Background and Aims
The effects of low‐level alcohol consumption on fatty liver disease and the potential for effect modification by obesity is uncertain. We investigated associations among low‐level ...alcohol consumption, obesity status, and the development of incident hepatic steatosis (HS), either with or without an increase in noninvasive liver fibrosis score category (from low to intermediate or high category).
Approach and Results
A total of 190,048 adults without HS and a low probability of fibrosis with alcohol consumption less than 30 g/day (men) and less than 20 g/day (women) were followed for up to 15.7 years. Alcohol categories of no, light, and moderate consumption were defined as 0, 1‐9.9, and 10‐29.9 g/day (10‐19.9 g/day for women), respectively. HS was diagnosed by ultrasonography, and the probability of fibrosis was estimated using the fibrosis‐4 index (FIB‐4). Parametric proportional hazards models were used to estimate multivariable‐adjusted hazard ratios (HRs) and 95% confidence intervals (CIs). A total of 43,466 participants developed HS, 2,983 of whom developed HS with an increase in FIB‐4 index (to intermediate or high scores). Comparing light drinkers and moderate drinkers with nondrinkers, multivariable‐adjusted HRs (95% CI) for incident HS were 0.93 (0.90‐0.95) and 0.90 (0.87‐0.92), respectively. In contrast, comparing light drinkers and moderate drinkers with nondrinkers, multivariable‐adjusted HRs (95% CI) for developing HS plus intermediate/high FIB‐4 were 1.15 (1.04‐1.27) and 1.49 (1.33‐1.66), respectively. The association between alcohol consumption categories and incident HS plus intermediate/high FIB‐4 was observed in both nonobese and obese individuals, although the association was stronger in nonobese individuals (P for interaction by obesity = 0.017).
Conclusions
Light/moderate alcohol consumption has differential effects on the development of different stages of fatty liver disease, which is modified by the presence of obesity.
The global burden of obesity has multiplied owing to its rapidly growing prevalence and obesity-related morbidity and mortality. In addition to the classic role of depositing extra energy, adipose ...tissue actively interferes with the metabolic balance by means of secreting bioactive compounds called adipokines. While most adipokines give rise to inflammatory conditions, the others with anti-inflammatory properties have been the novel focus of attention for the amelioration of cardiometabolic complications. This review compiles the current evidence on the roles of anti-inflammatory adipokines, namely, adiponectin, vaspin, the C1q/TNF-related protein (CTRP) family, secreted frizzled-related protein 5 (SFRP5), and omentin-1 on cardiometabolic health. Further investigations on the mechanism of action and prospective human trials may pave the way to their clinical application as innovative biomarkers and therapeutic targets for cardiovascular and metabolic disorders.
Low modulus, compliant systems of sensors, circuits and radios designed to intimately interface with the soft tissues of the human body are of growing interest, due to their emerging applications in ...continuous, clinical-quality health monitors and advanced, bioelectronic therapeutics. Although recent research establishes various materials and mechanics concepts for such technologies, all existing approaches involve simple, two-dimensional (2D) layouts in the constituent micro-components and interconnects. Here we introduce concepts in three-dimensional (3D) architectures that bypass important engineering constraints and performance limitations set by traditional, 2D designs. Specifically, open-mesh, 3D interconnect networks of helical microcoils formed by deterministic compressive buckling establish the basis for systems that can offer exceptional low modulus, elastic mechanics, in compact geometries, with active components and sophisticated levels of functionality. Coupled mechanical and electrical design approaches enable layout optimization, assembly processes and encapsulation schemes to yield 3D configurations that satisfy requirements in demanding, complex systems, such as wireless, skin-compatible electronic sensors.
Several recent studies showed that next-generation sequencing (NGS)-based human leukocyte antigen (HLA) typing is a feasible and promising technique for variant calling of highly polymorphic regions. ...To date, however, no method with sufficient read depth has completely solved the allele phasing issue. In this study, we developed a new method (HLAscan) for HLA genotyping using NGS data.
HLAscan performs alignment of reads to HLA sequences from the international ImMunoGeneTics project/human leukocyte antigen (IMGT/HLA) database. The distribution of aligned reads was used to calculate a score function to determine correctly phased alleles by progressively removing false-positive alleles. Comparative HLA typing tests using public datasets from the 1000 Genomes Project and the International HapMap Project demonstrated that HLAscan could perform HLA typing more accurately than previously reported NGS-based methods such as HLAreporter and PHLAT. In addition, the results of HLA-A, -B, and -DRB1 typing by HLAscan using data generated by NextGen were identical to those obtained using a Sanger sequencing-based method. We also applied HLAscan to a family dataset with various coverage depths generated on the Illumina HiSeq X-TEN platform. HLAscan identified allele types of HLA-A, -B, -C, -DQB1, and -DRB1 with 100% accuracy for sequences at ≥ 90× depth, and the overall accuracy was 96.9%.
HLAscan, an alignment-based program that takes read distribution into account to determine true allele types, outperformed previously developed HLA typing tools. Therefore, HLAscan can be reliably applied for determination of HLA type across the whole-genome, exome, and target sequences.
This study was designed to investigate associations among five factor personality traits, perceived stress, and depressive symptoms and to examine the roles of personality and perceived stress in the ...relationship between gender and depressive symptoms. The participants (N = 3,950) were part of a cohort study for health screening and examination at the Kangbuk Samsung Hospital. Personality was measured with the Revised NEO Personality Inventory (NEO-PI-R). Depressive symptoms were assessed using the Center for Epidemiologic Studies Depression Scale (CES-D). Perceived stress level was evaluated with a self-reported stress questionnaire developed for the Korea National Health and Nutrition Examination Survey. A higher degree of neuroticism and lower degrees of extraversion, agreeableness, and conscientiousness were significantly associated with greater perceived stress and depressive symptoms. Neuroticism and extraversion had significant direct and indirect effects (via stress as a mediator) on depressive symptoms in both genders. Agreeableness and conscientiousness had indirect effects on depression symptoms in both genders. Multiple mediation models were used to examine the mediational roles of each personality factor and perceived stress in the link between gender and depressive symptoms. Four of the personality factors (except openness) were significant mediators, along with stress, on the relationship between gender and depressive symptoms. Our findings suggest that the links between personality factors and depressive symptoms are mediated by perceived stress. As such, personality is an important factor to consider when examining the link between gender and depression.
Retinal biomarkers reflecting in vivo brain Alzheimer disease (AD) pathologic abnormalities could be a useful tool for screening cognitively normal (CN) individuals at the preclinical stage of AD.
To ...investigate the association of both functional and structural alterations of the retina with in vivo AD pathologic abnormalities in CN older adults and model a screening tool for detection of preclinical AD.
This cross-sectional study included a total of 49 CN individuals, and all assessment was done at the Seoul National University Hospital, Seoul, South Korea. All participants underwent complete ophthalmic examination, including swept-source optical coherence tomography (SS-OCT) and multifocal electroretinogram as well as amyloid-β (Aβ) positron emission tomography and magnetic resonance imaging. Data were collected from January 1, 2016, through October 31, 2017, and analyzed from February 1, 2018, through June 30, 2020.
For structural parameters of the retina, the thickness of the macula and layer-specific thicknesses, including peripapillary retinal nerve fiber layer and ganglion cell-inner plexiform layer measured by SS-OCT, were used for analysis. For functional parameters of the retina, implicit time and amplitude of rings 1 to 6 measured by multifocal electroretinogram were used.
Of the 49 participants, 25 were women (51.0%); mean (SD) age was 70.6 (9.4) years. Compared with 33 CN individuals without Aβ deposition (Aβ-CN), the 16 participants with Aβ (Aβ+CN) showed reduced inner nasal macular thickness (mean SD, 308.9 18.4 vs 286.1 22.5 μm; P = .007) and retinal nerve fiber layer thickness, particularly in the inferior quadrant (133.8 17.9 vs 103.8 43.5 μm; P = .003). In addition, the Aβ+CN group showed prolonged implicit time compared with the Aβ-CN group, particularly in ring 5 (41.3 4.0 vs 38.2 1.3 milliseconds; P = .002). AD-related neurodegeneration was correlated with the thickness of the ganglion cell-inner plexiform layer only (r = 0.41, P = .005). The model to differentiate the Aβ+CN vs Aβ-CN groups derived from the results showed 90% accuracy.
The findings of this study showing both functional as well as structural changes of retina measured by multifocal electroretinogram and SS-OCT in preclinical AD suggest the potential use of retinal biomarkers as a tool for early detection of in vivo AD pathologic abnormalities in CN older adults.
Vesicular acidification and trafficking are associated with various cellular processes. However, their pathologic relevance to cancer remains elusive. We identified transmembrane protein 9 (TMEM9) as ...a vesicular acidification regulator. TMEM9 is highly upregulated in colorectal cancer. Proteomic and biochemical analyses show that TMEM9 binds to and facilitates assembly of vacuolar-ATPase (v-ATPase), a vacuolar proton pump, resulting in enhanced vesicular acidification and trafficking. TMEM9-v-ATPase hyperactivates Wnt/β-catenin signalling via lysosomal degradation of adenomatous polyposis coli (APC). Moreover, TMEM9 transactivated by β-catenin functions as a positive feedback regulator of Wnt signalling in colorectal cancer. Genetic ablation of TMEM9 inhibits colorectal cancer cell proliferation in vitro, ex vivo and in vivo mouse models. Moreover, administration of v-ATPase inhibitors suppresses intestinal tumorigenesis of APC mouse models and human patient-derived xenografts. Our results reveal the unexpected roles of TMEM9-controlled vesicular acidification in hyperactivating Wnt/β-catenin signalling through APC degradation, and propose the blockade of TMEM9-v-ATPase as a viable option for colorectal cancer treatment.
Lithium-ion (Li-ion) batteries are widely used in high-performance energy storage applications because of their high energy density. However, safety concerns related to thermal runaway remain a ...significant challenge for Li-ion batteries. Electrolyte leakage and dendrite formation can trigger thermal runaway, and these factors typically damage traditional polyethylene (PE) separators. Consequently, these separators struggle under extreme conditions and fail to control dendrite growth. In this study, we proposed a solution by coating PE separators with graphene oxide (GO) layers. GO, as a ceramic material, provides superior thermal and mechanical stability compared with polymers. Moreover, GO-coated PE separators (GO-S) do not compromise the advantages of PE separators and effectively manage dendrite growth. In this study, the as-prepared GO-S exhibits excellent electrochemical properties in terms of high ionic conductivity, suppression of Li dendrite growth during charge/discharge process, and long-term cyclability for 7,000 h (3,500 cycles) as well as high thermal stability even after heat treatment of 100°C. Thus, we expect that this research can highlight the potential application of functionalized GO sheets in addressing the thermal and mechanical limitations of polymer-based separators, thereby enhancing the safety and reliability of Li-ion batteries.
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