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This study investigated the influence mechanism of DBC on the aggregation and deposition behaviors, which provides new insights into the stability and transport of PSs in complex aquatic environments.Despite advances in conceptual understanding, single-stressor abatement approaches remain common in the management of fresh waters, even though they can produce unexpected ecological responses when multiple stressors interact. Here we identify limitations restricting the development of multiple-stressor management strategies and address these, bridging theory and practice, within a novel empirical framework. Those critical limitations include that (i) monitoring schemes fall short of accounting for theory on relationships between multiple-stressor interactions and ecological responses, (ii) current empirical modelling approaches neglect the prevalence and intensity of multiple-stressor interactions, and (iii) mechanisms of stressor interactions are often poorly understood. We offer practical recommendations for the use of empirical models and experiments to predict the effects of freshwater degradation in response to changes in multiple stressors, demonstrating this approach in a case study. Drawing on our framework, we offer practical recommendations to support the development of effective management strategies in three general multiple-stressor scenarios.Support for caregivers of people with dementia has been identified as an action area in the Global Action Plan on the Public Health Response to Dementia 2017-2025 by the World Health Organization (WHO). As a step towards that, WHO developed iSupport - an online program to provide support and training for caregivers of people with dementia. To address the need of caregivers in India, the iSupport program was adapted to the Indian cultural setting. The process of adaptation consisted of four phases (a) information gathering (review of literature and focus group discussions), (b) preliminary adaptation design (modifications using an adaptation guide), (c) preliminary adaptation tests (face-to-face interviews and online test run), and (d) adaptation refinement (final modifications to the intervention and study process). The initial adaptation was carried out by effecting changes in words, names, resources, caregiving scenarios and audio files to make the English version of iSupport suitable to the Indian cultural context. The results of the qualitative adaptation tests provided additional recommendations like changing the links to India specific websites, revising the eligibility criterion for caregiving duration, re-wording of e-mail texts, inclusion of a time estimate required to complete the assessments and decreasing the numbers of screens that the caregivers had to navigate in the program, which were incorporated in the final phase. Preliminary data showed that the caregivers who participated in the adaptation process found the changes acceptable. Translation of iSupport to different Indian languages could be undertaken after initial effectiveness of the program is established.As an indispensable part of the marine ecosystem, phytoplankton are important prey for zooplankton and various marine animals with important commercial value. The influence of seawater warming and eutrophication on phytoplankton communities is well known, but few studies have explained the effects of the interaction between temperature and nutrients on marine phytoplankton. Through meta-analysis and meta-regression, the phytoplankton responses to the effects of nutrient addition and seawater warming were evaluated in this study. Nitrogen (N) addition led to an increase in phytoplankton biomass, while phosphorus (P) had no significant effect on phytoplankton biomass. However, this result may be biased by the uneven distribution of the research area. N limitation is widespread in the areas where these collected studies were conducted, including many parts of North and South Atlantic and West Pacific Oceans. The key limiting nutrient in other areas lacking corresponding experiments, however, remain unclear. The effect of seawater warming was not significant, which indicates the uncertainty about the effect of temperature on phytoplankton. click here The results of ANOVA show that nutrient addition and seawater warming had similar effects in various marine habitats (coastal regions, estuaries and open seas), while salinity could have caused the difference in the N effects among the three habitats. Furthermore, our results showed that the impact of temperature depends on nutrient conditions, especially N status, which has rarely been considered before. This result demonstrated the importance of evaluating nutrient limitation patterns when studying climate warming. The impact of rising temperatures may need to be reevaluated because N limitation is common.Colchicine binding site inhibitors (CBSIs) hold great potential for the treatment of various tumors and they can overcome multidrug resistance which the existing tubulin inhibitors such as paclitaxel and vinorelbine are faced with. Herein, we report the design, synthesis and biological evaluation of a series of tetrahydro-quinoxaline derivatives as colchicine binding site inhibitors. All the synthesized compounds were evaluated for their in vitro antiproliferative activities against HT-29 and Hela cancer cell lines, and most of the target compounds demonstrated moderate to strong activities towards two tumor cell lines. In addition, the structure-activity relationships of these derivatives were also discussed. Among them, compounds 11a and 11b showed the most potent activities. Moreover, compound 11a inhibited the tubulin polymerization in both cell-free and cellular assays. Further profiling of compound 11a revealed that it arrested cell cycle in G2/M and induced cell apoptosis in a dose-dependent manner. Furthermore, molecular docking study proved that compound 11a acted on the colchicine binding site. Therefore, 11a is a promising candidate for the discovery of colchicine binding site inhibitors.Thirteen alkaloids, which include three new diketopiperazines, namely, 3-hydroxyprotuboxepin K (4), 3,15-dehydroprotuboxepin K (5), and versiamide A (6), together with ten known alkaloid derivatives (1-3 and 7-13), were isolated from the marine red algal-derived fungus Aspergillus creber EN-602. Versiamide A (6) represents the first example of a naturally occurring quinazolinone alkaloid with a diketopiperazine ring that is derived from phenylalanine (Phe) and leucine (Leu). The structures of these compounds were elucidated by detailed interpretation of their 1D/2D NMR spectroscopic and mass spectrometric data, while the absolute configurations of compounds 1-6 were established on the basis of X-ray crystallographic analysis and time-dependent density functional (TDDFT) calculations of the ECD spectra. Compounds 1, 2, and 4 exhibited inhibitory activity against the angiotensin converting enzyme (ACE) with IC50 values of 11.2, 16.0, and 22.4 μM, respectively, and compounds 5 and 6 inhibited various aquatic bacteria with MIC values that ranged from 8 to 64 μg/mL. The intermolecular interactions and potential binding sites between compounds 1-6 and ACE were investigated via molecular docking simulations.

Freezing of gait (FOG) is a common symptom in Parkinson's Disease (PD) patients. Previous studies have reported relationships between FOG, substantia nigra (SN) degeneration, dopamine transporter (DAT) concentration, as well as amyloid β deposition. However, there is a paucity of research on the concurrent impact of white matter damage.

To assess the inter-relationships between these different co-morbidities, their impact on future FOG and whether they act independently of each other.

We used baseline MRI and longitudinal gait data from 423 de novo PD patients from the Parkinson's Progression Markers Initiative (PPMI). We used deformation based morphometry (DBM) from T1-weighted MRI to measure SN atrophy, and segmentation of white matter hyperintensities (WMH) as a measure of WM pathological load. Putamen and caudate DAT levels from SPECT as well as cerebrospinal fluid (CSF) amyloid β were obtained directly from the PPMI. Following correlation analyses, we investigated whether WMH burden mediates the impact of amyloid β on future FOG.

SN DBM, WMH load, putamen and caudate DAT activity and CSF amyloid β levels were significantly different between PD patients with and without future FOG (p<0.008). Mediation analysis demonstrated an effect of CSF amyloid β levels on future FOG via WMH load, independent of SN atrophy and striatal DAT activity levels.

Amyloid β might impact future FOG in PD patients through an increase in WMH burden, in a pathway independent of Lewy body pathology.

Amyloid β might impact future FOG in PD patients through an increase in WMH burden, in a pathway independent of Lewy body pathology.

Huntington's disease (HD) is a severe neurodegenerative disorder with no effective treatment. Minimally-invasive biomarkers such as blood neurofilament light chain (NfL) in HD are therefore needed to quantitatively characterize neuronal loss. NfL levels in HD are known to correlate with disease progression and striatal atrophy, but whether they also reflect cortical degeneration remains elusive.

In a sample of 35 HD patients, we characterized the cortical macro (cortical thickness) and microstructural (increased intracortical diffusivity) correlates of plasma NfL levels. We further investigated whether NfL-related cortical alterations correlated with clinical indicators of disease progression.

Increased plasma NfL levels in HD reflected posterior-cortical microstructural degeneration, but not reduced cortical thickness (p<0.05, corrected). Importantly, these imaging alterations correlated, in turn, with more severe motor, cognitive and behavioral symptoms.

Plasma NfL levels may be useful for tracking clinically-meaningful cortical deterioration in HD. Additionally, our results further reinforce the role of intracortical diffusivity as a valuable imaging indicator in movement disorders.

Plasma NfL levels may be useful for tracking clinically-meaningful cortical deterioration in HD. Additionally, our results further reinforce the role of intracortical diffusivity as a valuable imaging indicator in movement disorders.MicroRNAs (miRNAs) are a group of small non-coding RNAs that post-transcriptionally control expression of genes by targeting mRNAs. miRNA alterations partake in the establishment and progression of different types of human cancer. Consequently, expression profiling of miRNA in human cancers has correlations with cancer detection, staging, progression, and response to therapies. Particularly, amplification, deletion, abnormal pattern of epigenetic factors and the transcriptional factors that mediate regulation of primary miRNA frequently change the landscape of miRNA expression in cancer. Indeed, changes in the quantity and quality of miRNAs are associated with the initiation of cancer, its progression and metastasis. Additionally, miRNA profiling has been used to categorize genes that can affect oncogenic pathways in cancer. Here, we discuss several circulating miRNA signatures, their expression profiles in different types of cancer and their impacts on cellular processes.