathogenesis. Lysosomal associated membrane protein 2 isoform A (LAMP-2A) has been implicated in the regulation of CD4+ T cell responses, therefore we aim to evaluate the activation state of CD4+ T cells in PBC, and to investigate the role of LAMP-2A in it. The peripheral blood of PBC patients (PBC, n=42) and healthy controls (HC, n=20) were phenotypically analyzed, and LAMP-2A expression in CD4+ T cells was assessed by flow cytometry. Naïve CD4+ T cells of PBC patients were isolated and activated in vitro to estimate their activation responses. Additionally, we assessed the changes induced by silencing LAMP-2A expression. We found that CD4+ T cells of PBC patients exhibited significant hyperactivity, and naïve CD4+ T cells showed high LAMP-2A expression, which could be a novel biomarker for PBC activity. Moreover, by interfering with LAMP-2A expression in vitro, the overreactions of PBC naïve CD4+ T cells were reversed. Our study will help to clarify that increased LAMP-2A expression in the naïve CD4+ T cells of PBC patients may lead to a tendency for increased activation responses, which may be involved in the development and progression of PBC. To reverse the hyperactivity of CD4+ T cells and reduce the resulting biliary injury, LAMP-2A could be a novel therapeutic target for the treatment of PBC.

Mycorrhizal fungi alter their host plant’s resistance to herbivores and their competitive ability. However, most studies on how mycorrhizae alter resistance have been conducted in single plant studies, and so the interacting effects of mycorrhizae and competition on constitutive and induced plant resistance is largely unexplored. We tested whether mycorrhizal colonization with Rhizophagus intraradice would alter herbivore performance and the expression of chemical resistance traits in tomato plants with and without intraspecific competition. We treated the plants with jasmonic acid to measure their induced chemical resistance traits which we evaluated by measuring leaf consumption by Trichoplusia ni caterpillars and two traits that affect herbivore performance: protease inhibitors, an antinutritive protein, and carbon/nitrogen ratio, a metric of plant nutritional quality. Mycorrhizae decreased resistance (increased leaf consumption) to herbivores when the plants were not in competition but had no effect in competition. While mycorrhizae reduced protease inhibitors, independent of competition or treatment with jasmonic acid, this did not increase caterpillar feeding. However, mycorrhizae, competition and induction with jasmonic acid interacted to decrease plant nutrition, measured as C/N ratio, which was correlated with caterpillar feeding. Here, we show that mycorrhizae induced decreases in plant nutritional quality; a novel mechanism by which mycorrhizae affect resistance to herbivores. Mycorrhizae and competition interact to decrease plant nutritional quality and alter resistance to herbivores.

A combined experimental work and molecular electron density theory (MEDT) analysis was performed to reveal the strict click of 1,2,3-triazole derivatives by Ag(I)-catalyzed azide-alkyne cycloaddition (AgAAC) reaction and its corresponding mechanistic pathway. Such straightforward protocol for the click formation of 1,4-disubstituted-1,2,3-triazoles makes use of AgCl as catalyst in water as solvent under ambient conditions., with excellent yields and simple experimental work-up. MEDT study was performed by using DFT calculations at the B3LYP/6-31G(d,p) (LANL2DZ for Ag) level in order to understand the observed regioselectivity in AgAAC reactions, and to delineate the number of silver(I) species and their roles in this clickable 1,2,3-triazole formation. The comparison of the mononuclear Ag(I)-acetylide and binuclear Ag(I)-acetylide in the AgAAC reaction paths concerning the AgAAC reactions, shows that the values of the energy barriers for the binuclear processes are smaller than that of the mononuclear one. The intramolecular nature of these AgAAC reactions accounts for the regioselective formation of the 1,4-regiosisomeric triazole derivatives. The ionic nature of the starting metallated species is revealed for the first time, ruling out any covalent interaction involving the silver(I) complexes throughout the reaction as supported by the ELF topological analysis of the electronic structure of the stationary points, reaffirming the zw-type mechanism of the AgAAC reactions.

A document by Mattia Andreoletti. Click on the document to view its contents.

In this paper, the Dirichlet and Neumann boundary value problems for the steady-state Stokes system of partial differential equations for a compressible viscous fluid with variable viscosity coefficient is considered in two-dimensional bounded domain. Using an appropriate parametrix, this problem is reduced to a system of direct segregated boundary-domain integral equations (BDIEs). The BDIEs in the two-dimensional case have special properties in comparison with the three dimension because of the logarithmic term in the parametrix for the associated partial differential equations. Consequently, we need to set conditions on the function spaces or on the domain to ensure the invertibility of corresponding parametrix-based hydrodaynamic single layer and hypersingular potentials and hence the unique solvability of BDIEs. Equivalence of the BDIE systems to the Dirichlet and Neumann BVPs and the invertibility of the corresponding boundary-domain integral operators in appropriate Sobolev spaces are shown.

In this paper, the Boundary-Domain Integral Equations (BDIEs) for the mixed boundary value problem(BVP) for a compressible Stokes system of partial differential equation(PDE) with variable coefficient in 2D is considered . An appropriate parametrix is used to reduce this BVP to the BDIEs. Although the theory of BDIEs in 3D is well developed, the BDIEs in 2D need a special consideration due to their different equivalence properties. As a result, we need to set conditions on the domain or on the spaces to ensure the invertibility of corresponding parametrix-based integral layer potentials and hence the unique solvability of BDIEs. The properties of corresponding potential operators are investigated. Equivalence of the BDIE systems to the mixed BVP and invertibility of the matrix operators associated with the BDIE systems in appropriate Sobolev spaces are proved.

Vulnerability assessment has become a critical issue and an important approach for regional sustainable development. The Qinghai Province, located in the northeastern part of the Qinghai-Tibet Plateau, suffers a severe grassland degradation caused by climate change and human activities. The degradation constrains the development of local animal husbandry and further affects the vulnerability of social system. In this study, based on the vulnerability assessment framework of exposure-sensitivity-adaptability, two index systems were established including ecological and social aspects. The entropy weight method was used to determine the index weight. The dynamic changes of the ecological vulnerability and social vulnerability of Qinghai province were assessed from 1995 to 2015. Results indicated that ecological vulnerability in Qinghai province increased from eastern part to the west, and decreased from northern to southern part, while social vulnerability showed an opposite trend. Key ecologically fragile areas were mainly located in the Qaidam Basin and western Three-River Headwaters Region (TRHR), while key social vulnerability areas were mainly distributed in the Qilian Mountains and eastern Qinghai province. The overall ecological vulnerability showed a decreasing trend through time, but increased in several local areas. Social vulnerability dropped significantly, especially in the eastern part of Qinghai province. The results will help to identify key vulnerable areas of Qinghai province and provide references for the ecological protection and restoration and the formulation of ecosystem management policies.

Rationale, aims and objectives: Little is known about the effect of electronic audit and feedback (A&F) in primary care and its features affecting intervention effectiveness. The aim of this systematic review is: 1) to assess electronic A&F’s effectiveness in primary care and 2) to investigate facilitating factors of electronic A&F in primary care, as proposed in previous research. These factors are the use of benchmarks, frequency, cognitive load and evidence-based aspect of the feedback. Methods: The authors searched MEDLINE, Embase, CINAHL and CENTRAL from 2010 onwards by replicating the search strategy provided in the last Cochrane review on A&F. Two independent reviewers assessed the records for their eligibility, performed the data extraction and evaluated the risk of bias of the included studies using a tool provided by Cochrane. Results: Our search resulted in 8,744 records, including the 140 RCTs from the last Cochrane Review, of which 431 full-text articles were assessed for their eligibility. Twenty-nine articles were included, of which 22 studies (76%) showed an effect of the electronic A&F intervention. Of these, only 3 studies (10.5%), targeting the quality of diabetes care and the prescription of antibiotics by dentist & physicians, met all the investigated feedback features and were effective. There was a high heterogeneity in the results and the design of the A&F interventions, causing a meta-analysis to be unreliable. Conclusion: This systematic review included 29 articles describing an electronic A&F intervention in primary care, of which 22 studies (76%) showed an effect of the intervention. It was not feasible to compare the different electronic A&F interventions and their facilitating factors because they were designed and implemented very diversely. Developing a framework or methodology for automated A&F interventions in primary care could be useful for investigating future interventions although further research is necessary.

Objectives: Older adults living in long-term care facilities (LTCFs) are particularly at risk during transitions in care, most notably from acute care back to their LCTF. Issues surrounding miscommunication of information or medications are often mentioned as important challenges. Transitional care interventions (TCi) have emerged as solutions to improve outcomes. The objective of this review was therefore to determine the effects of TCi on several indicators of quality of care, clinical outcomes, healthcare services use and satisfaction among older patients discharged from acute care to LTCFs. Methods: Medline, CINAHL, EMBASE, Cochrane Central and Social Work Abstracts were searched. Study selection (title/abstract, full-text), data extraction and assessment of study quality were conducted by two independent reviewers. A narrative synthesis of the data was performed. Results: From the 5,506 references identified, 11 were included. Eight studies reported on quality of care: six on medication problems, and two on advance directives. Four studies reported on clinical outcomes: three on mortality, two on mobility/function and one on confusion/behavioral symptoms. Seven studies reported on healthcare services use: six on hospital readmissions/ED visits, and five on hospital days. Three studies reported on satisfaction with TCi. While satisfaction levels were high with TCi, other outcomes were inconclusive. Medications problems appeared to be the outcome most likely to benefit from TCi. Discussion: TCi targeting the acute to long-term care transition have obtained inconclusive results so far. More studies investigating the outcomes of quality of care, clinical outcomes, healthcare services use are needed.