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1.
Stem Cell Res Ther ; 12(1): 489, 2021 Sep 01.
Artigo em Inglês | MEDLINE | ID: mdl-34470673

RESUMO

OBJECTIVES: Adipose-derived stem cells are frequently used for bone regeneration both in vitro and in vivo. N6-methyladenosine (m6A) is the most abundant post-transcriptional modification on eukaryotic RNAs and plays multifaceted roles in development and diseases. However, the regulatory mechanisms of m6A in osteogenic differentiation of human adipose-derived stem cells (hASCs) remain elusive. The present study aimed to build the transcriptome-wide m6A methylome during the osteogenic differentiation of hASCs. MATERIALS AND METHODS: hASCs were harvested after being cultured in a basic or osteogenic medium for 7 days, and the osteogenic differentiation was validated by alkaline phosphatase (ALP) and Alizarin Red S staining, ALP activity assay, and qRT-PCR analysis of ALP, RUNX2, BGLAP, SPP1, SP7, and COL1A1 genes. The m6A level was colorimetrically measured, and the expression of m6A regulators was confirmed by qRT-PCR and western blot. Moreover, m6A MeRIP-seq and RNA-seq were performed to build the transcriptome and m6A methylome. Furthermore, bioinformatic analyses including volcano plots, Venn plots, clustering analysis, Gene Ontology (GO), Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway, gene sets enrichment analysis, and protein-protein interaction analysis were conducted. RESULTS: In total, 1145 differentially methylated peaks, 2261 differentially expressed genes, and 671 differentially methylated and expressed genes (DMEGs) were identified. GO and KEGG pathway analyses conducted for these DMEGs revealed extensive and osteogenic biological functions. The "PI3K-Akt signaling pathway"; "MAPK signaling pathway"; "parathyroid hormone synthesis, secretion, and action"; and "p53 signaling pathway" were significantly enriched, and the DMEGs in these pathways were identified as m6A-specific key genes. A protein-protein interaction network based on DMEGs was built, and VEGFA, CD44, MMP2, HGF, and SPARC were speculated as the hub DMEGs. CONCLUSIONS: The total m6A level was reduced with osteogenic differentiation of hASCs. The transcriptome-wide m6A methylome built in the present study indicated quite a few signaling pathways, and hub genes were influenced by m6A modification. Future studies based on these epigenetic clues could promote understanding of the mechanisms of osteogenic differentiation of hASCs.

2.
Psychol Health Med ; : 1-16, 2021 Aug 31.
Artigo em Inglês | MEDLINE | ID: mdl-34465255

RESUMO

The aim of this meta-analysis was to compare health-related quality of life (HRQoL) of Osteoarthritis (OA) patients and controls. A systematic literature search was performed on PubMed, Web of Science and EMBASE from database inception to 7 January 2020. Random effect model was performed to summarize the scores of each domain and the forest plot was used to compare the scores of OA patients with healthy controls. Subgroup analyses were conducted to explore the source of heterogeneity. Statistical analyses were executed using Review Manager (version 5.1). In total, six studies were included in this study, including 7094 patients with OA and 12 100 healthy controls, which were all reliable to summarize the scores of the Medical Outcomes Study 36-item Short-Form Health Survey (SF-36). Meta-analyses found that pooled mean HRQoL score for the SF-36 each domain (physical function, physical role function, body pain, general health, vitality, social function, emotional role function, mental health) was lower in patients with OA than in healthy controls, especially the score in the dimension of physical role function. OA have a substantial impact HRQoL. HRQoL is a significant component of measuring overall health, which contributes to formulate successful self-disease management plan, patient-centered care, and develop effective interventions target confidence.

3.
J Glob Antimicrob Resist ; 27: 63-66, 2021 Sep 02.
Artigo em Inglês | MEDLINE | ID: mdl-34482020

RESUMO

OBJECTIVES: The aim of this study was to characterise the co-occurrence of blaKPC and blaNDM in a K64-ST11 carbapenem-resistant Klebsiella pneumoniae strain. METHODS: Antimicrobial susceptibility was determined by the disk diffusion method. Whole-genome sequencing was performed using Illumina MiSeq and PacBio II sequencers. High-quality reads were de novo assembled using the SOAPdenovo package. Genome annotation was performed using the NCBI Prokaryotic Genome Annotation Pipeline (PGAP), and genome characteristics were analysed using bioinformatics methods. RESULTS: Klebsiella pneumoniae strain KPWX136 was resistant to most of the tested antibiotics, being susceptible only to polymyxin B and tigecycline. The genome of strain KPWX136 is composed of a single chromosome (5 473 976 bp) and six plasmids including pA (191 359 bp), pB (134 972 bp), pC (117 844 bp), pD (87 095 bp), pE (11 970 bp) and pF (5596 bp). Complete sequence analysis revealed the resistome of isolate KPWX136, which included blaKPC-2 and blaNDM-5 together with 23 other resistance genes, of which 6 resistance genes were located on the chromosome and 19 on plasmids. Virulome analysis showed that KPWX136 carried a large number of virulence-associated genes. Meanwhile, 26 genomic islands and 6 prophages were predicted within the genome. CONCLUSION: Genetic characterisation of K. pneumoniae KPWX136 co-harbouring blaNDM-5 and blaKPC-2 showed that it carried not only 25 resistance genes and a large number virulence factors but also various mobile genetic elements (MGEs) such as plasmids and genomic islands. Therefore, we must be alert to the transmission of resistance genes and virulence determinants via MGEs.

4.
Int J Mol Sci ; 22(17)2021 Aug 30.
Artigo em Inglês | MEDLINE | ID: mdl-34502300

RESUMO

Folate depletion causes chromosomal instability by increasing DNA strand breakage, uracil misincorporation, and defective repair. Folate mediated one-carbon metabolism has been suggested to play a key role in the carcinogenesis and progression of hepatocellular carcinoma (HCC) through influencing DNA integrity. Methylenetetrahydrofolate reductase (MTHFR) is the enzyme catalyzing the irreversible conversion of 5,10-methylenetetrahydrofolate to 5-methyltetrahydrofolate that can control folate cofactor distributions and modulate the partitioning of intracellular one-carbon moieties. The association between MTHFR polymorphisms and HCC risk is inconsistent and remains controversial in populational studies. We aimed to establish an in vitro cell model of liver origin to elucidate the interactions between MTHFR function, folate status, and chromosome stability. In the present study, we (1) examined MTHFR expression in HCC patients; (2) established cell models of liver origin with stabilized inhibition of MTHFR using small hairpin RNA delivered by a lentiviral vector, and (3) investigated the impacts of reduced MTHFR and folate status on cell cycle, methyl group homeostasis, nucleotide biosynthesis, and DNA stability, all of which are pathways involved in DNA integrity and repair and are critical in human tumorigenesis. By analyzing the TCGA/GTEx datasets available within GEPIA2, we discovered that HCC cancer patients with higher MTHFR had a worse survival rate. The shRNA of MTHFR (shMTHFR) resulted in decreased MTHFR gene expression, MTHFR protein, and enzymatic activity in human hepatoma cell HepG2. shMTHFR tended to decrease intracellular S-adenosylmethionine (SAM) contents but folate depletion similarly decreased SAM in wildtype (WT), negative control (Neg), and shMTHFR cells, indicating that in cells of liver origin, shMTHFR does not exacerbate the methyl group supply in folate depletion. shMTHFR caused cell accumulations in the G2/M, and cell population in the G2/M was inversely correlated with MTHFR gene level (r = -0.81, p < 0.0001), MTHFR protein expression (r = -0.8; p = 0.01), and MTHFR enzyme activity (r = -0.842; p = 0.005). Folate depletion resulted in G2/M cell cycle arrest in WT and Neg but not in shMTHFR cells, indicating that shMTHFR does not exacerbate folate depletion-induced G2/M cell cycle arrest. In addition, shMTHFR promoted the expression and translocation of nuclei thymidine synthetic enzyme complex SHMT1/DHFR/TYMS and assisted folate-dependent de novo nucleotide biosynthesis under folate restriction. Finally, shMTHFR promoted nuclear MLH1/p53 expression under folate deficiency and further reduced micronuclei formation and DNA uracil misincorporation under folate deficiency. In conclusion, shMTHFR in HepG2 induces cell cycle arrest in G2/M that may promote nucleotide supply and assist cell defense against folate depletion-induced chromosome segregation and uracil misincorporation in the DNA. This study provided insight into the significant impact of MTHFR function on chromosome stability of hepatic tissues. Data from the present study may shed light on the potential regulatory mechanism by which MTHFR modulates the risk for hepatic malignancies.

5.
Int J Mol Sci ; 22(17)2021 Sep 03.
Artigo em Inglês | MEDLINE | ID: mdl-34502485

RESUMO

Seashore paspalum is a major warm-season turfgrass requiring frequent mowing. The use of dwarf cultivars with slow growth is a promising method to decrease mowing frequency. The present study was conducted to provide an in-depth understanding of the molecular mechanism of T51 dwarfing in the phenylpropane pathway and to screen the key genes related to dwarfing. For this purpose, we obtained transcriptomic information based on RNA-Seq and proteomic information based on iTRAQ for the dwarf mutant T51 of seashore paspalum. The combined results of transcriptomic and proteomic analysis were used to identify the differential expression pattern of genes at the translational and transcriptional levels. A total of 8311 DEGs were detected at the transcription level, of which 2540 were upregulated and 5771 were downregulated. Based on the transcripts, 2910 proteins were identified using iTRAQ, of which 392 (155 upregulated and 237 downregulated) were DEPs. The phenylpropane pathway was found to be significantly enriched at both the transcriptional and translational levels. Combined with the decrease in lignin content and the increase in flavonoid content in T51, we found that the dwarf phenotype of T51 is closely related to the abnormal synthesis of lignin and flavonoids in the phenylpropane pathway. CCR and HCT may be the key genes for T51 dwarf. This study provides the basis for further study on the dwarfing mechanism of seashore paspalum. The screening of key genes lays a foundation for further studies on the molecular mechanism of seashore paspalum dwarfing.

6.
J Nanobiotechnology ; 19(1): 275, 2021 Sep 09.
Artigo em Inglês | MEDLINE | ID: mdl-34503490

RESUMO

BACKGROUND: Skin injury and the resultant defects are common clinical problems, and usually lead to chronic skin ulcers and even life-threatening diseases. Copper, an essential trace element of human body, has been reported to promote the regeneration of skin by stimulating proliferation of endothelial cell and enhance angiogenesis. RESULTS: Herein, we have prepared a new donut-like metal-organic frameworks (MOF) of copper-nicotinic acid (CuNA) by a simple solvothermal reaction. The rough surface of CuNA is beneficial for loading/release basic fibroblast growth factor (bFGF). The CuNAs with/without bFGF are easily processed into a light-responsive composite hydrogel with GelMA, which not only show excellent mechanical properties, but also display superior biocompatibility, antibacterial ability and bioactivity. Moreover, in the in vivo full-thickness defect model of skin wound, the resultant CuNA-bFGF@GelMA hydrogels significantly accelerate the wound healing, by simultaneously inhibiting the inflammatory response, promoting the new blood vessels formation and the deposition of collagen and elastic fibers. CONCLUSIONS: Considering the superior biocompatibility, antibacterial ability and bioactivity, the CuNA and its composite light-responsive hydrogel system will be promising in the applications of skin and even other tissue regeneration.

7.
Front Immunol ; 12: 728082, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34512660

RESUMO

CD8+ T cells are major components of adaptive immunity and confer robust protective cellular immunity, which requires adequate T-cell numbers, targeted migration, and efficient T-cell proliferation. Altered CD8+ T-cell homeostasis and impaired proliferation result in dysfunctional immune response to infection or tumorigenesis. However, intrinsic factors controlling CD8+ T-cell homeostasis and immunity remain largely elusive. Here, we demonstrate the prominent role of Brd4 on CD8+ T cell homeostasis and immune response. By upregulating Myc and GLUT1 expression, Brd4 facilitates glucose uptake and energy production in mitochondria, subsequently supporting naïve CD8+ T-cell survival. Besides, Brd4 promotes the trafficking of naïve CD8+ T cells partially through maintaining the expression of homing receptors (CD62L and LFA-1). Furthermore, Brd4 is required for CD8+ T cell response to antigen stimulation, as Brd4 deficiency leads to a severe defect in clonal expansion and terminal differentiation by decreasing glycolysis. Importantly, as JQ1, a pan-BRD inhibitor, severely dampens CD8+ T-cell immune response, its usage as an anti-tumor agent or latency-reversing agent for human immunodeficiency virus type I (HIV-1) should be more cautious. Collectively, our study identifies a previously-unexpected role of Brd4 in the metabolic regulation of CD8+ T cell-mediated immune surveillance and also provides a potential immunomodulation target.

8.
Math Biosci Eng ; 18(5): 6709-6723, 2021 Aug 09.
Artigo em Inglês | MEDLINE | ID: mdl-34517553

RESUMO

OBJECTIVE: We aimed to construct a novel prognostic model based on N6-methyladenosine (m6A)-related autophagy genes for predicting the prognosis of lung squamous cell carcinoma (LUSC). METHODS: Gene expression profiles and clinical information of Patients with LUSC were downloaded from The Cancer Genome Atlas (TCGA) database. In addition, m6A- and autophagy-related gene profiles were obtained from TCGA and Human Autophagy Database, respectively. Pearson correlation analysis was performed to identify the m6A-related autophagy genes, and univariate Cox regression analysis was conducted to screen for genes associated with prognosis. Based on these genes, LASSO Cox regression analysis was used to construct a prognostic model. The corresponding prognostic score (PS) was calculated, and patients with LUSC were assigned to low- and high-risk groups according to the median PS value. An independent dataset (GSE37745) was used to validate the prognostic ability of the model. CIBERSORT was used to calculate the differences in immune cell infiltration between the high- and low-risk groups. RESULTS: Seven m6A-related autophagy genes were screened to construct a prognostic model: CASP4, CDKN1A, DLC1, ITGB1, PINK1, TP63, and EIF4EBP1. In the training and validation sets, patients in the high-risk group had worse survival times than those in the low-risk group; the areas under the receiver operating characteristic curves were 0.958 and 0.759, respectively. There were differences in m6A levels and immune cell infiltration between the high- and low-risk groups. CONCLUSIONS: Our prognostic model of the seven m6A-related autophagy genes had significant predictive value for LUSC; thus, these genes may serve as autophagy-related therapeutic targets in clinical practice.

9.
ACS Appl Mater Interfaces ; 13(36): 42451-42460, 2021 Sep 15.
Artigo em Inglês | MEDLINE | ID: mdl-34486369

RESUMO

A sunscreen offers indispensable skin protection against UV damage and related skin diseases. However, due to the poor interfacial stability of sunscreen coatings on the skin, the synthetic ingredients in sunscreen creams easily fall off and enter aquatic environments, causing large ecological hazards and skin protection failure. Herein, we tackle this issue by introducing amyloid-like protein aggregates into a sunscreen to noticeably enhance the interfacial robustness of sunscreen coatings on the skin. The synthesis of such an agent to suppress sunscreen leakage can be achieved by manipulating the phase transition of bovine serum albumin (BSA) in a mild aqueous solution at room temperature. The resulting phase-transitioned BSA (PTB) aggregates effectively entrap the sunscreen ingredients to generate a uniform cream coating on the skin with robust amyloid-mediated interfacial adhesion stability. With continuous flushing in aquatic environments, such as salt water and seawater, this PTB-modified sunscreen (PTB sunscreen) coated on the skin maintains a retention ratio as high as >92%, which is 2-10 times higher than those of commercially available sunscreen products. The high retention ratio of the PTB sunscreen in aquatic environments demonstrates the great potential of amyloid-like protein aggregates in the development of leakage-free sunscreens with low ecosystem hazards and long-lasting UV protection in aquatic environments.

10.
BMJ Open ; 11(9): e048530, 2021 09 07.
Artigo em Inglês | MEDLINE | ID: mdl-34493513

RESUMO

OBJECTIVE: To investigate the association between maternal pregestational blood glucose level and adverse pregnancy outcomes. DESIGN: Retrospective cohort study. SETTING: This study was conducted in the Chongqing Municipality of China between April 2010 and December 2016. PARTICIPANTS: A total of 60 222 women (60 360 pregnancies) from all 39 counties of Chongqing who participated in the National Free Preconception Health Examination Project and had pregnancy outcomes were included. PRIMARY OUTCOME MEASURES: Adverse pregnancy outcomes included spontaneous abortion, induced abortion or labour due to medical reasons, stillbirth, preterm birth (PTB), macrosomia, large for gestational age, low birth weight (LBW) and small for gestational age. RESULTS: Of the 60 360 pregnancies, rates of hypoglycaemic, normoglycaemia, impaired fasting glycaemia (IFG) and diabetic hyperglycaemic before conception were 5.06%, 89.30%, 4.59% and 1.05%, respectively. Compared with women with normoglycaemia, women with pregestational glucose at the diabetic level (≥7.0 mmol/L) might have a higher rate of macrosomia (6.18% vs 4.16%), whereas pregestational IFG seemed to be associated with reduced risks of many adverse outcomes, including spontaneous abortion, induced abortion due to medical reasons, PTB and LBW. After adjusting for potential confounders, pregestational diabetic hyperglycaemic was remained to be significantly associated with an increased risk of macrosomia (adjusted risk ratio 1.49, 95% CI 1.07 to 2.09). Abnormal maternal glucose levels before pregnancy (either hypoglycaemic or hyperglycaemic) seemed to have no significant negative effect on spontaneous abortion or induced abortion due to medical reasons. CONCLUSION: Although without overt diabetes mellitus, women with once diabetic fasting glucose level during their preconception examinations could be associated with an increased risk for macrosomia. Uniform guidelines are needed for maternal blood glucose management during pre-pregnancy care to improve pregnancy outcomes.


Assuntos
Nascimento Prematuro , Estudos de Coortes , Feminino , Macrossomia Fetal/epidemiologia , Glucose , Humanos , Recém-Nascido , Gravidez , Resultado da Gravidez/epidemiologia , Estudos Retrospectivos
11.
BMJ Open ; 11(9): e050221, 2021 09 07.
Artigo em Inglês | MEDLINE | ID: mdl-34493519

RESUMO

OBJECTIVE: To describe how mothers of late preterm infants experienced the provision of intermittent kangaroo mother care (KMC) in four postnatal wards in different hospitals in China, under a pilot KMC project. DESIGN: A concurrent mixed-methods approach incorporating quantitative maternal questionnaires and qualitative semistructured interviews. SETTING: Four postnatal wards in level-III hospitals based in different provinces of Southeast and Northwest China. PARTICIPANTS: All 752 mothers who provided intermittent KMC to their late preterm newborns in the four participating postnatal wards consented to participate in the study (quantitative component), as well as six nurses, two obstetricians and two mothers from two of the participating postnatal wards (qualitative component). OUTCOME MEASURES: Maternal KMC experiences during a hospital stay, patients' perceptions of KMC initiation, processes, benefits and challenges. RESULTS: Most mothers had not heard of KMC before being introduced to it in the postnatal ward. On average, mothers and newborns stayed in postnatal wards for 3.6 days; during their stay, mothers provided an average of 3.5 KMC sessions, which is an average of 1.1 sessions a day. Each KMC session lasted an average of 68 min, though there was much variation in the length of a session. Common reasons given for discontinuing a KMC session included restroom use, infant crying and perceived time limitations. Some mothers would have preferred to provide KMC for longer periods of time and nurses encouraged this. Most mothers experienced no difficulty providing KMC, received support from family and medical staff and intended to continue with KMC postdischarge. CONCLUSION: In order to improve the maternal experience of KMC, it is recommended that raising awareness of KMC should be included in antenatal care and after birth. Longer periods of KMC provision should be encouraged, greater privacy should be provided for mothers providing KMC in postnatal wards and family members should be encouraged to support KMC.


Assuntos
Método Canguru , Assistência ao Convalescente , Criança , China , Feminino , Hospitais , Humanos , Recém-Nascido , Recém-Nascido Prematuro , Mães , Alta do Paciente , Gravidez
12.
BMC Med ; 19(1): 206, 2021 Sep 13.
Artigo em Inglês | MEDLINE | ID: mdl-34511132

RESUMO

BACKGROUND: ROS1-rearranged lung cancers benefit from first-line crizotinib therapy; however, clinical and molecular factors that could affect crizotinib efficacy in ROS1-rearranged lung cancers are not yet well-elucidated. Our retrospective study aimed to compare the efficacy of chemotherapy and crizotinib in the first-line treatment of ROS1-rearranged advanced lung cancer and evaluate various clinical and molecular factors that might impact crizotinib efficacy in real-world practice. METHODS: Treatment responses, survival outcomes, and patterns of disease progression were analyzed for 235 patients with locally advanced to advanced disease who received first-line chemotherapy (n = 67) or crizotinib (n = 168). RESULTS: The overall response rate was 85.7% (144/168) for first-line crizotinib and 41.8% (28/67) for chemotherapy. Patients treated with first-line crizotinib (n = 168) had significantly longer median progression-free survival (PFS) than chemotherapy (n = 67) (18.0 months vs. 7.0 months, p < 0.001). Patients harboring single CD74-ROS1 (n = 90) had significantly shorter median PFS with crizotinib than those harboring non-CD74 ROS1 fusions (n = 69) (17.0 months vs. 21.0 months; p = 0.008). Patients with baseline brain metastasis (n = 45) had a significantly shorter PFS on first-line crizotinib than those without brain metastasis (n = 123) (16.0 months vs. 22.0 months; p = 0.03). At progression, intracranial-only progression (n = 40), with or without baseline CNS metastasis, was associated with longer median PFS than those with extracranial-only progression (n = 64) (19.0 months vs. 13.0 months, p < 0.001). TP53 mutations were the most common concomitant mutation, detected in 13.1% (7/54) of patients with CD74-ROS1 fusions, and 18.8% (6/32) with non-CD74 ROS1 fusions. Patients with concomitant TP53 mutations (n=13) had significantly shorter PFS than those who had wild-type TP53 (n = 81) (6.5 months vs. 21.0 months; p < 0.001). PFS was significantly shorter for the patients who harbored concomitant driver mutations (n = 9) (11.0 months vs 24.0 months; p = 0.0167) or concomitant tumor suppressor genes (i.e., TP53, RB1, or PTEN) (n = 25) (9.5 months vs 24.0 months; p < 0.001) as compared to patients without concomitant mutations (n = 58). CONCLUSION: Our results demonstrate that baseline brain metastatic status and various molecular factors could contribute to distinct clinical outcomes from first-line crizotinib therapy of patients with ROS1-rearranged lung cancer. CLINICAL TRIALS REGISTRATION: CORE, NCT03646994.

13.
Appl Environ Microbiol ; : AEM0106521, 2021 Sep 15.
Artigo em Inglês | MEDLINE | ID: mdl-34524897

RESUMO

Recent omics studies have provided invaluable insights into the metabolic potential, adaptation and evolution of novel archaeal lineages from a variety of extreme environments. We have utilized a genome-resolved metagenomic approach to recover eight medium- to high-quality metagenome-assembled genomes (MAGs) that likely represent a new order ("Candidatus Sysuiplasmatales") within Thermoplasmata from mine tailings and acid mine drainage (AMD) sediments sampled from two copper mines in South China. 16S rRNA gene based analyses revealed a narrow habitat range for these uncultured archaea limiting to AMD and hot spring-related environments. Metabolic reconstruction indicated a facultatively anaerobic heterotrophic lifestyle. This may allow the archaea to adapt to oxygen fluctuations and is thus in marked contrast to the majority of lineages in the domain Archaea which typically show obligately anaerobic metabolisms. Notably, "Ca. Sysuiplasmatales" could conserve energy through degradation of fatty acids, amino acid metabolism and oxidation of reduced inorganic sulfur compounds (RISCs), suggesting that they may contribute to acid generation in the extreme mine environments. Unlike its closely related Methanomassiliicoccales and "Ca. Gimiplasmatales", "Ca. Sysuiplasmatales" lack the capacity to perform methanogenesis and carbon fixation. Ancestral state reconstruction indicated that "Ca. Sysuiplasmatales" and its closely related Methanomassiliicoccales, "Ca. Gimiplasmatales", and the SG8-5 and the RBG-16-68-12 orders originated from a facultatively anaerobic ancestor capable of carbon fixation via the bacterial-type H4F Wood-Ljungdahl pathway (WLP). Their metabolic divergence might be attributed to different evolutionary paths. Importance A wide array of archaea populate Earth's extreme environments thereby they may play important roles in mediating biogeochemical processes such as iron and sulfur cycling. However, our knowledge of archaeal biology and evolution is still limited considering the uncultured majority of archaeal diversity. For instance, most order-level lineages except Thermoplasmatales, Aciduliprofundales and Methanomassiliicoccales within Thermoplasmata do not have cultured representatives. Here, we report the discovery and genomic characterization of a novel order, namely "Ca. Sysuiplasmatales", within Thermoplasmata in the extremely acidic mine environments. "Ca. Sysuiplasmatales" are inferred to be facultatively anaerobic heterotrophs and likely contribute to acid generation through the oxidation of RISCs. The physiological divergence between "Ca. Sysuiplasmatales" and its closely related Thermoplasmata lineages may be attributed to different evolutionary paths. These results expand our knowledge of archaea in the extreme mine ecosystem.

14.
J Agric Food Chem ; 69(36): 10749-10759, 2021 Sep 15.
Artigo em Inglês | MEDLINE | ID: mdl-34474557

RESUMO

Gestational diabetes mellitus (GDM) not only has a bad effect on the development of infants but also causes variations in breastmilk composition. This study aims to investigate the changes in the protein profile of colostrum between mothers with GDM and healthy mothers (H) by sequential windowed acquisition of all theoretical fragment ion proteomics techniques. A total of 1295 proteins were detected, with 192 proteins being significantly different between GDM and H. These significantly different proteins were enriched with the carbohydrate and lipid metabolism pathway as well as immunity. Some proteins had an AOC value of 1, such as apolipoprotein E and lipoprotein lipase. In addition, we identified 42 glycated and 93 glycosylated peptides in colostrum without any enrichment, with glycated peptides being upregulated and glycosylated peptides being downregulated in colostrum with GDM. These results help us to better understand the GDM-induced changes in proteomes and glycated and glycosylated level and provide guidance on infant formula adjustment for infants from mothers with GDM.


Assuntos
Diabetes Gestacional , Colostro , Feminino , Humanos , Leite Humano , Gravidez , Proteoma , Proteômica
15.
Chemosphere ; 282: 131150, 2021 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-34470175

RESUMO

Epidemiologic studies focus on combined effects of multiple metals on bone mineral density (BMD) are scarce. Therefore, this study was conducted to examine associations of multiple metals exposure with BMD. Data of adults aged ≥20 years (n = 2545) from the US National Health and Nutrition Examination Survey (NHANES, 2011-2016) were collected and analyzed. Concentrations of metals were measured in blood (cadmium [Cd], lead [Pb], mercury [Hg], and manganese [Mn]) and serum (copper [Cu], selenium [Se], and zinc [Zn]) using inductively coupled plasma mass spectrometry and inductively coupled plasma dynamic reaction cell mass spectrometry, respectively. The weighted quantile sum (WQS) and Bayesian kernel machine regression (BKMR) models were performed to determine the joint effects of multiple metals exposure on lumbar and total BMD. The linear regression analyses showed Pb was negatively associated with BMDs. The WQS regression analyses revealed that the WQS index was inversely related to lumbar (ß = -0.022, 95% CI: -0.036, -0.008) and total BMD (ß = -0.015, 95% CI: -0.024, -0.006), and Se, Mn, and Pb were the main contributors for the combined effects. Additionally, nonlinear dose-response relationships between Pb, Mn, and Se and BMD, as well as a synergistic interaction of Pb and Mn, were found in the BKMR analyses. Our findings suggested co-exposure to Cd, Pb, Hg, Mn, Cu, Se, and Zn (above their 50th percentiles) was associated with reduced BMD, and Pb, Mn, and Se were the main contributors driving the overall effects.


Assuntos
Densidade Óssea , Metais , Teorema de Bayes , Cádmio , Inquéritos Nutricionais
16.
Artigo em Inglês | MEDLINE | ID: mdl-34478541

RESUMO

OBJECTIVE: The immune system plays a central role in the pathophysiology of gestational diabetes mellitus (GDM). Monocytes, the main innate immune cells, are especially important in the maintenance of a normal pregnancy. Here, we investigated the potential effect of monocytes in GDM.Materials and Methods: Monocyte count was monitored throughout pregnancy in 214 women with GDM and 926 women without in a case-control and cohort study. Circulating levels of inflammatory cytokines, placenta-derived macrophages and their products were measured. RESULTS: Throughout pregnancy, monocyte count was significantly decreased in women with GDM, and closely associated with glucose level, insulin resistance and newborn weight. First-trimester monocyte count outperformed that of the second and third trimester as a risk factor and diagnostic predictor of GDM and macrosomia in both the case-control and cohort study. In addition, our cohort study showed that as first-trimester monocyte count decreased, GDM and macrosomia incidence, glucose level and newborn weight increased in a stepwise manner. Risk of GDM started to decrease rapidly when first-trimester monocyte count exceeded 0.48 × 10 9/L. Notably, CD206 and IL-10 were significantly lower, while CD80, CD86, TNF-α and IL-6 were higher in both GDM placental tissue and peripheral blood. First-trimester monocyte count was positively related to IL-10 and CD206, but negatively related to CD80, CD86, TNF-α and IL-6. CONCLUSIONS: Decreased monocyte count throughout pregnancy was closely-associated with the development of GDM, macrosomia and the chronic inflammatory state of GDM. First-trimester monocyte count has great potential as an early diagnostic marker of GDM.

17.
J Appl Clin Med Phys ; 2021 Sep 04.
Artigo em Inglês | MEDLINE | ID: mdl-34480832

RESUMO

OBJECTIVES: This study was aimed to systematically review the existing literature and explore more the diagnostic value of T1 and T2 mapping in acute myocarditis. METHODS: Studies were searched from five electronic databases. Sensitivity, specificity, diagnostic odds ratio (DOR), and summary receiver operating characteristic curves (SROC) were calculated to present diagnostic performance. A meta-regression and subgroup analysis was performed based on validation (endomyocardial biopsy [EMB] vs. clinical criteria). RESULTS: A total of 10 studies were included, with 400 myocarditis patients and 266 controls. Native T1, T2, and extracellular volume (ECV) values were significantly increased in the myocarditis group. Pooled sensitivities for T1, T2 mapping, and ECV were 0.84 (0.78-0.88), 0.77 (0.69-0.83), and 0.69 (0.50-0.83), respectively. Pooled specificities were 0.86 (0.69-0.95), 0.83 (0.73-0.89), and 0.77 (0.63-0.87), respectively. The DORs were 32 (12-87), 16 (8-30), and 7 (4-14), respectively. The areas under the curve (AUC) of SROC were 0.87 (0.84-0.90), 0.86 (0.82-0.89), and 0.80 (0.76-0.83), respectively. In the meta-regression and subgroup analysis, significantly lower specificities of T1 and T2 mapping were observed in EMB studies (p < 0.01). CONCLUSION: The currently available evidence shows that T1 and T2 mapping including ECV alone offer comparably good diagnostic performance for the detection of acute myocarditis. The reason for the observed mismatch with EMB findings should be further investigated.

18.
Pediatr Investig ; : e12282, 2021 Aug 12.
Artigo em Inglês | MEDLINE | ID: mdl-34540320

RESUMO

Importance: The Coronavirus disease 2019 (COVID-19) global pandemic poses a considerable challenge for pediatricians. Objective: This study aimed to identify the epidemiological characteristics and clinical features of pediatric patients with COVID-19 in China. Methods: This multicenter retrospective study included pediatric patients from 46 hospitals in China, covering 12 provinces and two municipalities. Epidemiological, demographic, clinical, laboratory, treatment, and outcome data were analyzed. Results: In total, 211 pediatric patients with COVID-19 were included in this study. The median age was 7.0 years (range: 22 days to 18 years). Approximately 16.3% of the patients exhibited asymptomatic infections, 23.0% had upper respiratory tract infections, and 60.7% had pneumonia, including two with severe pneumonia and one with critical illness. Approximately 78.7% of the pediatric patients occurred in familial clusters. The most three common symptoms or signs at onset in children with COVID-19 were fever (54.5%), cough (49.3%), and pharyngeal congestion (20.8%). Only 17.6% of the patients presented with decreased lymphocyte count, whereas 13.6% had increased lymphocyte count. Among the patients with pneumonia who exhibited abnormal chest computed tomography findings, 18.2% (23/127) of the patients had no other symptoms. Generally, the chest radiographs showed abnormalities that affected both lungs (49.6%); ground-glass opacity (47.2%) was the most common manifestation. The cure and improvement rates were 86.7% (183/211) and 13.3% (28/211), respectively. Only one patient with an underlying condition received invasive mechanical ventilation; none of the patients died. Interpretation: Similar to adults, children of all age groups are susceptible to COVID-19. Fortunately, most pediatric patients have mild symptoms or remain asymptomatic, despite the high incidence of pneumonia. Decreased proportions of white blood cells and lymphocytes are less frequent in children than in adults.

19.
Ren Fail ; 43(1): 1329-1337, 2021 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-34541999

RESUMO

BACKGROUND: This study sought to investigate incidence and risk factors for acute kidney injury (AKI) in hospitalized COVID-19. METHODS: In this retrospective study, we enrolled 823 COVID-19 patients with at least two evaluations of renal function during hospitalization from four hospitals in Wuhan, China between February 2020 and April 2020. Clinical and laboratory parameters at the time of admission and follow-up data were recorded. Systemic renal tubular dysfunction was evaluated via 24-h urine collections in a subgroup of 55 patients. RESULTS: In total, 823 patients were enrolled (50.5% male) with a mean age of 60.9 ± 14.9 years. AKI occurred in 38 (40.9%) ICU cases but only 6 (0.8%) non-ICU cases. Using forward stepwise Cox regression analysis, we found eight independent risk factors for AKI including decreased platelet level, lower albumin level, lower phosphorus level, higher level of lactate dehydrogenase (LDH), procalcitonin, C-reactive protein (CRP), urea, and prothrombin time (PT) on admission. For every 0.1 mmol/L decreases in serum phosphorus level, patients had a 1.34-fold (95% CI 1.14-1.58) increased risk of AKI. Patients with hypophosphatemia were likely to be older and with lower lymphocyte count, lower serum albumin level, lower uric acid, higher LDH, and higher CRP. Furthermore, serum phosphorus level was positively correlated with phosphate tubular maximum per volume of filtrate (TmP/GFR) (Pearson r = 0.66, p < .001) in subgroup analysis, indicating renal phosphate loss via proximal renal tubular dysfunction. CONCLUSION: The AKI incidence was very low in non-ICU patients as compared to ICU patients. Hypophosphatemia is an independent risk factor for AKI in patients hospitalized for COVID-19 infection.

20.
Cancer Biomark ; 2021 Sep 17.
Artigo em Inglês | MEDLINE | ID: mdl-34542063

RESUMO

BACKGROUND: Distinguishing between benign and malignant bile duct strictures has long been a diagnostic challenge in clinical practice. OBJECTIVE: This study aimed to discover novel biomarkers in bile to improve the diagnostic accuracy of malignant biliary strictures. METHODS: Bile samples were collected from 6 patients with malignant or benign biliary stricture, respectively. Protein profiles of the bile were analyzed with a semi-quantitative human antibody array of 440 proteins. Then the differential expressed proteins were screened by Venn diagram analysis. Following this, the accuracy of these potential biomarkers for discriminating between malignant and non-malignant biliary strictures was validated in a larger (n= 40) group of patients using lasso analysis. RESULTS: Twenty proteins were found differentially expressed in malignant versus benign biliary strictures, 6 of which were identified by Venn diagram analysis to be up-regulated regardless of the location of biliary strictures. Among the 6 biomarkers, bile lipocalin-2, P-cadherin, and adipsin showed better diagnostic utility than that of bile CA19-9. Lasso analysis identified that lipocalin-2, P-cadherin and CA19-9 as a group of makers best distinguished malignant from benign strictures. CONCLUSIONS: Lipocalin-2 and P-cadherin measurements in bile could be clinically useful for the detection of malignant biliary strictures.

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