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Sterol regulatory element-binding protein 2 (SREBP2) is considered to be a major regulator to control cholesterol homeostasis in mammals. However, the role of SREBP2 in teleost remains poorly understand. Here, we explored the molecular characterization of SREBP2 and identified SREBP2 as a key modulator for 3-hydroxy-3-methylglutaryl-coenzyme A reductase (HMGCR) and 7-dehydrocholesterol reductase (DHCR7) which were rate-limiting enzymes of cholesterol biosynthesis. Moreover, dietary palm oil (PO) in vivo or palmitic acid (PA) treatment in vitro elevated cholesterol content through triggering SREBP2-mediated cholesterol biosynthesis in large yellow croaker. Furthermore, our results also found that PA-induced activation of SREBP2 was dependent on the stimulating of endoplasmic reticulum stress (ERS) in croaker myocytes and inhibition of ERS by 4-Phenylbutyric acid alleviated PA-induced SREBP2 activation and cholesterol biosynthesis. In summary, our findings reveal a novel insight for understanding the role of SREBP2 in regulation of cholesterol metabolism in fish and may deepen the link between dietary fatty acid and cholesterol biosynthesis.
The Community Research Advisory Council (C-RAC) of the Johns Hopkins Institute for Clinical and Translational Research was established in 2009 to provide community-engaged research consultation services. In 2016–2017, C-RAC members and researchers were surveyed on their consultation experiences. Survey results and a 2019 stakeholder meeting proceeding helped redesign the consultation services. Transitioning to virtual consultations during COVID-19, the redesigning involved increasing visibility, providing consultation materials in advance, expanding member training, and effective communications. An increase in consultations from 28 (2009–2017) to 114 (2020–2022) was observed. Implementing stakeholder-researcher inputs is critical to holistic and sustained community-engaged research.
It is very challenging for robots to perform grinding and polishing tasks on surfaces with unknown geometry. Most existing methods solve this problem by modeling the relationship between the force sensing information and surface normal vectors by analyzing the forces on special end tools such as spherical tools and cylindrical tools and simplified friction model. In this paper, we propose a normal vectors learning method to simultaneously control end-effector force and direction on unknown surfaces. First, the relation that mapping the force sensing information to the surface normal vectors is learned from the demonstrated data on the known plane using locally weighted regression. Next, the learned relation is used to estimate surface normal vectors on the unknown surface. To improve the force control precision on the unknown geometry surface, the adaptive force control is developed. To improve the direction control precision due to friction, the iterative learning control is developed. The proposed method is verified by comparative simulations and experiments using the Franka robot. Results show that the end-effector can be controlled perpendicular to the surface with a certain force.
The axial offset joint has two rotating axes that do not intersect but have a specific offset in space. It is used widely in parallel manipulators (PMs). The offset-joint workspace can directly affect the PM workspace. This study performed a theoretical derivation and workspace analysis of a class of axial offset joints. First, a theoretical parametric model describing the rotation range of the offset joint is established that considers the interference of the offset joint because of the contact between the upper- and lower-joint brackets during movement. Second, the analytical expressions of the offset-joint workspace are formulated based on the coordinate system transformation. The offset-joint workspace is theoretically calculated in this study using formulations. Then, through a comparative analysis, the superiority of the offset joint compared with the universal joint is verified. The theoretical formulations in this paper can be used to calculate the workspace of a class of axial offset joints. Finally, based on a workspace analysis of three types of PMs using offset, universal, and spherical joints, the offset-joint PM workspace is much larger than those of the other two types.
Childhood maltreatment exerts long-term consequences on sleep health, and different subtypes could constitute maltreatment patterns. However, how naturally occurring patterns of childhood maltreatment affect subsequent sleep quality and the underlying mechanisms remain relatively unclear, particularly in youths undergoing a transitional period and in the Chinese cultural context. In this study, we identified childhood maltreatment patterns and explored how these patterns predicted sleep problems through differential emotion regulation strategies. We tracked 1929 Chinese youths (Mage = 18.49; 63.1% females) for one year. Three latent profiles were identified: low maltreatment exposure, high physical and emotional maltreatment, and high sexual abuse. Compared with “low maltreatment exposure,” youths in “high physical and emotional maltreatment” used fewer cognitive reappraisal strategies, and those in “high sexual abuse” used more expressive suppression, and then leading to more sleep problems. This study reveals new insights into the patterns of childhood maltreatment in Chinese youths and implies that individuals exposed to sexual abuse or a combination of physical and emotional maltreatment experience sleep problems through the impairment of differential emotion regulation processes. It also highlights the necessity of setting differential targets on emotion regulation strategies for distinct groups of maltreatment and considering the co-occurrence of physical and emotional maltreatment.
Mammalian oocytes not fertilized immediately after ovulation can undergo ageing and a rapid decline in quality. The addition of antioxidants can be an efficient approach to delaying the oocyte ageing process. Onion peel extract (OPE) contains quercetin and other flavonoids with natural antioxidant activities. In this study, we investigated the effect of OPE on mouse oocyte ageing and its mechanism of action. The oocytes were aged in vitro in M16 medium for 16 h after adding OPE at different concentrations (0, 50, 100, 200, and 500 μg/ml). The addition of 100 μg/ml OPE reduced the oocyte fragmentation rate, decreased the reactive oxygen species (ROS) level, increased the glutathione (GSH) level, and improved the mitochondrial membrane potential compared with the control group. The addition of OPE also increased the expression of SOD1, CAT, and GPX3 genes, and the caspase-3 activity in OPE-treated aged oocytes was significantly lower than that in untreated aged oocytes and similar to that in fresh oocytes. These results indicated that OPE delayed mouse oocyte ageing by reducing oxidative stress and apoptosis and enhancing mitochondrial function.
The selection of an analogical source is a critical step in the design-by-analogy process. Previous researchers have explored the reasons and preferences of individual designers or design teams in selecting analogical sources. Non-designers, who instead have more knowledge of other fields, may offer new possibilities for retrieving novel analogical sources. This study focuses on differences in the selection of analogical sources between collaborative design teams composed of designers and nondesigners. There are indeed significant differences in the selection of the source type, the reasons for selecting the source, the level of abstraction in inspiration stimuli, and the novelty of design ideas between designers and non-designers. This work may provide theoretical guidance for the development of collaborative design tools and methods for teams composed of designers and non-designers with different knowledge bases.
Obsessive-compulsive disorder (OCD) is a chronic mental illness characterized by abnormal functional connectivity among distributed brain regions. Previous studies have primarily focused on undirected functional connectivity and rarely reported from network perspective.
To better understand between or within-network connectivities of OCD, effective connectivity (EC) of a large-scale network is assessed by spectral dynamic causal modeling with eight key regions of interests from default mode (DMN), salience (SN), frontoparietal (FPN) and cerebellum networks, based on large sample size including 100 OCD patients and 120 healthy controls (HCs). Parametric empirical Bayes (PEB) framework was used to identify the difference between the two groups. We further analyzed the relationship between connections and Yale-Brown Obsessive Compulsive Scale (Y-BOCS).
OCD and HCs shared some similarities of inter- and intra-network patterns in the resting state. Relative to HCs, patients showed increased ECs from left anterior insula (LAI) to medial prefrontal cortex, right anterior insula (RAI) to left dorsolateral prefrontal cortex (L-DLPFC), right dorsolateral prefrontal cortex (R-DLPFC) to cerebellum anterior lobe (CA), CA to posterior cingulate cortex (PCC) and to anterior cingulate cortex (ACC). Moreover, weaker from LAI to L-DLPFC, RAI to ACC, and the self-connection of R-DLPFC. Connections from ACC to CA and from L-DLPFC to PCC were positively correlated with compulsion and obsession scores (r = 0.209, p = 0.037; r = 0.199, p = 0.047, uncorrected).
Our study revealed dysregulation among DMN, SN, FPN, and cerebellum in OCD, emphasizing the role of these four networks in achieving top-down control for goal-directed behavior. There existed a top-down disruption among these networks, constituting the pathophysiological and clinical basis.
Mental disorders, including depression, obsessive compulsive disorder (OCD), and schizophrenia, share a common neuropathy of disturbed large-scale coordinated brain maturation. However, high-interindividual heterogeneity hinders the identification of shared and distinct patterns of brain network abnormalities across mental disorders. This study aimed to identify shared and distinct patterns of altered structural covariance across mental disorders.
Subject-level structural covariance aberrance in patients with mental disorders was investigated using individualized differential structural covariance network. This method inferred structural covariance aberrance at the individual level by measuring the degree of structural covariance in patients deviating from matched healthy controls (HCs). T1-weighted anatomical images of 513 participants (105, 98, 190 participants with depression, OCD and schizophrenia, respectively, and 130 age- and sex-matched HCs) were acquired and analyzed.
Patients with mental disorders exhibited notable heterogeneity in terms of altered edges, which were otherwise obscured by group-level analysis. The three disorders shared high difference variability in edges attached to the frontal network and the subcortical-cerebellum network, and they also exhibited disease-specific variability distributions. Despite notable variability, patients with the same disorder shared disease-specific groups of altered edges. Specifically, depression was characterized by altered edges attached to the subcortical-cerebellum network; OCD, by altered edges linking the subcortical-cerebellum and motor networks; and schizophrenia, by altered edges related to the frontal network.
These results have potential implications for understanding heterogeneity and facilitating personalized diagnosis and interventions for mental disorders.
Few studies examined the association of energy, macronutrients and food consumption at dinner v. breakfast with hypercholesterolaemia. A total of 27 911 participants from the National Health and Nutrition Examination Survey (2003–2016) were included in the cross-sectional study. Energy, macronutrients and food consumption at breakfast, dinner and the difference at dinner v. breakfast (Δratio) were calculated. Multiple logistic regression models and substitution effects of foods at dinner with breakfast were also performed. After adjustment for potential covariates, compared with the lowest quintile, participants in the highest quintile of Δratio in terms of energy had a higher risk of prevalent hypercholesterolaemia (ORΔratio of energy 1·16, 95 % CI (1·01, 1·33)) mainly due to Δratio of low-quality carbohydrates and plant protein (ORΔratio of low-quality carbohydrates 1·19; 95 % CI (1·05, 1·35)); ORΔratio of plant protein 1·13; 95 % CI (1·01, 1·28)). ΔAdded sugars and Δnuts were associated with hypercholesterolaemia (ORΔadded sugars 1·01; 95 % CI (1·00, 1·02)); ORΔnuts 1·08; 95 % CI (1·01, 1·16)). Furthermore, the substitution of added sugars, nuts and processed meat at dinner with breakfast could reduce the OR of hypercholesterolaemia. This study indicated that among US adults, overconsumption of energy, macronutrients including low-quality carbohydrates and plant protein at dinner than breakfast was significantly associated with a higher risk of prevalent hypercholesterolaemia. The replacing of added sugar, nuts and processed meat at dinner with breakfast reduced the risk of prevalent hypercholesterolaemia. This study emphasised the importance of meal timing in the prevention of hypercholesterolaemia.
Previous studies have confirmed that miR-146a-5p overexpression suppresses neurogenesis, thereby enhancing depression-like behaviors. However, it remains unclear how miR-146a-5p dysregulation produces in vivo brain structural abnormalities in patients with major depressive disorder (MDD).
In this case–control study, we combined cortical morphology analysis of magnetic resonance imaging (MRI) and miR-146a-5p quantification to investigate the neuropathological effect of miR-146a-5p on cortical thickness in MDD patients. Serum-derived exosomes that were considered to readily cross the blood-brain barrier and contain miR-146a-5p were isolated for miRNA quantification. Moreover, follow-up MRI scans were performed in the MDD patients after 6 weeks of antidepressant treatment to further validate the clinical relevance of the relationship between miR-146a-5p and brain structural abnormalities.
In total, 113 medication-free MDD patients and 107 matched healthy controls were included. Vertex-vise general linear model revealed miR-146a-5p-dependent cortical thinning in MDD patients compared with healthy individuals, i.e., overexpression of miR-146a-5p was associated with reduced cortical thickness in the left orbitofrontal cortex (OFC), anterior cingulate cortex, bilateral lateral occipital cortices (LOCs), etc. Moreover, this relationship between baseline miR-146a-5p and cortical thinning was nonsignificant for all regions in the patients who had received antidepressant treatment, and higher baseline miR-146a-5p expression was found to be related to greater longitudinal cortical thickening in the left OFC and right LOC.
The findings of this study reveal a relationship between miR-146a-5p overexpression and cortical atrophy and thus may help specify the in vivo mediating effect of miR-146a-5p dysregulation on brain structural abnormalities in patients with MDD.
Direct numerical simulations of turbulent pipe flow subjected to streamwise-varying wall rotation are performed. This control method is able to achieve drag reduction and even relaminarize the flow under certain control parameters at friction Reynolds number $Re_\tau =180$. Two control parameters, which are velocity amplitude and wavelength, are considered. It is found that increasing the wavelength rather than increasing the amplitude seems to be a better choice to improve the control efficiency. An annular boundary layer, called the spatial Stokes layer (SSL), is formed by the wall rotation. Based on the thickness of the SSL, two types of drag-reduction scenarios can be identified roughly. When the thickness is low, the SSL acts as a spacer layer, inhibiting the formation of streamwise vortices and thereby reducing the shear stress. The flow structures outside the SSL are stretched in the streamwise direction due to the increased velocity gradient. Within the SSL, the turbulence intensity diminishes dramatically. When the thickness is large, a streamwise wavy pattern of near-wall streaks is formed. The streak orientation is dominated by the mean shear-strain vector outside the viscous sublayer, and there is a phase difference between the streak orientation and local mean velocity vector. The streamwise scales of near-wall flow structures are reduced significantly, resulting in the disruption of downstream development of flow structures and hence leading to the drag reduction. Furthermore, it is found that it requires both large enough thickness of the SSL and velocity amplitude to relaminarize the turbulence. The relaminarization mechanism is that the annular SSL can absorb energy continuously from wall-normal stress due to the rotational effect, thereby the turbulence self-sustaining process cannot be maintained. For the relaminarization cases, the laminar state is stable to even extremely large perturbations, which possibly makes the laminar state the only fixed point for the whole system.
Due to the lack of research between the inner layers in the structure of colonic mucous and the metabolism of fatty acid in the constipation model, we aim to determine the changes in the mucous phenotype of the colonic glycocalyx and the microbial community structure following treatment with Rhubarb extract in our research. The constipation and treatment models are generated using adult male C57BL/6N mice. We perform light microscopy and transmission electron microscopy (TEM) to detect a Muc2-rich inner mucus layer attached to mice colon under different conditions. In addition, 16S rDNA sequencing is performed to examine the intestinal flora. According to TEM images, we demonstrate that Rhubarb can promote mucin secretion and find direct evidence of dendritic structure-linked mucus structures with its assembly into a lamellar network in a pore size distribution in the isolated colon section. Moreover, the diversity of intestinal flora has noticeable changes in constipated mice. The present study characterizes a dendritic structure and persistent cross-links have significant changes accompanied by the alteration of intestinal flora in feces in models of constipation and pretreatment with Rhubarb extract.
This study compares the detection rates of haemoglobin absorption spectral imaging and white light imaging in laryngeal papilloma surgery.
Seventeen patients with laryngeal papilloma who underwent surgery in our department from September 2019 to September 2021 were selected. All patients underwent carbon dioxide laser surgery under a microscope. The lesion sites were explored in white light mode and haemoglobin absorption spectral imaging mode. The pharynx and larynx anatomical sites were evaluated using Derkay's all-position scoring system. The numbers and scores for lesions observed in the two modes were compared.
In 17 cases, there were statistically significant differences in the numbers of laryngeal papillomas (Derkay score) detected by white light mode and haemoglobin absorption spectral imaging mode. In 9 of 17 patients (52.94 per cent), the haemoglobin absorption spectral imaging mode showed additional diseased tissues.
The haemoglobin absorption spectral imaging mode can dynamically identify diseased tissues in carbon dioxide laser surgery under a microscope and improve the laryngeal papilloma detection rate.
The hydrodynamic interactions (HIs) of two colloidal spheres characterized by the translation–translation (T–T) couplings have been studied under various confinements, but little is known regarding the HIs of anisotropic particles and rotational motions, which are common in nature and industry. Here, we study the T–T, rotation–rotation (R–R) and translation–rotation (T–R) hydrodynamic couplings of two colloidal ellipsoids sediment on the bottoms of channels in experiment, theory and simulation. We find that the degree of confinement and the particle shape anisotropy are critical tuning factors resulting in anomalous hydrodynamic and diffusive behaviours. The negative R–R coupling reflects the tendency of opposite rotations of two neighbouring ellipsoids. The positive T–R coupling reflects that an ellipsoid rotates away from the channel axis as another ellipsoid approaches. As the channel width increases, the positive T–T coupling changes to an abnormal negative coupling, indicating that the single-file diffusion can exist even in wide channels. By contrast, only positive T–T couplings were observed for spheres in channels. The T–T coupling increases with the aspect ratio p. The R–R coupling is the maximum at a moderate p ~ 2.8. The T–R coupling is the maximum at a moderate degree of confinement. The spatial range of HIs is longer than that of spheres and increases with p. We propose a simple model which reproduces some coupling phenomena between two ellipsoids, and it is further confirmed by low-Reynolds-number hydrodynamic simulation. These findings shed new light on anisotropic particle diffusion in porous media, transport through membranes, microfluidics and microrheology.
We aimed to investigate the associations between dietary branched-chain amino acids (BCAA) intake and long-term risks of CVD, cancer and all-cause mortality in nationwide survey participants aged ≥ 18.
This was a prospective cohort study. Dietary intakes of BCAA (leucine, isoleucine and valine) were determined from the total nutrient intake document. The main outcomes were CVD, cancer and all-cause mortality.
A nationally representative sample of US adults were recruited by the National Center for Health Statistics (NCHS) from 1988 to 1994.
A total of 14 397 adults aged ≥ 18 who participated in the United States National Health and Nutrition Examination Survey III (NHANES III) were included.
During 289 406 person-years of follow-up, we identified 4219 deaths, including 1133 from CVD and 926 from cancer. After multivariate adjustment, the hazard ratios (95 % confidence intervals) of all-cause mortality in the highest dietary BCAA and isoleucine intake quintile (reference: lowest quintiles) were 0·68 (0·48, 0·97) and 0·68 (0·48, 0·97), respectively. Each one-standard-deviation increase in total dietary BCAA or isoleucine intake was associated with an 18 % or 21 % decrease in the risk of all-cause mortality, respectively. The serum triglyceride (TAG) concentration was found to modify the association between the dietary BCAA intake and all-cause mortality (Pfor interaction = 0·008).
In a nationally representative cohort, higher dietary intakes of BCAA and isoleucine were independently associated with a lower risk of all-cause mortality, and these associations were stronger in participants with higher serum TAG concentrations.
Angiopoietin-like 4 (ANGPTL4) is a potent regulator of TAG metabolism, but knowledge of the mechanisms underlying ANGPTL4 transcription in response to fatty acids is still limited in teleost. In the current study, we explored the molecular characterisation of ANGPTL4 and regulatory mechanisms of ANGPTL4 in response to fatty acids in large yellow croaker (Larimichthys crocea). Here, croaker angptl4 contained a 1416 bp open reading frame encoding a protein of 471 amino acids with highly conserved 12-amino acid consensus motif. Angptl4 was widely expressed in croaker, with the highest expression in the liver. In vitro, oleic and palmitic acids (OA and PA) treatments strongly increased angptl4 mRNA expression in croaker hepatocytes. Moreover, angptl4 expression was positively regulated by PPAR family (PPAR-α, β and γ), and expression of PPARγ was also significantly increased in response to OA and PA. Moreover, inhibition of PPARγ abrogated OA- or PA-induced angptl4 mRNA expression. Beyond that, PA might increase angptl4 expression partly via the insulin signalling. Overall, the expression of ANGPTL4 is strongly upregulated by OA and PA via PPARγ in the liver of croaker, which contributes to improve the understanding of the regulatory mechanisms of ANGPTL4 in fish.