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BACKGROUND: Spirometry quality assurance is a challenging task across levels of healthcare tiers, especially in primary care. Deep learning may serve as a support tool for enhancing spirometry quality. We aimed to develop a high accuracy and sensitive deep learning-based model aiming at assisting high-quality spirometry assurance. METHODS: Spirometry PDF files retrieved from one hospital between October 2017 and October 2020 were labeled according to ATS/ERS 2019 criteria and divided into training and internal test sets. Additional files from three hospitals were used for external testing. A deep learning-based model was constructed and assessed to determine acceptability, usability, and quality rating for FEV1 and FVC. System warning messages and patient instructions were also generated for general practitioners (GPs). RESULTS: A total of 16,502 files were labeled. Of these, 4592 curves were assigned to the internal test set, the remaining constituted the training set. In the internal test set, the model generated 95.1%, 92.4%, and 94.3% accuracy for FEV1 acceptability, usability, and rating. The accuracy for FVC acceptability, usability, and rating were 93.6%, 94.3%, and 92.2%. With the assistance of the model, the performance of GPs in terms of monthly percentages of good quality (A, B, or C grades) tests for FEV1 and FVC was higher by ~ 21% and ~ 36%, respectively. CONCLUSION: The proposed model assisted GPs in spirometry quality assurance, resulting in enhancing the performance of GPs in quality control of spirometry.
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Aprendizado Profundo , Volume Expiratório Forçado , Humanos , Controle de Qualidade , Testes de Função Respiratória , Espirometria , Capacidade VitalRESUMO
BACKGROUND: Due to the similar symptoms of upper airway obstruction to asthma, misdiagnosis is common. Spirometry is a cost-effective screening test for upper airway obstruction and its characteristic patterns involving fixed, variable intrathoracic and extrathoracic lesions. We aimed to develop a deep learning model to detect upper airway obstruction patterns and compared its performance with that of lung function clinicians. METHODS: Spirometry records were reviewed to detect the possible condition of airway stenosis. Then they were confirmed by the gold standard (e.g., computed tomography, endoscopy, or clinic diagnosis of upper airway obstruction). Images and indices derived from flow-volume curves were used for training and testing the model. Clinicians determined cases using spirometry records from the test set. The deep learning model evaluated the same data. RESULTS: Of 45,831 patients' spirometry records, 564 subjects with curves suggesting upper airway obstruction, after verified by the gold standard, 351 patients were confirmed. These cases and another 200 cases without airway stenosis were used as the training and testing sets. 432 clinicians evaluated 20 cases of each of the three patterns and 20 no airway stenosis cases (n = 80). They assigned an accuracy of 41.2% (±15.4) (interquartile range: 27.5-52.5%), with poor agreements (κ = 0.12). For the same cases, the model generated a correct detection of 81.3% (p < 0.0001). CONCLUSIONS: Deep learning could detect upper airway obstruction patterns from other classic patterns of ventilatory defects with high accuracy, whereas clinicians presented marked errors and variabilities. The model may serve as a support tool to enhance clinicians' correct diagnosis of upper airway obstruction using spirometry.
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Obstrução das Vias Respiratórias , Asma , Aprendizado Profundo , Transtornos Respiratórios , Obstrução das Vias Respiratórias/diagnóstico , Asma/diagnóstico , Constrição Patológica , Humanos , EspirometriaRESUMO
Background Cerebral aneurysm detection is a challenging task. Deep learning may become a supportive tool for more accurate interpretation. Purpose To develop a highly sensitive deep learning-based algorithm that assists in the detection of cerebral aneurysms on CT angiography images. Materials and Methods Head CT angiography images were retrospectively retrieved from two hospital databases acquired across four different scanners between January 2015 and June 2019. The data were divided into training and validation sets; 400 additional independent CT angiograms acquired between July and December 2019 were used for external validation. A deep learning-based algorithm was constructed and assessed. Both internal and external validation were performed. Jackknife alternative free-response receiver operating characteristic analysis was performed. Results A total of 1068 patients (mean age, 57 years ± 11 [standard deviation]; 660 women) were evaluated for a total of 1068 CT angiograms encompassing 1337 cerebral aneurysms. Of these, 534 CT angiograms (688 aneurysms) were assigned to the training set, and the remaining 534 CT angiograms (649 aneurysms) constituted the validation set. The sensitivity of the proposed algorithm for detecting cerebral aneurysms was 97.5% (633 of 649; 95% CI: 96.0, 98.6). Moreover, eight new aneurysms that had been overlooked in the initial reports were detected (1.2%, eight of 649). With the aid of the algorithm, the overall performance of radiologists in terms of area under the weighted alternative free-response receiver operating characteristic curve was higher by 0.01 (95% CI: 0.00, 0.03). Conclusion The proposed deep learning algorithm assisted radiologists in detecting cerebral aneurysms on CT angiography images, resulting in a higher detection rate. © RSNA, 2020 Online supplemental material is available for this article. See also the editorial by Kallmes and Erickson in this issue.
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Angiografia por Tomografia Computadorizada/métodos , Aprendizado Profundo , Interpretação de Imagem Assistida por Computador/métodos , Aneurisma Intracraniano/diagnóstico por imagem , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Reprodutibilidade dos Testes , Estudos Retrospectivos , Sensibilidade e EspecificidadeRESUMO
Dual targeting of EGFR/HER2 receptor is an attractive strategy for cancer therapy. Four series of 4-anilinoquinoline-3-carbonitrile derivatives were designed and prepared by introducing various functional groups, including a polar hydrophilic group (carboxylic acid), a heterocyclic substituent possessing polarity to some extent, and an unpolar hydrophobic phenyl portion, at the C-6 position of the quinoline skeleton. All of the prepared derivatives were screened for their inhibitory activities against EGFR /HER2 receptors and their antiproliferative activities against the SK-BR-3 and A431 cell lines. Compounds 6a, 6 g and 6d exhibited significant activities against the target cell lines. In particular, the antiproliferative activity of 6d (IC50 = 1.930 µM) against SK-BR-3 was over 2-fold higher than that of neratinib (IC50 = 3.966 µM), and comparable to that of Lapatinib (IC50 = 2.737 µM). On the other hand, 6d (IC50 = 1.893 µM) was more active than the reference drug Neratinib (IC50 = 2.151 µM), and showed comparable potency to Lapatinib (IC50 = 1.285 µM) against A431. Cell cycle analysis and apoptosis assays indicated that 6d arrests the cell cycle in the S phase, and it is a potent apoptotic inducer. Moreover, molecular docking exhibited the binding modes of compound 6d in EGFR and HER2 binding sites, respectively. Compound 6d can be considered as a candidate for further investigation as a more potent anticancer agent.
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Antineoplásicos/farmacologia , Apoptose/efeitos dos fármacos , Desenho de Fármacos , Inibidores de Proteínas Quinases/farmacologia , Quinolinas/farmacologia , Receptor ErbB-2/antagonistas & inibidores , Antineoplásicos/síntese química , Antineoplásicos/química , Linhagem Celular Tumoral , Proliferação de Células/efeitos dos fármacos , Relação Dose-Resposta a Droga , Ensaios de Seleção de Medicamentos Antitumorais , Receptores ErbB/antagonistas & inibidores , Receptores ErbB/metabolismo , Humanos , Simulação de Acoplamento Molecular , Estrutura Molecular , Inibidores de Proteínas Quinases/síntese química , Inibidores de Proteínas Quinases/química , Quinolinas/síntese química , Quinolinas/química , Receptor ErbB-2/metabolismo , Relação Estrutura-AtividadeRESUMO
BACKGROUND: Small plateau (SP) on the flow-volume curve was found in parts of patients with suspected asthma or upper airway abnormalities, but it lacks clear scientific proof. Therefore, we aimed to characterize its clinical features. METHODS: We involved patients by reviewing the bronchoprovocation test (BPT) and bronchodilator test (BDT) completed between October 2017 and October 2020 to assess the characteristics of the sign. Patients who underwent laryngoscopy were assigned to perform spirometry to analyze the relationship of the sign and upper airway abnormalities. SP-Network was developed to recognition of the sign using flow-volume curves. RESULTS: Of 13,661 BPTs and 8,168 BDTs completed, we labeled 2,123 (15.5%) and 219 (2.7%) patients with the sign, respectively. Among them, there were 1,782 (83.9%) with the negative-BPT and 194 (88.6%) with the negative-BDT. Patients with SP sign had higher median FVC and FEV1% predicted (both P < .0001). Of 48 patients (16 with and 32 without the sign) who performed laryngoscopy and spirometry, the rate of laryngoscopy-diagnosis upper airway abnormalities in patients with the sign (63%) was higher than those without the sign (31%) (P = 0.038). SP-Network achieved an accuracy of 95.2% in the task of automatic recognition of the sign. CONCLUSIONS: SP sign is featured on the flow-volume curve and recognized by the SP-Network model. Patients with the sign are less likely to have airway hyperresponsiveness, automatic visualizing of this sign is helpful for primary care centers where BPT cannot available.
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Asma/diagnóstico , Testes de Provocação Brônquica/estatística & dados numéricos , Testes de Provocação Brônquica/normas , Volume Expiratório Forçado , Laringoscopia/normas , Adolescente , Adulto , Testes de Provocação Brônquica/métodos , Criança , China , Aprendizado Profundo , Feminino , Humanos , Laringoscopia/métodos , Masculino , Pessoa de Meia-Idade , Estudos Retrospectivos , Espirometria , Adulto JovemRESUMO
OBJECTIVE: To investigate the feasibility of establishing a model of allograft penile transplantation in adult beagle dogs and explore the conditions for constructing a stable animal model of penis transplant. METHODS: Following the principles of similarity, repeatability, feasibility, applicability, and controllability in the construction of experimental animal models, we compared the major anatomic features of the penis of 20 adult beagle dogs with those of 10 adult men. Using microsurgical techniques, we performed cross-transplantation of the penis in the 20 (10 pairs) beagle dogs and observed the survival rate of the transplanted penises by FK506+MMF+MP immune induction. We compared the relevant indexes with those of the 10 cases of microsurgical replantation of the amputated penis. RESULTS: High similarities but no statistically significant differences were observed in penile anatomic features between the 20 beagle dogs and 10 men. All the 10 cases of cross-transplantation of the penis were successfully completed in the 20 beagle dogs, of which the transplanted glans survived with normal micturition in 12 but developed necrosis in the other 8; the success rate of one-time venous anastomosis was 95.0% (38/40) and that of one-time arterial anastomosis was 87.5% (35/40), with an average vascular anastomosis time of (71.0±9.0) minutes, a mean operation time of (133.0±10.3) minutes, and a mean blood loss of (135.8±41.4) ml. In the 10 cases of penile replantation, the success rate of one-time venous anastomosis was 100% (20/20) and that of one-time arterial anastomosis was 90.0% (18/20), with an average vascular anastomosis time of (65.0±7.9) minutes, a mean operation time of (117.4±10.0) minutes, and a mean blood loss of (85.0±10.8) ml. In the 12 cases of replantation of the amputated penis, the success rate of one-time venous anastomosis was 100% (24/24) and that of one-time arterial anastomosis was 95.8% (23/24), with an average vascular anastomosis time of (79.0±17.6) minutes, a mean operation time of (125.0±20.6) minutes, and a mean blood loss of (140.0±44.3) ml. No statistically significant differences were found in the relevant indexes among the three groups. CONCLUSIONS: The anatomic structure of the corpus cavernosum penis of beagle dogs is highly similar to that of men, almost the same in cross-section anatomy. Microsurgical replantation and allograft transplantation of the penis were both successfully performed in beagle dogs, which showed similar operative indexes to those of human penile replantation. The construction of the allograft penile transplantation model in adult beagle dogs is feasible clinically, with the advantages of operability and repeatability.
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Sobrevivência de Enxerto , Modelos Animais , Transplante Peniano , Reimplante , Adulto , Anastomose Cirúrgica , Animais , Artérias/cirurgia , Cães , Estudos de Viabilidade , Humanos , Masculino , Microcirurgia , Necrose/etiologia , Duração da Cirurgia , Pênis/anatomia & histologia , Pênis/patologia , Complicações Pós-Operatórias/etiologia , Taxa de Sobrevida , Micção , Veias/cirurgiaRESUMO
Our previous investigations have demonstrated that microinjection of acetylcholine (ACh) or muscarinic ACh receptor activation in the cerebellar cortex induces a systemic blood pressure depressor response. This study aimed to determine the role of muscarinic ACh receptor-2 (M2 receptor) in the cerebellar cortex in cardiovascular function regulation in rats. A nonselective muscarinic receptor agonist (oxotremorine M, OXO; 30 mM), a selective M2 receptor agonist (arecaidine but-2-ynyl ester tosylate, ABET; 3, 10, and 30 mM), 30 mM OXO mixed with a selective M2 receptor antagonist (methoctramine hydrate, MCT; 0.3, 1, and 3 mM), and normal saline (0.9 % NaCl) were separately microinjected (0.5 µl/5 s) into the cerebellar cortex (lobule VI) of anaesthetized rats. We measured the mean arterial pressure (MAP), maximum change in MAP, and reactive time (RT; the duration required for the blood pressure to return to basal levels), heart rate (HR) and the maximum change in HR during the RT in response to drug activation. The results demonstrated that ABET dose-dependently decreased MAP and HR, increased the maximum change in MAP and the maximum change in HR, and prolonged the RT. Furthermore, MCT dose-dependently blocked the OXO-mediated cardiovascular depressor response. This study provides the first evidence that M2 receptors in the cerebellar cortex are involved in cardiovascular regulation, the activation of which evokes significant depressor and bradycardic responses.
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Pressão Sanguínea/efeitos dos fármacos , Córtex Cerebelar/metabolismo , Frequência Cardíaca/efeitos dos fármacos , Agonistas Muscarínicos/farmacologia , Receptor Muscarínico M2/metabolismo , Animais , Relação Dose-Resposta a Droga , Masculino , Microinjeções , Antagonistas Muscarínicos/farmacologia , Ratos Sprague-DawleyRESUMO
It has long been known that serotonergic afferent inputs are the third largest afferent population in the cerebellum after mossy fibers and climbing fibers. However, the role of serotonergic inputs in cerebellar-mediated motor behaviors is still largely unknown. Here, we show that only 5-HT2A receptors among the 5-HT2 receptor subfamily are expressed and localized in the rat cerebellar fastigial nucleus (FN), one of the ultimate outputs of the spinocerebellum precisely regulating trunk and limb movements. Remarkably, selective activation of 5-HT2A receptors evokes a postsynaptic excitatory effect on FN neurons in a concentration-dependent manner in vitro, which is in accord with the 5-HT-elicited excitation on the same tested neurons. Furthermore, selective 5-HT2A receptor antagonist M100907 concentration-dependently blocks the excitatory effects of 5-HT and TCB-2, a 5-HT2A receptor agonist, on FN neurons. Consequently, microinjection of 5-HT into bilateral FNs significantly promotes rat motor performances on accelerating rota-rod and balance beam and narrows stride width rather than stride length in locomotion gait. All these motor behavioral effects are highly consistent with those of selective activation of 5-HT2A receptors in FNs, and blockage of the component of 5-HT2A receptor-mediated endogenous serotonergic inputs in FNs markedly attenuates these motor performances. All these results demonstrate that postsynaptic 5-HT2A receptors greatly contribute to the 5-HT-mediated excitatory effect on cerebellar FN neurons and promotion of the FN-related motor behaviors, suggesting that serotonergic afferent inputs may actively participate in cerebellar motor control through their direct modulation on the final output of the spinocerebellum.
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Núcleos Cerebelares/metabolismo , Potenciais Pós-Sinápticos Excitadores , Locomoção , Receptor 5-HT2A de Serotonina/metabolismo , Neurônios Serotoninérgicos/metabolismo , Animais , Núcleos Cerebelares/citologia , Núcleos Cerebelares/fisiologia , Fluorbenzenos/farmacologia , Masculino , Piperidinas/farmacologia , Ratos , Ratos Sprague-Dawley , Receptor 5-HT2A de Serotonina/genética , Neurônios Serotoninérgicos/fisiologia , Antagonistas da Serotonina/farmacologiaRESUMO
Air pollution is a danger to economies throughout the European Union. Industry, population expansion, a building boom owing to housing and infrastructure development, increasing vehicle traffic, crowded streets, a lack of availability of clean fuel, and ineffective control programs are the primary causes. Toxic air is a double-edged sword for a country's health since it affects just a tiny fraction of Europe's population. The financial burden and healthcare expenses for people rise when health expenditures rise. The present research looks at how dangerous air levels, healthcare costs, and the expansion of the European Union's economy are all connected. The findings are based on data collected over 29 years and account for the abovementioned variables. The results of the unit root test have the significant probability values of all variables: health expenditures (HE), gross domestic product (GDP), nitrous oxides (NOX), and carbon dioxides (CO2) emissions at both level and first difference. We used the Johansen, Kao, and Pedroni cointegration tests to test the null hypothesis of no cointegration to see that sample variables had a long-term association. The PMG-ARDL test was used to get these findings. The results confirmed the significant probability values of dependent variables in long- and short-run results that GDP has a positive and significant effect on health expenditure, while NOX and CO2 emissions have a negative and significant impact on (HE), in the European Union. To verify the results, we applied the robustness test, fully modified OLS (FMOLD), and dynamic OLS (DOLS); the robustness test results validated the PMG-ARDL test results. Environmental pollution (CO2, NOX) has a significant and negative impact on healthcare expenditures and a significant effect on GDP (HE) in the EU region. The findings of this research have implications for a wide range of parties, including those who would examine the link between factors in a study meant to improve air quality, distribute health resources, or develop strategies for economic development.
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Poluição do Ar , Gastos em Saúde , Humanos , Desenvolvimento Econômico , União Europeia , Dióxido de Carbono/análise , Poluição do Ar/análiseRESUMO
Background: Epigenetic alterations driven by chromatin regulators (CRs) are well-recognized cancer hallmarks. Growing evidence suggests that the imbalance of CRs may lead to the occurrence of various diseases including tumors. However, the role and prognostic value of CRs in clear cell renal cell carcinoma (ccRCC) remain undefined. Methods: Consensus clustering analysis was used to identify different subtypes. Univariate and multivariate Cox regression analysis were performed to identify prognosis-related CRs and constructed a risk model. Transcriptome sequencing was used to verify gene expression levels. Kaplan-Meier survival analysis was used to compare overall survival (OS) between high- and low-risk groups. The area under the curve (AUC) value of the receiver operating characteristic (ROC) curve was used to evaluate the performance of the model. The ESTIMATE algorithm and single-sample gene set enrichment analysis (ssGSEA) were executed to evaluate the immune characteristics of samples. Correlation analysis was used to assess the relationship between risk score and immune checkpoint genes, the relationship between expression levels of CRs and immune cell infiltration and drug therapeutic response. Finally, we also compared differences in drug sensitivity between low- and high-risk groups. Results: We identified three CRs-related subtypes with different characteristics. A prognostic model was built with four CRs and can precisely predict the OS of patients in different risk groups. The model has good stability and applicability and was further verified in the internal and external dataset. The transcriptomic levels of the four CRs were also validated, and the risk score was an independent prognostic factor for ccRCC. Obvious differences in the immune microenvironment and the expression levels of immune checkpoints were observed in low- and high-risk group. Higher immune activity and immune cell infiltration were found in the high-risk group. Besides, the expression levels of CRs were associated with drug therapeutic response. Patients with high-risk score may be more sensitive to gemcitabine, vinblastine, paclitaxel, axitinib, sunitinib, and temsirolimus. Conclusions: CRs were strongly associated with the occurrence and development of ccRCC. Targeting CRs may become a new therapeutic strategy for ccRCC. Besides, CRs-related gene signature can predict the prognosis and therapeutic significance of ccRCC, which provides an important reference for clinical decision-making.
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Ventral tegmental area (VTA) dopamine (DA) neurons have been found to substantially associate with post-traumatic stress disorder (PTSD) pathology, however, whether and how these DA neurons affect fear memory management in PTSD individuals remains largely unknown. In this study, we utilized auditory conditioned foot-shock to evaluate the fear memory retrieval and retention characteristics in a single prolonged stress-induced PTSD rat model. We employed chemogenetic technology to specifically activate VTA DA neurons to examine the freezing behaviors responding to the conditioned stimuli. In vivo extracellular electrophysiological analyses were used to identify VTA DA neuronal firing alterations due to the chemogenetic activation. The results demonstrated that PTSD model rats showed comparable fear memory retrieval (Day 2 after the conditioned foot-shock), but significant enhancements in fear memory retention (Day 8 after the conditioned foot-shock), compared to normal control rats. Chemogenetic activation of VTA DA neurons markedly diminished the retention of fear memory in PTSD model rats, which appeared concomitantly with increases in the firing activities of the DA neurons. These findings revealed that PTSD induced the persistence of fear memory, which could be attenuated by activation of VTA DA neurons. It is presumed that VTA dopaminergic signals may serve as a prospective option for PTSD treatment.
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Deep convolutional neural networks (CNNs) have achieved impressive performance in medical image segmentation; however, their performance could degrade significantly when being deployed to unseen data with heterogeneous characteristics. Unsupervised domain adaptation (UDA) is a promising solution to tackle this problem. In this work, we present a novel UDA method, named dual adaptation-guiding network (DAG-Net), which incorporates two highly effective and complementary structural-oriented guidance in training to collaboratively adapt a segmentation model from a labelled source domain to an unlabeled target domain. Specifically, our DAG-Net consists of two core modules: 1) Fourier-based contrastive style augmentation (FCSA) which implicitly guides the segmentation network to focus on learning modality-insensitive and structural-relevant features, and 2) residual space alignment (RSA) which provides explicit guidance to enhance the geometric continuity of the prediction in the target modality based on a 3D prior of inter-slice correlation. We have extensively evaluated our method with cardiac substructure and abdominal multi-organ segmentation for bidirectional cross-modality adaptation between MRI and CT images. Experimental results on two different tasks demonstrate that our DAG-Net greatly outperforms the state-of-the-art UDA approaches for 3D medical image segmentation on unlabeled target images.
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Coração , Redes Neurais de Computação , Processamento de Imagem Assistida por ComputadorRESUMO
As the dominant histological subtype of kidney cancer, clear cell renal cell carcinoma (ccRCC) poorly responds to conventional chemotherapy and radiotherapy. Although novel immunotherapies such as immune checkpoint inhibitors could have a durable effect in treating ccRCC patients, the limited availability of dependable biomarkers has restricted their application in clinic. In the study of carcinogenesis and cancer therapies, there has been a recent emphasis on researching programmed cell death (PCD). In the current study, we discovered the enriched and prognostic PCD in ccRCC utilizing gene set enrichment analysis (GSEA) and investigate the functional status of ccRCC patients with different PCD risks. Then, genes related to PCD that had prognostic value in ccRCC were identified for the conduction of non-negative matrix factorization to cluster ccRCC patients. Next, the tumor microenvironment, immunogenicity, and therapeutic response in different molecular clusters were analyzed. Among PCD, apoptosis and pyroptosis were enriched in ccRCC and correlated with prognosis. Patients with high PCD levels were related to poor prognosis and a rich but suppressive immune microenvironment. PCD-based molecular clusters were identified to differentiate the clinical status and prognosis of ccRCC. Moreover, the molecular cluster with high PCD levels may correlate with high immunogenicity and a favorable therapeutic response to ccRCC. Furthermore, a simplified PCD-based gene classifier was established to facilitate clinical application and used transcriptome sequencing data from clinical ccRCC samples to validate the applicability of the gene classifier. We thoroughly extended the understanding of PCD in ccRCC and constructed a PCD-based gene classifier for differentiation of the prognosis and therapeutic efficacy in ccRCC.
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Pyroptosis is a kind of programmed cell death triggered by the inflammasome. Growing evidence has revealed the crucial utility of pyroptosis in tumors. However, the potential mechanism of pyroptosis in clear cell renal cell carcinoma (ccRCC) is still unclear. In this research, we systematically analyze the genetic and transcriptional alterations of pyroptosis-related genes (PRGs) in ccRCC, identify pyroptosis-related subtypes, analyze the clinical and microenvironmental differences among different subtypes, develop a corresponding prognostic model to predict the prognosis of patients, and interpret the effect of pyroptosis on ccRCC microenvironment. This study provides a new perspective for a comprehensive understanding of the role of pyroptosis in ccRCC and its impact on the immune microenvironment, and a reliable scoring system was established to predict patients' prognosis.
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Carcinoma de Células Renais , Carcinoma , Neoplasias Renais , Humanos , Carcinoma de Células Renais/genética , Piroptose/genética , Microambiente Tumoral/genética , Neoplasias Renais/genéticaRESUMO
Oil is one of the main components in maize kernels. Increasing the total oil content (TOC) is favorable to optimize feeding requirement by improving maize quality. To better understand the genetic basis of TOC, quantitative trait loci (QTL) in four double haploid (DH) populations were explored. TOC exhibited continuously and approximately normal distribution in the four populations. The moderate to high broad-sense heritability (67.00-86.60%) indicated that the majority of TOC variations are controlled by genetic factors. A total of 16 QTLs were identified across all chromosomes in a range of 3.49-30.84% in term of phenotypic variation explained. Among them, six QTLs were identified as the major QTLs that explained phenotypic variation larger than 10%. Especially, qOC-1-3 and qOC-2-3 on chromosome 9 were recognized as the largest effect QTLs with 30.84% and 21.74% of phenotypic variance, respectively. Seventeen well-known genes involved in fatty acid metabolic pathway located within QTL intervals. These QTLs will enhance our understanding of the genetic basis of TOC in maize and offer prospective routes to clone candidate genes regulating TOC for breeding program to cultivate maize varieties with the better grain quality.
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Post-traumatic stress disorder (PTSD) is a debilitating sequela of extraordinary traumatic sufferings that threaten personal health and dramatically attenuate the patient's quality of life. Accumulating lines of evidence suggest that functional disorders in the ventral tegmental area (VTA) dopaminergic system contribute substantially to PTSD symptomatology. Notably, music therapy has been shown to greatly ameliorate PTSD symptoms. In this literature review, we focused on whether music improved PTSD symptoms, based on VTA dopaminergic action, including the effects of music on dopamine (DA)-related gene expression, the promotion of DA release and metabolism, and the activation of VTA functional activities. In addition, the strengths and limitations of the studies concerning the results of music therapy on PTSD are discussed. Collectively, music therapy is an effective approach for PTSD intervention, in which the VTA dopaminergic system may hold an important position.
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Starch is the principal carbohydrate source in maize kernels. Understanding the genetic basis of starch content (SC) benefits greatly in improving maize yield and optimizing end-use quality. Here, four double haploid (DH) populations were generated and were used to identify quantitative trait loci (QTLs) associated with SC. The phenotype of SC exhibited continuous and approximate normal distribution in each population. A total of 13 QTLs for SC in maize kernels was detected in a range of 3.65-16.18% of phenotypic variation explained (PVE). Among those, only some partly overlapped with QTLs previously known to be related to SC. Meanwhile, 12 genes involved in starch synthesis and metabolism located within QTLs were identified in this study. These QTLs will lay the foundation to explore candidate genes regulating SC in maize kernel and facilitate the application of molecular marker-assisted selection for a breeding program to cultivate maize varieties with a deal of grain quality.
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Post-traumatic stress disorder (PTSD) is a debilitating psychiatric condition that arises after extremely traumatic events, with clinically significant and lasting impacts on both physical and psychological health. The present study examined the role of ventral tegmental area (VTA) dopaminergic signaling in anxiety-like behaviors and the underlying mechanisms in PTSD model rats. Chemogenetic technology was employed to specifically activate VTA dopamine (DA) neurons in rats subjected to single prolonged stress (SPS), and open field and elevated plus maze tests were applied to evaluate the anxiety-like manifestations. Subsequently, in vivo extracellular electrophysiological analyses were used to examine alterations in the firing characteristics of VTA DA neurons. Chemogenetic activation enhanced the firing and burst rates of VTA DA neurons in SPS-induced PTSD model rats and concomitantly mitigated the anxiety-like behavioral phenotypes. Collectively, these findings reveal a direct association between PTSD-relevant anxiety behaviors and VTA dopaminergic activity, and further suggest that interventions designed to enhance VTA dopaminergic activity may be a potential strategy for PTSD treatment.
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Transtornos de Estresse Pós-Traumáticos , Área Tegmentar Ventral , Ratos , Animais , Área Tegmentar Ventral/fisiologia , Neurônios Dopaminérgicos/fisiologia , Ansiedade/psicologia , DopaminaRESUMO
Arecoline is the principle psychoactive alkaloid in areca nuts. Areca nuts are chewable seeds of Areca catechu L., which are epidemic plants that grow in tropical and subtropical countries and cause dependency after long-term use. However, the mechanisms underlying such dependency remain largely unclear, and therefore, no effective interventions for its cessation have been developed. The present study aimed to examine the effects of arecoline on neurons of the ventral tegmental area (VTA). After rats were anesthetized and craniotomized, electrophysiological electrodes were lowered into the VTA to obtain extracellular recordings. The mean firing rate of dopaminergic and GABAergic neurons were then calculated and analyzed before and after arecoline treatment. The burst characteristics of the dopaminergic neurons were also analyzed. The results showed that arecoline evoked a significant enhancement of the firing rate of dopaminergic neurons, but not GABAergic neurons. Moreover, arecoline evoked remarkable burst firings in the dopaminergic neurons, including an increase in the burst rate, elongation in the burst duration, and an enhancement in the number of spikes per burst. Collectively, the findings revealed that arecoline significantly excited VTA dopaminergic neurons, which may be a mechanism underlying areca nut dependency and a potential target for areca nut cessation therapy.
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[This corrects the article DOI: 10.1038/s42256-021-00421-z.].