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Background: The biochemical and genetic characteristics of four very-long-chain acyl-coenzyme A dehydrogenase deficiency (VLCADD) patients, clarifying their pathogenic genetic factors and evaluating the application value of genetic diagnosis in the early diagnosis of VLCADD, are reported and discussed in this article.Methods: Patients underwent blood tandem mass spectrometry (MS/MS), urine gas chromatography (GC/MS), and high-throughput sequencing technology. New variants were analyzed for pathogenicity using bioinformatics software. Swiss-PdbViewer software was used to predict the effect of variants on the structure of the very-long-chain acyl-CoA dehydrogenase (VLCAD) protein.Result: A total of four VLCADD patients were diagnosed. They revealed elevated levels of C14, C14:1, C14:2, C14:1/C2, C14:1/C10, and C14:1/C12:1. Two patients were early-onset neonatal cases and died during infancy and the neonatal period, respectively. Seven kinds of variants were detected, including four novel variants. Bioinformatics software revealed that the variants were harmful, and the Swiss-PdbViewer results suggest that variation affects protein conformation.Conclusion: This study identified four novel ACADVL gene variants. These findings contribute to the understanding of the genetic basis and pathogenesis of VLCADD. Meanwhile, the study enriches the genetic mutation spectrum and the correlation between genotypes and phenotypes of VLCADD, indicating that genetic diagnosis plays an essential role in the early diagnosis and treatment of VLCADD.

Abstract Peripheral T‐cell lymphoma (PTCL) is a highly heterogeneous group of mature T‐cell malignancies. The efficacy of current first‐line treatment is dismal, and novel agents are urgently needed to improve patient outcomes. A close association between the cyclic GMP‐AMP synthase‐stimulator of interferon genes (cGAS‐STING) pathway and tumor promotion exists, revealing prospective therapeutic targets. This study, investigates the role of the cGAS‐STING pathway and its underlying mechanisms in PTCL progression. Single‐cell RNA sequencing showes that the cGAS‐STING pathway is highly expressed and closely associated with PTCL proliferation. cGAS inhibition suppresses tumor growth and impaires DNA damage repair. Moreover, Cdc2‐like kinase 1 (CLK1) is critical for residual tumor cell survival after treatment with cGAS inhibitors, and CLK1 suppression enhances sensitivity to cGAS inhibitors. Single‐cell dynamic transcriptomic analysis indicates reduced proliferation‐associated nascent RNAs as the underlying mechanism. In first‐line therapy, chemotherapy‐triggered DNA damage activates the cGAS‐STING pathway, and cGAS inhibitors can synergize with chemotherapeutic agents to kill tumors. The cGAS‐STING pathway is oncogenic in PTCL, whereas targeting cGAS suppresses tumor growth, and CLK1 may be a sensitivity indicator for cGAS inhibitors. These findings provide a theoretical foundation for optimizing therapeutic strategies for PTCL, especially in patients with relapsed/refractory disease.

Abstract Background The currently preferred minimally invasive approaches have substantially improved outcomes of infected walled-off pancreatic necrosis (iWON). However, iWON with deep extension (iWONde) still poses a tricky challenge for sufficient necrosis evacuation by one stand-alone approach, often requiring repeated interventions. The aim of this study was to assess the effectiveness and safety of a minimal-access video-assisted retroperitoneal and/or transperitoneal debridement (hereafter called VARTD) in the management of iWONde. Methods Patients who had developed an iWONde were recruited to receive the VARTD in this prospective single-arm study. The primary efficacy endpoint was clinical improvement up to day 28 after the VARTD, defined as a ≥ 75% reduction in size of necrotic collection (in any axis) on CT and clinical resolution of sepsis or organ dysfunction. The primary safety endpoint was a composite of major complications or death during follow-up. Six-month postdischarge follow-up was available. Results Between July 18, 2018, and November 12, 2020, we screened 95 patients with necrotizing pancreatitis; of these, 21 iWONde patients (mean [SD] age, 42.9 [11.7] years; 10 [48%] women) were finally enrolled. The primary efficacy endpoint was achieved by most participants (14/21, 67%). No participants required repeated interventions. The primary safety endpoint occurred in six patients (29%). Except one in-hospital death attributable to repeated intra-abdominal hemorrhage, others were discharged without any major complication. Conclusions The VARTD approach appears to have a reasonable efficacy with acceptable complication rates and thus might be an option for improving clinical management of iWONde. Trial registration This study is registered with Chinese Clinical Trial Registry (chictr.org.cn number, ChiCTR1800016950).

Abstract. Background:. Insufficient cerebral perfusion is suggested to play a role in the development of Alzheimer disease (AD). However, there is a lack of direct evidence indicating whether hypoperfusion causes or aggravates AD pathology. We investigated the effect of chronic cerebral hypoperfusion on AD-related pathology in humans. Methods:. We enrolled a group of cognitively normal patients (median age: 64 years) with unilateral chronic cerebral hypoperfusion. Regions of interest with the most pronounced hypoperfusion changes were chosen in the hypoperfused region and were then mirrored in the contralateral hemisphere to create a control region with normal perfusion. 11C-Pittsburgh compound-positron emission tomography standard uptake ratios and brain atrophy indices were calculated from the computed tomography images of each patient. Results:. The median age of the 10 participants, consisting of 4 males and 6 females, was 64 years (47–76 years). We found that there were no differences in standard uptake ratios of the cortex (volume of interest [VOI]: P = 0.721, region of interest [ROI]: P = 0.241) and grey/white ratio (VOI: P = 0.333, ROI: P = 0.445) and brain atrophy indices (Bicaudate, Bifrontal, Evans, Cella, Cella media, and Ventricular index, P > 0.05) between the hypoperfused regions and contralateral normally perfused regions in patients with unilateral chronic cerebral hypoperfusion. Conclusion:. Our findings suggest that chronic hypoperfusion due to large vessel stenosis may not directly induce cerebral β-amyloid deposition and neurodegeneration in humans.

Background: Maple syrup urine disease (MSUD) is a rare autosomal recessive amino acid metabolic disease. This study is to identify the pathogenic genetic factors of six cases of MUSD and evaluates the application value of high-throughput sequencing technology in the early diagnosis of MUSD.Methods: Clinical examination was carried out for patients and used blood tandem mass spectrometry (MS/MS), urine gas chromatography-mass spectrometry (GC/MS), and the application of high-throughput sequencing technology for detection. Validate candidate mutations by polymerase chain reaction (PCR)—Sanger sequencing technology. Bioinformatics software analyzed the variants’ pathogenicity. Using Swiss PDB Viewer software to predict the effect of mutation on the structure of BCKDHA and BCKDHB proteins.Result: A total of six MSUD patients were diagnosed, including four males and two females. Nine variants were found in three genes of six MSUD families by high-throughput sequencing, including four missense mutations: c.659C>T(p.A220V), c.818C>T(p.T273I), c.1134C>G(p.D378E), and c.1006G>A(p.G336S); two non-sense mutations: c.1291C>T(p.R431*) and c.331C>T(p.R111*); three deletion mutations: c.550delT (p.S184Pfs*46), c.718delC (p.P240Lfs*14), and c.795delG (p.N266Tfs*64). Sanger sequencing’s results were consistent with the high-throughput sequencing. The bioinformatics software revealed that the mutations were harmful, and the prediction results of Swiss PDB Viewer suggest that variation affects protein conformation.Conclusion: This study identified nine pathogenic variants in the BCKDHA, BCKDHB, and DBT genes in six MSUD families, including two novel pathogenic variants in the BCKDHB gene, which enriched the genetic mutational spectrum of the disease. High-throughput sequencing is essential for the MSUD’s differential diagnosis, early treatment, and prenatal diagnosis.

Abstract Background Duplication of the portal vein is a rare type of anatomic variant of the portal vein (PV) system that can be incidentally found and can lead to various challenges and consequences. Herein, we report an unusual case to increase our understanding of such anatomic variants. Case presentation A 67-year-old asymptomatic woman was diagnosed with a liver space-occupying lesion by ultrasonography on a routine physical examination. The laboratory examinations from a local hospital suggested that her liver function tests were normal. The liver appeared normal on pre-contrast enhanced CT images. However, there were multiple complex abnormalities of PV found on contrast-enhanced CT scans, including two independent sources of PV (duplication), preduodenal PV, circum-portal pancreas, mimic cavernous transformation, abnormal branches of PV, and transient abnormal perfusion in the left lobe of the liver. MRI showed fatty infiltration in the left lobe of the liver. Conclusion This case extends our current understanding of the anatomical variations of the PV system. Knowledge of these complex and rare anatomical variations will help clinical doctors make a confident diagnosis or assist with proper planning of a surgical procedure.

Phytoextraction in phytoremediation is one of the environmentally friendly methods used for restoring soils contaminated by heavy metals (HMs). The screening and identification of HM-resistant plants and their regulatory genes associated with HM ion transport are the key research aims in this field. In this study, a plant cadmium (Cd) resistance (PCR) gene family member, SlPCR6, was identified in roots of Salix linearistipularis, which exhibits strong HM resistance. The results revealed that SlPCR6 expression was induced in S. linearistipularis roots in response to Cd stress. Furthermore, SlPCR6 was mainly localized on the plasma membrane. Compared with the wild type, SlPCR6 overexpression reduced the Cd and copper (Cu) contents in the transgenic poplar (84 K) and increased its Cd and Cu resistance. The roots of transgenic poplar seedlings had lower net Cd and Cu uptake rates than wild type roots. Further investigation revealed that the transcript levels of multiple HM ion transporters were not significantly different between the roots of the wild type and those of the transgenic poplar. These results suggest that SlPCR6 is directly involved in Cd and Cu transport in S. linearistipularis roots. Therefore, SlPCR6 can serve as a candidate gene to improve the phytoextraction of the HMs Cd and Cu through genetic engineering.

Objectives: We aimed to identify and characterize potential factors, both individually and jointly as a nomogram, associated with short stature and pre-shortness in Chinese preschool-aged children. Methods: Total of 9501 children aged 3–6 years were recruited from 30 kindergartens in Beijing and Tangshan from September to December 2020 using a stratified random sampling method. Effect-size estimates are expressed as odds rat io (OR) and 95% CI. Results: The prevalence of short stature and pre-shortness in preschool-aged children was 3.9% (n = 375) and 13.1% (n = 1616), respectively. Factors simultaneously associated with the significant risk for short stature, pre-shortness and b oth included BMI, paternal height, maternal height, birth weight, birth height, l atter birth order (≥2) and less parental patience to children. Besides, breastfeeding dura tion (≥12 months) was exclusively associated with pre-shortness (OR, 95% CI, P: 1.16, 1.01 to 1.33, 0.037), and childhood obesity with both short stature (3.45, 2.62 to 4.54,

Attention deficit hyperactivity disorder (ADHD) is the most common childhood-onset neurodevelopmental disorder. Currently, increasing amounts of attention have been focused on the epidemiologic profiling of ADHD in children, viewed as a continuously distributed risk dimension throughout the whole lifespan. This study aimed to identify and characterize potential influential factors susceptible to ADHD-related symptoms among preschool-aged children. A comprehensive questionnaire was self-designed for both children and their parents or guardians and was distributed to 30 kindergartens from Beijing and Hebei, collecting potential influential factors in susceptibility to ADHD. ADHD was assessed by the Conner’s Abbreviated Symptom Questionnaire (C-ASQ), and 7,938 children were analyzed. Least absolute shrinkage and selection operator (LASSO) regression and hierarchical degree of adjustment were used to control possible covariates. Five factors, namely, children’s secondhand smoking exposure, breastfeeding duration, sleep mode, maternal pregnancy smoking exposure, and parental self-rating for patience, were identified to be independently and significantly associated with ADHD susceptibility. Meanwhile, dose–response relationships were observed between breastfeeding duration, parental self-rating for patience, and ADHD-related symptoms. Finally, a nomogram model was created for predicting ADHD susceptibility based on significant and conventional attributes under each criterion.

This study was prepared to identify and characterize potential factors associated with childhood asthma and wheeze in Chinese preschool-aged children. A comprehensive questionnaire was designed for children aged 3–6 years and their parents or guardians in Beijing and Tangshan from September to December 2020. The least absolute shrinkage and selection operator (LASSO) model was used to identify factors in a significant association with childhood asthma and wheeze, respectively. The LASSO model was internally validated using bootstrap resampling with 100 replications. A total of 9,529 questionnaires were certified as eligible for inclusion after stringent quality control. The prevalence of doctor-diagnosed childhood asthma and parent-reported wheeze was 2.8 and 6.2%, respectively. Factors simultaneously associated with childhood asthma and wheeze were children with a history of allergic rhinitis, hay fever, eczema, initial age of using antibiotics, body mass index category, and family history of asthma. Specifically, children's vitamin D supplement duration was significantly associated with childhood asthma, whereas the association with childhood wheeze was significant for intake frequency of night meals for children and their screen time. Modeling of significant factors in nomograms had decent prediction accuracies, with C-index reaching 0.728 and 0.707 for asthma and wheeze, respectively. In addition, internal validation was good, with bootstrap C-statistic of being 0.736 for asthma and 0.708 for wheeze. Taken together, our findings indicated that the development of asthma and wheeze among preschool-aged children was probably determined by the joint contribution of multiple factors including inherited, nutritional, unhealthy lifestyles, and history of allergic disease. Further validation in other groups is necessary.

ObjectivesBased on data from the China National Health Survey, we aimed to examine the association between body height and cardiometabolic disease (CMD) in a large adult population from Shaanxi province, and further to test whether this association was hinged upon other population characteristics.MethodsThis population-based study was conducted in 2014 in Shaanxi Province, China. Utilizing a multi-stage stratified cluster sampling method, total 5,905 adults with complete data were eligible for analysis, and 1,151 (19.5%) of them had CMD. Of 1,151 CMD patients, 895 (15.1%) had one disorder and 256 (4.4%) had ≥2 disorders.ResultsUsing the bi-directional stepwise method and all-subsets regression, five factors—age, body mass index, family histories of CMD, exercise, and height—constituted the optimal model when predicting CMD risk. Restricted cubic spline regression showed a reduced tendency towards CMD with the increase of body height, with per 10 cm increment in body height corresponding to 14% reduced risk. Ordinal Logistic regression supported the contribution of body height on both continuous and categorical scales to CMD risk before and after adjustment, yet this contribution was significantly confounded by exercise and education, especially by exercise, which can explain 65.4% of total impact. For example, short stature was associated with an increased risk of CMD after multivariable adjustment not including exercise and education (odds ratio, 95% confidence interval, P: 1.42, 1.21 to 1.66,

Neovascularization is required in high-grade glioma (HGG). The objective of this study was to explore neovascularization-related genes and their corresponding MRI biomarkers during the early-growth stage of HGG. Tumor tissues from 30 HGG patients underwent perfusion MRI scanning prior to surgery were used to establish orthotopic xenograft models, pathologically analyze the tumor vasculature and perform transcriptome sequencing. The cases were divided into two groups based on whether the xenograft was successfully established. Microvascular density and BMPER, CXCL10, and HOXA9 expression of surgical specimens in the xenograft-forming group was significantly elevated and the microvascular diameter was significantly reduced, in vitro inhibition of BMPER, CXCL10, or HOXA9 in the glioma stem cell significantly suppressed its tube formation abilities. The in vivo experiment showed that BMPER was highly expressed in the early tumor growth phase (20 days), CXCL10 and HOXA9 expression was elevated with tumor progress, and spatially associated with tumor vasculature. Perfusion weighted MRI (PWI-MRI) derived parameters, rCBV, rCBF, Ktrans, and Vp, were also increased in the xenograft-forming group. In conclusion BMPER, CXCL10, and HOXA9 promote early tumor growth and progression by stimulating neovascularization of primary HGG. The rCBV, rCBF, Ktrans, and Vp can be used as imaging biomarkers to predict the expression statuses of these genes.

The objective of the current study was to investigate the effects of dietary ω-6/ω-3 polyunsaturated fatty acid (PUFA) ratios on lipid metabolism in goslings. One hundred and sixty 21-day-old Yangzhou geese of similar weight were randomly divided into 4 groups. They were fed different PUFA-supplemented diets (the 4 diets had ω-6/ω-3 PUFA ratios of 12:1, 9:1, 6:1, or 3:1). The geese were slaughtered and samples of liver and muscle were collected at day 70. The activities and the gene expression of enzymes involved in lipid metabolism were measured. The results show that the activities of acetyl coenzyme A carboxylase (ACC), malic enzyme (ME), and fatty acid synthase (FAS) were lower (p

The sedimentary facies, diagenetic facies and fracture facies of the Upper Triassic Yanchang Formation Member 8 (Chang 8) reservoir in the Jiyuan region were studied using core observation, thin section, logging and drilling data. On this basis, the petrophysical faices of Chang 8 oil layers were examined to evaluate the pore structure by classification and predict zones with high porosity and permeability. The petrophysical facies were divided according to the superposition and combination of sedimentary facies, diagenetic facies and fracture facies. A number of petrophysical facies of Chang 8 oil layers such as underwater distributary channel, dissolution of unstable components, high-angle fracture, were identified in this way. Four main categories of petrophysical facies were summed up according to the constructive and destructive impact of sedimentary facies, diagenetic facies and fracture facies on the reservoir property and pore structure. Since the reservoir quality index (RQI) is an optimal indicator for describing the reservoir micro-pore structure quantitatively, the value of RQI of different petrophysical facies was calculated respectively. So the classification and evaluation of Chang 8 reservoir pore structure in a single well were realized by the division of petrophysical facies combined with logging data. At last, the vertical and horizontal distribution of sedimentary micro-facies and diagenetic facies of each single layer of Chang 8 oil layers were mapped, the distribution of favorable petrophysical facies can be used to predict the zones with high porosity and permeability. Key words: petrophysical facies, sedimentary facies, diagenetic facies, fracture facies, pore structure, classification and evaluation, Ordos basin, Chang 8 oil layers

Aspergillus fumigatus AFPAB1 is the ortholog of the Aspergillus oryzae cytoplasmic messenger ribonucleoprotein granules AOPAB1 that function to depress the initiation of translation during stress. A. fumigatus can regulate its cellular physiology in response to environmental stresses, but there has been no research on Pab1 in A. fumigatus. The associated gene afpab1 was replaced with a hygromycin-selectable marker to generate the strain Δafpab1. Phenotypic analysis showed that the Δafpab1 grew more weakly than the wild-type strain. Also the germination rate of Δafpab1 was decreased when exposed to oxidative stress. The morphology of Δafpab1 spores also showed great changes. The killing rate of Δafpab1 by RAW264.7 murine macrophage cells was increased, and the reactive oxygen species (ROS) scavenging ability of Δafpab1 was decreased. Pathogenicity testing showed that the deletion strain had decreased virulence. Therefore, we conclude that afpab1 activity is correlated with susceptibility to oxidative stress, and deletion of afpab1 from A. fumigatus possibly leads to observed hypovirulence in an immunosuppressed mouse model.

Adriamycin (ADM) has been effective against many types of solid tumors in clinical applications. However, its use is limited because of systemic toxicities, primarily cardiotoxicity, and multidrug resistance. In this study, a new active receptor-mediated complex, ADM conjugated with 2-amino-2-deoxy-D-glucose and succinic acid (2DG-SUC-ADM), was designed to target tumor cells through glucose transporter 1 (GLUT1). MTT assay and confocal images showed that the complex had better inhibition rate to tumor cells and low toxicity to normal cells. Most importantly, the complex displayed a potential to reverse overcome multidrug resistance in cancer cells, with more complex transported into the nucleus of tumor cells. Our in vivo experiments also showed that this new complex could significantly decrease organ toxicity and enhance the antitumor efficacy compared with free ADM, indicating a promising drug of 2DG-SUC-ADM for targeted cancer therapy. [ABSTRACT FROM AUTHOR]