MFPred: prediction of ncRNA families based on multi-feature fusion.

Non-coding RNA (ncRNA) plays a critical role in biology. ncRNAs from the same family usually have similar functions, as a result, it is essential to predict ncRNA families before identifying their functions. There are two primary methods for predicting ncRNA families, namely, traditional biological methods and computational methods. In traditional biological methods, a lot of manpower and resources are required to predict ncRNA families. Therefore, this paper proposed a new ncRNA family prediction method called MFPred based on computational methods. MFPred identified ncRNA families by extracting sequence features of ncRNAs, and it possessed three primary modules, including (1) four ncRNA sequences encoding and feature extraction module, which encoded ncRNA sequences and extracted four different features of ncRNA sequences, (2) dynamic Bi_GRU and feature fusion module, which extracted contextual information features of the ncRNA sequence and (3) ResNet_SE module that extracted local information features of the ncRNA sequence. In this study, MFPred was compared with the previously proposed ncRNA family prediction methods using two frequently used public ncRNA datasets, NCY and nRC. The results showed that MFPred outperformed other prediction methods in the two datasets.

Fast inflows as the adjacent fuel of supermassive black hole accretion disks in quasars.

Quasars, which are exceptionally bright objects at the centres (or nuclei) of galaxies, are thought to be produced through the accretion of gas into disks surrounding supermassive black holes1-3. There is observational evidence at galactic and circumnuclear scales4 that gas flows inwards towards accretion disks around black holes, and such an inflow has been measured at the scale of the dusty torus that surrounds the central accretion disk5. At even smaller scales, inflows close to an accretion disk have been suggested to explain the results of recent modelling of the response of gaseous broad emission lines to continuum variations6,7. However, unambiguous observations of inflows that actually reach accretion disks have been elusive. Here we report the detection of redshifted broad absorption lines of hydrogen and helium atoms in a sample of quasars. The lines show broad ranges of Doppler velocities that extend continuously from zero to redshifts as high as about 5,000 kilometres per second. We interpret this as the inward motion of gases at velocities comparable to freefall speeds close to the black hole, constraining the fastest infalling gas to within 10,000 gravitational radii of the black hole (the gravitational radius being the gravitational constant multiplied by the object mass, divided by the speed of light squared). Extensive photoionization modelling yields a characteristic radial distance of the inflow of approximately 1,000 gravitational radii, possibly overlapping with the outer accretion disk.

Injectable Peptide Hydrogels Loaded with Murine Embryonic Stem Cells Relieve Ischemia In Vivo after Myocardial Infarction.

Myocardial infarction (MI) is a major cause of morbidity and mortality worldwide, especially in aging and metabolically unhealthy populations. A major target of regenerative tissue engineering is the restoration of viable cardiomyocytes to preserve cardiac function and circumvent the progression to heart failure post-MI. Amelioration of ischemia is a crucial component of such restorative strategies. Angiogenic ß-sheet peptides can self-assemble into thixotropic nanofibrous hydrogels. These syringe aspiratable cytocompatible gels were loaded with stem cells and showed excellent cytocompatibility and minimal impact on the storage and loss moduli of hydrogels. Gels with and without cells were delivered into the myocardium of a mouse MI model (LAD ligation). Cardiac function and tissue remodeling were evaluated up to 4 weeks in vivo. Injectable peptide hydrogels synergized with loaded murine embryonic stem cells to demonstrate enhanced survival after intracardiac delivery during the acute phase post-MI, especially at 7 days. This approach shows promise for post-MI treatment and potentially functional cardiac tissue regeneration and warrants large-scale animal testing prior to clinical translation.

Development of brain state dynamics involved in working memory.

Human functional brain networks are dynamically organized to enable cognitive and behavioral flexibility to meet ever-changing environmental demands. Frontal-parietal network (FPN) and default mode network (DMN) are recognized to play an essential role in executive functions such as working memory. However, little is known about the developmental differences in the brain-state dynamics of these two networks involved in working memory from childhood to adulthood. Here, we implemented Bayesian switching dynamical systems approach to identify brain states of the FPN and DMN during working memory in 69 school-age children and 51 adults. We identified five brain states with rapid transitions, which are characterized by dynamic configurations among FPN and DMN nodes with active and inactive engagement in different task demands. Compared with adults, children exhibited less frequent brain states with the highest activity in FPN nodes dominant to high demand, and its occupancy rate increased with age. Children preferred to attain inactive brain states with low activity in both FPN and DMN nodes. Moreover, children exhibited lower transition probability from low-to-high demand states and such a transition was positively correlated with working memory performance. Notably, higher transition probability from low-to-high demand states was associated with a stronger structural connectivity across FPN and DMN, but with weaker structure-function coupling of these two networks. These findings extend our understanding of how FPN and DMN nodes are dynamically organized into a set of transient brain states to support moment-to-moment information updating during working memory and suggest immature organization of these functional brain networks in childhood, which is constrained by the structural connectivity.

Default mode network scaffolds immature frontoparietal network in cognitive development.

The default mode network (DMN) is a workspace for convergence of internal and external information. The frontal parietal network (FPN) is indispensable to executive functioning. Yet, how they interplay to support cognitive development remains elusive. Using longitudinal developmental fMRI with an n-back paradigm, we show a heterogeneity of maturational changes in multivoxel activity and network connectivity among DMN and FPN nodes in 528 children and 103 young adults. Compared with adults, children exhibited prominent longitudinal improvement but still inferior behavioral performance, which paired with less pronounced DMN deactivation and weaker FPN activation in children, but stronger DMN coupling with FPN regions. Children's DMN reached an adult-like level earlier than FPN at both multivoxel activity pattern and intranetwork connectivity levels. Intrinsic DMN-FPN internetwork coupling in children mediated the relationship between age and working memory-related functional coupling of these networks, with posterior cingulate cortex (PCC)-dorsolateral prefrontal cortex (DLPFC) coupling emerging as most prominent pathway. Coupling of PCC-DLPFC may further work together with task-invoked activity in PCC to account for longitudinal improvement in behavioral performance in children. Our findings suggest that the DMN provides a scaffolding effect in support of an immature FPN that is critical for the development of executive functions in children.

ncDENSE: a novel computational method based on a deep learning framework for non-coding RNAs family prediction.

BACKGROUND: Although research on non-coding RNAs (ncRNAs) is a hot topic in life sciences, the functions of numerous ncRNAs remain unclear. In recent years, researchers have found that ncRNAs of the same family have similar functions, therefore, it is important to accurately predict ncRNAs families to identify their functions. There are several methods available to solve the prediction problem of ncRNAs family, whose main ideas can be divided into two categories, including prediction based on the secondary structure features of ncRNAs, and prediction according to sequence features of ncRNAs. The first type of prediction method requires a complicated process and has a low accuracy in obtaining the secondary structure of ncRNAs, while the second type of method has a simple prediction process and a high accuracy, but there is still room for improvement. The existing methods for ncRNAs family prediction are associated with problems such as complicated prediction processes and low accuracy, in this regard, it is necessary to propose a new method to predict the ncRNAs family more perfectly. RESULTS: A deep learning model-based method, ncDENSE, was proposed in this study, which predicted ncRNAs families by extracting ncRNAs sequence features. The bases in ncRNAs sequences were encoded by one-hot coding and later fed into an ensemble deep learning model, which contained the dynamic bi-directional gated recurrent unit (Bi-GRU), the dense convolutional network (DenseNet), and the Attention Mechanism (AM). To be specific, dynamic Bi-GRU was used to extract contextual feature information and capture long-term dependencies of ncRNAs sequences. AM was employed to assign different weights to features extracted by Bi-GRU and focused the attention on information with greater weights. Whereas DenseNet was adopted to extract local feature information of ncRNAs sequences and classify them by the full connection layer. According to our results, the ncDENSE method improved the Accuracy, Sensitivity, Precision, F-score, and MCC by 2.08[Formula: see text], 2.33[Formula: see text], 2.14[Formula: see text], 2.16[Formula: see text], and 2.39[Formula: see text], respectively, compared with the suboptimal method. CONCLUSIONS: Overall, the ncDENSE method proposed in this paper extracts sequence features of ncRNAs by dynamic Bi-GRU and DenseNet and improves the accuracy in predicting ncRNAs family and other data.

HAHNet: a convolutional neural network for HER2 status classification of breast cancer.

OBJECTIVE: Breast cancer is a significant health issue for women, and human epidermal growth factor receptor-2 (HER2) plays a crucial role as a vital prognostic and predictive factor. The HER2 status is essential for formulating effective treatment plans for breast cancer. However, the assessment of HER2 status using immunohistochemistry (IHC) is time-consuming and costly. Existing computational methods for evaluating HER2 status have limitations and lack sufficient accuracy. Therefore, there is an urgent need for an improved computational method to better assess HER2 status, which holds significant importance in saving lives and alleviating the burden on pathologists. RESULTS: This paper analyzes the characteristics of histological images of breast cancer and proposes a neural network model named HAHNet that combines multi-scale features with attention mechanisms for HER2 status classification. HAHNet directly classifies the HER2 status from hematoxylin and eosin (H&E) stained histological images, reducing additional costs. It achieves superior performance compared to other computational methods. CONCLUSIONS: According to our experimental results, the proposed HAHNet achieved high performance in classifying the HER2 status of breast cancer using only H&E stained samples. It can be applied in case classification, benefiting the work of pathologists and potentially helping more breast cancer patients.

Developmental Sex Differences in Negative Emotion Decision-Making Dynamics: Computational Evidence and Amygdala-Prefrontal Pathways.

Sex differences in human emotion and related decision-making behaviors are recognized, which can be traced back early in development. However, our understanding of their underlying neurodevelopmental mechanisms remains elusive. Using developmental functional magnetic resonance imaging and computational approach, we investigated developmental sex differences in latent decision-making dynamics during negative emotion processing and related neurocognitive pathways in 243 school-aged children and 78 young adults. Behaviorally, girls exhibit higher response caution and more effective evidence accumulation, whereas boys show more impulsive response to negative facial expression stimuli. These effects parallel sex differences in emotion-related brain maturity linking to evidence accumulation, along with age-related decrease in emotional response in the basolateral amygdala and medial prefrontal cortex (MPFC) in girls and an increase in the centromedial amygdala (CMA) in boys. Moreover, girls exhibit age-related decreases in BLA-MPFC coupling linked to evidence accumulation, but boys exhibit increases in CMA-insula coupling associated with response caution. Our findings highlight the neurocomputational accounts for developmental sex differences in emotion and emotion-related behaviors and provide important implications into the neurodevelopmental mechanisms of sex differences in latent emotional decision-making dynamics. This informs the emergence of sex differences in typical and atypical neurodevelopment of children's emotion and related functions.

Aberrant dynamic functional network connectivity in vestibular migraine patients without peripheral vestibular lesion.

PURPOSE: This study aimed to investigate changes in dynamic functional network connectivity (FNC) in patients with vestibular migraine (VM) and explore their relationship with clinical manifestations. METHODS: Resting-state functional magnetic resonance imaging (rs-fMRI) data were scanned from 35 VM patients without peripheral vestibular lesion and 40 age-, sex- and education-matched healthy controls (HC). Independent component analysis (ICA), sliding window (SW) and k-means clustering analysis were performed to explore the difference in FNC and temporal characteristics between two groups. Additionally, Pearson's partial correlation analysis was adopted to investigate the relationship between clinical manifestations and rs-fMRI results in patients with VM. RESULTS: Compared with HC, patients with VM showed increased FNC in pairs of extrastriate visual network (eVN)-ventral attention network (VAN), eVN-default mode network (DMN) and eVN-left frontoparietal network (lFPN), and exhibited decreased FNC in pairs of VAN-auditory network (AuN). The altered FNC was correlated with clinical manifestations of patients with VM. Additionally, we found increased mean dwell time and fractional windows in state 2 in VM patients compared with HC. Mean dwell time was positively correlated with headache impact test-6 (HIT-6) scores, fractional windows was positively associated with dizziness handicap inventory (DHI) scores. CONCLUSION: Our results indicated that patients with VM showed altered FNC primarily between sensory networks and networks related to cognitive, emotional and attention implementation, with more time spent in a state characterized by positive FNC between sensor cortex system and dorsal attention network (DAN). These findings could help reinforce the understanding on the neural mechanisms of VM.

Differential Interventional Effects of Omega-6 and Omega-3 Polyunsaturated Fatty Acids on High Fat Diet-Induced Obesity and Hepatic Pathology.

Current Dietary Guidelines for Americans recommend replacing saturated fat (SFA) intake with polyunsaturated fatty acids (PUFAs) and monosaturated fatty acids (MUFAs) but do not specify the type of PUFAs, which consist of two functionally distinct classes: omega-6 (n-6) and omega-3 (n-3) PUFAs. Given that modern Western diets are already rich in n-6 PUFAs and the risk of chronic disease remains high today, we hypothesized that increased intake of n-3 PUFAs, rather than n-6 PUFAs, would be a beneficial intervention against obesity and related liver diseases caused by high-fat diets. To test this hypothesis, we fed C57BL/6J mice with a high-fat diet (HF) for 10 weeks to induce obesity, then divided the obese mice into three groups and continued feeding for another 10 weeks with one of the following three diets: HF, HF+n-6 (substituted half of SFA with n-6 PUFAs), and HF+n-3 (substituted half of SFA with n-3 PUFAs), followed by assessment of body weight, fat mass, insulin sensitivity, hepatic pathology, and lipogenesis. Interestingly, we found that the HF+n-6 group, like the HF group, had a continuous increase in body weight and fat mass, while the HF+n-3 group had a significant decrease in body weight and fat mass, although all groups had the same calorie intake. Accordingly, insulin resistance and fatty liver pathology (steatosis and fat levels) were evident in the HF+n-6 and HF groups but barely seen in the HF+n-3 group. Furthermore, the expression of lipogenesis-related genes in the liver was upregulated in the HF+n-6 group but downregulated in the HF+n-3 group. Our findings demonstrate that n-6 PUFAs and n-3 PUFAs have differential effects on obesity and fatty liver disease and highlight the importance of increasing n-3 PUFAs and reducing n-6 PUFAs (balancing the n-6/n-3 ratio) in clinical interventions and dietary guidelines for the management of obesity and related diseases.

Enhancing Methane Removal Efficiency of ZrMnFe Alloy by Partial Replacement of Fe with Co.

High-purity hydrogen is extensively employed in chemical vapor deposition, and the existence of methane impurity significantly impacts the device performance. Therefore, it is necessary to purify hydrogen to remove methane. The ZrMnFe getter commonly used in the industry reacts with methane at a temperature as high as 700 ∘C, and the removal depth is not sufficient. To overcome these limitations, Co partially substitutes Fe in the ZrMnFe alloy. The alloy was prepared by suspension induction melting method, and was characterized by means of XRD, ICP, SEM and XPS. The concentration of methane at the outlet was detected by gas chromatography to characterize the hydrogen purification performance of the alloy. The removal effect of the alloy on methane in hydrogen increases first and then decreases with the increase in substitution amount, and increases with the increase in temperature. Specifically, the ZrMnFe0.7Co0.3 alloy reduces methane levels in hydrogen from 10 ppm to 0.215 ppm at 500 ∘C. ZrMnFe0.7Co0.3 alloy can remove 50 ppm of methane in helium to less than 0.01 ppm at 450 ∘C, demonstrating its excellent methane reactivity. Moreover, Co substitution reduces the formation energy barrier of ZrC, and Co in the electron-rich state demonstrates superior catalytic activity for methane decomposition.

Increased lipogenesis is critical for self-renewal and growth of breast cancer stem cells: Impact of omega-3 fatty acids.

Aberrant lipid metabolism has recently been recognized as a new hallmark of malignancy, but the characteristics of fatty acid metabolism in breast cancer stem cells (BCSC) and potential interventions targeting this pathway remain to be addressed. Here, by using the in vitro BCSC models, mammosphere-derived MCF-7 cells and HMLE-Twist-ER cells, we found that the cells with stem cell-like properties exhibited a very distinct profile of fatty acid metabolism compared with that of their parental cancer cells, characterized by increased lipogenesis, especially the activity of stearoyl-CoA desaturase 1 (SCD1) responsible for the production of monounsaturated fatty acids, and augmented synthesis and utilization of the omega-6 arachidonic acid (AA). Suppression of SCD1 activity by either enzyme inhibitors or small interfering RNA (siRNA) knockdown strikingly limited self-renewal and growth of the BCSC, suggesting a key role for SCD1 in BCSC proliferation. Furthermore, elevated levels of SCD1 and other lipogenic enzymes were observed in human breast cancer tissues relative to the noncancer tissues from the same patients and correlated with the pathological grades. Interestingly, treatment of BCSC with omega-3 fatty acids, eicosapentaenoic acid and docosahexaenoic acid, effectively downregulated the expression of the lipogenic enzymes and markedly suppressed BCSC self-renewal and growth. Dietary supplementation of nude mice bearing BCSC-derived tumors with omega-3 fatty acids also significantly reduced their tumor load. These findings have demonstrated that increased lipogenesis is critical for self-renewal and growth of BCSC, and that omega-3 fatty acids are effective in targeting this pathway to exert their anticancer effect.

Omega-3 Polyunsaturated Fatty Acids Protect against High-Fat Diet-Induced Morphological and Functional Impairments of Brown Fat in Transgenic Fat-1 Mice.

The role of omega-3 polyunsaturated fatty acids (n-3 PUFAs) in the regulation of energy homeostasis remains poorly understood. In this study, we used a transgenic fat-1 mouse model, which can produce n-3 PUFAs endogenously, to investigate how n-3 PUFAs regulate the morphology and function of brown adipose tissue (BAT). We found that high-fat diet (HFD) induced a remarkable morphological change in BAT, characterized by "whitening" due to large lipid droplet accumulation within BAT cells, associated with obesity in wild-type (WT) mice, whereas the changes in body fat mass and BAT morphology were significantly alleviated in fat-1 mice. The expression of thermogenic markers and lypolytic enzymes was significantly higher in fat-1 mice than that in WT mice fed with HFD. In addition, fat-1 mice had significantly lower levels of inflammatory markers in BAT and lipopolysaccharide (LPS) in plasma compared with WT mice. Furthermore, fat-1 mice were resistant to LPS-induced suppression of UCP1 and PGC-1 expression and lipid deposits in BAT. Our data has demonstrated that high-fat diet-induced obesity is associated with impairments of BAT morphology (whitening) and function, which can be ameliorated by elevated tissue status of n-3 PUFAs, possibly through suppressing the effects of LPS on inflammation and thermogenesis.

General, Straightforward, and Atom-Economical Synthesis of Vinyl Triflimides.

Vinyl triflimides were only accessible recently and their chemistry is yet to be discovered. Herein, we describe a general, straightforward and atom-economical synthesis of these materials from alkynes and triflimide. A vast array of terminal and internal alkynes with broad spectrum of functionalities could be employed to generate various di- and trisubstituted vinyl triflimides regiospecifically with high to specific stereoselectivity. Moreover, the protocol could be conducted on gram scale using terminal and internal alkynes. Preliminarily attempts to probe the unprecedented reactivity of vinyl triflimides revealed part of its chemical properties.

A Facile Reaction Strategy for the Synthesis of MOF-Based Pine-Needle-Like Nanocluster Hierarchical Structure for Efficient Overall Water Splitting.

Solvothermal reactions of Co(NO3)2·6H2O, 3-amino-1,2,4-triazole, and 1,2,4,5-benzenetetracarboxylic acid afforded a Co-MOF: {[Co2(Hatz)(bta)]·H2O}n. Furthermore, a unique metal-organic-framework-based pine-needle-like nanocluster hierarchical architecture has been rationally designed and prepared on a nickel foam skeleton via a simple solvothermal method based on the Co(OH)F intermediate and directly adopted as an optimum bifunctional electrocatalyst for overall water splitting. The Co-MOF/NF exhibited enhanced catalytic performance for both the hydrogen evolution reaction (HER) and the oxygen evolution reaction (OER). The optimized catalyst reveals the highest electrocatalytic characteristics, affording current densities of 50 mA cm-2 at an overpotential of 266 mV for the OER and 10 mA cm-2 at an overpotential of 115 mV forthe HER in 1 M KOH. Meanwhile, the catalyst exhibits an ultrastability in the OER process and long-term test at 20 mA cm-2 for 100 h led to only a 9.4% increase in overpotential. Furthermore, an electrolytic cell assembled from the bifunctional Co-MOF/NF delivers a current density of 10 mA cm-2 at a cell voltage of 1.548 V. This excellent performance is believed to be the result of the exotic pine-needle-like nanocluster structure with effective accessibility of dense catalytically active sites, as well as the high specific surface area and the promotion of reversible chemisorption for oxygen species due to the linkers interacting with Co ions. Further SEM, TEM, and XPS analyses of the catalyst after OER stability tests reveal that the formation of Co3O4 on the surface and unconsolidated architecture withinthe electrode materials are responsible for the high catalytic activity. This work extends the applications of MOFs in the field of electrocatalysis.

Reduced Thalamus Volume and Enhanced Thalamus and Fronto-Parietal Network Integration in the Chess Experts.

The ability of chess experts depends to a large extent on spatial visual processing, attention, and working memory, all of which are thought to be mediated by the thalamus. This study explored whether continued practice and rehearsal over a long period of time results in structural changes in the thalamic region. We found smaller gray matter volume regions in the thalami of expert Chinese chess players in comparison with novice players. We then used these regions as seeds for resting-state functional connectivity analysis and observed significantly strengthened integration between the thalamus and fronto-parietal network in expert Chinese chess players. This strengthened integration that includes a group of brain regions showing an increase in activation to external stimulation, particularly during tasks relying on working memory and attention. Our findings demonstrate structural changes in the thalamus caused by a wide range of engagement in chess problem solving, and that this strengthened functional integration with widely distributed circuitry better supports high-level cognitive control of behavior.

Cerebellar thickness changes associated with heavy cannabis use: A 3-year longitudinal study.

Cannabis is the most frequently used illicit drug in the world. Cross-sectional neuroimaging studies have revealed that chronic cannabis exposure and the development of cannabis use disorders may affect cerebllar morphology. However, cross-sectional studies cannot make a conclusive distinction between causes and consequences, and there is a lack of longitudinal neuroimaging studies. In the current study, we used longitudinal neuroimaging data to explore whether persistent cannabis use and higher levels of cannabis exposure in young adults are related to cerebellar thickness alterations. Twenty heavy cannabis users (CBs) and 22 non-cannabis-using controls (HCs) completed a comprehensive psychological assessment and a T1-structural MRI scan at baseline and a 3-year follow-up. Except for lobuleVIIB, all cerebellar subregions showed significant effects of age in both the CB and HC groups. Both VI and CrusI had higher rates of increase in CBs than in HCs. In addition, we examined the relationship between changes in cerebellar thickness and cannabis use characteristics. We found that alterations in lobule VI and CrusI were related to the age at onset first cannabis use but not the age at onset frequent cannabis use. The changes in lobule VI and CrusI were associated with the CUDIT score, even when controlling for the AUDIT score. The results indicated that an increased rate of cerebellar thickness is a risk factor for heavy cannabis use in early adulthood. Cannabis use affects the cerebellar structure, and monitoring cerebellar structural alterations that could be used as biomarkers may help guide the development of clinical tools.

Detection of functional networks within white matter using independent component analysis.

Spontaneous fluctuations in MRI signals from gray matter (GM) in the brain are interpreted as originating from variations in neural activity, and their inter-regional correlations may be analyzed to reveal functional connectivity. However, most studies of intrinsic neuronal activity have ignored the spontaneous fluctuations that also arise in white matter (WM). In this work, we explore spontaneous fluctuations in resting state MRI signals in WM based on spatial independent component analyses (ICA), a data-driven approach that separates signals into independent sources without making specific modeling assumptions. ICA has become widely accepted as a valuable approach for identifying functional connectivity within cortex but has been rarely applied to derive equivalent structures within WM. Here, BOLD signal changes in WM of a group of subjects performing motor tasks were first detected using ICA, and a spatial component whose time course was consistent with the task was found, demonstrating the analysis is sensitive to evoked BOLD signals in WM. Secondly, multiple spatial components were derived by applying ICA to identify those voxels in WM whose MRI signals showed similar temporal behaviors in a resting state. These functionally-related structures are grossly symmetric and coincide with corresponding tracts identified from diffusion MRI. Finally, functional connectivity was quantified by calculating correlations between pairs of structures to explore the synchronicity of resting state BOLD signals across WM regions, and the experimental results revealed that there exist two distinct groupings of functional correlations in WM tracts at rest. Our study provides further insights into the nature of activation patterns, functional responses and connectivity in WM, and support previous suggestions that BOLD signals in WM show similarities with cortical activations and are characterized by distinct underlying structures in tasks and at rest.

A Moderate-Fat Diet with One Avocado per Day Increases Plasma Antioxidants and Decreases the Oxidation of Small, Dense LDL in Adults with Overweight and Obesity: A Randomized Controlled Trial.

BACKGROUND: Avocados are a nutrient-dense source of MUFAs and are rich in antioxidants. Avocados have an additional LDL cholesterol (LDL-C) lowering effect beyond that observed when their MUFAs are substituted for SFAs, especially on small, dense LDL (sdLDL) particles, which are susceptible to in vivo oxidation and associated with increased risk of cardiovascular disease (CVD). OBJECTIVES: We investigated whether a healthy diet with 1 avocado daily decreased the following secondary outcomes: circulating oxidized LDL (oxLDL) and related oxidative stress markers. METHODS: A randomized, crossover, controlled feeding trial was conducted with 45 men and women, aged 21-70 y, with overweight or obesity and elevated LDL-C (25th-90th percentile). Three cholesterol-lowering diets were provided (5 wk each) in random sequences: a lower-fat (LF) diet (24% calories from fat-7% SFAs, 11% MUFAs, 6% PUFAs) and 2 moderate-fat (MF) diets (34% calories from fat-6% SFAs, 17% MUFAs, 9% PUFAs): the avocado (AV) diet included 1 Hass avocado (∼136 g) per day, and the MF diet used high oleic acid oils to match the fatty acid profile of 1 avocado. A general linear mixed model was used to analyze the treatment effects. RESULTS: Compared with baseline, the AV diet significantly decreased circulating oxLDL (-7.0 U/L, -8.8%, P = 0.0004) and increased plasma lutein concentration (19.6 nmol/L, 68.7%, P < 0.0001), and both changes differed significantly from that after the MF and LF diets (P ≤ 0.05). The change in oxLDL caused by the AV diet was significantly correlated with the changes in the number of sdLDL particles (r = 0.32, P = 0.0002) but not large, buoyant LDL particles. CONCLUSIONS: One avocado a day in a heart-healthy diet decreased oxLDL in adults with overweight and obesity, and the effect was associated with the reduction in sdLDL. This trial was registered at http://www.clinicaltrials.gov as NCT01235832.

Synthesis of tetracyclic oxindoles and evaluation of their α-glucosidase inhibitory and glucose consumption-promoting activity.

A series of tetracyclic oxindole derivatives was synthesized by asymmetric 1, 3-dipole reaction in 2-4 steps in 57-86% overall yields. These compounds were evaluated for α-glucosidase inhibitory and glucose consumption-promoting activity in vitro. Compound 4l competitively and reversibly inhibited α-glucosidase (IC50 = 3.64 µM) with activity 14-fold higher than that of acarbose. Docking analysis substantiated these findings. In addition, compound 4l exhibited significant glucose consumption promoting activity at 1 µM.