RESUMO
BACKGROUND: The triglyceride-glucose (TyG) index performs better at reflecting insulin resistance when combined with waist circumference (WC), body mass index (BMI), and waist-to-height ratio (WHtR) than when used alone. This study aimed to prospectively examine the relationships between TyG, TyG-BMI, TyG-WC, and TyG-WHtR with the incidence of myocardial infarction (MI) and its subtypes. METHODS: This cohort study included 370,390 participants from the UK Biobank. The Cox proportional hazards model and restricted cubic spline regression model were used to assess the associations of TyG, TyG-BMI, TyG-WC, and TyG-WHtR with MI, ST-elevation MI (STEMI) and non-ST-elevation MI (NSTEMI). The receiver operating characteristic (ROC) curve and the area under the curve (AUC) were employed to examine the predictive value of four indicators. RESULTS: The hazard ratios (HRs) and 95% confidence intervals (CIs) of MI in the highest quartiles for TyG, TyG-BMI, TyG-WC, and TyG-WHtR were 1.36 (1.28-1.44), 1.47 (1.39-1.56), 1.53 (1.43-1.64), and 1.58 (1.48-1.68) in the fully-adjusted model. Comparable findings were observed when the outcomes were reclassified as STEMI or NSTEMI. However, the associations of TyG-BMI, TyG-WC, and TyG-WHtR with the risk of STEMI were weaker than MI and NSTEMI. A linear dose-response association between TyG and the risk of MI and NSTEMI were demonstrated. TyG-BMI, TyG-WC, and TyG-WHtR all showed nonlinear patterns in their associations with the risk of MI, STEMI, and NSTEMI. TyG-WC was most effective in diagnosing MI (AUC: 0.648, 95% CI: 0.644-0.653), STEMI (AUC: 0.631, 95% CI: 0.622-0.639), and NSTEMI (AUC: 0.647, 95% CI: 0.641-0.654). CONCLUSION: The TyG index was linearly associated with increased risk of MI and NSTEMI, whereas TyG-BMI, TyG-WC, and TyG-WHtR were nonlinearly associated with increased risk of MI and NSTEMI. There were distinct patterns in the relationships between these indicators with STEMI. TyG-WC provided the best diagnostic effectiveness for MI, STEMI, and NSTEMI.
RESUMO
Purple/red appearance is one of the common phenotypic variations in leaves, stems, and siliques of oilseed rape (Brassica napus L.) but very rare in flowers. In this study, the causal genes for the purple/red traits in stems and flowers in two accessions of oilseed rape (DH_PR and DH_GC001, respectively) derived from the wide hybridization were fine mapped, and candidate genes were determined by methods combined with bulked segregant analysis (BSA) and RNA-seq analysis. Both traits of purple stem and red flowers were mapped to the locus as AtPAP2 homologous genes (BnaPAP2.C6a and BnaPAP2.A7b, respectively) belonging to the R2R3-MYB family. Sequence comparisons of full-length allelic genes revealed several InDels and SNPs in intron 1 as well as exons, and completely different promoter region of BnaPAP2.C6a and a 211 bp insertion was identified in the promoter region of BnaPAP2.A7b of DH_GC001. Our results not only contribute to a better understanding of anthocyanin inheritance in B. napus, but also provide a useful toolbox for future breeding of cultivars with purple/red traits through the combination of different functional alleles and homologs. Supplementary Information: The online version contains supplementary material available at 10.1007/s11032-023-01365-5.
RESUMO
OBJECTIVE: Circular RNAs (circRNAs), a new subgroup of non-coding RNAs in the human transcriptome, are crucial in atherosclerosis (AS). Here, a newly identified circRNA circDLGAP4 was demonstrated to be downregulated in oxidized forms of low-density lipoprotein (ox-LDL)-induced HUVECs. METHODS: This research adopted ox-LDL to stimulate human umbilical vein endothelial cells (HUVECs) to mimic AS in vitro. To further validate the protective action of circDLGAP4 in AS, a mouse model of AS was constructed with a high-fat diet. Functional assays evaluated circDLGAP4 role in AS in vitro and in vivo. Moreover, mechanism assays evaluated association of circDLGAP4/miR-134-5p/PTPN4. RESULTS: CircDLGAP4 was induced to promote cell proliferative behavior and autophagy, inhibit apoptotic and inflammatory activities in ox-LDL-treated HUVECs, and attenuated endothelial barrier function. CircDLGAP4 regulated PTPN4 by directly targeting miR-134-5p. Meanwhile, inhibiting miR-134-5p reduced ox-LDL-induced cell dysfunction. Knockout of PTPN4 reversed circDLGAP4 overexpression or miR-134-5p downregulation in vitro. In addition, reducing circDLGAP4 or overexpressing miR-134-5p increased the red atherosclerotic plaque and lesion area of AS mice, reduced autophagy level, and promoted the release of inflammatory cytokines. CONCLUSION: This study extends the role of circRNA in AS by inducing autophagy and improving endothelial dysfunction in AS via the circDLGAP4/miR-134-5p/PTPN4 axis.
Assuntos
Aterosclerose , MicroRNAs , RNA Circular , Animais , Humanos , Camundongos , Apoptose , Aterosclerose/genética , Aterosclerose/patologia , Autofagia , Células Endoteliais da Veia Umbilical Humana/patologia , Camundongos Knockout , MicroRNAs/genética , Proteína Tirosina Fosfatase não Receptora Tipo 4 , RNA Circular/genéticaRESUMO
Global estuarine ecosystems are experiencing severe nitrogen pollution and ocean acidification (OA) simultaneously. Sedimentary denitrification is an important way of reactive nitrogen removal but at the same time leads to the emission of large amounts of nitrous oxide (N2O), a potent greenhouse gas. It is known that OA in estuarine regions could impact denitrification and N2O production; however, the underlying mechanism is still underexplored. Here, sediment incubation and pure culture experiments were conducted to explore the OA impacts on microbial denitrification and the associated N2O emissions in estuarine sediments. Under neutral (in situ) conditions, fungal N2O emission dominated in the sediment, while the bacterial and fungal sources had a similar role under acidification. This indicated that acidification decreased the sedimentary fungal denitrification and likely inhibited the activity of fungal denitrifiers. To explore molecular mechanisms, a denitrifying fungal strain of Penicillium janthinellum was isolated from the sediments. By using deuterium-labeled single-cell Raman spectroscopy and isobaric tags for relative and absolute quantitation proteomics, we found that acidification inhibited electron transfers in P. janthinellum and downregulated expressions of the proteins related to energy production and conservation. Two collaborative pathways of energy generation in the P. janthinellum were further revealed, that is, aerobic oxidative phosphorylation and TCA cycle and anoxic pyruvate fermentation. This indicated a distinct energy supply strategy from bacterial denitrification. Our study provides insights into fungi-mediated nitrogen cycle in acidifying aquatic ecosystems.
Assuntos
Desnitrificação , Gases de Efeito Estufa , Bactérias/metabolismo , Deutério/metabolismo , Ecossistema , Gases de Efeito Estufa/metabolismo , Concentração de Íons de Hidrogênio , Nitrogênio/análise , Óxido Nitroso/análise , Oceanos e Mares , Piruvatos/metabolismo , Água do MarRESUMO
Ocean acidification in nitrogen-enriched estuaries has raised global concerns. For decades, biotic and abiotic denitrification in estuarine sediments has been regarded as the major ways to remove reactive nitrogen, but they occur at the expense of releasing greenhouse gas nitrous oxide (N2 O). However, how these pathways respond to acidification remains poorly understood. Here we performed a N2 O isotopocules analysis coupled with respiration inhibition and molecular approaches to investigate the impacts of acidification on bacterial, fungal, and chemo-denitrification, as well as N2 O emission, in estuarine sediments through a series of anoxic incubations. Results showed that acidification stimulated N2 O release from sediments, which was mainly mediated by the activity of bacterial denitrifiers, whereas in neutral environments, N2 O production was dominated by fungi. We also found that the contribution of chemo-denitrification to N2 O production cannot be ignored, but was not significantly affected by acidification. The mechanistic investigation further demonstrated that acidification changed the keystone taxa of sedimentary denitrifiers from N2 O-reducing to N2 O-producing ones and reduced microbial electron-transfer efficiency during denitrification. These findings provide novel insights into how acidification stimulates N2 O emission and modulates its pathways in estuarine sediments, and how it may contribute to the acceleration of global climate change in the Anthropocene.
Assuntos
Desnitrificação , Água do Mar , Bactérias/genética , Concentração de Íons de Hidrogênio , Nitrogênio , Óxido NitrosoRESUMO
The sound transmission across two coupled cavities along a rectangular duct in the presence of a low Mach number flow is examined experimentally in the present study. An effort is also made for a deeper understanding of how the flow, excitation sound frequency, and excitation level influence the sound transmission loss. The results confirm that the high sound transmission loss across the cavities is associated with the strong out-of-phase pressure fluctuations within the cavities. The sound transmission loss deteriorates significantly once the flow speed exceeds a threshold value. A different length scale is proposed. This length scale, together with the threshold flow speed and the peak sound transmission loss frequency, gives a Strouhal number, which is basically independent of the cavity offset for a fixed cavity length. The present finding extends the previous effort of the authors, enabling the prediction of the flow speed limit and operating frequency of the coupled cavities for duct silencing at a low Mach number.
RESUMO
Significant developments in cancer treatment have been made since the advent of immune therapies. However, there are still some patients with malignant tumors who do not benefit from immunotherapy. Tumors without immunogenicity are called "cold" tumors which are unresponsive to immunotherapy, and the opposite are "hot" tumors. Immune suppressive cells (ISCs) refer to cells which can inhibit the immune response such as tumor-associated macrophages (TAMs), myeloid-derived suppressor cells (MDSCs), regulatory T (Treg) cells and so on. The more ISCs infiltrated, the weaker the immunogenicity of the tumor, showing the characteristics of "cold" tumor. The dysfunction of ISCs in the tumor microenvironment (TME) may play essential roles in insensitive therapeutic reaction. Previous studies have found that epigenetic mechanisms play an important role in the regulation of ISCs. Regulating ISCs may be a new approach to transforming "cold" tumors into "hot" tumors. Here, we focused on the function of ISCs in the TME and discussed how epigenetics is involved in regulating ISCs. In addition, we summarized the mechanisms by which the epigenetic drugs convert immunotherapy-insensitive tumors into immunotherapy-sensitive tumors which would be an innovative tendency for future immunotherapy in "cold" tumor.
Assuntos
Epigênese Genética , Imunoterapia , Neoplasias , Microambiente Tumoral , Humanos , Imunoterapia/métodos , Neoplasias/imunologia , Neoplasias/terapia , Neoplasias/genética , Microambiente Tumoral/imunologia , Animais , Células Supressoras Mieloides/imunologia , Macrófagos Associados a Tumor/imunologia , Linfócitos T Reguladores/imunologiaRESUMO
Stem diameter is a critical phenotypic parameter for maize, integral to yield prediction and lodging resistance assessment. Traditionally, the quantification of this parameter through manual measurement has been the norm, notwithstanding its tedious and laborious nature. To address these challenges, this study introduces a non-invasive field-based system utilizing depth information from RGB-D cameras to measure maize stem diameter. This technology offers a practical solution for conducting rapid and non-destructive phenotyping. Firstly, RGB images, depth images, and 3D point clouds of maize stems were captured using an RGB-D camera, and precise alignment between the RGB and depth images was achieved. Subsequently, the contours of maize stems were delineated using 2D image processing techniques, followed by the extraction of the stem's skeletal structure employing a thinning-based skeletonization algorithm. Furthermore, within the areas of interest on the maize stems, horizontal lines were constructed using points on the skeletal structure, resulting in 2D pixel coordinates at the intersections of these horizontal lines with the maize stem contours. Subsequently, a back-projection transformation from 2D pixel coordinates to 3D world coordinates was achieved by combining the depth data with the camera's intrinsic parameters. The 3D world coordinates were then precisely mapped onto the 3D point cloud using rigid transformation techniques. Finally, the maize stem diameter was sensed and determined by calculating the Euclidean distance between pairs of 3D world coordinate points. The method demonstrated a Mean Absolute Percentage Error (MAPE) of 3.01%, a Mean Absolute Error (MAE) of 0.75 mm, a Root Mean Square Error (RMSE) of 1.07 mm, and a coefficient of determination (R²) of 0.96, ensuring accurate measurement of maize stem diameter. This research not only provides a new method of precise and efficient crop phenotypic analysis but also offers theoretical knowledge for the advancement of precision agriculture.
RESUMO
BACKGROUND: The causal relationship between childhood adiposity and adult risk of heart diseases has not been clearly demonstrated. This study aims to ascertain whether genetically predicted childhood body mass index (BMI) and childhood obesity are causally associated with adult coronary heart disease, myocardial infarction, heart failure, atrial fibrillation, hypertrophic cardiomyopathy, and pulmonary heart disease. METHODS AND RESULTS: To investigate the causative relationships and underlying mechanisms between childhood adiposity and adult heart diseases, 3 main methods of Mendelian randomization were used: 2-sample Mendelian randomization, multivariable Mendelian randomization with controlling for several cardiometabolic risk variables, and mediation analysis. Every 1-SD rise in genetically predicted childhood body mass index was associated with 24% (odds ratio [OR], 1.24 [95% CI, 1.12-1.37]), 28% (OR, 1.28 [95% CI, 1.14-1.42]), 28% (OR, 1.28 [95% CI, 1.14-1.42]), and 27% (OR, 1.27 [95% CI, 1.04-1.49]) higher risk of coronary heart disease, myocardial infarction, heart failure, and atrial fibrillation, respectively. Every 1-unit increase in log-odds in childhood obesity was associated with 11% (OR, 1.11 [95% CI, 1.06-1.16]), 14% (OR, 1.14 [95% CI, 1.04-1.23]), 10% (OR, 1.10 [95% CI, 1.03-1.18]), and 20% (OR, 1.20 [95% CI, 1.08-1.32]) higher risk of coronary heart disease, myocardial infarction, heart failure, and atrial fibrillation, respectively. The link between childhood adiposity and adult heart diseases was found to be mediated by high-density lipoprotein cholesterol, triglyceride, hypertension, and type 2 diabetes. CONCLUSIONS: Our findings support the causal relationships between childhood adiposity and risk of adult coronary heart disease, myocardial infarction, heart failure, and atrial fibrillation. Blood lipids, hypertension, and type 2 diabetes are factors that mediate the aforementioned associations.
Assuntos
Adiposidade , Índice de Massa Corporal , Análise da Randomização Mendeliana , Obesidade Infantil , Humanos , Adiposidade/genética , Obesidade Infantil/genética , Obesidade Infantil/epidemiologia , Obesidade Infantil/diagnóstico , Criança , Adulto , Cardiopatias/epidemiologia , Cardiopatias/genética , Medição de Risco , Masculino , Feminino , Fatores de Risco , Predisposição Genética para Doença , Fatores de Risco de Doenças Cardíacas , Fatores EtáriosRESUMO
BACKGROUND: To examine whether parental corporal punishment is associated with increased risk of concurrent and later sleep disturbances among preschoolers, and whether the association is time-sensitive or dose-responsive. METHODS: This 3-year prospective cohort study used data from the Shanghai Children's Health, Education and Lifestyle Evaluation, Preschool(SCHEDULE-P). Participants were newly enrolled preschoolers in November 2016(wave 1) and followed up in April 2018(wave 2) and April 2019(wave 3). Parents reported the children's corporal punishment experiences and sleep disturbances at each wave survey. Children's risk of sleep disturbances in relation to corporal punishment was examined using logistic regression, adjusting for children's age, gender, emotional/behavioral problems, family annual income, and maternal educational level. RESULTS: The participants of 19,668 children included 9436(47.98 %) females, with a mean age of 3.73(SD = 0.29) years at wave 1. Exposure to corporal punishment was associated with increased odds of concurrent sleep disturbances at wave 1, 2, and 3 (aOR,1.57; 95 % CI, 1.40-1.75; P < .001; aOR,1.60; 95 % CI, 1.43-1.80; P < .001; aOR,1.74; 95 % CI, 1.54-1.95; P < .001), respectively. Exposure to corporal punishment at any wave of preschool was associated with increased odds of sleep disturbances at wave 3, and the risks were greater for proximal and accumulative corporal punishment exposure. CONCLUSION: There is a time-sensitive and dose-responsive association between corporal punishment and sleep disturbance among preschoolers, with greater risk of sleep disturbances for proximal and accumulative exposure of corporal punishment. Promoting positive parenting strategies and avoiding corporal punishment can be a promising strategy to prevent and intervene sleep disturbances in preschoolers.
Assuntos
Punição , Transtornos do Sono-Vigília , Humanos , Feminino , Punição/psicologia , Pré-Escolar , Masculino , Estudos Prospectivos , Transtornos do Sono-Vigília/epidemiologia , China/epidemiologia , Fatores de Tempo , Relações Pais-Filho , Poder Familiar/psicologiaRESUMO
PURPOSE: Youth suicide has been increasing and became a public health concern worldwide. Identifying insufficient sleep as the potential risk factor is critical to reducing suicide risk and increasing trends. This study aimed to determine whether insufficient sleep is associated with increasing trends in suicidal behaviors and disparities by sex, age, and race/ethnicity among school adolescents. METHODS: The present study used biennial data from the US nationally representative Youth Risk Behavior Survey from 2007 to 2019. Joinpoint regression models were used to estimate biennial percent changes (BPCs) and average BPCs (ABPCs) of suicidal behaviors by sleep duration. Logistic regression models were used to examine the association between insufficient sleep and suicidal behaviors. RESULTS: Of 73,356 adolescent students included (mean [standard deviation] age, 16.11 [1.23] years), 50.03% were female. Suicidal ideation and suicide plan among insufficient sleep group increased from 2007 to 2019 (BPC = 2.88% [95% confidence interval {CI}: 1.65%, 4.13%]; BPC = 3.42% [95% CI: 2.09%, 4.77%]), but were nonsignificant among sufficient sleep group. Trends in suicidal ideation (ABPC = 3.03% [95% CI: 1.35%, 4.73%]) and suicide plan (ABPC = 4.03% [95% CI: 2.47%, 5.62%]) among female adolescents with insufficient sleep increased, but nonsignificant among male adolescents with insufficient sleep. Suicidal ideation (ABPC = 1.73% [95% CI: 0.51%, 2.97%]) and suicide plan (ABPC = 2.31% [95% CI: 0.70%, 3.95%]) increased among younger adolescents only with insufficient sleep, whereas suicide trends by sleep duration were similar among older adolescents. Suicide plan among insufficient sleep group increased across the four racial groups, with BPC highest for the White (BPC = 3.48% [95% CI: 1.31%, 5.69%]), and lowest for the Hispanic/Latino (BPC = 1.18% [95% CI: 0.15%, 2.23%]), but were nonsignificant among sufficient sleep group except for the White (BPC = 2.83% [95% CI: 0.62%, 5.09%]). DISCUSSION: Insufficient sleep was disproportionately associated with increasing trends in suicidal behaviors among female, younger, and non-White adolescent students. Ensuring sufficient sleep can potentially reduce suicide among school adolescents.
Assuntos
Comportamento do Adolescente , Ideação Suicida , Humanos , Adolescente , Feminino , Masculino , Estados Unidos/epidemiologia , Comportamento do Adolescente/psicologia , Fatores de Risco , Privação do Sono/epidemiologia , Tentativa de Suicídio/estatística & dados numéricos , Tentativa de Suicídio/tendências , Suicídio/estatística & dados numéricos , Suicídio/tendênciasRESUMO
The estuarine plastisphere, a novel ecological habitat in the Anthropocene, has garnered global concerns. Recent geochemical evidence has pointed out its potential role in influencing nitrogen biogeochemistry. However, the biogeochemical significance of the plastisphere and its mechanisms regulating nitrogen cycling remain elusive. Using 15N- and 13C-labelling coupled with metagenomics and metatranscriptomics, here we unveil that the plastisphere likely acts as an underappreciated nitrifying niche in estuarine ecosystems, exhibiting a 0.9 ~ 12-fold higher activity of bacteria-mediated nitrification compared to surrounding seawater and other biofilms (stone, wood and glass biofilms). The shift of active nitrifiers from O2-sensitive nitrifiers in the seawater to nitrifiers with versatile metabolisms in the plastisphere, combined with the potential interspecific cooperation of nitrifying substrate exchange observed among the plastisphere nitrifiers, collectively results in the unique nitrifying niche. Our findings highlight the plastisphere as an emerging nitrifying niche in estuarine environment, and deepen the mechanistic understanding of its contribution to marine biogeochemistry.
Assuntos
Bactérias , Biofilmes , Estuários , Nitrificação , Água do Mar , Água do Mar/microbiologia , Bactérias/metabolismo , Bactérias/genética , Biofilmes/crescimento & desenvolvimento , Ecossistema , Microbiota/fisiologia , Metagenômica , Filogenia , Ciclo do Nitrogênio , Nitrogênio/metabolismo , Isótopos de Nitrogênio/metabolismoRESUMO
The phyllosphere is a fluctuant micro-environment habitat that harbors diverse microbial communities that have the potential to influence plant growth through their effect on host fitness. However, we know little about the driving factors of phyllosphere microbial functional traits, e.g., genes related to nutrient cycling and microbial community structure under anthropic disturbance. Here, we characterized phyllosphere microbial communities and the abundance of genes related to nutrient cycling from diverse plant species between urban and natural habitats. We measured leaf functional traits to investigate the potential drivers of the phyllosphere microbial profile. Results indicated that phyllosphere microbial communities differed significantly between urban and natural habitats, and that this variation was dependent upon plant species. Host plant species had a greater influence on the abundance of genes involved in nutrient cycling in the phyllosphere than habitat. In addition, phyllosphere microbial diversity and functional gene abundance were significantly correlated. Furthermore, host leaf functional traits (e.g., specific leaf area and nutrient content) were potential driving factors of both phyllosphere microbial community structure and the abundance of genes involved in nutrient cycling. These findings contribute to a better understanding of the phyllosphere microbiome and its biotic and abiotic controlling factors, which improves our understanding of plant-microbe interactions and their ecosystem functions under anthropic disturbance.
Assuntos
Microbiota , Plantas , Nutrientes , Folhas de Planta/químicaRESUMO
"Plastisphere", microbial communities colonizing plastic debris, has sparked global concern for marine ecosystems. Microbiome inhabiting this novel human-made niche has been increasingly characterized; however, whether the plastisphere holds crucial roles in biogeochemical cycling remains largely unknown. Here we evaluate the potential of plastisphere in biotic and abiotic denitrification and nitrous oxide (N2O) production in estuaries. Biofilm formation provides anoxic conditions favoring denitrifiers. Comparing with surrounding bulk water, plastisphere exhibits a higher denitrifying activity and N2O production, suggesting an overlooked N2O source. Regardless of plastisphere and bulk water, bacterial and fungal denitrifications are the main regulators for N2O production instead of chemodenitrification. However, the contributions of bacteria and fungi in the plastisphere are different from those in bulk water, indicating a distinct N2O production pattern in the plastisphere. These findings pinpoint plastisphere as a N2O source, and provide insights into roles of the new biotope in biogeochemical cycling in the Anthropocene.
Assuntos
Microbiota , Plásticos , Bactérias , Humanos , Óxido Nitroso , ÁguaRESUMO
Aims: We sought to objectively assess left ventricular myocardial work (MW) parameters after right ventricular septal pacing (VSP) and His-Purkinje system area pacing (HPSAP) procedures. Materials and methods: Patients undergoing double-chamber pacemaker implantation for III-degree atrioventricular block (III° AVB) were assessed 1 year after implantation. VSP and HPSAP groups (20 and 23 patients, respectively) were compared against 40 healthy age-matched volunteers. Two-dimensional ultrasound speckle tracking imaging was used to obtain the global myocardial work index (GWI), global myocardial work efficiency (GWE), global myocardial constructive work (GCW), global myocardial wasted work (GWW), left ventricular stratified strain, and peak strain dispersion (PSD). Results: GWI, GWE, and GCW parameters were improved in HPSAP compared to VSP, while GWW was significantly larger in the VSP group compared to the HPSAP group (all p < 0.05). HPSAP outperformed the VSP group in comparisons of global left ventricular longitudinal strain and stratified strain. Compared to controls, the GCW of all segmental myocardium (17/17 segments) in the VSP group was significantly reduced, while 70.59% (12/17 segments) in the HPSAP group was lower than the control group. GCW in the left ventricular segment of the HPSAP group was bigger than the VSP group (29.41%; 5/17 segments) and mainly concentrated in the ventricular septum and inferior wall. Conclusion: Our findings suggest that HPSAP performance outcomes are improved over VSP after 1 year, especially in left ventricular contractile synchrony, and HPSAP is beneficial to the effective myocardial work of the left ventricle.
RESUMO
All-trans retinoid acid (ATRA) can induce terminal differentiation of acute promyelocytic leukemia (APL), also known as the M3 subtype of acute myeloid leukemia (AML). However, non-APL types of AML respond poorly to ATRA-induced differentiation, and the mechanism underlying cell-type-specific resistance against ATRA remains unclear. Here, we use single-cell transcriptome analysis to compare the differentiation trajectories of two AML cell types during ATRA treatment. We show that in NB4 (APL/AML-M3) cells, ATRA activates canonical myeloid lineage factors-including SPI1, CEBPE, and STAT1-to direct near-normal differentiation toward mature granulocytes. By contrast, in HL60 (AML-M2) cells, ATRA-induced differentiation is incomplete and promiscuous, which is characterized by coinduction of both myelopoiesis and lymphopoiesis gene expression programs, as well as transient activation of cis-regulatory elements associated with myeloid differentiation. Our study suggests that the differentiation inducing capacity of ATRA in certain subtypes of AML may be compromised by therapy-induced lineage promiscuity.
RESUMO
Nanomaterials have shown great potential for application in microextraction due to their distinguishing nanoscale architectures and superior physicochemical properties. Herein, novel poly(lactic-co-glycolic acid) (PLGA) solid-phase microextraction (SPME) fibers, which were incorporated with a self-assembled graphene oxide (GO)-coated γ-Al2O3 composite (Al2O3@GO), were fabricated on stainless steel wires via an electrospinning method. The as-spun nanofibers were further sheathed through the self-polymerization of noradrenaline (NA), an agonist found in oysters, to provide a compatible biointerface and antifouling capacity. Acting as the coating substrate of the as-prepared fibers, PLGA is known for its prominent biocompatibility and biodegradability, while the adsorptive Al2O3@GO particles helped to increase their loading capacity. The modified PLGA-based electrospun nanofibers exhibited much higher extraction efficiency compared with the thicker polydimethylsiloxane (PDMS) coatings (165 µm) and polyacrylate (PA) coatings (85 µm). Due to the fine biointerface of the PLGA-based nanofibers, a rapid extraction equilibrium was observed and sampling with the custom-made Al2O3@GO-PLGA@PNA fibers could be accomplished within 15 min. The fibers were then successfully employed for simultaneous in vivo sampling of tetrodotoxin (TTX) and sulfonamides (SAs) in the dorsal-epaxial muscle of living pufferfish (Takifugu obscurus), and satisfactory sensitivities with limits of detection (LODs) in the range of 0.52-2.30 ng g-1 and comparable accuracies to the conventional liquid extraction (LE) method were achieved. In vivo sampling of target pharmaceuticals with the modified nanofibers showed their feasibility for further metabolomics and pharmacokinetics studies in biotissues.
RESUMO
Fluoroquinolones (FQs) are a group of antimicrobial agents that have been widely used for therapeutic purposes in clinical medicine for human and veterinary diseases, as well as in aquaculture production. Their residues, however, may survive in foods of animal origin, thus causing health risks for human. In this study, a rapid and sensitive method based on in vivo solid-phase microextraction (SPME) coupled with liquid chromatography-tandem mass spectrometry (LC-MS/MS) was developed to detect the residues of five FQs in cultured puffer fish (Takifugu obscurus). In vitro fiber evaluation experiment demonstrated that, compared with the thicker polydimethylsiloxane (PDMS) coating (165µm), the custom-made biocompatible C18-PAN fibers (45µm) exhibited much higher extraction efficiencies towards FQs (approximately 9-31 times). The custom-made C18-PAN coating also possessed excellent reproducibility in fish muscle with the intra-fiber relative standard deviations (RSDs) ranging from 11.2% to 14.3% (n = 6) and inter-fiber RSDs ranging from 13.1% to 16.1% (n = 6), which was suitable for in vivo sampling. The custom-made SPME fibers were subsequently applied to determine fluoroquinolones in dorsal-epaxial muscle of living puffer fish. The accuracies were verified through the comparison with traditional liquid extraction (LE) method, and the sensitivities were demonstrated to be satisfying with the limits of detection (LODs) ranging from 0.3ngg-1 to 1.5ngg-1. In general, this study presented a convenient and high-efficient method to determine fluoroquinolones in puffer fish by in vivo sampling.
Assuntos
Anti-Infecciosos/análise , Fluoroquinolonas/análise , Músculos/química , Microextração em Fase Sólida/métodos , Takifugu , Espectrometria de Massas em Tandem/métodos , Animais , Aquicultura , Cromatografia Líquida/economia , Cromatografia Líquida/métodos , Limite de Detecção , Reprodutibilidade dos Testes , Microextração em Fase Sólida/economia , Takifugu/metabolismo , Espectrometria de Massas em Tandem/economiaRESUMO
Tetrodotoxin (TTX) is one of the most toxic substances of non-protein in nature. In present study, a rapid and sensitive method based on in vivo solid-phase microextraction (SPME) coupled to liquid chromatography tandem mass spectrometry (LC-MS/MS) was developed to detect the endogenous TTX in pufferfish (Fugu). Fiber evaluation experiments demonstrated that, compared with the commercial PDMS and PA fibers, the home-made electrospun PS@PDA-GA fibers exhibited much better extraction performance towards to TTX in water (120 times and 20 times, respectively), under the optimized conditions. Then, the home-made SPME fibers were employed to extract TTX in spiked homogeneous fish muscle samples, and a LC-MS-MS was used for the analysis. The reproducibilities (RSDs of inter and intra fiber were 12.1%, and 7.9% respectively), linear range (10-1000ngg-1, R2=0.9963) and sensitivity (the LOD was 2.3ngg-1) of the method were found to be excellent and satisfactory for further in vivo experiments. Especially the LOD of the established method is lower than the National Standard Method of China (GB/T 23217-2008, LOD 50ngg-1). Subsequently, the method was successfully applied to detect the TTX in the dorsal muscle of living pufferfish, and the accuracy was verified with traditional liquid extraction (LE) method. In general, this is the first study to detect TTX in pufferfish by in vivo sampling method, which provided a promising alternative method for the studies of TTX, and also advanced the implementation of SPME for more in vivo studies.