To examine the usefulness of childhood low-density lipoprotein cholesterol (LDL-C) measurement for predicting future dyslipidemia and other cardiovascular risk in adulthood.
A longitudinal cohort ...over 15 years was identified from a community study of the natural course of arteriosclerosis: 1169 individuals (34% black), aged 5 to 14 years, were included at initial study.
Levels of lipoprotein variables in childhood were associated with levels in adulthood, more strongly for total cholesterol (r = .4-.6) and LDL-C (r = .4-.6) than for high-density lipoprotein cholesterol (r = .2-.4) and triglycerides (r = .1-.4). In a stepwise multiple regression, the childhood level was most predictive of the adulthood level, followed by change in body mass index (weight in kilograms/height in meters squared) from childhood to adulthood, with explained variability (R2) of .29, .30, .27, and .19 for total cholesterol, LDL-C, high-density lipoprotein cholesterol, and triglycerides, respectively. Adulthood dyslipidemia, as defined by the National Cholesterol Education Program criterion, was best predicted by childhood LDL-C level among other lipoprotein variables. Compared with subjects with acceptable childhood risk (LDL-C level, < 2.84 mmol/L < 110 md/dL), those (6%) with high childhood risk (LDL-C level, > or = 3.36 mmol/L > or = 130 mg/dL) not only had a higher prevalence of dyslipidemic total cholesterol level (24%, 8.3-fold), LDL-C level (28%, 5.4-fold), triglyceride level (7%, sevenfold) and lower HDL-C level (14%, 2.1-fold), but also had a significantly higher (P < .05) prevalence of obesity (43%, 1.6-fold) and hypertension (19%, 2.4-fold). In addition, if the childhood LDL-C elevation (> 90th percentile) was persistent, the prevalence of adult dyslipidemia would be markedly increased (P < .001).
Adverse levels of LDL-C in childhood persist over time, progress to adult dyslipidemia, and relate to obesity and hypertension as well. National Cholesterol Education Program guidelines to classify cardiovascular risk on the basis of LDL-C level are helpful in targeting individuals at risk early in life.
Aberrant mechanical factor is one of the etiologies of the intervertebral disc (IVD) degeneration (IVDD). However, the exact molecular mechanism of spinal mechanical loading stress-induced IVDD has ...yet to be elucidated due to a lack of an ideal and stable IVDD animal model. The present study aimed to establish a stable IVDD mouse model and evaluated the effect of aberrant spinal mechanical loading on the pathogenesis of IVDD. Eight-week-old male mice were treated with lumbar spine instability (LSI) surgery to induce IVDD. The progression of IVDD was evaluated by μCT and Safranin O/Fast green staining analysis. The metabolism of extracellular matrix, ingrowth of sensory nerves, pyroptosis in IVDs tissues were determined by immunohistological or real-time PCR analysis. The apoptosis of IVD cells was tested by TUNEL assay. IVDD modeling was successfully produced by LSI surgery, with substantial reductions in IVD height, BS/TV, Tb.N. and lower IVD score. LSI administration led to the histologic change of disc degeneration, disruption of the matrix metabolism, promotion of apoptosis of IVD cells and invasion of sensory nerves into annulus fibrosus, as well as induction of pyroptosis. Moreover, LSI surgery activated Wnt signaling in IVD tissues. Mechanical instability caused by LSI surgery accelerates the disc matrix degradation, nerve invasion, pyroptosis, and eventually lead to IVDD, which provided an alternative mouse IVDD model.
Quantitative susceptibility mapping (QSM) is a technique for obtaining quantitative information on tissue susceptibility and has shown promising potential for clinical applications, in which the ...magnetic susceptibility is calculated by solving an ill-posed inverse problem. Recently, deep learning-based methods are proposed to address this issue, but the diversity of data distribution was not well considered, and thus the model generalization is limited in clinical applications. In this paper, we propose a Latent Code based Multi-Variable modulation network for QSM reconstruction (LCMnet). Particularly, a specific modulation module is exploited to incorporate three variables, i.e., field map, magnitude image, and initial susceptibility. The latent code in the modulated convolution is learned from feature maps of the field data using the encoder-decoder framework. The susceptibility map pre-estimated from simple thresholding is the constant input of the module, thereby enhancing the network stability and accelerating training convergence. As another input, multi-level features generated by a cross-fusion block integrate the information of field and magnitude data effectively. Experimental results on
human brain data, challenge data, clinical data and synthetic data demonstrate that the proposed method LCMnet can achieve outstanding performance on accurate susceptibility measurement and also excellent generalization.
Individuals with gallbladder carcinoma (GBC), the most aggressive malignancy of the biliary tract, have a poor prognosis. Here we report the identification of somatic mutations for GBC in 57 ...tumor-normal pairs through a combination of exome sequencing and ultra-deep sequencing of cancer-related genes. The mutation pattern is defined by a dominant prevalence of C>T mutations at TCN sites. Genes with a significant frequency (false discovery rate (FDR)<0.05) of non-silent mutations include TP53 (47.1%), KRAS (7.8%) and ERBB3 (11.8%). Moreover, ErbB signaling (including EGFR, ERBB2, ERBB3, ERBB4 and their downstream genes) is the most extensively mutated pathway, affecting 36.8% (21/57) of the GBC samples. Multivariate analyses further show that cases with ErbB pathway mutations have a worse outcome (P=0.001). These findings provide insight into the somatic mutational landscape in GBC and highlight the key role of the ErbB signaling pathway in GBC pathogenesis.
Increasing numbers of lithium-ion batteries for new energy vehicles that have been retired pose a threat to the ecological environment, making their disassembly and recycling methods a research ...priority. Due to the variation in models and service procedures, numerous lithium-ion battery brands, models, and retirement states exist. This uncertainty contributes to the complexity of the disassembly procedure, which calls for a great deal of adaptability. Human–Robot Collaboration Disassembly (HRCD) mode maximizes the advantages of both humans and robots, progressively replacing single-person disassembly and single-machine disassembly to become the standard method for disassembling end-of-life lithium-ion batteries (LIBs). However, the HRCD process has more dimensions and uncertainties. In light of the obstacles above, this paper developed an HRCD environment with virtual and real interaction functions, which recommended real-time cooperation strategies in the dynamic production process and significantly enhanced the flexibility of disassembly operations. Based on the genetic algorithm (GA), the Disassembly Sequence Planning (DSP) is developed for waste LIBs in the source domain and imported into the knowledge base. Then, the rapid adaptive generation of HRCD task strategy for LIBs is generated, utilizing the transfer learning approach in the target domain. Two types of end-of-life automobile LIBs are analyzed as case study products. The results demonstrated that the proposed method could plan an effective action sequence, effectively reduce the design time of the target domain disassembly strategy, and enhance the flexibility of HRCD.
Exosomal microRNAs(miRNAs) transfer from tumor to stromal cells is reportedly associated with cancer progression and metastasis in various epithelial cancers. However, the role of exosomal miRNA in ...the metastasis of osteosarcoma(OS) -the most common bone malignancy-still largely remains unknown. In this study, we purified exosomes with a median size close to 100 nm from cell culture media as well as patient serum, and proved that exosomes derived from the metastatic, but not the non-metastatic OS cells increase the migration and invasion of non-malignant fibroblast cells (hFOB1.19) in vitro. Furthermore, the differential miRNA cargo between metastatic and non-metastatic OS is identified by small RNA sequencing and RT-PCR validation, we found a highly expression of exosomal, but not cellular miR-675 level in the metastatic OS cell-lines compared with non-metastatic counterparts. Meanwhile, we also found that exosomal miR-675 could down-regulate CALN1 expression in recipient cell, which may influence the invasion and migration of hFOB1.19. Finally, the up regulation serum exosomal miR-675 and down regulation of CALN1 in tumor specimen was also found to be associated with the metastatic phenotype in OS patients. Our findings indicate that the exosomal miR-675 is a gene associated with OS and serum exosomal miR-675 expression may serve as a novel biomarker for the metastasis of OS.
•Metastatic OS-derived exosomes induce the migration and invasion of osteoblast.•The expression of miR-675 is higher in metastatic OS-derived exosomes.•Exosomal miR-675 regulate the migration and invasion of osteoblast by down-regulating the expression of CALN1.•The expression of exosomal miR-675 is higher in metastatic OS patients' serum sample.
In this study, we systematically investigated the structural characterization and
fermentation patterns of crude black mulberry fruit polysaccharides (BMPs), either extracted by water (BMP) or by ...enzymatic treatment. Different enzymatic treatments were pectinase-extracted (PE)-BMP, pectin lyase-extracted (PL)-BMP, cellulase-extracted (CE)-BMP, and compound enzymes-extracted (M)-BMP (pectinase:pectin lyase:cellulase = 1:1:1). Our results show that enzymatic treatment improved the polysaccharide yield and led to a different chemical composition and structure for the polysaccharides. Change dynamics during the
fermentation indicated that BMPs could indeed be degraded and consumed by human fecal microbiota and that different BMPs showed different degrees of fermentability. In addition, BMPs stimulated the growth of Bacteroidetes and Firmicutes, inhibited the growth of Fusobacteria and Proteobacteria (except for CE-BMP), and induced the production of short-chain fatty acids (SCFAs). Furthermore, we found that BMP and PL-BMP exhibited better fermentability and prebiotic potential than the other polysaccharides.
Objective
This study aimed to investigate the impact of the different domains of intrinsic capacity (IC) and chronic disease burden on health-related quality of life (HRQoL) and domain-specific HRQoL ...in Chinese community-dwelling older adults.
Design
A cross-sectional observational study of a community-based cohort.
Participants
We evaluated Chinese older adults (
n
= 429, mean age, 72.91 ± 7.014 years; female proportion, 57.30%).
Measurements
IC contains five domains, namely locomotion, vitality, cognition, psychological, and sensory capacity. Locomotion dysfunction was defined as grip and/or gait decline. Vitality decline was defined if two of the following three parameters were present: fatigue, physical inactivity, and weight loss or overweight. Cognition was classified into normal cognition, pre-mild cognitive impairment (pre-MCI), and MCI according to the normative
z
-scores of the neuropsychological test battery. Psychological dysfunction was diagnosed based on depressive symptoms. Sensory dysfunction was defined as hearing and/or vision impairment. HRQoL was assessed using the AQoL-8D scale, which comprised physical (including independent living, senses, and pain) and psychosocial (including mental health, happiness, self-worth, coping, and relationships) dimensions. Low HRQoL (HRQoL score or subscores in the highest quintile) was used as a dependent variable in logistic regression analyses adjusted for demographic, health-related, and psychological confounders.
Results
Sensory impairment was an independent determinant of senses, and locomotion impairment was significantly associated with overall HRQoL, independent living, and pain in the physical dimension of HRQoL. Cognition was an independent determinant of the senses. Vitality was independently associated with overall HRQoL, senses, and pain in the physical dimension and mental health and relationships in the psychological dimension of HRQoL. The psychological domain of IC was independently associated with overall and domain-specific HRQoL apart from senses after adjustment for all confounders. The number of multimorbidities mainly had a significant impact on independent living after adjustment for all confounders.
Conclusion
IC domains and chronic disease burden had heterogeneous influences on overall and domain-specific HRQoL. The impairment of sensory and locomotion domains had a synergistic impact on the overall and physical dimensions of HRQoL. The vitality and psychological domains of IC had more profound effects on HRQoL. Older people with high morbidity might have a higher risk of poor independent living.
The number of semiconducting MXenes with direct band gaps is extremely low; thus, it is highly desirable to broaden the MXene family beyond carbides and nitrides to expand the palette of desired ...chemical and physical properties. Here, we theoretically report the existence of the single-layer (SL) dititanium oxide 2H-Ti2O MOene (MXene-like 2D transition oxides), showing an Ising superconducting feature. Moreover, SL halogenated 2H- and 1T-Ti2O monolayers display tunable semiconducting features and strong light-harvesting ability. In addition, the external strains can induce Weyl fermions via quantum phase transition in 2H-Ti2OF2 and Ti2OCl2 monolayers. Specifically, 2H- and 1T-Ti2OF2 are direct semiconductors with band gaps of 0.82 and 1.18 eV, respectively. Furthermore, the carrier lifetimes of SL 2H- and 1T-Ti2OF2 are evaluated to be 0.39 and 2.8 ns, respectively. This study extends emerging phenomena in a rich family of 2D MXene-like MOene materials, which provides a novel platform for next-generation optoelectronic and photovoltaic fields.
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