MOFs-derived Co3O4@MnO2@Carbon dots with enhanced nanozymes activity for photoelectrochemical detection of cancer cells in whole blood.

Nanozymes have attracted widespread attention, and rationally designing high-activity nanozymes to improve their application performance are a long-term objective. Herein, taking metal-organic frameworks-derived Co3O4 polyhedron with large surface area and high porosity as nanoconfinement carriers, Co3O4@MnO2@CDs polyhedron was successfully synthesized by the room-temperature reduction of MnO4- ions and physical load of carbon dots (CDs). Through cancer cells-triggered double antibody sandwich strategy, the Co3O4@MnO2@CDs polyhedron were introduced to the TiO2 nanoparticle (NPs) modified electrode, leading to the decreased photocurrent. The Co3O4@MnO2@CDs polyhedron can not only quench the photocurrent of TiO2 NPs, also act as nanozymes to catalyze precipitates. Moreover, the precipitates can not only reduce the photoelectrochemical (PEC) response, also increase the quenching capacity of the Co3O4@MnO2@CDs polyhedron. Additionally, the steric hindrance effect of the Co3O4@MnO2@CDs-Ab conjugates further weaken the photocurrent. Based on the multifunctional Co3O4@MnO2@CDs polyhedron, the proposed PEC biosensor for the detection of A549 cancer cells exhibits a wide linear range from 102 to 106 cells/mL and a low detection limit of 11 cells/mL. Furthermore, this strategy can differentiate between lung cancer patients and healthy individuals. The designed multifunctional Co3O4@MnO2@CDs nanozymes provide a new horizon for PEC detection of cancer cells, and may have great potential in early clinical diagnosis and biomedical research.

Identification and prediction of milk-derived bitter taste peptides based on peptidomics technology and machine learning method.

Bitter taste peptides (BPs) are vital for drug and nutrition research, but large-scale screening of them is still time-consuming and costly. This study developed a complete workflow for screening BPs based on peptidomics technology and machine learning method. Using an expanded dataset and a new combination of BPs' characteristic factors, a novel classification prediction model (CPM-BP) based on the Light Gradient Boosting Machine algorithm was constructed with an accuracy of 90.3 % for predicting BPs. Among 724 significantly different peptides between spoiled and fresh UHT milk, 180 potential BPs were predicted using CPM-BP and eleven of them were previously reported. One known BP (FALPQYLK) and three predicted potential BPs (FALPQYL, FFVAPFPEVFGKE, EMPFPKYP) were verified by determination of calcium mobilization of HEK293T cells expressing human bitter taste receptor T2R4 (hT2R4). Three potential BPs could activate the hT2R4 and are demonstrated to be BPs, which proved the effectiveness of CPM-BP.

Interactions between phosvitin and aldehydes affect the release of flavor from Russian sturgeon caviar.

The release mechanism of flavor during caviar storage was studied by the interaction between phosvitin and four aldehydes. Gas chromatography-mass spectrometry showed that the binding rate of phosvitin with 3-methylbutanal, nonanal, (E,Z)-2,6-nonadienal, and (E)-2-octenal decreased with an increase in the aldehyde concentrations. Among them, (E,Z)-2,6-Nonadienal (0.5 mM) had the highest binding rate (84.47%). The main quenching mechanism of (E,Z)-2,6-nonadienal with phosvitin was static quenching and the binding force comprised spontaneous hydrophobic interactions. An increase in the aldehyde concentrations reduced the α-helix content of phosvitin and led to aggregation of the microstructure of phosvitin. The results of molecular docking showed that tyr residue contributed the most to the binding of phosvitin to aldehydes. This study has elucidated the mechanism of the effect of caviar protein on changes in the caviar flavor during storage and provides effective strategies for regulation of caviar flavor during storage.

Decoding the effect of demographic factors on environmental health based on city-level PM2.5 pollution in China.

Although considerable health effects are gained from air quality improvement action plans implemented in China recently, they may have been amplified or offset due to the complexity and uncertainty of the changing demographic factors. In this study, we developed a framework for analyzing the effects of demographic factors on environmental health effects, focusing on three aspects: population scale, age structure, and spatial distribution. We quantified the above three effects by investigating how the health endpoint changed by the three demographic factors, based on a strategy of counterfactual and step-by-step relaxing hypothesis. We found that the increasing population scale and population aging caused 44,279 to 292,442 premature deaths, which offset the health effect of air quality improvement efforts for China. The change in population spatial distribution, in general, has little impact on the health effects of air quality improvement. Furthermore, the three effects are distributed unevenly across regions, especially the spatial distribution effect. Considering the widespread effect of demographic factors, PM2.5 concentration should be further reduced, and the aged population and mega-cities should be targeted for managing air quality in a cost-effective manner.

Attenuated AKT signaling by miR-146a-5p interferes with chicken granulosa cell proliferation, lipid deposition and progesterone biosynthesis.

Steroid hormones play a crucial role in the growth and maturation of poultry ovarian follicles, with progesterone secretion by granulosa cells (GC) being essential. According to our previous transcriptome analysis, it apparented that miR-146a-5p expressions were upregulated in the follicles undergoing atresia. In this study, we delved the depth to explore the underlying mechanisms by miR-146a-5p in the regulation of follicle functions in chicken. The study demonstrated that miR-146a-5p suppressed cell growth, lipids accumulation, and progesterone biosynthesis in chicken GC. Through targeting association validations, we identified delta 4-desaturase, sphingolipid 1 (DEGS1) as capable of interacting with miR-146a-5p. Co-transfection experiments further confirmed that DEGS1 reversed the impairment of GC functions by miR-146a-5p. Moreover, we discovered that miR-146a-5p suppressed AKT phosphorylation, while DEGS1 enhanced AKT phosphorylation. Phosphatidylinositol-3 kinase (PI3K) inhibitor (LY294002) studies showed that miR-146a-5p would inhibit AKT phosphorylation by governing the DEGS1/AKT pathway, which in turn regulates GC function. In summary, the findings revealed that miR-146a-5p suppressed cell growth, lipid deposition, and progesterone biosynthesis via the DEGS1/AKT pathway. These results may further enrich our understandings of how non-coding RNA regulates productive performance in chickens.

Heterogeneity and synaptic plasticity analysis of hippocampus based on db-/- mice induced diabetic encephalopathy.

Chronic hyperglycemia can cause changes in synaptic plasticity of hippocampal cells, which has accelerated the pathological process of cognitive dysfunction. However, the heterogeneity of the hippocampal cell populations under long term high glucose statement remains largely unknown. To mimic chronic hyperglycemia induced cognitive function deficit in vivo, db-/- diabetic mice was selected and Novel Object Recognition(NOR) behavior tests were performed. Based on diabetic induced cognitive impairment(CI) animal model, single-cell RNA sequencing was performed in the hippocampus of CI group (21,379 cells) or control group (20,045 cells), and single cell RNA sequencing was applied, and then the single cell atlas of gene expression was profiled. The comprehensive analysis explicated 18 nerve cell clusters, including 9 distinct sub-clusters, More in-depth analysis of oligodendrocyte precursor cells(OPCs) showed five distinct OPCs sub-clusters including expressing marker gene Lingo2-OPCs, Kcnc1-OPCs, Sst-OPCs, Slc6a1-OPCs and Lhfpl3-OPCs, which seems to be able to proliferate, migrate, and finally differentiate into mature oligodendrocytes and produce myelin. To be noted, differentially expressed genes(DEGs) of the Sst-OPCs sub-cluster indicated that the genes participating in neuroactive ligand-receptor interaction, nervous system development and inflammatory process were up-regulated in diabetic induced cognitive impairment(DCI) groups compared to normal control groups. Integrating the data of neuroplasticity regulation, the 20th top-enriched biological process was associated with neuroplasticity regulation in CI groups compared to control groups. Among these neuroplasticity-related genes, the intersectional gene Sstr2 may play an important role in neuroplasticity regulation. Focused on neuroplasticity regulation and its related specific genes may provide potential new clues for the treatment of diabetes mellitus complicated with cognitive impairment. In summary, we showed the comprehensively transcriptional landscape of hippocampal cells in the db-/- diabetic mice with cognitive dysfunction, distinctive cell sub-clusters and the gene expression characteristics were identified, and also their special functions were proposed, which may give new clues and potential targets for diagnosis and treatment of diabetic encephalopathy.

Mesenchymal Stem Cell-derived Type II Alveolar Epithelial Progenitor Cells Attenuate LPS-induced Acute Lung Injury and Reduce P63 Expression.

AIM: Acute respiratory distress syndrome (ARDS)/acute lung injury (ALI) is a severe clinical respiratory-failure disease mainly characterized by acute damage to the alveolar epithelium and pulmonary vascular endothelial cells. Stem cell therapy has emerged as a potential regenerative strategy for ARDS/ALI, however, the outcome is limited, and the underlying mechanisms are unclear. INTRODUCTION: We established a differentiation system for bone marrow-derived mesenchymal stem cellderived (BM-MSC) type II alveolar epithelial progenitor cells (AECIIs) and assessed their regulatory effects on lipopolysaccharide (LPS)-induced ALI. METHODS: We induced BM-MSC differentiation into AECIIs using a specific conditioned medium. After 26 days of differentiation, 3×105 BM-MSC-AECIIs were used to treat mice with LPS-induced ALI through tracheal injection. RESULTS: After tracheal injection, BM-MSC-AECIIs migrated to the perialveolar area and reduced LPSinduced lung inflammation and pathological injury. RNA-seq suggested that P63 protein was involved in the effects of BM-MSC-AECIIs on lung inflammation. CONCLUSION: Our results suggest that BM-MSC-AECIIs may reduce LPS-induced acute lung injury by decreasing P63 expression.

Association of changes in self-reported vision and hearing impairments with depressive symptoms in middle-aged and older adults: Evidence from a nationwide longitudinal study in China.

OBJECTIVE: This study assessed the longitudinal relationship between changes in self-reported vision impairment (VI) and hearing impairment (HI), and depressive symptoms in adults aged ≥45 years. METHODS: Data from the China Health and Retirement Longitudinal Study for 2015 and 2018 were used, with a sample size of 10,050. VI and HI were self-reported. The 10-item Center for Epidemiologic Studies Depression Scale (CES-D10) was used to assess depressive symptoms. Total scores and clinically significant depressive symptoms (CES-D10 scores ≥ 10) were used as outcomes and analyzed using generalized estimating equations with identity link and logit link functions. RESULTS: Of all changes in HI with good vision, only persistent HI was associated with higher CES-D10 scores (OR 95% CI: 1.09-3.30). Both new-onset and persistent VI with good hearing were associated with CES-D10 scores (OR 95% CI, new-onset: 1.70-3.52; persistent: 1.58-2.78) and clinically significant depressive symptoms (OR 95% CI, new-onset: 1.41-2.56; persistent: 1.36-2.27). Persistent dual sensory impairment (DSI) was associated with the highest CES-D10 scores (OR 95% CI: 3.63-5.97) and the highest risk of clinically significant depressive symptoms (OR 95% CI: 1.78-2.85). Those who self-reported improvements in vision and hearing still had higher CES-D10 scores (OR 95% CI: 1.35-2.83) and a higher risk of clinically significant depressive symptoms (OR 95% CI: 1.03-2.02) than those maintaining good vision and hearing. CONCLUSION: Self-reported VI and DSI are closely associated with depressive symptoms. Because VI and DSI are modifiable, interventions for them could also prevent depressive symptoms.

Qufeng Xuanbi Formula inhibited benzo[a]pyrene-induced aggravated asthma airway mucus secretion by AhR/ROS/ERK pathway.

ETHNOPHARMACOLOGICAL RELEVANCE: Excessive secretion of airway mucus may be an important pathological factor of air pollution-induced acute asthma attacks. Treatment of airway mucus hypersecretion improves asthma aggravated by air pollutants. Qufeng Xuanbi Formula (QFXBF) has been used to treat asthma for more than 30 years. However, whether QFXBF inhibits asthmatic mucus secretion exacerbated by air pollutants has not yet been established. AIM OF THE STUDY: This study aimed to evaluate the effect of QFXBF on airway mucus secretion and the mechanism of action in an air pollutant benzo[a]pyrene (BaP)-induced mouse model of aggravated asthma. MATERIALS AND METHODS: Ovalbumin (OVA) and BaP co-exposure were used to establish the aggravated asthma model. The average enhanced pause (Penh), serum OVA-specific IgE, and changes in lung histopathology were determined. 16HBE cells exposed to BaP, treatment with QFXBF, arylhydrocarbon receptor (AhR) signal antagonist SR1, reactive oxygen species (ROS) antagonist NAC, or extracellular signal-regulated kinase (ERK1/2) signal antagonist U0126 were established to investigate the effect of QFXBF on BaP-induced mucus secretion and its target. The mRNA and protein expression levels of MUC5AC in the lung tissue and 16HBE cells were examined. We also studied the effect of QFXBF on ROS production. Finally, the protein expression of AhR, phospho-extracellular signal-regulated kinases (p-ERK1/2), and ERK1/2 in 16HBE cells and lung tissues was determined by western blotting. RESULTS: Administration of QFXBF significantly alleviated the pathological symptoms, including Penh, serum OVA-specific IgE, and changes in lung histopathology in a BaP-induced mouse model of aggravated asthma. QFXBF inhibited MUC5AC expression in asthmatic mice and 16HBE cells exposed to BaP. ROS production, AhR expression, and ERK1/2 phosphorylation were significantly increased in BaP-induced asthmatic mice and 16HBE cells. Signaling pathway inhibitors StemRegenin 1 (SR1), NAC, and U0126 significantly inhibitedBaP-induced MUC5AC expression in 16HBE cells. SR1 reversed Bap-induced ROS production and ERK activation, and NAC inhibited Bap-induced ERK activation. In addition, QFXBF regulated AhR signaling, inhibited ROS production, reversed ERK activation, and downregulated mucus secretion to improve asthma aggravated by air pollutant BaP. CONCLUSIONS: QFXBF can ameliorate mucus secretion in BaP-induced aggravated asthmatic mice and 16HBE cells, and the specific mechanism may be related to the inhibition of the AhR/ROS/ERK signaling pathway.

Persistent organic pollutants in global surface soils: Distributions and fractionations.

The distribution and fractionation of persistent organic pollutants (POPs) in different matrices refer to how these pollutants are dispersed and separated within various environmental compartments. This is a significant study area as it helps us understand the transport efficiencies and long-range transport potentials of POPs to enter remote areas, particularly polar regions. This study provides a comprehensive review of the progress in understanding the distribution and fractionation of POPs. We focus on the contributions of four intermedia processes (dry and wet depositions for gaseous and particulate POPs) and determine their transfer between air and soil. These processes are controlled by their partitioning between gaseous and particulate phases in the atmosphere. The distribution patterns and fractionations can be categorized into primary and secondary types. Equations are developed to quantificationally study the primary and secondary distributions and fractionations of POPs. The analysis results suggest that the transfer of low molecular weight (LMW) POPs from air to soil is mainly through gas diffusion and particle deposition, whereas high molecular weight (HMW) POPs are mainly via particle deposition. HMW-POPs tend to be trapped near the source, whereas LMW-POPs are more prone to undergo long-range atmospheric transport. This crucial distinction elucidates the primary reason behind their temperature-independent primary fractionation. However, the secondary distribution and fractionation can only be observed along a temperature gradient, such as latitudinal or altitudinal transects. An animation is produced by a one-dimensional transport model to simulate conceptively the transport of CB-28 and CB-180, revealing the similarities and differences between the primary and secondary distributions and fractionations. We suggest that the decreasing temperature trend along latitudes is not the major reason for POPs to be fractionated into the polar ecosystems, but drives the longer-term accumulation of POPs in cold climates or polar cold trapping.

From heat to flavor: Unlocking new chemical signatures to discriminate Wuyi rock tea under light and moderate roasting.

Roasting is crucial for the distinct flavor of Wuyi rock tea (WRT). This study applied untargeted metabolomics to investigate the effects of roasting on 139 WRT samples roasted at light fire (LF) or moderate fire (MF) intensities. Compared to LF, MF roasting led to a decrease in the cis/trans flavanol ratio by 56% and theanine by 85%, while increasing the levels of N-ethyl-2-pyrrolidione-substituted flavanols (EPSFs), flavonol aglycones and flavone C-glycosides. Two new roast markers, 3-p-coumaroyl 1,5-lactone and 4-p-coumaroyl 1,5-lactone, were identified in WRT and their formation increased with roasting temperature. MF roasting facilitated the formation of diverse heterocycles (e.g., pyrazines) and aldehydes (e.g., (Z)-4-heptenal and (E,E)-2.4-decadienal) that contributed to the augmented roasted and fatty odors in WRT. Additionally, the Maillard product furfuryl methyl ether was solely detected in MF samples. These findings provide novel insights into roast markers in WRT with implications for improving quality control measures during tea roasting.

A multi-signal mitochondria-targeted fluorescent probe for simultaneously distinguishing biothiols and realtime visualizing its metabolism in cancer cells and tumor models.

Biothiols and its metabolite SO2 derivatives play vital roles in various physiological processes. Although a few probes have been designed for monitoring the metabolism of biothiols, developing multi-signal fluorescent probes with practicability for simultaneously distinguishing biothiols (GSH, Cys and Hcy) and real-time visualizing SO2 derivatives is an enormous challenge. To better visualize biothiols metabolism in vitro and vivo, we developed a novel multi-signal NIR fluorescent probe (probe 2) with mitochondria-targeted for distinguishing biothiols and its metabolism, based on an ICT-PET synergetic mechanism. Probe 2 with dual recognition sites distinguishing detected Cys/Hcy (Red-Green), GSH (Green) and SO32- (Blue) via three channels. First probe 2 distinguished Cys and GSH to estimate main biothiols in living cells through the ratio changes of two well-defined emission bands (Red-Green), and then imaged its metabolite SO2 with ratiometric fluorescence (Red-Blue), eliminating the interference by different biothiols. Notably, probe 2 exhibits satisfactory sensitivity (detection limit: 0.21, 0.13, 0.14 and 3.06 µM for Cys, Hcy, GSH and SO32-, respectively), high selectivity, reliability at physiological pH, and rapid fluorescence response (within 10 min). Given these advantages, probe 2 has been successfully applied to the real-time monitor GSH metabolic process in MCF-7 cells and biothiols metabolism in breast cancer, suggesting biothiols metabolic changes might be a diagnostic indicator during cancer treatment. So probe 2 is a convenient and efficient tool for understanding the physiological functions of biothiols and its metabolism.

[Clinical, genetic, and pathological analysis in 165 children with disorders of sex development]. / 165ä¾‹å„¿ç«¥æ€§å‘è‚²å¼‚å¸¸ç–¾ç— çš„ä¸´åºŠã€é—ä¼ å­¦ä¸Žç— ç†å­¦åˆ†æž.

OBJECTIVES: To investigate the clinical phenotypes, genetic characteristics, and pathological features of children with disorders of sex development (DSD). METHODS: A retrospective analysis was conducted on epidemiological, clinical phenotype, chromosomal karyotype, gonadal pathology, and genotype data of 165 hospitalized children with DSD at Children's Hospital of Hebei Province and Tangshan Maternal and Child Health Hospital from August 2008 to December 2022. RESULTS: Among the 165 children with DSD, common presenting symptoms were short stature (62/165, 37.6%), clitoromegaly (33/165, 20.0%), cryptorchidism (28/165, 17.0%), hypospadias (24/165, 14.5%), and skin pigmentation abnormalities/exteriorized pigmented labia majora (19/165, 11.5%). Chromosomal karyotype analysis was performed on 127 cases, revealing 36 cases (28.3%) of 46,XX DSD, 34 cases (26.8%) of 46,XY DSD, and 57 cases (44.9%) of sex chromosome abnormalities. Among the sex chromosome abnormal karyotypes, the 45,X karyotype (11/57, 19%) and 45,X/other karyotype mosaicism (36/57, 63%) were more common. Sixteen children underwent histopathological biopsy of gonadal tissues, resulting in retrieval of 25 gonadal tissues. The gonadal tissue biopsies revealed 3 cases of testes, 3 cases of dysplastic testes, 6 cases of ovaries, 11 cases of ovotestes, and 1 case each of streak gonad and agenesis of gonads. Genetic testing identified pathogenic/likely pathogenic variants in 23 cases (23/36, 64%), including 12 cases of 21-hydroxylase deficiency congenital adrenal hyperplasia caused by CYP21A2 pathogenic variants. CONCLUSIONS: Short stature, clitoromegaly, cryptorchidism, hypospadias, and skin pigmentation abnormalities are common phenotypes in children with DSD. 45,X/other karyotype mosaicism and CYP21A2 compound heterozygous variants are major etiological factors in children with DSD. The most commonly observed gonadal histopathology in children with DSD includes ovotestes, ovaries, and testes/dysgenetic testes.

Comparative analysis of whole-transcriptome RNA expression of lung tissue of Chinese soft-shell turtle infected by Trionyx sinensis Hemorrhagic Syndrome Virus.

Trionyx sinensis Hemorrhagic Syndrome Virus (TSHSV), the first aquatic arterivirus identified in China, causes severe mortality to T. sinensis. In this study, we sought to determine the functions of T. sinensis mRNAs and non-coding RNAs (ncRNAs) that were differentially expressed (DE) over different periods of TSHSV infection of T. sinensis lung. We used RT-qPCR to validate the sequencing results of select RNAs, confirming their reliable and referable nature. Gene Ontology (GO) annotation and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment analysis were used to predict multiple biological functions and signaling pathways in various comparison groups (1-day versus mock, 3-day versus 1-day, and 5-day versus 3-day). Multiple types of differentially expressed RNA, including mRNA, lncRNA, circRNA, and miRNA, were associated with cardiac dysfunction, coagulation abnormalities, and arachidonic acid metabolism at day 1. Pre-inflammatory cytokines and inflammatory factors such as PLA2G4A, cPLA2, γ-GGT1, TNFRSF14, TCP11L2, PTER CYP2J2 and LTC4S, were noticeably regulated at the same time. On day 3, multiple GO terms and KEGG pathways were implicated, including those related to virus defense, apoptosis, pyroptosis, and inflammatory response. Notably, key genes such as RSAD2, TRIM39, STAT4, CASP1, CASP14, MYD88, CXCL3, CARD11, ZBP1, and ROBO4 exhibited significant regulation. The lncRNAs and circRNAs that targeted the genes involved in viral recognition (TLR5), apoptosis (CARD11), pyroptosis (ZBP1), inflammatory processes (NEK7, RASGRP4, and SELE) and angiogenesis (ROBO4) exhibited significant regulation. Significantly regulated miRNAs were primarily linked to genes involved in apoptosis (Let-7f-3p, miR-1260a, miR-455-3p), and inflammation (miR-146a, miR-125a, miR-17a, miR-301b, and miR-30a-3p). The findings could advance our understanding of the host immunological response to TSHSV and offer new ideas for developing effective strategies to prevent infection of T. sinensis.

Sphingolipids in Childhood Asthma and Obesity (SOAP Study): A Protocol of a Cross-Sectional Study.

Asthma and obesity are two of the most common chronic conditions in children and adolescents. There is increasing evidence that sphingolipid metabolism is altered in childhood asthma and is linked to airway hyperreactivity. Dysregulated sphingolipid metabolism is also reported in obesity. However, the functional link between sphingolipid metabolism, asthma, and obesity is not completely understood. This paper describes the protocol of an ongoing study on sphingolipids that aims to examine the pathophysiology of sphingolipids in childhood asthma and obesity. In addition, this study aims to explore the novel biomarkers through a comprehensive multi-omics approach including genomics, genome-wide DNA methylation, RNA-Seq, microRNA (miRNA) profiling, lipidomics, metabolomics, and cytokine profiling. This is a cross-sectional study aiming to recruit 440 children from different groups: children with asthma and normal weight (n = 100), asthma with overweight or obesity (n = 100), overweight or obesity (n = 100), normal weight (n = 70), and siblings of asthmatic children with normal weight, overweight, or obesity (n = 70). These participants will be recruited from the pediatric pulmonology, pediatric endocrinology, and general pediatric outpatient clinics at Sidra Medicine, Doha, Qatar. Information will be obtained from self-reported questionnaires on asthma, quality of life, food frequency (FFQ), and a 3-day food diary that are completed by the children and their parents. Clinical measurements will include anthropometry, blood pressure, biochemistry, bioelectrical impedance, and pulmonary function tests. Blood samples will be obtained for sphingolipid analysis, serine palmitoyltransferase (SPT) assay, whole-genome sequencing (WGS), genome-wide DNA methylation study, RNA-Seq, miRNA profiling, metabolomics, lipidomics, and cytokine analysis. Group comparisons of continuous outcome variables will be carried out by a one-way analysis of variance or the Kruskal-Wallis test using an appropriate pairwise multiple comparison test. The chi-squared test or a Fisher's exact test will be used to test the associations between categorical variables. Finally, multivariate analysis will be carried out to integrate the clinical data with multi-omics data. This study will help us to understand the role of dysregulated sphingolipid metabolism in obesity and asthma. In addition, the multi-omics data from the study will help to identify novel genetic and epigenetic signatures, inflammatory markers, and mechanistic pathways that link asthma and obesity in children. Furthermore, the integration of clinical and multi-omics data will help us to uncover the potential interactions between these diseases and to offer a new paradigm for the treatment of pediatric obesity-associated asthma.

The discriminatory diagnostic value of multimodal ultrasound combined with blood cell analysis for granulomatous lobular mastitis and invasive ductal carcinoma of the breast.

OBJECTIVE: To explore the discriminatory diagnostic value of multimodal ultrasound(US) combined with blood cell analysis(BCA) for Granulomatous Lobular Mastitis (GLM) and Invasive Ductal Carcinoma(IDC) of the breast. METHODS: A total of 157 breast disease patients were collected and divided into two groups based on postoperative pathological results: the GLM group(57 cases with 57 lesions) and the IDC group(100 cases with 100 lesions). Differences in multimodal ultrasound features and the presence of BCA were compared between the two groups. The receiver operating characteristic(ROC) curve was used to calculate the optimal cutoff values, sensitivity, specificity, 95% confidence interval(CI), and the area under the curve(AUC) for patient age, lesion size, lesion resistive index(RI), and white blood cell(WBC) count in BCA. Sensitivity, specificity, positive predictive value, negative predictive value, diagnostic accuracy, and AUC were calculated for different diagnostic methods. RESULTS: There were statistically significant differences(P <  0.05) observed between GIM and IDC patients in terms of age, breast pain, the factors in Conventional US(lesion size, RI, nipple delineation, solitary/multiple lesions, margin, liquefaction area, growth direction, microcalcifications, posterior echogenicity and abnormal axillary lymph nodes), the factors in CEUS(contrast agent enhancement intensity, enhancement pattern, enhancement range, and crab-like enhancement) and the factors in BCA(white blood cells, neutrophils, lymphocytes and monocytes). ROC curve analysis results showed that the optimal cutoff values for distinguishing GLM from IDC were 40.5 years for age, 7.15 cm for lesion size, 0.655 for lesion RI, and 10.525*109/L for white blood cells. The diagnostic accuracy of conventional US combined with CEUS(US-CEUS) was the highest(97.45%). The diagnostic performance AUCs for US-CEUS, CEUS, and US were 0.965, 0.921 and 0.832, respectively. CONCLUSION: Multifactorial analysis of multimodal ultrasound features and BCA had high clinical application value in the differential diagnosis of GLM and IDC.

Retraction Notice to: miR-140-3p Inhibits Cutaneous Melanoma Progression by Disrupting AKT/p70S6K and JNK Pathways through ABHD2.

[This retracts the article DOI: 10.1016/j.omto.2020.03.009.].

Altered metabolome and microbiome features provide clues in predicting recurrence of ulcerative colitis.

PURPOSE: Many studies have shown that the imbalance of the intestinal flora and metabolite can lead to the development of ulcerative colitis (UC), but their role in recurrent-UC is still unclear. We studied the intestinal flora and metabolites associated with recurrent-UC to elucidate the mechanism and biomarkers of recurrent-UC. METHODS: Ulcerative colitis (UC) models in active, remission, and recurrence stages were established, and the abundance of intestinal flora was determined by 16 S rRNA sequencing. The changes in the metabolites present in feces and serum were analyzed by UPLC-MS/MS. RESULTS: We identified 24 metabolites in feces and serum, which might be used as diagnostic and predictive biomarkers of recurrent-UC. The dominant flora of recurrent-UC included Romboutsia, UCG-005, etc. The results of a network analysis found that long-chain fatty acids and phenylalanine were strongly correlated with Firmicutes and Proteobacteria, which indicated that the recurrence of UC might be closely related to metabolites and microorganisms. CONCLUSION: The changes in intestinal microbiota and metabolites are closely related to the development of UC. Microbiota is an important inducer of UC, which can regulate metabolites through the 'microorganism-gut-metabolite' axis. It may provide a new method for the prediction and treatment of UC.