Photoelectrochemical sensor based on AuNPs@WO3@TpPa-1-COF for quantification of DNA methylation levels.

A "signal-off" photoelectrochemical (PEC) sensing platform has been designed for the ultrasensitive detection of DNA methylation levels and multiple methylated sites. The platform employs tungsten trioxide and TpPa-1-COF loaded by gold nanoparticle (AuNPs@WO3@TpPa-1-COF) composite material as the photoactive component and p-type reduced graphene (rGO) as an efficient quencher. The PEC signal of AuNPs@WO3@TpPa-1-COF composite is effectively quenched in the presence of p-type rGO, because p-type rGO can compete with AuNPs@WO3@TpPa-1-COF to deplete light energy and electron donors. In addition, a hybrid strand reaction (HCR) amplification strategy fixes more target DNA and then combines with rGO-modified anti-5-methylcytosine antibody to facilitate ultrasensitive DNA methylation detection. Under optimal conditions, DNA methylation can be measured within a linear concentration range of 10-14 to 10-8 M, with an exceptionally low detection limit of 0.19 fM (S/N = 3). At the same time, the platform can conduct quantitative determination of multi-site methylation, with the linear equation △I = 44.19LogA + 61.43, and the maximum number of methylation sites is 5. The sensor demonstrates high sensitivity, excellent selectivity, and satisfactory stability. Furthermore, the proposed signal-off PEC strategy was successfully employed to detect DNA methylation in spiked human serum samples, with recoveries ranging from 93.17 to 107.28% and relative standard deviation (RSD) ranging from 1.15 to 5.49%.

Extracellular vesicles from normal tissues orchestrate the homeostasis of macrophages and attenuate inflammatory injury of sepsis.

Extracellular vesicles (EVs) exist throughout our bodies. We recently revealed the important role of intracardiac EVs induced by myocardial ischemia/reperfusion on cardiac injury and dysfunction. However, the role of EVs isolated from normal tissues remains unclear. Here we found that EVs, derived from murine heart, lung, liver and kidney have similar effects on macrophages and regulate the inflammation, chemotaxis, and phagocytosis of macrophages. Interestingly, EV-treated macrophages showed LPS resistance with reduced expressions of inflammatory cytokines and enhanced phagocytic activity. Furthermore, we demonstrated that the protein content in EVs contributed to the activation of inflammation, while the RNA component mainly limited the excessive inflammatory response of macrophages to LPS. The enrichment of miRNAs, including miR-148a-3p, miR-1a-3p and miR-143-3p was confirmed in tissue EVs. These EV-enriched miRNAs contributed to the inflammation remission in LPS induced macrophages through multiple pathways, including STAT3, P65 and SAPK/JNK. Moreover, administration of both EVs and EV-educated macrophages attenuated septic injury and cytokine storm in murine CLP models. Taken together, the present study disclosed that EVs from normal tissues can orchestrate the homeostasis of macrophages and attenuate inflammatory injury of sepsis. Therefore, tissue derived EVs or their derivatives may serve as potential therapeutic strategies in inflammatory diseases.

Factors Related to Limb Occlusion After Endovascular Abdominal Aortic Aneurysm Repair (EVAR).

BACKGROUND: Limb occlusion is a potentially serious consequence of endovascular abdominal aortic aneurysm (EVAR). This case-control study identifies factors that predispose to limb occlusion. METHODS: A consecutive series of patients from 2 centers undergoing EVAR over an 11-year period 2007-2017 were identified retrospectively. Patient records were interrogated allowing collations of demographics, intraoperative and perioperative data and surveillance data. The preoperative computed tomography angiogram was analyzed to determine EVAR relevant anatomical data. The primary outcome was occlusion of the iliac limb of the implanted EVAR. Raw data are presented as percentages, with comparative data analyzed using Mann-Whitney U-test and binomial logistic regression. RESULTS: A total of 787 patients (702 males; median age 78 years, range 53-94 years old) were analyzed. Fifty patients reached the primary outcome, resulting in an overall limb occlusion rate of 6.35%. Factors predictive of limb occlusion were oversizing by >10% native vessel diameter, with oversizing of >20% in 50% of those that occluded. External iliac artery landing zone (12/50 limb occlusions) 24% and postoperative kinking (5/50 limb occlusions) 10% were also more common in those that occluded. Fifty randomly selected controls with similar baseline characteristics were studied. Oversizing of the iliac endograft was found to be significantly greater in the limb occlusion group compared to the controls (P < 0.001) which remained significant on regression analysis. There was no correlation with iliac tortuosity. The Cook stent graft had a 9% limb occlusion rate across sites. Medtronic and Vascutek endografts had 2.4% and 2.5% limb occlusion rates respectively. CONCLUSIONS: Oversizing of iliac limbs by >20% could be a contributing factor to limb occlusion after EVAR and judicious oversizing should be used.

Extracellular vesicles derived from different tissues attenuate cardiac dysfunction in murine MI models.

BACKGROUND: Extracellular vesicles (EVs) derived from various cell sources exert cardioprotective effects during cardiac ischemic injury. Our previous study confirmed that EVs derived from ischemic-reperfusion injured heart tissue aggravated cardiac inflammation and dysfunction. However, the role of EVs derived from normal cardiac tissue in myocardial ischemic injury remains elusive. RESULTS: In the present study, normal heart-derived EVs (cEVs) and kidney-derived EVs (nEVs) were isolated and intramyocardially injected into mice after myocardial infarction (MI). We demonstrated that administration of both cEVs and nEVs significantly improved cardiac function, reduced the scar size, and alleviated inflammatory infiltration into the heart. In addition, cardiomyocyte apoptosis was inhibited, whereas angiogenesis was enhanced in the hearts receiving cEVs or nEVs treatment. Moreover, intramyocardial injection of cEVs displayed much better cardiac protective efficacy than nEVs in murine MI models. RNA-seq and protein-protein interaction (PPI) network analysis revealed the protective mRNA clusters in both cEVs and nEVs. These mRNAs were involved in multiple signaling pathways, which may synergistically orchestrate to prevent the heart from further damage post MI. CONCLUSIONS: Collectively, our results indicated that EVs derived from normal heart tissue may represent a promising strategy for cardiac protection in ischemic heart diseases.

Serum and urine metabolomics study revealed the amelioration of Gynura bicolor extract on high fat diet-fed and streptozotocin-induced type 2 diabetic mice based on UHPLC-MS/MS.

Type 2 diabetes mellitus (T2DM) has been the most prevalent disease and has become a serious public health threat worldwide. Gynura bicolor (Willd.) DC. (GB) contains a variety of nutrients and possesses numerous activities, which might benefit those with diabetes. The current study aimed to confirm the improvement of metabolic disorders and explore the potential mechanism of GB in high fat diet-fed (HFD) and streptozotocin (STZ)-induced T2DM mice. The aboveground sample of GB was extracted with alcohol, and identified by highperformance liquid chromatography (HPLC) and liquid chromatography-Mass Spectrometry/Mass Spectrometry (LC-MS/MS) analysis. HFD and STZ-induced T2DM mice were administrated with GB extract. Biochemical and histopathologic examinations were conducted, and metabolomics evaluation was performed in serum and urine. GB significantly reduced body weight and liver weight, reversed hyperlipidemia, hyperglycemia, insulin resistance, oxidative stress and inflammation, improved hepatic histopathological changes and lipid deposition and mitigated liver injury in T2DM mice. Serum and urine metabolomics demonstrated a variety of significantly disturbed metabolites in T2DM and these changes were reversed after GB administration, including 13S-hydroxyoctadecadienoic acid, arachidonic acid, L-Valine and so on. According to the Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment analysis, the overlapping enriched pathways in the normal control group and GB group were identified, including linoleic acid metabolism, PPAR signaling pathway, protein digestion and absorption, biosynthesis of amino acids and so on. This study demonstrates that the ethanol extract of GB remarkably attenuates metabolic disorders and maintains the dynamic balance of metabolites in T2DM, providing a scientific basis for GB in the treatment of T2DM and metabolism diseases.

The complete chloroplast genome of Castanopsis hystrix Hook. f. & Thomson ex A. DC. 1863 (Fagaceae).

Castanopsis hystrix Hook. f. & Thomson ex A. DC. 1863 (Fagaceae) is an evergreen broad-leaved tree with high economic and ecological value. In this study, the complete chloroplast genome of C. hystrix was sequenced, assembled and annotated. The plastome (plastid genome) of C. hystrix was 160,624 bp in size, consisting of a pair of inverted repeats (IRs, 25,699 bp), a large-single-copy (LSC, 90,276 bp) region, and a small-single-copy (SSC, 18,950 bp). The overall GC content of C. hystrix was 36.8%. A total of 133 genes were annotated, including 88 protein-coding genes (PCG), 37 transfer RNA genes (tRNA), and eight ribosomal RNA genes (rRNA). A maximum likelihood analysis showed that the Castanopsis species form a monophyletic clade. C. hystrix is most closely related to C. tibetana with 100% bootstrap support value. The result enriches the genomic data for the genus Castanopsis, which will contribute to future studies in phylogenetics and evolution.

1,2,4-Oxadiazole as a potential scaffold in agrochemistry: a review.

N,O-containing heterocycles have been incorporated into various approved pesticides and pesticide candidates. The persistent challenge in contemporary crop protection lies in the continuous pursuit of novel N,O-heterocycle-containing compounds with pesticidal properties. Among them, the 1,2,4-oxadiazole scaffold is one of the most extensively explored heterocycles in new pesticide discovery and development. This review focuses on elucidating the molecular design strategy employed along with highlighting the bioactivity of 1,2,4-oxadiazole derivatives since 2012. Throughout this time frame, tioxazafen and flufenoxadiazam have emerged as prominent examples in which 1,2,4-oxadiazole derivatives were utilized as the core active structure within numerous applications. Additionally, the preparation methods for substituted 1,2,4-oxadiazole derivatives are elaborated upon, and their potential value within agrochemistry is discussed.

IL-27 promotes cardiac fibroblast activation and aggravates cardiac remodeling post myocardial infarction.

Excessive and chronic inflammation post myocardial infarction (MI) causes cardiac fibrosis and progressive ventricular remodeling, which leads to heart failure. We previously found high levels of IL-27 in the heart and serum until day 14 in murine cardiac ischemia‒reperfusion injury models. However, whether IL-27 is involved in chronic inflammation-mediated ventricular remodeling remains unclear. In the present study, we found that MI triggered high IL-27 expression in murine cardiac macrophages. The increased expression of IL-27 in serum is correlated with cardiac dysfunction and aggravated fibrosis after MI. Furthermore, the addition of IL-27 significantly activated the JAK/STAT signaling pathway in cardiac fibroblasts (CFs). Meanwhile, IL-27 treatment promoted the proliferation, migration and extracellular matrix (ECM) production of CFs induced by angiotensin II (Ang II). Collectively, high levels of IL-27 mainly produced by cardiac macrophages post MI contribute to the activation of CFs and aggravate cardiac fibrosis.

Co-existing squamous cell carcinoma and chronic myelomonocytic leukemia with ASXL1 and EZH2 gene mutations: A case report.

BACKGROUND: Chronic myelomonocytic leukemia (CMML), a rare clonal hematopoietic stem cell disorder characterized by myelodysplastic syndrome and myeloproliferative neoplasms, has a generally poor prognosis, and easily progresses to acute myeloid leukemia. The simultaneous incidence of hematologic malignancies and solid tumors is extremely low, and CMML coinciding with lung malignancies is even rarer. Here, we report a case of CMML, with ASXL1 and EZH2 gene mutations, combined with non-small cell lung cancer (lung squamous cell carcinoma). CASE SUMMARY: A 63-year-old male, suffering from toothache accompanied by coughing, sputum, and bloody sputum for three months, was given a blood test after experiencing continuous bleeding resulting from a tooth extraction at a local hospital. Based on morphological results, the patient was diagnosed with CMML and bronchoscopy was performed in situ to confirm the diagnosis of squamous cell carcinoma in the lower lobe of the lung. After receiving azacitidine, programmed cell death protein 1, and platinum-based chemotherapy drugs, the patient developed severe myelosuppression and eventually fatal leukocyte stasis and dyspnea. CONCLUSION: During the treatment and observation of CMML and be vigilant of the growth of multiple primary malignant tumors.

Role of microglial metabolic reprogramming in Parkinson's disease.

Parkinson's disease (PD) is a common age-related neurodegenerative disorder characterized by damage to nigrostriatal dopaminergic neurons. Key pathogenic mechanisms underlying PD include alpha-synuclein misfolding and aggregation, impaired protein clearance, mitochondrial dysfunction, oxidative stress, and neuroinflammation. However, to date, no study has confirmed the specific pathogenesis of PD. Similarly, current PD treatment methods still have shortcomings. Although some emerging therapies have proved effective for PD, the specific mechanism still needs further clarification. Metabolic reprogramming, a term first proposed by Warburg, is applied to the metabolic energy characteristics of tumor cells. Microglia have similar metabolic characteristics. Pro-inflammatory M1 type and anti-inflammatory M2 type are the two types of activated microglia, which exhibit different metabolic patterns in glucose, lipid, amino acid, and iron metabolism. Additionally, mitochondrial dysfunction may be involved in microglial metabolic reprogramming by activating various signaling mechanisms. Functional changes in microglia resulting from metabolic reprogramming can cause changes in the brain microenvironment, thus playing an important role in neuroinflammation or tissue repair. The involvement of microglial metabolic reprogramming in PD pathogenesis has been confirmed. Neuroinflammation and dopaminergic neuronal death can effectively be reduced by inhibiting certain metabolic pathways in M1 microglia or reverting M1 cells to the M2 phenotype. This review summarizes the relationship between microglial metabolic reprogramming and PD and provides strategies for PD treatment.

Intravenously Administered Human Umbilical Cord-Derived Mesenchymal Stem Cell (HucMSC) Improves Cardiac Performance following Infarction via Immune Modulation.

Overactive inflammatory responses contribute to progressive cardiac dysfunction after myocardial infarction (MI). Mesenchymal stem cell (MSC) has generated significant interest as potent immune modulators that can regulate excessive immune responses. We hypothesized that intravenous (iv) administration of human umbilical cord-derived MSC (HucMSC) exerts systemic and local anti-inflammation effects, leading to improved heart function after MI. In murine MI models, we confirmed that single iv administration of HucMSC (30 × 104) improved cardiac performance and prevented adverse remodeling after MI. A small proportion of HucMSC is trafficked to the heart, preferentially in the infarcted region. HucMSC administration increased CD3+ T cell proportion in the periphery while decreased T cell proportion in both infarcted heart and mediastinal lymph nodes (med-LN) at 7-day post-MI, indicating a systematic and local T cell interchange mediated by HucMSC. The inhibitory effects of HucMSC on T cell infiltration in the infarcted heart and med-LN sustained to 21-day post-MI. Our findings suggested that iv administration of HucMSC fostered systemic and local immunomodulatory effects that contributed to the improvement of cardiac performance after MI.

Direct administration of mesenchymal stem cell-derived mitochondria improves cardiac function after infarction via ameliorating endothelial senescence.

Mitochondrial dysfunction is considered to be a key contributor to the development of heart failure. Replacing injured mitochondria with healthy mitochondria to restore mitochondrial bioenergy in myocardium holds great promise for cardioprotection after infarction. This study aimed to investigate whether direct transplantation of exogenous mitochondria derived from mesenchymal stem cells (MSC-mt) is beneficial and superior in protecting cardiac function in a mouse model of myocardial infarction (MI) compared to mitochondria derived from skin fibroblast (FB-mt) and to explore the underlying mechanisms from their effects on the endothelial cells. The isolated MSC-mt presented intact mitochondrial morphology and activity, as determined by electron microscopy, JC-1 mitochondrial membrane potential assay, and seahorse assay. Direct injection of MSC-mt into the peri-infarct region in a mouse MI model enhanced blood vessel density, inhibited cardiac remodeling and apoptosis, thus improving heart function compared with FB-mt group. The injected MSC-mt can be tracked in the endothelial cells. In vitro, the fluorescence signal of MSC-mt can be detected in human umbilical vein endothelial cells (HUVECs) by confocal microscopy and flow cytometry after coculture. Compared to FB-mt, MSC-mt more effectively protected the HUVECs from oxidative stress-induced apoptosis and reduced mitochondrial production of reactive oxygen species. MSC-mt presented superior capacity in inducing tube formation, enhancing SCF secretion, ATP content and cell proliferation in HUVECs compared to FB-mt. Mechanistically, MSC-mt administration alleviated oxidative stress-induced endothelial senescence via activation of ERK pathway. These findings suggest that using MSCs as sources of mitochondria is feasible and that proangiogenesis could be the mechanism by which MSC-mt transplantation attenuates MI. MSC-mt transplantation might serve as a new therapeutic strategy for treating MI.

Recent research progress on metabolic syndrome and risk of Parkinson's disease.

Parkinson's disease (PD) is one of the most widespread neurodegenerative diseases. PD is associated with progressive loss of substantia nigra dopaminergic neurons, including various motor symptoms (e.g., bradykinesia, rigidity, and resting tremor), as well as non-motor symptoms (e.g., cognitive impairment, constipation, fatigue, sleep disturbance, and depression). PD involves multiple biological processes, including mitochondrial or lysosomal dysfunction, oxidative stress, insulin resistance, and neuroinflammation. Metabolic syndrome (MetS), a collection of numerous connected cerebral cardiovascular conditions, is a common and growing public health problem associated with many chronic diseases worldwide. MetS components include central/abdominal obesity, systemic hypertension, diabetes, and atherogenic dyslipidemia. MetS and PD share multiple pathophysiological processes, including insulin resistance, oxidative stress, and chronic inflammation. In recent years, MetS has been linked to an increased risk of PD, according to studies; however, the specific mechanism remains unclear. Researchers also found that some related metabolic therapies are potential therapeutic strategies to prevent and improve PD. This article reviews the epidemiological relationship between components of MetS and the risk of PD and discusses the potentially relevant mechanisms and recent progress of MetS as a risk factor for PD. Furthermore, we conclude that MetS-related therapies are beneficial for the prevention and treatment of PD.

Fibrinogen function indexes are potential biomarkers for evaluating the occurrence and severity of diabetic foot.

BACKGROUND AND OBJECTIVES: Research suggests that fibrinogen (Fib) concentrations are used to assess the occurrence and severity of diabetic foot (DF) and to monitor the progression of diabetic foot in patients. However, its correlation with Fib function has not been reported. Here, angle α and k value, reflecting the Fib function, were used to analyse its correlation with DF, and their potential as biological indicators for evaluating the occurrence and severity of DF was explored. SUBJECTS AND METHODS: This clinical study enrolled 163 type 2 diabetes mellitus (T2DM) patients, who were divided into the diabetes with DF (84 cases) group, diabetes with no DF (79 cases) group. Meanwhile, 90 healthy unrelated subjects were enrolled as controls. RESULTS: Angle α and fibrinogen levels increased greatly in subjects with DF compared with those without. The k value levels greatly decreased in subjects with DF compared with those without (P < 0.01). Spearman correlation analysis showed that angle α and fibrinogen were positively correlated with DF grading (r = 0.635, P < 0.01; r = 0.616, P < 0.01), k value was negatively correlated with DF (r= - 0.589, P < 0.01). ROC curve analysis showed that the optimal cut-off point for angle α to distinguish patients with DF from those without was 62.85 deg, with a sensitivity of 78.6% and specificity of 78.7%. The optimal cut-off point for k value was 1.75 min, with a sensitivity of 82.1% and specificity of 65.8%. The optimal cut-off point for fibrinogen was 3.85 g/l, with a sensitivity of 63.1% and specificity of 98.2%. The optimal cut-off point for angle α to evaluate the risk of diabetic foot progression was 70.20 deg, with a sensitivity of 73.2% and specificity of 90.7%. The optimal cut-off point for k value was 1.25 min, with a sensitivity of 67.9% and specificity of 90.8%. The optimal cut-off point for fibrinogen was 4.12 g/l, with a sensitivity of 85.7% and specificity of 93.5%. CONCLUSION: Angle α, k-value and fibrinogen have clinical significance on the risk of occurrence and development of diabetic foot, which can contribute to early diagnosis and early clinical intervention in DF.

Examining COVID-19 mortality rates by race and ethnicity among incarcerated people in 11 U.S. state prisons (March-October 2021).

Background: Populations who are incarcerated have experienced disproportionately high coronavirus disease 2019 (COVID-2019) mortality rates compared to the general population. However, mortality rates by race/ethnicity from federal, state, and local carceral settings are largely unavailable due to unregulated reporting; therefore, racial/ethnic inequities have yet to be examined. We aimed to estimate coronavirus disease 2019 (COVID-19) mortality rates among individuals incarcerated in U.S. state prisons by race and ethnicity (RE). Methods: Public records requests to state Departments of Corrections were used to identify deaths from COVID-19 among incarcerated adults occurring from March 1-October 1, 2020. We requested race, ethnicity, and age specific data on deaths and custody populations; sufficient data to calculate age-adjusted rates were obtained for 11 state systems. Race and ethnic specific unadjusted deaths rates per 100,000 persons were calculated overall and by state, based on March 1, 2020 custody populations. Rate ratios (RR) and 95% confidence intervals (95%CI) compared aggregated age-adjusted death rates by race and ethnicity, with White individuals as the reference group. Results: Of all COVID-related deaths in U.S. prisons through October 2020, 23.35% (272 of 1165) were captured in our analyses. The average age at COVID-19 death was 63 years (SD = 10 years) and was significantly lower among Black (60 years, SD = 11 years) compared to White adults (66 years, SD = 10 years; p < 0.001). In age-standardized analysis, COVID-19 death rates were significantly higher among Black (RR = 1.93, 95% CI: 1.25-2.99), Hispanic (RR = 1.81, 95% CI: 1.10-2.96) and those of Other racial and ethnic groups (RR = 2.60, 95% CI: 1.01-6.67) when compared to White individuals. Conclusions: Age-standardized death rates were higher among incarcerated Black, Hispanic and those of Other racial and ethnic groups compared to their White counterparts. Greater data transparency from all carceral systems is needed to better understand populations at disproportionate risk of COVID-19 morbidity and mortality.

Alterations of long noncoding RNAs and mRNAs in extracellular vesicles derived from the murine heart post-ischemia-reperfusion injury.

Extracellular vesicles (EVs) play important roles in cardiovascular diseases by delivering their RNA cargos. However, the features and possible role of the lncRNAs and mRNAs in cardiac EVs during ischemia-reperfusion (IR) remain unclear. Therefore, we performed RNA sequencing analysis to profile the features of lncRNAs and mRNAs and predicted their potential functions. Here, we demonstrated that the severity of IR injury was significantly correlated with cardiac EV production. RNA sequencing identified 73 significantly differentially expressed (DE) lncRNAs (39 upregulated and 34 downregulated) and 720 DE-mRNAs (317 upregulated and 403 downregulated). Gene Ontology (GO) and pathway analysis were performed to predict the potential functions of the DE-lncRNAs and mRNAs. The lncRNA-miRNA-mRNA ceRNA network showed the possible functions of DE-lncRNAs with DE-mRNAs which are enriched in the pathways of T cell receptor signalling pathway and cell adhesion molecules. Moreover, the expressions of ENSMUST00000146010 and ENSMUST00000180630 were negatively correlated with the severity of IR injury. A significant positive correlation was revealed between TCONS_00010866 expression and the severity of the cardiac injury. These findings revealed the lncRNA and mRNA profiles in the heart derived EVs and provided potential targets and pathways involved in cardiac IR injury.

Update on the application of mesenchymal stem cell-derived exosomes in the treatment of Parkinson's disease: A systematic review.

Parkinson's disease (PD) has become the second largest neurodegenerative disease after Alzheimer's disease, and its incidence is increasing year by year. Traditional dopamine replacement therapy and deep brain stimulation can only alleviate the clinical symptoms of patients with PD but cannot cure the disease. In recent years, stem cell therapy has been used to treat neurodegenerative diseases. Many studies have shown that stem cell transplantation has a therapeutic effect on PD. Here, we review recent studies indicating that exosomes derived from mesenchymal stem cells also have the potential to treat PD in animal models, but the exact mechanism remains unclear. This article reviews the mechanisms through which exosomes are involved in intercellular information exchange, promote neuroprotection and freely cross the blood-brain barrier in the treatment of PD. The increase in the incidence of PD and the decline in the quality of life of patients with advanced PD have placed a heavy burden on patients, families and society. Therefore, innovative therapies for PD are urgently needed. Herein, we discuss the mechanisms underlying the effects of exosomes in PD, to provide new insights into the treatment of PD. The main purpose of this article is to explore the therapeutic potential of exosomes derived from mesenchymal stem cells and future research directions for this degenerative disease.

A Comprehensive 2D-LC/MS/MS Profile of the Normal Human Urinary Metabolome.

Profiling bodily fluids is crucial for monitoring and discovering metabolic markers of disease. In this study, a comprehensive analysis approach based on 1D-LC-MS/MS and 2D-LC-MS/MS was applied to profile normal human urine metabolites from 348 children and 315 adults. A total of 2357 metabolites were identified, including 1831 endogenous metabolites and 526 exogenous ones. In total, 1005 metabolites were identified in urine for the first time. The urinary metabolites were mainly involved in amino acid metabolism, small molecule biochemistry, lipid metabolism and cellular compromise. The comparison of adult's and children's urine metabolomes showed adults urine had more metabolites involved in immune response than children's, but the function of binding of melatonin, which belongs to the endocrine system, showed a higher expression in children. The urine metabolites detected by the 1D-LC-MS/MS method were mainly related to amino acid metabolism and lipid metabolism, and the 2D-LC-MS/MS method not only explored metabolites from 1D-LC-MS/MS but also metabolites related to cell signaling, cell function and maintenance, etc. Our analysis comprehensively profiled and functionally annotated the metabolome of normal human urine, which would benefit the application of urinary metabolome to clinical research.

Corrigendum: CircAFF1 aggravates vascular endothelial cell dysfunction mediated by miR-516b/SAV1/YAP1 axis.

[This corrects the article DOI: 10.3389/fphys.2020.00899.].

The complete chloroplast genome of Gynura japonica and its phylogenetic implications.

Gynura japonica (Asteraceae) is a folk herbal medicine with multi-pharmacological functions involving analgesic, hemostatic and antiangiogenic activities. The study was conducted to assemble the complete chloroplast (cp) genome of G. japonica through a genome-skimming approach. The assembled cp genome was 151,023 bp in size, with 62.8% AT content, consisting of a large single copy (LSC) of 83,185 bp, two copies of inverted repeat (IRa and IRb) of 24,847 bp, and a small single copy (SSC) of 18,144 bp. The cp genome of G. japonica contained 133 genes, including eight ribosomal RNA genes (rRNAs), 37 transfer RNA genes (tRNAs), 86 protein-coding genes (PCGs), and two pseudogenes (ψycf1 and ψrps19). Our phylogenomic analysis based on whole plastid genomes strongly supports G. japonica is a sister to the clade including Crassocephalum crepidioides and Jacobaea vulgaris.