The Association between Dietary Nutrient Intake and Acceleration of Aging: Evidence from NHANES.

The acceleration of aging is a risk factor for numerous diseases, and diet has been identified as an especially effective anti-aging method. Currently, research on the relationship between dietary nutrient intake and accelerated aging remains limited, with existing studies focusing on the intake of a small number of individual dietary nutrients. Comprehensive research on the single and mixed anti-aging effects of dietary nutrients has not been conducted. This study aimed to comprehensively explore the effects of numerous dietary nutrient intakes, both singly and in combination, on the acceleration of aging. Data for this study were extracted from the 2015-2018 National Health and Nutrition Examination Surveys (NHANES). The acceleration of aging was measured by phenotypic age acceleration. Linear regression (linear), restricted cubic spline (RCS) (nonlinear), and weighted quantile sum (WQS) (mixed effect) models were used to explore the association between dietary nutrient intake and accelerated aging. A total of 4692 participants aged ≥ 20 were included in this study. In fully adjusted models, intakes of 16 nutrients were negatively associated with accelerated aging (protein, vitamin E, vitamin A, beta-carotene, vitamin B1, vitamin B2, vitamin B6, vitamin K, phosphorus, magnesium, iron, zinc, copper, potassium, dietary fiber, and alcohol). Intakes of total sugars, vitamin C, vitamin K, caffeine, and alcohol showed significant nonlinear associations with accelerated aging. Additionally, mixed dietary nutrient intakes were negatively associated with accelerated aging. Single dietary nutrients as well as mixed nutrient intake may mitigate accelerated aging. Moderately increasing the intake of specific dietary nutrients and maintaining dietary balance may be key strategies to prevent accelerated aging.

Disordered Ballistic Bismuth Nano-waveguides for Highly Efficient Thermoelectric Energy Conversion.

Junctions based on electronic ballistic waveguides, such as semiconductor nanowires or nanoribbons with transverse structural variations in the order of a large fraction of their Fermi wavelength, are suggested as highly efficient thermoelectric (TE) devices. Full harnessing of their potential requires a capability to either deterministically induce structural variations that tailor their transmission properties at the Fermi level or alternatively to form waveguides that are disordered (chaotic) but can be structurally modified continuously until favorable TE properties are achieved. Well-established methods to realize either of these routes do not exist. Here, disordered bismuth (Bi) waveguides are reported, which are both formed and structurally tuned by electromigration until their efficiency as TE devices is maximized. In accordance with theory, the conductance of the most efficient TE waveguides is in the sub quantum of conductance regime. The stability of these structures is found to be substantially higher than other actively studied devices such as single molecule junctions.

Remnant cholesterol traits and risk of stroke: A multivariable Mendelian randomization study.

Observational epidemiological studies have reported a relationship between remnant cholesterol and stroke. However, the results are inconclusive, and causality remains unclear due to confounding or reverse causality. Our objective in this study was to investigate the causal relevance of remnant cholesterol and the risk of stroke and its subtypes using the Mendelian randomization (MR) approach. Genome-wide association studies (GWASs) including 115,082 European individuals (UK Biobank) were used to identify instruments for remnant cholesterol, including intermediate-density lipoprotein (IDL) cholesterol and very-low-density lipoprotein (VLDL) cholesterol. Summary-level data for total stroke, intracerebral hemorrhage, subarachnoid hemorrhage, ischemic stroke (IS), and IS subtypes were obtained from GWAS meta-analyses conducted by the MEGASTROKE consortium. Univariable and multivariable MR analyses were performed. The GWAS identified multiple single-nucleotide polymorphisms after clumping for remnant cholesterol (n = 52), IDL cholesterol (n = 62), and VLDL cholesterol (n = 67). Assessed individually using MR, remnant cholesterol (weighted median: odds ratio [OR] 1.32 per 1-SD higher trait; 95% CI: 1.04-1.67; P = 0.024) had effect estimates consistent with a higher risk of LAS-IS, driven by IDL cholesterol (OR 1.32; 95% CI: 1.04-1.68; P = 0.022). In multivariable MR, IDL cholesterol (OR 1.46; 95% CI: 1.10-1.93; P = 0.009) retained a robust effect on LAS-IS after controlling for VLDL cholesterol and high-density lipoprotein cholesterol. The MR analysis did not indicate causal associations between remnant cholesterol and other stroke subtypes. This study suggests that remnant cholesterol is causally associated with the risk of LAS-IS driven by IDL cholesterol.

Association of impaired sensitivity to thyroid hormones with hyperuricemia through obesity in the euthyroid population.

BACKGROUND: Impaired sensitivity to thyroid hormones is a newly proposed clinical entity associated with hyperuricemia in the subclinical hypothyroid population. However, it is unknown whether the association exists in the euthyroid population. This study aimed to explore the association of impaired sensitivity to thyroid hormones (assessed by the thyroid feedback quantile-based index [TFQI], parametric thyroid feedback quantile-based index [PTFQI], thyrotrophic thyroxine resistance index [TT4RI] and thyroid-stimulating hormone index [TSHI]) with hyperuricemia and quantify the mediating effect of body mass index BMI in the euthyroid population. METHODS: This cross-sectional study enrolled Chinese adults aged ≥ 20 years who participated in the Beijing Health Management Cohort (2008-2019). Adjusted logistic regression models were used to explore the association between indices of sensitivity to thyroid hormones and hyperuricemia. Odds ratios [OR] and absolute risk differences [ARD] were calculated. Mediation analyses were performed to estimate direct and indirect effects through BMI. RESULTS: Of 30,857 participants, 19,031 (61.7%) were male; the mean (SD) age was 47.3 (13.3) years; and 6,515 (21.1%) had hyperuricemia. After adjusting for confounders, individuals in the highest group of thyroid hormone sensitivity indices were associated with an increased prevalence of hyperuricemia compared with the lowest group (TFQI: OR = 1.18, 95% CI 1.04-1.35; PTFQI: OR = 1.20, 95% CI 1.05-1.36; TT4RI: OR = 1.17, 95% CI 1.08-1.27; TSHI: OR = 1.12, 95% CI 1.04-1.21). BMI significantly mediated 32.35%, 32.29%, 39.63%, and 37.68% of the associations of TFQI, PTFQI, TT4RI and TSHI with hyperuricemia, respectively. CONCLUSIONS: Our research revealed that BMI mediated the association between impaired sensitivity to thyroid hormones and hyperuricemia in the euthyroid population. These findings could provide useful evidence for understanding the interaction between impaired sensitivity to thyroid hormone and hyperuricemia in euthyroid individuals and suggest the clinical implications of weight control in terms of impaired thyroid hormones sensitivity.

Retrospective motion correction for preclinical/clinical magnetic resonance imaging based on a conditional generative adversarial network with entropy loss.

Multishot scan magnetic resonance imaging (MRI) acquisition is inherently sensitive to motion, and motion artifact reduction is essential for improving the image quality in MRI. This work proposes and validates a new end-to-end motion-correction method for the multishot sequence that incorporates a conditional generative adversarial network with minimum entropy (cGANME) of MR images. The cGANME contains an encoder-decoder generator to obtain motion-corrected images and a PatchGAN discriminator to classify the image as either real (motion-free) or fake (motion-corrected). The entropy of the images is set as one loss item in the cGAN's loss as the entropy increases monotonically with the motion artifacts. An ablation experiment of the different weights of entropy loss was performed to evaluate the function of entropy loss. The preclinical dataset was acquired with a fast spin echo pulse sequence on a 7.0-T scanner. After the simulation, we had 10,080/2880/1440 slices for training, testing, and validating, respectively. The clinical dataset was downloaded from the Human Connection Project website, and 11,300/3500/2000 slices were used for training, testing, and validating after simulation, respectively. Extensive experiments for different motion patterns, motion levels, and protocol parameters demonstrate that cGANME outperforms traditional and some state-of-the-art, deep learning-based methods. In addition, we tested cGANME on in vivo awake rats and mitigated the motion artifacts, indicating that the model has some generalizability.

Molecular ensemble junctions with inter-molecular quantum interference.

We report of a high yield method to form nanopore molecular ensembles junctions containing ~40,000 molecules, in which the semimetal bismuth (Bi) is a top contact. Conductance histograms of these junctions are double-peaked (bi-modal), a behavior that is typical for single molecule junctions but not expected for junctions with thousands of molecules. This unique observation is shown to result from a new form of quantum interference that is inter-molecular in nature, which occurs in these junctions since the very long coherence length of the electrons in Bi enables them to probe large ensembles of molecules while tunneling through the junctions. Under such conditions, each molecule within the ensembles becomes an interference path that modifies via its tunneling phase the electronic structure of the entire junction. This new form of quantum interference holds a great promise for robust novel conductance effects in practical molecular junctions.

Long non-coding RNA BRCAT54 sponges microRNA-21 in vestibular schwannoma to suppress cell proliferation.

BRCAT54 (also known as MRPS30 divergent transcript) is an anti-tumor long non-coding RNA (lncRNA) in lung cancer, while its role in vestibular schwannoma (VS) is unclear. We predicted that BRCAT54 could interact with microRNA (miR)-21, which suppresses VS cell proliferation. This study was then carried out to study the interaction between BRCAT54 and miR-21 in VS. A total of 56 VS samples and 42 normal vestibular nerve (VN) samples were included in this study. The expression of BRCAT54 and miR-21 in these samples were analyzed with RT-qPCR. Subcellular location of BRCAT54 in primary VS cells was analyzed by subcellular fractionation assay. The direct interaction between BRCAT54 and miR-21 was analyzed through RNA pull-down assay. Overexpression assay was performed to explore the interaction between BRCAT54 and miR-21. The role of BRCAT54 and miR-21 in primary VS cell proliferation was analyzed using BrdU assay. We found that BRCAT54 was downregulated in VS samples than that in VN samples, while miR-21 was upregulated in VS samples. BRCAT54 and miR-21 were not closely correlated. BRCAT54 was detected in both nuclear and cytoplasm samples, and BRCAT54 directly interacted with miR-21. However, BRCAT54 and miR-21 did not affect the expression of each other. BRCAT54 suppressed primary VS cell proliferation and inhibited the role of miR-21 in promoting cell proliferation. Therefore, BRCAT54 may sponge miR-21 to suppress cell proliferation in VS.

Damage to the blood­brain barrier and activation of neuroinflammation by focal cerebral ischemia under hyperglycemic condition.

Hyperglycemia aggravates brain damage caused by cerebral ischemia/reperfusion (I/R) and increases the permeability of the blood­brain barrier (BBB). However, there are relatively few studies on morphological changes of the BBB. The present study aimed to investigate the effect of hyperglycemia on BBB morphological changes following cerebral I/R injury. Streptozotocin­induced hyperglycemic and citrate­buffered saline­injected normoglycemic rats were subjected to 30 min middle cerebral artery occlusion. Neurological deficits were evaluated. Brain infarct volume was assessed by 2,3,5­triphenyltetrazolium chloride staining and BBB integrity was evaluated by Evans blue and IgG extravasation following 24 h reperfusion. Changes in tight junctions (TJ) and basement membrane (BM) proteins (claudin, occludin and zonula occludens­1) were examined using immunohistochemistry and western blotting. Astrocytes, microglial cells and neutrophils were labeled with specific antibodies for immunohistochemistry after 1, 3 and 7 days of reperfusion. Hyperglycemia increased extravasations of Evan's blue and IgG and aggravated damage to TJ and BM proteins following I/R injury. Furthermore, hyperglycemia suppressed astrocyte activation and damaged astrocytic endfeet surrounding cerebral blood vessels following I/R. Hyperglycemia inhibited microglia activation and proliferation and increased neutrophil infiltration in the brain. It was concluded that hyperglycemia­induced BBB leakage following I/R might be caused by damage to TJ and BM proteins and astrocytic endfeet. Furthermore, suppression of microglial cells and increased neutrophil infiltration to the brain may contribute to the detrimental effects of pre­ischemic hyperglycemia on the outcome of cerebral ischemic stroke.

Experimental Study on Distribution of Landslide Thrust in Pile-Anchor Structure based on Photoelastic Technique.

This paper aimed to perform systematical study on the distribution of landslide thrust in pile-anchor support system, which has been a widely applicable treatment method in landslide control with safety, highly efficiency and adaptation. The advantage of photoelastic technique is visualization of strain and stress fields, therefore photoelastic model tests are conducted to show the distribution of landslide thrust in pile-anchor structure before failure in landslide. The effects of different materials and pile lengths are investigated by 6 photoelastic test cases under different loading conditions. It can be found from quantitative analysis of experimental results that load proportion of anchor would increase gradually with the decrease of pile embedded depth or the increase of landslide thrust force. Meanwhile, landslide thrust distribution in pile-anchor structure is directly affected by the stiffness of piles. The pile-anchor structure is significantly better at reducing bending moment value and optimizing bending moment distribution of pile. Finally, some theoretical analysis and design suggestions are proposed based on the experimental study.

Risk factors analysis of mirror aneurysms: A multi-center retrospective study based on clinical and demographic profile of patients.

As a special subgroup of multiple intracranial aneurysms, mirror aneurysms are located bilaterally on the corresponding intracranial arteries. The current study sought to compare the clinical and demographic features of patients harboring mirror aneurysm, and to elucidate the corresponding risk factors. We performed a retrospective cohort study of 2641 intracranial aneurysms patients, who were admitted to our hospitals between January 2005 and June 2014. Patients were subdivided into three groups based on the inclusion criteria: (i) single (n=2250); (ii) non-mirror multiple (n=285); and (iii) mirror aneurysms (n=106). Clinical and demographic files of the three groups were collected and compared, and medical histories including stroke, hyperlipemia, hypertension, hyperglycemia, valvular heart disease were considered as potential risk factors. Potential morphological reasons for mirror cerebral aneurysms rupture, including aneurysms size, irregular walls and cerebral hemispheric dominance, were also compared. Our data showed that the male to female ratio of mirror aneurysms patients was 1:3.61, which was significantly different from that of single aneurysm (1:1.27) and multiple aneurysms (1:2.00). The prevalence of mirror aneurysms in women is higher than that in men (P<0.001). Older patients (especially 60-69 years old) also appear to be more vulnerable to mirror aneurysm than single aneurysm (P<0.001). In 84 mirror aneurysm patients the aneurysms were located on the internal carotid arteries (79.2%), most typically at the PComA or in the Cavernous ICA. Patients with medical history of hyperlipemia appear to have an increased risk of harboring mirror aneurysms. Larger aneurysm size and presence of an irregular aneurysm wall appear to be the morphological factors that predispose for mirror aneurysms rupture.

Water-soluble coenzyme q10 inhibits nuclear translocation of apoptosis inducing factor and cell death caused by mitochondrial complex I inhibition.

The objectives of the study were to explore the mechanism of rotenone-induced cell damage and to examine the protective effects of water-soluble Coenzyme Q10 (CoQ10) on the toxic effects of rotenone. Murine hippocampal HT22 cells were cultured with mitochondrial complex I inhibitor rotenone. Water-soluble CoQ10 was added to the culture media 3 h prior to the rotenone incubation. Cell viability was determined by alamar blue, reactive oxygen species (ROS) production by dihydroethidine (DHE) and mitochondrial membrane potential by tetramethyl rhodamine methyl ester (TMRM). Cytochrome c, caspase-9 and apoptosis-inducing factor (AIF) were measured using Western blotting after 24 h rotenone incubation. Rotenone caused more than 50% of cell death, increased ROS production, AIF nuclear translocation and reduction in mitochondrial membrane potential, but failed to cause mitochondrial cytochrome c release and caspase-9 activation. Pretreatment with water-soluble CoQ10 enhanced cell viability, decreased ROS production, maintained mitochondrial membrane potential and prevented AIF nuclear translocation. The results suggest that rotenone activates a mitochondria-initiated, caspase-independent cell death pathway. Water-soluble CoQ10 reduces ROS accumulation, prevents the fall of mitochondrial membrane potential, and inhibits AIF translocation and subsequent cell death.

The selenoproteome exhibits widely varying, tissue-specific dependence on selenoprotein P for selenium supply.

Selenoprotein P (Sel P) is a selenium-rich glycoprotein believed to play a key role in selenium (Se) transport throughout the body. Development of a Sel P knockout mouse model has supported this notion and initial studies have indicated that selenium supply to various tissues is differentially affected by genetic deletion of Sel P. Se in the form of the amino acid, selenocysteine, is incorporated into selenoproteins at UGA codons. Thus, Se availability affects not only selenoprotein levels, but also the turnover of selenoprotein mRNAs via the nonsense-mediated decay pathway. We investigated how genetic deletion of Sel P in mice affected levels of the mRNAs encoding all known members of the murine selenoprotein family, as well as three non-selenoprotein factors involved in their synthesis, selenophosphate synthetase 1 (SPS1), SECIS-binding protein 2 (SBP2) and SECp43. Our findings present a comprehensive description of selenoprotein mRNA expression in the following murine tissues: brain, heart, intestine, kidney, liver, lung, spleen and testes. We also describe how abundance of selenoproteins and selenoprotein-synthesis factors are affected by genetic deletion of Sel P in some of these tissues, providing insight into how the presence of this selenoprotein influences selenoprotein mRNA levels, and thus, the selenoproteome.

Overexpression of selenoprotein H reduces Ht22 neuronal cell death after UVB irradiation by preventing superoxide formation.

Selenoproteins have been shown to exhibit a variety of biological functions, including antioxidant functions, maintaining cellular redox balance, and heavy metal detoxification. UV irradiation-induced damage is partially mediated by increased oxygen radical production. The present study is designed to examine the antioxidative effects of human selenoprotein H (hSelH) after brief period of UVB irradiation on the murine hippocampal neuronal cell line Ht22. Ht22 cells were stably transfected with the hSelH gene or with MSCV empty vector and exposed to UVB irradiation with or without the presence of serum. The results showed that cell viability was significantly higher in hSelH-transfected cells compared to the MSCV vector-transfected cells after 24 h of recovery with or without the presence of serum in the media. Further studies revealed that while the number of superoxide anion (O2*-) positive cells was increased following a 7 mJ/cm(2) of UVB irradiation and 5 h of recovery, overexpression of hSelH significantly reduced superoxide production. These results suggest that hSelH overexpression protects cells from UVB irradiation-induced cell death by reducing the O2*- formation.

Streptozotocin-induced diabetes causes astrocyte death after ischemia and reperfusion injury.

Diabetes exacerbates neuronal cell death induced by cerebral ischemia. One contributing factor is enhanced acidosis during ischemia. Astrocytes are vulnerable to hypoxia under acidic conditions in vitro and may be targets of ischemia under diabetic conditions. The objective of this study was to determine whether diabetes would cause damage to astrocytes after an ischemic brain injury in vivo. Diabetic and nondiabetic rats were subjected to 5 min of forebrain ischemia and followed by 30 min, 6 h, or 1 or 3 days of recovery. The results showed that ischemia caused activation of astrocytes in nondiabetic rats. In contrast, diabetes caused astrocyte activation in early stage of reperfusion and astrocyte death in late stage of reperfusion. Remarkable astrocyte death was preceded by increased DNA oxidation. Further studies revealed that increased astrocyte damage coincided with enhanced production of free radicals. These data suggest that hyperglycemic ischemia worsens outcome in astrocytes, as it does in neurons.

Hyperglycemia increases superoxide production in the CA1 pyramidal neurons after global cerebral ischemia.

Transient global cerebral ischemia results in selective neuronal death in the vulnerable hippocampal CA1 pyramidal neurons in a delayed manner. Hyperglycemia accelerates and exacerbates neuronal damage in this region. The object of this study was to determine whether hyperglycemia-enhanced damage is associated with increased production of superoxide anion after ischemia. The results showed that hyperglycemic ischemia caused a significant increase of superoxide production in the hippocampal CA1 neurons compared to normoglycemic animals after 18 h of recirculation, suggesting that enhanced superoxide anion production may mediate the hyperglycemia-accelerated and -enhanced neuronal death in the hippocampal CA1 area after ischemia and reperfusion.

LOXL null mice demonstrate selective dentate structural changes but maintain dentate granule cell and CA1 pyramidal cell potentiation in the hippocampus.

Lysyl oxidase-like protein (LOXL), part of the lysyl oxidase copper-dependent amine oxidase family, is expressed in the extracellular matrix and in the nucleus. It likely plays a role in cross-linking collagen and elastin, possibly modulating cellular functions. Immunohistochemical studies show the presence of LOXL in the pyramidal cell layer of the hippocampus; and in this study, we report that cells in the granule cell layer have significantly smaller somas in LOXL -/- compared to LOXL +/+ mice. In addition we tested the hypothesis that these structural alterations in the dentate granule layer were associated with synaptic efficacy and thus muted long-term potentiation in mice lacking the protein. Electrical recordings were obtained in 300-mum hippocampal slices in dentate and CA1 pyramidal cell layers in age-matched wild type and LOXL null mice. Potentiation in the CA1 cell layer of 10 LOXL -/- and 8 LOXL +/+ mice was 191.0+/-9.3% and 181.6+/-9.1%, respectively (mean+/-S.E.M.). Dentate potentiation was 120.8+/-7.0% and 121.0+/-3.4% in 11 LOXL -/- and 11 LOXL +/+ mice, respectively. No phenotypic difference in potentiation of population spike amplitude (or in EPSP slope) in either layer was observed. Thus, contrary to expectation, structural changes in the hippocampus of LOXL -/- mice did not affect synaptic remodeling in a manner that impaired the establishment of LTP.

Induction of heat shock proteins by hyperglycemic cerebral ischemia.

Hyperglycemia worsens the neuronal death induced by cerebral ischemia. A previous study demonstrated that diabetic hyperglycemia suppressed the expression of heat shock protein 70 (HSP70) in the liver. The objective of this study is to determine whether hyperglycemia exacerbates ischemic brain damage by suppressing the expression of heat shock proteins (HSPs) in the brain. Both normoglycemic and hyperglycemic rats were subjected to a transient global cerebral ischemia of 15 min and followed by 0.5, 1 and 3 h of reperfusion. The expression of stress-related genes and levels of HSP proteins were determined by DNA microarray, immunocytochemistry and Western blot analyses. The results showed that hyperglycemic ischemia upregulated the expressions of hsp70, hsp90A, hsp90B, heat shock cognate 71 kD protein (hsc70) and mthsp70. Protein levels of HSP70 and HSP60 were enhanced by hyperglycemia compared with normoglycemia. The results suggested that hyperglycemia-exacerbated ischemic brain damage is not mediated by the suppression of the HSPs. The increased levels of HSPs and mthsp70 suggest that the cell and the mitochondrion had strong stress responses to hyperglycemic ischemia.

Bongkrekic acid ameliorates ischemic neuronal death in the cortex by preventing cytochrome c release and inhibiting astrocyte activation.

Mitochondrial release of cytochrome c (cyt-c) plays a critical role in initiating cell death after cerebral ischemia. The objective of this study was to determine whether bongkrekic acid (BKA) ameliorates ischemic neuronal damage by inhibiting the release of cyt-c. These results showed that a 10min period of global ischemia caused neuronal death, increased the release of cyt-c and activated astrocytes in the cortex and CA1. BKA treatment reduced ischemic-induced neuronal death, prevented cyt-c release and inhibited astrocyte activation in the cortex, but not in the CA1. These results suggest that the neuroprotective effect of BKA is associated with its ability to prevent cyt-c release and to inhibit astrocyte activation.

Diabetes increases expression of ICAM after a brief period of cerebral ischemia.

The objective of present study was to determine whether leukocyte-endothelial cell adhesive molecule, intercellular cell adhesion molecule-1 (ICAM-1) was increased after ischemia in diabetic rats. The immunohistochemistry of ICAM showed that numbers of ICAM-1 positively stained microvessels in the cortex were markedly increased at 3 days of reperfusion in diabetic, but not in non-diabetic rats. These were further confirmed by Western analysis. Western analyses also showed that interlukin-1beta (IL-1beta), but not TNF-alpha, was increased at 3 days of the reperfusion in diabetic rats. The results suggest that inflammatory responses may mediate diabetic hyperglycemia-aggravated brain damage induced by ischemia and reperfusion.