Autism spectrum disorder (ASD) is a highly heterogeneous neurodevelopmental disorder caused by a complex interaction between genetic and environmental risk factors. The balance between antioxidant ...capacity and oxidative stress (OS) induced free radicals may be crucial during the pathophysiological development of ASD.
In this study, 96 children with ASD who met the diagnostic and statistical manual of mental disorders were collected, and the number of children in the typical development (TD) group was matched by 1:1. Digital PCR (dPCR) for telomere length (TL) expression in ASD in peripheral blood leukocytes. Urine levels of 8-hydroxy-2-deoxyguanosine (8-OHdG) content were measured by tandem triple quadrupole mass spectrometry and corrected by urinary creatinine levels. The levels of superoxide dismutase (SOD), catalase (CAT), and capacity (AOC) were detected by kits.
The TL of the ASD group was shorter than the TD group (
< 0.01) and had some accurate predictive significance for the identification of ASD (AUC = 0.632, 95% CI: 0.533-0.710,
= 0.002). Both 8-OHdG content and SOD activity in the ASD group were significantly higher than those in the TD group (
< 0.05). Shortened TL (Monofactor: 2.20 (1.22, 3.96),
= 0.009; Multifactor: 2.22 (1.22, 4.00),
= 0.008) and reduced CAT activity (Monofactor: 2.31 (1.28, 4.17),
= 0.006; Multifactor: 2.31 (1.28, 4.18),
= 0.006) are risk factors for the development of ASD, while reduced 8-OHdG content (Monofactor: 0.29 (0.14, 0.60),
= 0.001; Multifactor: 0.27 (0.13, 0.57),
= 0.001) and reduced SOD activity (Monofactor: 0.55 (0.31, 0.98),
= 0.042; Multifactor: 0.54 (0.30, 0.98),
= 0.042) are protective factors for the development of ASD.
In this study, TL and OS were significantly different between the ASD group and the TD group. As guanine-rich telomere sequences were likely damaged by oxygen free radicals, creating OS, which is a factor in the incidence and progression of ASDs. In conclusion, oxidative damage occurs in the bodies of children with ASD, which may lead to sustained disease progression and severe clinical manifestations. We assume that timely supplementation of antioxidants is very likely to be a potential treatment for early intervention in children with ASD. Identification and detection of OS-related biomarkers may contribute to early diagnosis and timely interventions in young patients with ASD.
Although antibody-mediated immune responses are considered pathogenic and responsible for neural injury in anti-leucine-rich glioma-inactivated protein 1 (anti-LGI1) encephalitis, previous studies ...have indicated that cytokines and chemokines might play roles in the pathogenic process by serving as B cell enhancers. In this study, we detected the profiles of cytokines and chemokines in the cerebral fluid (CSF) and serum of patients with anti-LGI1 encephalitis to identify potential biomarkers.
Sixteen patients diagnosed with anti-LGI1 encephalitis and nine patients diagnosed with noninflammatory neurologic disorders were included in the study. Cytokines and chemokines including IL-6, IL-10, IL-17, CXCL12, CXCL13, BAFF and HMGB1 in serum and CSF were measured.
The serum and CSF levels of CXCL13 were significantly higher in patients with anti-LGI1 encephalitis (36.32±34.71 pg/mL and 2.23±2.41 pg/mL, respectively) than in controls (10.84±5.02 pg/mL and 0.34±0.21 pg/mL, respectively). There was no significant difference in serum or CSF levels of IL-6, IL-10, IL-17, CXCL12, BAFF and HMGB1 between the two groups.
CXCL13 is a potential biomarker of active inflammation in anti-LGI1 encephalitis. The distinctive response of cytokines and chemokines might be closely linked to the mechanisms underlying this condition.
Myopia is an increasingly serious health issue among children and adolescents worldwide. This study investigated the situation related to myopia among students in Chengdu, a city in western China, ...and analyzed the prevalence of myopia spectacle wear and myopia full-correction and their influencing factors to understand the current status of myopia prevention. This school-based cross-sectional study investigated 1582 schools in seven districts of Chengdu City, China, enrolling a total of 417,337 students aged 6–18 years (elementary, middle, and high school) from 2020 to 2022. Examination items included uncorrected visual acuity (UCVA), slit lamp examination and non-cycloplegic autorefraction. Myopia was defined as non-cycloplegic SE ≤ −0.50 D + UCVA> 0 log MAR (age ≥6). The prevalence of myopia spectacle wear is defined as the number of people wearing glasses for myopia/the number of people with myopia (%) within the study population, and myopia full-correction is defined as normal vision after wearing glasses for myopia (≤0 log MAR for 6 years and above). With the support of the government, this programme is conducted 1–2 times a year. Statistical analyses are conducted to determine the association between myopia and various parameters.
The average age of the entire survey population was 10.96 ± 3.5 years, and the overall prevalence of myopia was 48.7%, myopia spectacle wear was 65.7%, and myopia full-correction was 50.5%. With increasing age and educational levels, the prevalence of moderate to high myopia, the prevalence of myopia spectacle wear, and the prevalence of myopia full-correction all rise. The prevalence of mild myopia full-correction (46.5%) was higher than that for moderate myopia (47.1%) and even higher than that for high myopia (39.6%). The correct utilization rate of myopic spectacles was 33.17%, increasing with age and education levels, with the highest correct utilization rate of 40.7% among those with moderate myopia. The prevalence of myopia among children and adolescents in Chengdu is relatively low, and the prevalence of myopia spectacle wear and myopia full-correction need to be improved, and it was found that with the increase of myopia, the prevalence of myopia full-correction among adolescents decreased instead.
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GEOZS, IJS, IMTLJ, KILJ, KISLJ, NLZOH, NUK, OILJ, PNG, SAZU, SBCE, SBJE, UILJ, UL, UM, UPCLJ, UPUK, ZAGLJ, ZRSKP
Blood retinal barrier (BRB) damage is an important pathogenesis of diabetic retinopathy, and alleviating BRB damage has become a key target for DR treatment. We previously found that Lycopene seed ...polyphenols (LSP) maintained BRB integrity by inhibiting NLRP3 inflammasome-mediated inflammation. However, it is still unknown whether LSP inhibits retinal neovascularization with abnormal capillaries and its mechanism of action. Here, we employed db/db mice and hRECs to find that LSP increases the level of glycolipid metabolism, maintains the morphology of retinal endothelial cells and inhibits acellular capillary neogenesis. Mechanistic studies revealed that LSP inhibits the NLRP3 inflammasome, reduces cell apoptosis in retinal tissue, increases tight junction protein (TJ) expression, and reduces vascular endothelial growth factor (VEGF) and Ve-Cadherin in vivo and in vitro. Collectively, this study finds that LSP inhibits inflammation and angiogenesis to improve BRB function to ameliorate DR.
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●Inflammasomes, apoptosis, and angiogenesis coexist in the pathogenesis of DR, and multitargeted intervention is required to achieve good therapeutic effects.●LSP could exert anti-inflammatory, anti-apoptotic and TJ protective effects in a high glucose environment.●BRB dysfunction secondary to inflammasomes and apoptosis is a typical pathologic change in DR.●LSP improved BRB function by inhibiting inflammation, apoptosis and neovascularization to effectively treat DR.
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GEOZS, IJS, IMTLJ, KILJ, KISLJ, NLZOH, NUK, OILJ, PNG, SAZU, SBCE, SBJE, UILJ, UL, UM, UPCLJ, UPUK, ZAGLJ, ZRSKP
We report a case of a 58-year-old male who presented with stroke-like episodes and late-onset mitochondrial encephalopathy. Brain magnetic resonance imaging (MRI) revealed multiple lesions in ...different locations, including in the left hypothalamus, bilateral parietal lobe, left occipital lobe, centrum semiovale and right cerebellar hemisphere. Muscle histopathological analysis showed no myopathic changes. We identified a T14487C mutation in the mitochondrial DNA (mtDNA), which causes a M63V substitution in the mitochondrial NADH dehydrogenase 6 (ND6) of complex I of the mitochondrial respiratory chain. The mutation was heteroplasmic in muscle and urine sediment with different mutation loads, and it was absent in the patient's blood sample. This case further expands the clinical spectrum associated with m.14487T>C mutation.This is an open access article distributed under the terms of the Creative Commons Attribution-Non Commercial-No Derivatives License 4.0 (CCBY-NC-ND), where it is permissible to download and share the work provided it is properly cited. The work cannot be changed in any way or used commercially without permission from the journal. http://creativecommons.org/licenses/by-nc-nd/4.0.
Primary Hypertriglyceridemia refers to a loss-of-function genetic defect which prevents the triglyceride (TG) in chylomicrons (CM) from lipolysis, leading to the accumulation of TG. The mutation of ...lipoprotein lipase (LPL) gene has been recognized as the main cause of primary hypertriglyceridemia. Recently, a new LPL gene mutation p.C310R(c. T928C) was identified in a family with hypertriglyceridemia. The proband was manifested by severe hypertriglyceridemia and diabetes. Skeletal muscle is the major LPL-synthesizing tissue and insulin response target tissue. However, little is known about the effects of LPL gene mutation on skeletal muscle. This study is intended to observe the effects of LPL-C310R mutation on glycolipid metabolism and skeletal muscle. We found that a significantly decreased LPL plasma concentration, activity and the expression levels in skeletal muscle were observed in LplC310R/+ mice comparing to wild type mice. Those mutant mice also exhibited increased fasting plasma TG, free fat acids (FFA) and insulin, as well as FFA in muscle, and decreased glucose tolerance. Enhanced expression of BIP and elevated phosphorylation of IRE1α were observed in skeletal muscle, suggesting increased endoplasmic reticulum stress (ERS). Consistent with this, increased phosphorylation of JNK was also observed. Meanwhile, remarkably enhanced phosphorylation of IRS-1 (Ser307) and decreased phosphorylation of AKT were observed in skeletal muscle of mutant mice, suggesting impaired insulin signaling. Significant lipid deposition and morphological changes in endoplasmic reticulum and mitochondria were observed in the skeletal muscle of mutant mice but not in wild type control. Results demonstrate Lpl C310R mutation caused impaired glucose tolerance, ER stress and impaired insulin signaling in skeletal muscle.
•A new LPL gene mutation p.C310R(c. T928C) was identified in a family with hypertriglyceridemia.•Lpl-C310R knockin led to decrease of LPL concentration in plasma and the expression levels in skeletal muscle.•Lpl-C310R knockin resulted in impaired glucose tolerance, elevated free fatty acid levels in plasma and muscle.•Lpl-C310R knockin caused ER stress and impaired insulin signaling in skeletal muscle.
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GEOZS, IJS, IMTLJ, KILJ, KISLJ, NLZOH, NUK, OILJ, PNG, SAZU, SBCE, SBJE, UILJ, UL, UM, UPCLJ, UPUK, ZAGLJ, ZRSKP
Sanguinarine (Sang) is a natural alkaloid and distributed in several plants of Papaveraceae. The antitumor, antioxidant, antimicrobial and anti-inflammatory effects of Sang were extensively reported, ...but its speciality and mechanism against Lepidoptera insects were still unknown. In this study, detailed toxicological parameters of Sang against silkworms, Bombyx mori (B. mori), were determined by a toxicological test. Then, a nuclear magnetic resonance-based (NMR) metabolomics method was adopted to analyze the changes in hemolymph metabolites of silkworms after feeding Sang. The growth of fourth-instar larvae was significantly ceased by the oral administration of 0.05–0.3% Sang and vast deaths appeared in 0.3% Sang group on Day 4 and Day 5. The quantitative analysis of metabolites indicated that trehalose and citrate levels in hemolymph were increased after 24 h of feeding 0.3% Sang, whereas the concentrations of pyruvate, succinate, malate and fumarate were decreased. In addition, the enzymatic determination and reverse transcription quantitative PCR (RT-qPCR) showed that the trehalase (THL) activity and the transcriptional level of one gene coding THL were uniformly weakened by 0.3% Sang. One of the important mechanisms of Sang against silkworms might be interpreted as follows. Sang impaired trehalose hydrolysis, reduced THL activity and transcription, and led to the inhibition of energy metabolism, consequent antigrowth and high lethality in larvae of B. mori. Our findings offered new insights into the insecticidal effect of Sang from the perspective of energy metabolism and provided the basis for the application of Sang in the control of Lepidoptera pests.
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•The defensive roles of sanguinarine against the Lepidoptera insect were still unknown.•Sanguinarine significantly inhibited the growth of fourth-instar Bombyx mori larvae.•Sanguinarine targeted on trehalase and induced the systemic inhibition of energy metabolism in silkworms.•This study provided the basis for the application of Sang in the control of Lepidoptera pests.
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GEOZS, IJS, IMTLJ, KILJ, KISLJ, NLZOH, NUK, OILJ, PNG, SAZU, SBCE, SBJE, UILJ, UL, UM, UPCLJ, UPUK, ZAGLJ, ZRSKP
The solid component of subsolid nodules (SSNs) is closely associated with the invasiveness of lung adenocarcinoma, and its accurate assessment is crucial for selecting treatment method. Therefore, ...this study aimed to evaluate the accuracy of solid component size within SSNs measured on multiplanar volume rendering (MPVR) and compare it with the dimensions of invasive components on pathology.
A pilot study was conducted using a chest phantom to determine the optimal MPVR threshold for the solid component within SSN, and then clinical validation was carried out by retrospective inclusion of patients with pathologically confirmed solitary SSN from October 2020 to October 2021. The radiological tumor size on MPVR and solid component size on MPVR (RSS
) and on lung window (RSS
) were measured. The size of the tumor and invasion were measured on the pathological section, and the invasion, fibrosis, and inflammation within SSNs were also recorded. The measurement difference between computed tomography (CT) and pathology, inter-observer and inter-measurement agreement were analyzed. Receiver operating characteristic (ROC) analysis and Bland-Altman plot were performed to evaluate the diagnostic efficiency of MPVR.
A total of 142 patients (mean age, 54±11 years, 39 men) were retrospectively enrolled in the clinical study, with 26 adenocarcinomas in situ, 92 minimally invasive adenocarcinomas (MIAs), and 24 invasive adenocarcinomas (IAs). The RSS
was significantly smaller than pathological invasion size with fair inter-measurement agreement intraclass correlation coefficient (ICC) =0.562, P<0.001 and moderate interobserver agreement (ICC =0.761, P<0.001). The RSS
was significantly larger than pathological invasion size with the excellent inter-measurement agreement (ICC =0.829, P<0.001) and excellent (ICC =0.952, P<0.001) interobserver agreement. ROC analysis showed that the cutoff value of RSS
for differentiating adenocarcinoma in situ from MIA and MIA from IA was 1.85 and 6.45 mm (sensitivity: 93.8% and 95.5%, specificity: 85.7% and 88.2%, 95% confidence internal: 0.914-0.993 and 0.900-0.983), respectively. The positive predictive value-and negative predictive value of MPVR in predicting invasiveness were 92.8% and 100%, respectively.
Using MPVR to predict the invasive degree of SSN had high accuracy and good inter-observer agreement, which is superior to lung window measurements and helpful for clinical decision-making.
Ambient and high temperature creep experiments at constant stresses of 0.05MPa and 0.2MPa were conducted on a ceramic fiber-reinforced alumina aerogel. Experimental results show that at low ...temperature (below 300°C), there is no significant creep phenomenon at low stress level (0.05MPa), but time-dependent creep deformation is found at high stress level (0.2MPa) for the material. Scanning Electron Microscope (SEM) analysis was also conducted to understand the micro mechanism of the creep behavior. Crack initiation and propagation in matrix are the key factors that change the creep property. Comparative investigation of creep properties was also carried out between ceramic fiber-reinforced alumina and silica aerogel. Finally the application prospect of the two composites was discussed. The result shows that alumina aerogel has excellent creep resistance, thermal stability and heat insulation properties at high temperature (above 800°C), and it has a good application prospect in high temperature insulation fields, while the ceramic fiber-reinforced silica aerogel, limited by the sintering and poor creep resistance under high temperature, is more suitable for low temperature (below 600°C) insulation field.
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