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BACKGROUND: The endothelial-to-hematopoietic transition (EHT) process during definitive hematopoiesis is highly conserved in vertebrates. Stage-specific expression of transposable elements (TEs) has been detected during zebrafish EHT and may promote hematopoietic stem cell (HSC) formation by activating inflammatory signaling. However, little is known about how TEs contribute to the EHT process in human and mouse. RESULTS: We reconstructed the single-cell EHT trajectories of human and mouse and resolved the dynamic expression patterns of TEs during EHT. Most TEs presented a transient co-upregulation pattern along the conserved EHT trajectories, coinciding with the temporal relaxation of epigenetic silencing systems. TE products can be sensed by multiple pattern recognition receptors, triggering inflammatory signaling to facilitate HSC emergence. Interestingly, we observed that hypoxia-related signals were enriched in cells with higher TE expression. Furthermore, we constructed the hematopoietic cis-regulatory network of accessible TEs and identified potential TE-derived enhancers that may boost the expression of specific EHT marker genes. CONCLUSIONS: Our study provides a systematic vision of how TEs are dynamically controlled to promote the hematopoietic fate decisions through transcriptional and cis-regulatory networks, and pre-train the immunity of nascent HSCs.
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Elementos de DNA Transponíveis , Hematopoese , Células-Tronco Hematopoéticas , Análise de Célula Única , Animais , Elementos de DNA Transponíveis/genética , Análise de Célula Única/métodos , Camundongos , Hematopoese/genética , Humanos , Células-Tronco Hematopoéticas/metabolismo , Células Endoteliais/metabolismoRESUMO
BACKGROUND: Apo CIII (apolipoprotein CIII) is an important regulator of triglyceride metabolism and was associated with cardiovascular risk in several cohorts. It is present in 4 major proteoforms, a native peptide (CIII0a), and glycosylated proteoforms with zero (CIII0b), 1 (CIII1, most abundant), or 2 (CIII2) sialic acids, which may differentially modify lipoprotein metabolism. We studied the relationships of these proteoforms with plasma lipids and cardiovascular risk. METHODS: Apo CIII proteoforms were measured by mass spectrometry immunoassay in baseline plasma samples of 5791 participants of Multi-Ethnic Study of Atherosclerosis, an observational community-based cohort. Standard plasma lipids were collected for up to 16 years and cardiovascular events (myocardial infarction, resuscitated cardiac arrest, or stroke) were adjudicated for up to 17 years. RESULTS: Apo CIII proteoform composition differed by age, sex, race and ethnicity, body mass index, and fasting glucose. Notably, CIII1 was lower in older participants, men and Black and Chinese (versus White) participants, and higher in obesity and diabetes. In contrast, CIII2 was higher in older participants, men, Black, and Chinese persons, and lower in Hispanic individuals and obesity. Higher CIII2 to CIII1 ratio (CIII2/III1) was associated with lower triglycerides and higher HDL (high-density lipoprotein) in cross-sectional and longitudinal models, independently of clinical and demographic risk factors and total apo CIII. The associations of CIII0a/III1 and CIII0b/III1 with plasma lipids were weaker and varied through cross-sectional and longitudinal analyses. Total apo CIII and CIII2/III1 were positively associated with cardiovascular disease risk (n=669 events, hazard ratios, 1.14 [95% CI, 1.04-1.25] and 1.21 [1.11-1.31], respectively); however, the associations were attenuated after adjustment for clinical and demographic characteristics (1.07 [0.98-1.16]; 1.07 [0.97-1.17]). In contrast, CIII0b/III1 was inversely associated with cardiovascular disease risk even after full adjustment including plasma lipids (0.86 [0.79-0.93]). CONCLUSIONS: Our data indicate differences in clinical and demographic relationships of apo CIII proteoforms, and highlight the importance of apo CIII proteoform composition in predicting future lipid patterns and cardiovascular disease risk.
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Doenças Cardiovasculares , Idoso , Humanos , Masculino , Apolipoproteína C-III , Doenças Cardiovasculares/diagnóstico , Doenças Cardiovasculares/epidemiologia , Estudos Transversais , Fatores de Risco de Doenças Cardíacas , Obesidade , Fatores de Risco , TriglicerídeosRESUMO
Cadmium (Cd) and chromium (Cr) are widespread contaminants with a high risk to the environment and humans. Herein we isolated a novel strain of Serratia marcescens, namely strain S27, from soil co-contaminated with Cd and Cr. This strain showed strong resistance to Cd as well as Cr. S27 cells demonstrated Cd adsorption rate of 45.8% and Cr reduction capacity of 84.4% under optimal growth conditions (i.e., 30 °C, 200 rpm, and pH 7.5). Microscopic characterization of S27 cells revealed the importance of the functional groups C-O-C, C-H-O, C-C, C-H, and -OH, and also indicated that Cr reduction occurred on bacterial cell membrane. Cd(II) and Cr(VI) bioaccumulation on S27 cell surface was mainly in the form of Cd(OH)2 and Cr2O3, respectively. Further, metabolomic analyses revealed that N-arachidonoyl-l-alanine was the key metabolite that promoted Cd and Cr complexation by S27; it primarily promotes γ-linolenic acid (GLA) metabolism, producing siderophores and coordinating with organic acids to enhance metal bioavailability. To summarize, our results suggest that S27 is promising for the bioremediation of environments contaminated with Cd and Cr in tropical regions.
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Cádmio , Cromo , Humanos , Cromo/metabolismo , Serratia marcescens/metabolismo , Biodegradação Ambiental , AdsorçãoRESUMO
BACKGROUND: Femoral hernias often present with incarceration or strangulation that requires emergency surgery. However, recommendations vary regarding optimal approaches for incarcerated femoral hernia. The aim of this study is to compare clinical efficacy between mesh repair and suture repair for the treatment of incarcerated femoral hernia. METHODS: Retrospective, single-center analysis of the clinical data from 48 patients with incarcerated femoral hernia, including 16 patients who underwent mesh repair (mesh repair group) and 32 patients who underwent traditional suture repair (suture repair group). RESULTS: The mean age, body mass index, incarceration duration, hernia sac size, operation duration, and the rates of postoperative incision infection, recurrence, chronic pain, and mortality were not significantly different between the suture repair and mesh repair groups (P > 0.05 for all). In contrast, the female/male ratio; the rates of bowel obstruction, coexisting diseases, and nighttime operation; and the American Society of Anesthesiologists grade were higher and the rate of prophylactic antibiotic use and the mean cost of hospitalization were lower in the suture repair group than in the mesh repair group (P < 0.05 for all). CONCLUSION: The surgical approach should be chosen based on the patient's condition. Mesh repair for the emergency treatment of incarcerated femoral hernia is safe and effective, whereas suture repair is suitable for elderly patients, those with more coexisting diseases, and those with limited life expectancy.
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Hérnia Femoral , Hérnia Inguinal , Humanos , Masculino , Feminino , Idoso , Hérnia Femoral/cirurgia , Hérnia Femoral/complicações , Estudos Retrospectivos , Telas Cirúrgicas , Herniorrafia , Suturas , Hérnia Inguinal/cirurgia , RecidivaRESUMO
BACKGROUND: Ultrasound-assisted glycation is a promising method for decreasing the allergenicity of α-lactalbumin (ALA). However, there is a lack of in vivo studies on the allergenicity of ultrasound-assisted glycated ALA. In this study, the effects of the ultrasound-assisted glycation of ALA on the allergenicity and intestinal microflora were characterized using a BALB/c mouse model. RESULTS: Increased immunoglobulin -G/ immunoglobulin-E (IgG/IgE) and interleukin-4/6 (IL-4/6) secretions, and reduced interferon-γ (IFN-γ) secretions were found in the serum of ALA sensitized and challenged, mice in comparison with a control group. However, there was no significant difference between the mice fed with ultrasound-assisted glycated ALA and the control group. Mice that were sensitized and challenged with ALA showed disrupted intestinal microflora, manifesting in significantly decreased Firmicutes and significantly increased Proteobacteria. It was found that 100ALA-gal could maintain the intestinal microflora of mice in a normal state. Pearson's rank correlation showed that Proteobacteria and Spirochaetota were correlated positively with the IL-4/IL-6 level and were correlated negatively with the expression of IFN-γ. Proteobacteria were also significantly positively correlated with IL-6 and negatively correlated with IFN-γ (P < 0.05). CONCLUSION: These results suggested that ultrasound-assisted glycation on ALA can maintain the intestinal microflora in a normal state thus balancing the proportion of Th1/Th2 to decrease allergic reaction. © 2022 Society of Chemical Industry.
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Alérgenos , Lactalbumina , Animais , Camundongos , Alérgenos/química , Lactalbumina/química , Reação de Maillard , Interleucina-4 , Interleucina-6 , Imunoglobulina E , Interferon gama , Camundongos Endogâmicos BALB CRESUMO
Apolipoproteins (apo) C-I and C-II are key regulators of triglyceride and HDL metabolism. Both exist as full-size native and truncated (apoC-I'; apoC-II') posttranslational proteoforms. However, the determinants and the role of these proteoforms in lipid metabolism are unknown. Here, we measured apoC-I and apoC-II proteoforms by mass spectrometry immunoassay in baseline and 10-year follow-up plasma samples from the Multi-Ethnic Study of Atherosclerosis. We found that baseline total apoC-I (mean = 9.2 mg/dl) was lower in African Americans (AA), Chinese Americans (CA), and Hispanics (by 1.8; 1.0; 1.0 mg/dl vs. whites), higher in women (by 1.2 mg/dl), and positively associated with plasma triglycerides and HDL. Furthermore, we observed that the truncated-to-native apoC-I ratio (apoC-I'/C-I) was lower in CA, negatively associated with triglycerides, and positively associated with HDL. We determined that total apoC-II (8.8 mg/dl) was lower in AA (by 0.8 mg/dl) and higher in CA and Hispanics (by 0.5 and 0.4 mg/dl), positively associated with triglycerides, and negatively associated with HDL. In addition, apoC-II'/C-II was higher in AA and women, negatively associated with triglycerides, and positively associated with HDL. We showed that the change in triglycerides was positively associated with changes in total apoC-I and apoC-II and negatively associated with changes in apoC-I'/C-I and apoC-II'/C-II, whereas the change in HDL was positively associated with changes in total apoC-I and apoC-II'/C-II and negatively associated with change in total apoC-II. This study documents racial/ethnic variation in apoC-I and apoC-II plasma levels and highlights apolipoprotein posttranslational modification as a potential regulator of plasma lipids.
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Apolipoproteínas , Aterosclerose , Apolipoproteína C-II , Apolipoproteína C-III , Feminino , Humanos , TriglicerídeosRESUMO
Bacterial porin-encoding genes are often found under positive selection. Local recombination has also been identified in a few of them to facilitate bacterial rapid adaptation, although it remains unknown whether it is a common evolutionary mechanism for the porins or outer membrane proteins in Gram-negative bacteria. In this study, we investigated the beta-barrel (ß-barrel) porin-encoding genes in Escherichia coli that were reported under positive Darwinian selection. Besides fhuA that was found with ingenic local recombination previously, we identified four other genes, i.e., lamB, ompA, ompC, and ompF, all showing the similar mosaic evolution patterns. Comparative analysis of the protein sequences disclosed a list of highly variable regions in each family, which are mostly located in the convex of extracellular loops and coinciding with the binding sites of bacteriophages. For each of the porin families, mosaic recombination leads to unique combinations of the variable regions with different sequence patterns, generating diverse protein groups. Structural modeling indicated a conserved global topology among the different porins, with the extracellular surface varying a lot due to individual or combinatorial variable regions. The conservation of global tertiary structure would ensure the channel activity, while the wide diversity of variable regions may represent selection to avoid the invasion of phages, antibiotics or immune surveillance factors. Our study identified multiple bacterial porin genes with mosaic evolution. We hypothesize that this could be generalized strategy for outer membrane proteins to both maintain normal life processes and evade the attack of unfavored factors rapidly. IMPORTANCE Microevolution studies can disclose more elaborate evolutionary mechanisms of genes, appearing especially important for genes with multifaceted function such as those encoding outer membrane proteins. However, in most cases, the gene is considered as a whole unit, and the evolutionary patterns are disclosed. Here, we report that multiple bacterial porin proteins follow mosaic evolution, with local ingenic recombination combined with spontaneous mutations based on positive Darwinian selection, and conservation for most structural regions. This could represent a common mechanism for bacterial outer membrane proteins. The variable regions within each porin family showed large coincidence with the binding sites of bacteriophages, antibiotics, and immune factors and therefore would represent effective targets for the development of new antibacterial agents or vaccines.
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Escherichia coli , Porinas , Animais , Antibacterianos/metabolismo , Proteínas da Membrana Bacteriana Externa/metabolismo , Proteínas de Bactérias/genética , Escherichia coli/genética , Escherichia coli/metabolismo , Humanos , Porinas/genética , Porinas/metabolismo , OvinosRESUMO
INTRODUCTION: Glioma is the most aggressive and malignant type of tumors among primary intracranial tumors. miR-433-3p has been verified to be correlated with the formation and progression of many types of cancers. METHODS: In this study, the effects of miR-433-3p and AJUBA on the proliferation, migration, and invasion of glioma and the molecular mechanisms were investigated. We analyzed bioinformatics databases and conducted cell biology experiments to determine that compared with adjacent tissue and normal cells, the expression level of miR-433-3p in glioma tissue and cells was lower, while the expression level of AJUBA was higher. Overexpressing miR-433-3p could significantly inhibit the proliferation, migration, and invasion of glioma cells and promote cell apoptosis. RESULTS: In addition, after overexpressing miR-433-3p and AJUBA, it was found that overexpressing AJUBA could attenuate the inhibitory effect of overexpressing miR-433-3p on the proliferation, migration, and invasion of glioma cells, which suggested that miR-433-3p regulated the biological function of glioma by downregulating AJUBA expression. CONCLUSION: These results proved that miR-433-3p could target to inhibit the expression of AJUBA, thus inhibiting the biological function and malignant progression of glioma.
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Neoplasias Encefálicas , Glioma , Proteínas com Domínio LIM , MicroRNAs , Neoplasias Encefálicas/genética , Neoplasias Encefálicas/metabolismo , Neoplasias Encefálicas/patologia , Linhagem Celular Tumoral , Movimento Celular/fisiologia , Proliferação de Células/fisiologia , Glioma/genética , Glioma/metabolismo , Glioma/patologia , Humanos , Proteínas com Domínio LIM/biossíntese , Proteínas com Domínio LIM/genética , Proteínas com Domínio LIM/metabolismo , MicroRNAs/genética , MicroRNAs/metabolismoRESUMO
Plant transcriptomes encompass a large number of functional non-coding RNAs (ncRNAs), only some of which have protein-coding capacity. Since their initial discovery, ncRNAs have been classified into two broad categories based on their biogenesis and mechanisms of action, housekeeping ncRNAs and regulatory ncRNAs. With advances in RNA sequencing technology and computational methods, bioinformatics resources continue to emerge and update rapidly, including workflow for in silico ncRNA analysis, up-to-date platforms, databases, and tools dedicated to ncRNA identification and functional annotation. In this review, we aim to describe the biogenesis, biological functions, and interactions with DNA, RNA, protein, and microorganism of five major regulatory ncRNAs (miRNA, siRNA, tsRNA, circRNA, lncRNA) in plants. Then, we systematically summarize tools for analysis and prediction of plant ncRNAs, as well as databases. Furthermore, we discuss the silico analysis process of these ncRNAs and present a protocol for step-by-step computational analysis of ncRNAs. In general, this review will help researchers better understand the world of ncRNAs at multiple levels.
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RNA Longo não Codificante , RNA não Traduzido , Biologia Computacional/métodos , Plantas/genética , Plantas/metabolismo , RNA Longo não Codificante/genética , RNA não Traduzido/genética , RNA não Traduzido/metabolismo , Análise de Sequência de RNARESUMO
Stably Expressed Genes (SEGs) are a set of genes with invariant expression. Identification of SEGs, especially among both healthy and diseased tissues, is of clinical relevance to enable more accurate data integration, gene expression comparison and biomarker detection. However, it remains unclear how many global SEGs there are, whether there are development-, tissue- or cell-specific SEGs, and whether diseases can influence their expression. In this research, we systematically investigate human SEGs at single-cell level and observe their development-, tissue- and cell-specificity, and expression stability under various diseased states. A hierarchical strategy is proposed to identify a list of 408 spatial-temporal SEGs. Development-specific SEGs are also identified, with adult tissue-specific SEGs enriched with the function of immune processes and fetal tissue-specific SEGs enriched in RNA splicing activities. Cells of the same type within different tissues tend to show similar SEG composition profiles. Diseases or stresses do not show influence on the expression stableness of SEGs in various tissues. In addition to serving as markers and internal references for data normalization and integration, we examine another possible application of SEGs, i.e., being applied for cell decomposition. The deconvolution model could accurately predict the fractions of major immune cells in multiple independent testing datasets of peripheral blood samples. The study provides a reliable list of human SEGs at the single-cell level, facilitates the understanding on the property of SEGs, and extends their possible applications.
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Apolipoproteins C-I, C-II, and C-III interact with ApoE to regulate lipoprotein metabolism and contribute to Alzheimer's disease pathophysiology. In plasma, apoC-I and C-II exist as truncated isoforms, while apoC-III exhibits multiple glycoforms. This study aimed to 1) delineate apoC-I, C-II, and C-III isoform profiles in cerebrospinal fluid (CSF) and plasma in a cohort of nondemented older individuals (n = 61), and 2) examine the effect of APOE4 on these isoforms and their correlation with CSF Aß42, a surrogate of brain amyloid accumulation. The isoforms of the apoCs were immunoaffinity enriched and measured with MALDI-TOF mass spectrometry, revealing a significantly higher percentage of truncated apoC-I and apoC-II in CSF compared with matched plasma, with positive correlation between CSF and plasma. A greater percentage of monosialylated and disialylated apoC-III isoforms was detected in CSF, accompanied by a lower percentage of the two nonsialylated apoC-III isoforms, with significant linear correlations between CSF and plasma. Furthermore, a greater percentage of truncated apoC-I in CSF and apoC-II in plasma and CSF was observed in individuals carrying at least one APOE Æ4 allele. Increased apoC-I and apoC-II truncations were associated with lower CSF Aß42. Finally, monosialylated apoC-III was lower, and disialylated apoC-III greater in the CSF of Æ4 carriers. Together, these results reveal distinct patterns of the apoCs isoforms in CSF, implying CSF-specific apoCs processing. These patterns were accentuated in APOE Æ4 allele carriers, suggesting an association between APOE4 genotype and Alzheimer's disease pathology with apoCs processing and function in the brain.
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Doença de AlzheimerRESUMO
Complexity, cost, and content are three important factors that can impede translation of clinical protein mass spectrometry (MS) tests at a larger scale. Complexity stems from the many components/steps involved in bottom-up protein MS workflows, making them significantly more complicated than enzymatic immunoassays (EIA) that currently dominate clinical testing. This complexity inevitably leads to increased costs, which is detrimental in the price-competitive clinical marketplace. To successfully compete, new clinical protein MS tests need to offer something new and unique that EIAs cannot - a new content of proteoform detection. The preferred method for proteoform profiling is intact protein MS analysis, in which all proteins are measured as intact species thus allowing discovery of new proteoforms. To illustrate the importance of intact proteoform testing with MS and its potential clinical implications, we discuss here recent findings from multiple studies on the distribution of apolipoprotein C-III proteoforms and their correlations with key clinical measures of dyslipidemia. Such studies are only made possible with assays that are low in cost, avoid unnecessary complexity, and are unique in providing the content of proteoforms.
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Apolipoproteína C-III/análise , Animais , Anticorpos Imobilizados/imunologia , Apolipoproteína C-III/imunologia , Apolipoproteína C-III/metabolismo , Biomarcadores/análise , Biomarcadores/metabolismo , Dislipidemias/metabolismo , Humanos , Imunoensaio/métodos , Isoformas de Proteínas/análise , Isoformas de Proteínas/imunologia , Isoformas de Proteínas/metabolismo , Espectrometria de Massas por Ionização e Dessorção a Laser Assistida por Matriz/métodosRESUMO
WHAT IS KNOWN AND OBJECTIVE: Capsaicin, the major active ingredient of chili pepper, may play a "dual role" in tumourigenesis, acting as a carcinogen or as a cancer preventive agent. The aim of this study was to investigate the anticancer mechanisms of capsaicin and the effects of capsaicin on traditional chemotherapeutic drugs and radiotherapy in various cancer types and the potential for clinical application in cancer therapy. METHODS: We conducted extensive literature searches through PubMed to collect representative studies of capsaicin in different cancer types. These studies investigated the anticancer molecular mechanisms of capsaicin. We then searched for the effects of capsaicin on traditional chemotherapeutic drugs or radiotherapy. Finally, in terms of clinical application, we searched for the advances of capsaicin-loaded nanoparticles in malignant tumours. RESULTS AND DISCUSSION: In most studies, capsaicin is a potential anti-tumour compound and the anti-cancer mechanisms are mainly related to anti-proliferation, induction of apoptosis and autophagy, anti-angiogenesis and anti-metastasis. It is worth noting that the biological functions of capsaicin are greatly affected by its concentration and the effective concentration in different malignant tumours varies considerably. Furthermore, capsaicin can affect the anti-cancer activity of conventional chemotherapeutic drugs or radiation therapy and more and more capsaicin-loaded nanoparticles have been developed to prolong the drug retention of capsaicin in the blood circulation and allow active targeting of specific cancer cells to enhance its accurate delivery and targeting specificity, suggesting that capsaicin may be used as a potential chemopreventive or a new auxiliary therapeutic drug for cancer. However, there is still a need for well-controlled studies to assess the safety and efficacy of capsaicin, and further preclinical and clinical trials are needed to elucidate its anti-tumour effects when combined with other standard drugs or radiotherapy. WHAT IS NEW AND CONCLUSION: Capsaicin exhibits strong anti-cancer properties in various cancer types. The combination of capsaicin with conventional chemotherapy drugs or radiotherapy can improve the sensitivity, reduce the side effects and enhance the tolerance of patients to cancer treatment. The development of capsaicin-loaded nanoparticles may provide a very promising approach to chemotherapy for malignant tumours.
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Antineoplásicos/farmacologia , Capsaicina/farmacologia , Neoplasias/tratamento farmacológico , Animais , Antineoplásicos/administração & dosagem , Capsaicina/administração & dosagem , Terapia Combinada , Sistemas de Liberação de Medicamentos , Humanos , Nanopartículas , Neoplasias/patologiaRESUMO
Quality monitoring is important for farmland protection. Here, high-resolution remote sensing data obtained by unmanned aerial vehicles (UAVs) and long-term ground sensing data, obtained by wireless sensor networks (WSNs), are uniquely suited for assessing spatial and temporal changes in farmland quality. However, existing UAV-WSN systems are unable to fully integrate the data obtained from these two monitoring systems. This work addresses this problem by designing an improved UAV-WSN monitoring system that can collect both high-resolution UAV images and long-term WSN data during a single-flight mission. This is facilitated by a newly proposed data transmission optimization routing protocol (DTORP) that selects the communication node within a cluster of the WSN to maximize the quantity of data that can be efficiently transmitted, additionally combining individual scheduling algorithms and routing algorithms appropriate for three different distance scales to reduce the energy consumption incurred during data transmission between the nodes in a cluster. The performance of the proposed system is evaluated based on Monte Carlo simulations by comparisons with that obtained by a conventional system using the low-energy adaptive clustering hierarchy (LEACH) protocol. The results demonstrate that the proposed system provides a greater total volume of transmitted data, greater energy utilization efficiency, and a larger maximum revisit period than the conventional system. This implies that the proposed UAV-WSN monitoring system offers better overall performance and enhanced potential for conducting long-term farmland quality data collection over large areas in comparison to existing systems.
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Lung cancer is the leading cause of cancer death in women living in the United States, which accounts for approximately the same percentage of cancer deaths in women as breast, ovary, and uterine cancers combined. Targeted blood plasma glycomics represents a promising source of noninvasive diagnostic and prognostic biomarkers for lung cancer. Here, 208 samples from lung cancer patients and 207 age-matched controls enrolled in the Women Epidemiology Lung Cancer (WELCA) study were analyzed by a bottom-up glycan "node" analysis approach. Glycan features, quantified as single analytical signals, including 2-linked mannose, α2-6 sialylation, ß1-4 branching, ß1-6 branching, 4-linked GlcNAc, and antennary fucosylation, exhibited abilities to distinguish cases from controls (ROC AUCs: 0.68-0.92) and predict survival in patients (hazard ratios: 1.99-2.75) at all stages. Notable alterations of glycan features were observed in stages I-II. Diagnostic and prognostic glycan features were mostly independent of smoking status, age, gender, and histological subtypes of lung cancer.
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Biomarcadores Tumorais/metabolismo , Glicômica/métodos , Neoplasias Pulmonares/metabolismo , Polissacarídeos/metabolismo , Idoso , Biomarcadores Tumorais/sangue , Estudos de Casos e Controles , Feminino , Glicosilação , Humanos , Neoplasias Pulmonares/diagnóstico , Neoplasias Pulmonares/epidemiologia , Masculino , Pessoa de Meia-Idade , Estadiamento de Neoplasias , Polissacarídeos/sangue , Prognóstico , Curva ROC , Análise de SobrevidaRESUMO
BACKGROUND: Lung adenocarcinoma is the most common type of lung cancers. Whole-genome sequencing studies disclosed the genomic landscape of lung adenocarcinomas. however, it remains unclear if the genetic alternations could guide prognosis prediction. Effective genetic markers and their based prediction models are also at a lack for prognosis evaluation. METHODS: We obtained the somatic mutation data and clinical data for 371 lung adenocarcinoma cases from The Cancer Genome Atlas. The cases were classified into two prognostic groups (3-year survival), and a comparison was performed between the groups for the somatic mutation frequencies of genes, followed by development of computational models to discrete the different prognosis. RESULTS: Genes were found with higher mutation rates in good (≥ 3-year survival) than in poor (< 3-year survival) prognosis group of lung adenocarcinoma patients. Genes participating in cell-cell adhesion and motility were significantly enriched in the top gene list with mutation rate difference between the good and poor prognosis group. Support Vector Machine models with the gene somatic mutation features could well predict prognosis, and the performance improved as feature size increased. An 85-gene model reached an average cross-validated accuracy of 81% and an Area Under the Curve (AUC) of 0.896 for the Receiver Operating Characteristic (ROC) curves. The model also exhibited good inter-stage prognosis prediction performance, with an average AUC of 0.846 for the ROC curves. CONCLUSION: The prognosis of lung adenocarcinomas is related with somatic gene mutations. The genetic markers could be used for prognosis prediction and furthermore provide guidance for personal medicine.
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Adenocarcinoma de Pulmão/mortalidade , Biomarcadores Tumorais/genética , Neoplasias Pulmonares/mortalidade , Modelos Biológicos , Máquina de Vetores de Suporte , Adenocarcinoma de Pulmão/genética , Adenocarcinoma de Pulmão/patologia , Adenocarcinoma de Pulmão/terapia , Biologia Computacional , Conjuntos de Dados como Assunto , Estudos de Viabilidade , Genômica/métodos , Humanos , Neoplasias Pulmonares/genética , Neoplasias Pulmonares/patologia , Neoplasias Pulmonares/terapia , Mutação , Medicina de Precisão/métodos , Prognóstico , Curva ROC , Análise de Sobrevida , Taxa de SobrevidaRESUMO
Rapid and efficient assessment of cultivated land quality (CLQ) using remote sensing technology is of great significance for protecting cultivated land. However, it is difficult to obtain accurate CLQ estimates using the current satellite-driven approaches in the pressure-state-response (PSR) framework, owing to the limitations of linear models and CLQ spectral indices. In order to improve the estimation accuracy of CLQ, this study used four evaluation models (the traditional linear model; partial least squares regression, PLSR; back propagation neural network, BPNN; and BPNN with genetic algorithm optimization, GA-BPNN) to evaluate CLQ for determining the accurate evaluation model. In addition, the optimal satellite-derived indicator in the land state index was selected among five vegetation indices (the normalized vegetation index, NDVI; enhanced vegetation index, EVI; modified soil-adjusted vegetation index, MSAVI; perpendicular vegetation index, PVI; and soil-adjusted vegetation index, SAVI) to improve the prediction accuracy of CLQ. This study was conducted in Conghua District of Guangzhou, Guangdong Province, China, based on Gaofen-1 (GF-1) data. The prediction accuracies from the traditional linear model, PLSR, BPNN, and GA-BPNN were compared using observations. The results demonstrated that (1) compared with other models (the traditional linear model: R2 = 0.14 and RMSE = 91.53; PLSR: R2 = 0.33 and RMSE = 74.58; BPNN: R2 = 0.50 and RMSE = 61.75), the GA-BPNN model based on EVI in the land state index provided the most accurate estimates of CLQ, with the R2 of 0.59 and root mean square error (RMSE) of 56.87, indicating a nonlinear relationship between CLQ and the prediction indicator; and (2) the GA-BPNN-based evaluation approach of CLQ in the PSR framework was driven to map CLQ of the study area using the GF-1 data, leading to an RMSE of 61.44 at the regional scale, implying that the GA-BPNN-based evaluation approach has the potential to map CLQ over large areas. This study provides an important reference for the high-accuracy prediction of CLQ based on remote sensing technology.
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This study proposes a method for determining the optimal image date to improve the evaluation of cultivated land quality (CLQ). Five vegetation indices: leaf area index (LAI), difference vegetation index (DVI), enhanced vegetation index (EVI), normalized difference vegetation index (NDVI), and ratio vegetation index (RVI) are first retrieved using the PROSAIL model and Gaofen-1 (GF-1) images. The indices are then introduced into four regression models at different growth stages for assessing CLQ. The optimal image date of CLQ evaluation is finally determined according to the root mean square error (RMSE). This method is tested and validated in a rice growth area of Southern China based on 115 sample plots and five GF-1 images acquired at the tillering, jointing, booting, heading to flowering, and milk ripe and maturity stage of rice in 2015, respectively. The results show that the RMSEs between the measured and estimated CLQ from four vegetation index-based regression models at the heading to flowering stage are smaller than those at the other growth stages, indicating that the image date corresponding with the heading to flowering stage is optimal for CLQ evaluation. Compared with other vegetation index-based models, the LAI-based logarithm model provides the most accurate estimates of CLQ. The optimal model is also driven using the GF-1 image at the heading to flowering stage to map CLQ of the study area, leading to a relative RMSE of 14.09% at the regional scale. This further implies that the heading to flowering stage is the optimal image time for evaluating CLQ. This study is the first effort to provide an applicable method of selecting the optimal image date to improve the estimation of CLQ and thus advanced the literature in this field.
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The fhuACDB operon, present in a number of Enterobacteriaceae, encodes components essential for the uptake of ferric hydroxamate type siderophores. FhuA acts not only as a transporter for physiologically important chelated ferric iron but also as a receptor for various bacteriophages, toxins, and antibiotics, which are pathogenic to bacterial cells. In this research, fhuA gene distribution and sequence diversity were investigated in Enterobacteriaceae, especially Salmonella and Escherichia Comparative sequence analysis resulted in a fhuA phylogenetic tree that did not match the expected phylogeny of species or trees of the fhuCDB genes. The fhuA sequences showed a unique mosaic clustering pattern. On the other hand, the gene sequences showed high conservation for strains from the same serovar or serotype. In total, six clusters were identified from FhuA proteins in Salmonella and Escherichia, among which typical peptide fragment variations could be defined. Six fragmental insertions/deletions and two substitution fragments were discovered, for which the combination of polymorphism patterns could well classify the different clusters. Structural modeling demonstrated that all the six featured insertions/deletions and one substitution fragment are located at the apexes of the long loops present as part of the FhuA external pocket. These frequently mutated regions are likely under high selection pressure, with bacterial strains balancing escape from phage infection or toxin/antibiotics attack via fhuA gene mutations while maintaining the siderophore uptake activity essential for bacterial survival. The unusual fhuA clustering suggests that high-frequency exchange of fhuA genes has occurred between enterobacterial strains after distinctive species were established.
Assuntos
Proteínas da Membrana Bacteriana Externa/genética , Proteínas de Escherichia coli/genética , Escherichia/genética , Evolução Molecular , Variação Genética , Salmonella/genética , Proteínas da Membrana Bacteriana Externa/química , Análise por Conglomerados , Proteínas de Escherichia coli/química , Proteínas de Membrana Transportadoras/química , Proteínas de Membrana Transportadoras/genética , Modelos Moleculares , Filogenia , Receptores Virais/química , Receptores Virais/genética , Análise de Sequência de DNA , Homologia de SequênciaRESUMO
Here, charge-storage nonvolatile organic field-effect transistor (OFET) memory devices based on interfacial self-assembled molecules are proposed. The functional molecules contain various aromatic amino moieties (N-phenyl-N-pyridyl amino- (PyPN), N-phenyl amino- (PN), and N,N-diphenyl amino- (DPN)) which are linked by a propyl chain to a triethoxysilyl anchor group and act as the interface modifiers and the charge-storage elements. The PyPN-containing pentacene-based memory device (denoted as PyPN device) presents the memory window of 48.43 V, while PN and DPN devices show the memory windows of 24.88 and 8.34 V, respectively. The memory characteristic of the PyPN device can remain stable along with 150 continuous write-read-erase-read cycles. The morphology analysis confirms that three interfacial layers show aggregation due to the N atomic self-catalysis and hydrogen bonding effects. The large aggregate-covered PyPN layer has the full contact area with the pentacene molecules, leading to the high memory performance. In addition, the energy level matching between PyPN molecules and pentacene creates the smallest tunneling barrier and facilitates the injection of the hole carriers from pentacene to the PyPN layer. The experimental memory characteristics are well in agreement with the computational calculation.