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1.
Eur Radiol ; 34(3): 1524-1533, 2024 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-37644150

RESUMO

OBJECTIVES: To develop a mediastinal shift angle (MSA) measurement method applicable to right-sided congenital diaphragmatic hernia (RCDH) in fetal MRI and to validate the predictive value of MSA in RCDH. METHODS: Twenty-seven fetuses with isolated RCDH and 53 controls were included in our study. MSA was measured on MRI axial image at the level of four-chamber view of the fetal heart. The angle between the sagittal midline landmark line and the left boundary landmark line touching tangentially the lateral wall of the left ventricle was used to quantify MSA for RCDH. Appropriate statistical analyses were performed to determine whether MSA can be regarded as a valid predictive tool for postnatal outcomes. Furthermore, predictive performance of MSA was compared with that of lung area to head circumference ratio (LHR), observed/expected LHR (O/E LHR), total fetal lung volume (TFLV), and observed/expected TFLV (O/E TFLV). RESULTS: MSA was significantly higher in the RCDH group than in the control group. MSA, LHR, O/E LHR, TFLV, and O/E TFLV were all correlated with postnatal survival, pulmonary hypertension (PH), and extracorporeal membrane oxygenation (ECMO) therapy (p < 0.05). Value of the AUC demonstrated good predictive performance of MSA for postnatal survival (0.901, 95%CI: (0.781-1.000)), PH (0.828, 95%CI: (0.661-0.994)), and ECMO therapy (0.813, 95%CI: (0.645-0.980)), which was similar to O/E TFLV but slightly better than TFLV, O/E LHR, and LHR. CONCLUSIONS: We developed a measurement method of MSA for RCDH for the first time and demonstrated that MSA could be used to predict postnatal survival, PH, and ECMO therapy in RCDH. CLINICAL RELEVANCE STATEMENT: Newly developed MRI assessment method of fetal MSA in RCDH offers a simple and effective risk stratification tool for patients with RCDH. KEY POINTS: • We developed a measurement method of mediastinal shift angle for right-sided congenital diaphragmatic hernia for the first time and demonstrated its feasibility and reproducibility. • Mediastinal shift angle can predict more prognostic information other than survival in right-sided congenital diaphragmatic hernia with good performance. • Mediastinal shift angle can be used as a simple and effective risk stratification tool in right-sided congenital diaphragmatic hernia to improve planning of postnatal management.


Assuntos
Hérnias Diafragmáticas Congênitas , Hipertensão Pulmonar , Gravidez , Feminino , Humanos , Hérnias Diafragmáticas Congênitas/diagnóstico por imagem , Hérnias Diafragmáticas Congênitas/terapia , Pulmão/diagnóstico por imagem , Medidas de Volume Pulmonar/métodos , Reprodutibilidade dos Testes , Imageamento por Ressonância Magnética , Medição de Risco , Ultrassonografia Pré-Natal , Estudos Retrospectivos
2.
Phys Chem Chem Phys ; 26(12): 9424-9431, 2024 Mar 20.
Artigo em Inglês | MEDLINE | ID: mdl-38446138

RESUMO

Most transition metal dichalcogenide (TMD) heterostructures (HSs) exhibit a type II band alignment, leading to a charge transfer process accompanied by the transfer of spin-valley polarization and spontaneous formation of interlayer excitons. This unique band structure facilitates achieving a longer exciton lifetime and extended spin-valley polarization lifetime. However, the mechanism of charge transfer in type II TMD HSs is not fully comprehended. Here, the ultrafast charge transfer process is studied in MoSe2-WSe2 HS via valley-solved broadband pump-probe spectroscopy. Under the conditions of B-excitons of WSe2 and MoSe2 being resonantly pumped, a new charge transfer pathway through the higher energy state associated with the B-exciton is found. Meanwhile, the holes (electrons) in the WSe2 (MoSe2) layer of MoSe2-WSe2 HS produce obvious spin-valley polarization even under the condition of B-exciton of WSe2 (MoSe2) being resonantly pumped, and the lifetime can reach tens of ps, which is in stark contrast to the absence of A-exciton spin-valley polarization in monolayer WSe2 (MoSe2) under the same pumping condition. The results deepen the insight into the charge transfer process in type II TMD HSs and show the great potential of TMD HSs in the application of spin-valley electronics devices.

3.
Nucleic Acids Res ; 50(4): 2005-2018, 2022 02 28.
Artigo em Inglês | MEDLINE | ID: mdl-35137179

RESUMO

The second cell fate decision in the early stage of mammalian embryonic development is pivotal; however, the underlying molecular mechanism is largely unexplored. Here, we report that Prmt1 acts as an important regulator in primitive endoderm (PrE) formation. First, Prmt1 depletion promotes PrE gene expression in mouse embryonic stem cells (ESCs). Single-cell RNA sequencing and flow cytometry assays demonstrated that Prmt1 depletion in mESCs contributes to an emerging cluster, where PrE genes are upregulated significantly. Furthermore, the efficiency of extraembryonic endoderm stem cell induction increased in Prmt1-depleted ESCs. Second, the pluripotency factor Klf4 methylated at Arg396 by Prmt1 is required for recruitment of the repressive mSin3a/HDAC complex to silence PrE genes. Most importantly, an embryonic chimeric assay showed that Prmt1 inhibition and mutated Klf4 at Arg 396 induce the integration of mouse ESCs into the PrE lineage. Therefore, we reveal a regulatory mechanism for cell fate decisions centered on Prmt1-mediated Klf4 methylation.


Assuntos
Embrião de Mamíferos/metabolismo , Endoderma , Proteína-Arginina N-Metiltransferases/metabolismo , Animais , Diferenciação Celular , Desenvolvimento Embrionário , Endoderma/metabolismo , Feminino , Fator 4 Semelhante a Kruppel/metabolismo , Camundongos , Células-Tronco Embrionárias Murinas , Gravidez
4.
Environ Toxicol ; 2024 Apr 06.
Artigo em Inglês | MEDLINE | ID: mdl-38581229

RESUMO

Breast cancer stands as the foremost cause of cancer-related mortality among women, presenting a substantial economic impact on society. The limitations in current therapeutic options, coupled with poor patient tolerance, underscore the urgent need for novel treatments. Our study embarked on a genomic association exploration of breast cancer, leveraging whole-genome sequencing data from the Finngen database, complemented by expression quantitative trait loci (eQTL) insights from the eQTLGen and GTEx Consortiums. An initial investigation was conducted through summary-based Mendelian randomization (MR) to pinpoint primary eQTLs. Analysis of blood specimens revealed 103 eQTLs significantly correlated with breast cancer. Focusing our efforts, we identified 19 candidates with potential therapeutic significance. Further scrutiny via two-sample MR pinpointed UROD, LMO4, HORMAD1, and ZSWIM5 as promising targets for breast cancer therapy. Our research sheds light on new avenues for the treatment of breast cancer, highlighting the potential of genomic association studies in uncovering viable therapeutic targets.

5.
J Hepatol ; 78(3): 574-583, 2023 03.
Artigo em Inglês | MEDLINE | ID: mdl-36356684

RESUMO

BACKGROUND & AIMS: The Baveno VII consensus recommends that spleen stiffness measurement (SSM) ≤40 kPa is safe for ruling out high-risk varices (HRVs) and avoiding endoscopic screening in patients who do not meet the Baveno VI criteria. This study aimed to validate the performance of the Baveno VII algorithm in individuals with HBV-related cirrhosis. METHODS: Consecutive individuals with HBV-related cirrhosis who underwent liver stiffness measurement (LSM) and SSM - using a 50 Hz shear wave frequency, spleen diameter measurement, and esophagogastroduodenoscopy (EGD) were prospectively enrolled from June 2020. A 100 Hz probe has been adopted for additional SSM assessment since July 2021. RESULTS: From June 2020 to January 2022, 996 patients were screened and 504 were enrolled for analysis. Among the 504 patients in whom SSM was assessed using a 50 Hz probe, the Baveno VII algorithm avoided more EGDs (56.7% vs. 39.1%, p <0.001) than Baveno VI criteria, with a comparable missed HRV rate (3.8% vs. 2.5%). Missed HRV rates were >5% for all other measures: 11.3% for LSM-longitudinal spleen diameter to platelet ratio score, 20.0% for platelet count/longitudinal spleen diameter ratio, and 8.8% for Rete Sicilia Selezione Terapia-hepatitis. SSM@100 Hz was assessed in 232 patients, and the Baveno VII algorithm with SSM@100 Hz spared more EGDs (75.4% vs. 59.5%, p <0.001) than that with SSM@50 Hz, both with a missed HRV rate of 3.0% (1/33). CONCLUSIONS: We validated the Baveno VII algorithm, demonstrating the excellent performance of SSM@50 Hz and SSM@100 Hz in ruling out HRV in individuals with HBV-related cirrhosis. Furthermore, the Baveno VII algorithm with SSM@100 Hz could safely rule out more EGDs than that with SSM@50 Hz. CLINICAL TRIAL NUMBER: NCT04890730. IMPACT AND IMPLICATIONS: The Baveno VII guideline proposed that for patients who do not meet the Baveno VI criteria, SSM ≤40 kPa could avoid further unnecessary endoscopic screening. The current study validated the Baveno VII algorithm using 50 Hz and 100 Hz probes, which both exhibited excellent performance in ruling out HRVs in individuals with HBV-related cirrhosis. Compared with the Baveno VII algorithm with SSM@50 Hz, SSM@100 Hz had a better capability to safely rule out unnecessary EGDs. Baveno VII algorithm will be a practical tool to triage individuals with cirrhosis in future clinical practice.


Assuntos
Técnicas de Imagem por Elasticidade , Varizes Esofágicas e Gástricas , Varizes , Humanos , Vírus da Hepatite B , Cirrose Hepática/diagnóstico , Algoritmos
6.
Eur Radiol ; 33(12): 9390-9400, 2023 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-37392231

RESUMO

OBJECTIVES: To develop and validate a fully automated AI system to extract standard planes, assess early gestational weeks, and compare the performance of the developed system to sonographers. METHODS: In this three-center retrospective study, 214 consecutive pregnant women that underwent transvaginal ultrasounds between January and December 2018 were selected. Their ultrasound videos were automatically split into 38,941 frames using a particular program. First, an optimal deep-learning classifier was selected to extract the standard planes with key anatomical structures from the ultrasound frames. Second, an optimal segmentation model was selected to outline gestational sacs. Third, novel biometry was used to measure, select the largest gestational sac in the same video, and assess gestational weeks automatically. Finally, an independent test set was used to compare the performance of the system with that of sonographers. The outcomes were analyzed using the area under the receiver operating characteristic curve (AUC), sensitivity, specificity, and mean similarity between two samples (mDice). RESULTS: The standard planes were extracted with an AUC of 0.975, a sensitivity of 0.961, and a specificity of 0.979. The gestational sacs' contours were segmented with a mDice of 0.974 (error less than 2 pixels). The comparison showed that the relative error of the tool in assessing gestational weeks was 12.44% and 6.92% lower and faster (min, 0.17 vs. 16.6 and 12.63) than that of the intermediate and senior sonographers, respectively. CONCLUSIONS: This proposed end-to-end tool allows automatic assessment of gestational weeks in early pregnancy and may reduce manual analysis time and measurement errors. CLINICAL RELEVANCE STATEMENT: The fully automated tool achieved high accuracy showing its potential to optimize the increasingly scarce resources of sonographers. Explainable predictions can assist in their confidence in assessing gestational weeks and provide a reliable basis for managing early pregnancy cases. KEY POINTS: • The end-to-end pipeline enabled automatic identification of the standard plane containing the gestational sac in an ultrasound video, as well as segmentation of the sac contour, automatic multi-angle measurements, and the selection of the sac with the largest mean internal diameter to calculate the early gestational week. • This fully automated tool combining deep learning and intelligent biometry may assist the sonographer in assessing the early gestational week, increasing accuracy and reducing the analyzing time, thereby reducing observer dependence.


Assuntos
Aprendizado Profundo , Gravidez , Feminino , Humanos , Idade Gestacional , Ultrassonografia Pré-Natal , Estudos Retrospectivos , Biometria
7.
Eur Radiol ; 33(3): 1668-1676, 2023 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-36180644

RESUMO

OBJECTIVES: To investigate the predictive value of mediastinal shift angle (MSA) in congenital diaphragmatic hernia (CDH). METHODS: A retrospective analysis was performed on 87 fetuses with prenatally diagnosed left-sided CDH (LCDH) and 88 controls. MSA was measured on magnetic resonance imaging (MRI). Lung area to head circumference ratio (LHR), ratio of the observed/expected LHR (O/E LHR), total fetal lung volume (TFLV), and observed/expected total fetal lung volume (O/E TFLV) were also measured. Correlation of MSA with pulmonary hypertension (PH), extracorporeal membrane oxygenation (ECMO) use, duration of hospitalization and survival in neonates with CDH was analyzed. Performance of MSA in prediction of postnatal outcomes was compared with LHR, O/E LHR, TFLV, and O/E TFLV. RESULTS: There were significant differences in MSA values not only between the CDH group and the control group but also in CDH patients with different survival outcomes. MSA was inversely correlated with O/E LHR, O/E TFLV, and TFLV. MSA, LHR, O/E LHR, TFLV, and O/E TFLV could all be used to predict survival of CDH patients. In addition, the receiver operating characteristic (ROC) curve showed that the test performance of MSA was similar to that of TFLV, O/E TFLV, and O/E LHR, but superior to that of LHR. MSA was also correlated with PH, need for ECMO support, and duration of hospitalization. CONCLUSION: MRI measurement of MSA can provide various prognostic information for prenatally diagnosed LCDH, in addition to postnatal survival. The test performance of MSA is similar to TFLV, O/E TFLV, and O/E LHR. KEY POINTS: • Mediastinal shift angle (MSA) can be measured quickly and reproducibly on MRI images. • MSA could provide more prognostic information other than postnatal survival for LCDH with good test performance. • MSA should be incorporated into prenatal risk stratification for LCDH to improve planning of postnatal management.


Assuntos
Hérnias Diafragmáticas Congênitas , Hipertensão Pulmonar , Gravidez , Feminino , Recém-Nascido , Humanos , Hérnias Diafragmáticas Congênitas/diagnóstico por imagem , Pulmão/diagnóstico por imagem , Pulmão/patologia , Estudos Retrospectivos , Medidas de Volume Pulmonar/métodos , Feto/patologia , Hipertensão Pulmonar/diagnóstico , Ultrassonografia Pré-Natal , Imageamento por Ressonância Magnética , Medição de Risco , Idade Gestacional
8.
Org Biomol Chem ; 21(29): 6034-6038, 2023 Jul 26.
Artigo em Inglês | MEDLINE | ID: mdl-37439118

RESUMO

A strategy for the synthesis of multisubstituted propenylbenzenes using benzyl chlorides as starting materials is described. The palladium-catalyzed allylative dearomatization and the subsequent Wagner-Meerwein rearrangement as well as the olefin isomerization proceeded smoothly under mild conditions to produce propenylation products in good yields with high regioselectivity. Control experiments and cyclic voltammetry analysis suggest that Bu3SnCl, a by-product generated in the first step of allylative dearomatization, plays an essential role in the third step of olefin isomerization in the presence of a Brønsted acid.

9.
J Gastroenterol Hepatol ; 38(1): 129-137, 2023 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-36345143

RESUMO

BACKGROUND AND AIMS: The accuracy of model for end-stage liver disease (MELD) and MELD with sodium (MELD-Na) scores in reflecting the clinical outcomes of patients with cirrhosis and portal vein thrombosis (PVT) remains unclear. This study aimed to evaluate the performance of scores in predicting 90-day mortality in patients with cirrhosis and PVT. METHODS: Post hoc analysis was performed in two prospective cohorts (NCT02457637 and NCT03641872). The correlation between the MELD/MELD-Na score and 90-day liver transplantation (LT)-free mortality was investigated in patients with cirrhosis with and without PVT. RESULTS: In this study, 2826 patients with cirrhosis were included, and 255 (9.02%) had PVT. The cumulative incidence of 90-day LT-free mortality did not significantly differ between patients with and without PVT (log-rank P = 0.0854). MELD [area under the receiver operating curve (AUROC), 0.649 vs. 0.842; P = 0.0036] and MELD-Na scores (AUROC, 0.691 vs. 0.851; P = 0.0108) were compared in patients with and without PVT, regarding the prediction of 90-day LT-free mortality. In MELD < 15 and MELD-Na < 20 subgroups, patients with PVT had a higher 90-day LT-free mortality than those without PVT (7.91% vs. 2.64%, log-rank P = 0.0011; 7.14% vs. 3.43%, log-rank P = 0.0223), whereas in MELD ≥ 15 and MELD-Na ≥ 20 subgroups, no significant difference was observed between patients with and without PVT. CONCLUSIONS: The performance of MELD and MELD-Na scores in predicting 90-day LT-free mortality of patients with cirrhosis was compromised by PVT. MELD < 15 or MELD-Na < 20 may underestimate the 90-day LT-free mortality in patients with PVT.


Assuntos
Doença Hepática Terminal , Trombose Venosa , Humanos , Doença Hepática Terminal/etiologia , Cirrose Hepática/patologia , Veia Porta/patologia , Estudos Prospectivos , Índice de Gravidade de Doença , Sódio , Trombose Venosa/complicações
10.
Hepatobiliary Pancreat Dis Int ; 22(1): 54-63, 2023 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-36041973

RESUMO

BACKGROUND: Hepatocellular carcinoma (HCC) is the fourth leading cause of cancer-related death worldwide. Due to the high prevalence of hepatitis B virus (HBV) infection in China, the incidence of HCC in China is high, and liver cirrhosis caused by chronic hepatitis also brings great challenges to treatment. This paper reviewed the latest research progress on minimally invasive treatments for HCC, including percutaneous thermal ablation and new nonthermal ablation techniques, and introduced the principles, advantages, and clinical applications of various therapeutic methods in detail. DATA SOURCES: The data of treatments for HCC were systematically collected from the PubMed, ScienceDirect, American Chemical Society and Web of Science databases published in English, using "minimally invasive" and "hepatocellular carcinoma" or "liver cancer" as the keywords. RESULTS: Percutaneous thermal ablation is still a first-line strategy for the minimally invasive treatment of HCC. The effect of microwave ablation (MWA) on downgrading treatment before liver transplantation is better than that of radiofrequency ablation (RFA), while RFA is more widely used in the clinical practice. High-intensity focused ultrasound (HIFU) is mainly used for the palliative treatment of advanced liver cancer. Electrochemotherapy (ECT) delivers chemotherapeutic drugs to the target cells while reducing the blood supply around HCC. Irreversible electroporation (IRE) uses a microsecond-pulsed electric field that induces apoptosis and necrosis and triggers a systemic immune response. The nanosecond pulsed electric field (nsPEF) has achieved a good response in the ablation of mice with HCC, but it has not been reported in China for the treatment of human HCC. CONCLUSIONS: A variety of minimally invasive treatments provide a sufficient survival advantage for HCC patients. Nonthermal ablation will lead to a new wave with its unique advantage of antitumor recurrence and metastasis.


Assuntos
Técnicas de Ablação , Carcinoma Hepatocelular , Ablação por Cateter , Neoplasias Hepáticas , Ablação por Radiofrequência , Humanos , Animais , Camundongos , Carcinoma Hepatocelular/patologia , Neoplasias Hepáticas/patologia , Técnicas de Ablação/efeitos adversos , Técnicas de Ablação/métodos , Ablação por Cateter/efeitos adversos , Ablação por Cateter/métodos , Resultado do Tratamento
11.
J Environ Manage ; 328: 116973, 2023 Feb 15.
Artigo em Inglês | MEDLINE | ID: mdl-36525735

RESUMO

Microalgae appear to be a promising and ecologically safe way for nutrients removal from rare earth tailings (REEs) wastewater with CO2 fixation and added benefits of resource recovery and recycling. In this study, a pilot scale (50 L) co-flocculating microalgae photobioreactor (Ma-PBR) as constructed and operated for 140 days to treat REEs wastewater with low C/N ratio of 0.51-0.56. The removal rate of ammonia nitrogen (NH4+-N) reached 88.04% and the effluent residual concentration was as low as 9.91 mg/L that have met the Emission Standards of Pollutants from Rare Earths Industry (GB 26451-2011). Timely supplementation of trace elements was necessary to maintain the activity of microalgae and then prolonged the operation time. The dominant phyla in co-flocculating microalgae was Chlorophyta, the relative abundance of which was higher than 80%. Tetradesmus belonging to Chlorophyceae was the dominant genus with relative abundance of 80.35%. The results provided a practical support for the scaling-up of Ma-PBR to treat REEs wastewater.


Assuntos
Metais Terras Raras , Microalgas , Águas Residuárias , Fotobiorreatores , Projetos Piloto , Biomassa , Nitrogênio
12.
Phys Chem Chem Phys ; 24(27): 16538-16544, 2022 Jul 13.
Artigo em Inglês | MEDLINE | ID: mdl-35788232

RESUMO

Excitonic devices based on two-dimensional (2D) transition metal dichalcogenides (TMDCs) can combine spintronics with valleytronics due to its special energy band structure. In this work, we studied the generation and relaxation processes of spin/valley polarized excitons dynamics in monolayer WSe2 and its van der Waals (vdW) heterojunction with graphene using a circularly polarized femtosecond pump-probe system. The spin/valley depolarization dynamics of the A exciton in monolayer WSe2 is found to exhibit a biexponential decay. The fast relaxation process is due to the ultrafast intervalley electron-hole spin-flip exchange coupling and electron-phonon scattering. And the slow relaxation process originates from the recombination and relaxation of the trion states. Graphene has an electron extraction effect on WSe2, which prevents the formation of trions. Therefore, the spin/valley depolarization process of the A exciton in the heterojunction exhibits only a fast relaxation process. In both monolayer WSe2 and its heterojunction with graphene, B/A' excitons exhibit a negative spin/valley polarization which is mainly due to two-photon absorption and excited Bose scattering. Our work systematically studied the spin/valley depolarization dynamics of excitons and revealed possible mechanisms of their differences in isolated 2D WSe2 and vdW heterojunctions.

13.
Gut ; 70(7): 1253-1265, 2021 07.
Artigo em Inglês | MEDLINE | ID: mdl-33789966

RESUMO

OBJECTIVE: To characterise the oral microbiome, gut microbiome and serum lipid profiles in patients with active COVID-19 and recovered patients; evaluate the potential of the microbiome as a non-invasive biomarker for COVID-19; and explore correlations between the microbiome and lipid profile. DESIGN: We collected and sequenced 392 tongue-coating samples, 172 faecal samples and 155 serum samples from Central China and East China. We characterised microbiome and lipid molecules, constructed microbial classifiers in discovery cohort and verified their diagnostic potential in 74 confirmed patients (CPs) from East China and 37 suspected patients (SPs) with IgG positivity. RESULTS: Oral and faecal microbial diversity was significantly decreased in CPs versus healthy controls (HCs). Compared with HCs, butyric acid-producing bacteria were decreased and lipopolysaccharide-producing bacteria were increased in CPs in oral cavity. The classifiers based on 8 optimal oral microbial markers (7 faecal microbial markers) achieved good diagnostic efficiency in different cohorts. Importantly, diagnostic efficacy reached 87.24% in the cross-regional cohort. Moreover, the classifiers successfully diagnosed SPs with IgG antibody positivity as CPs, and diagnostic efficacy reached 92.11% (98.01% of faecal microbiome). Compared with CPs, 47 lipid molecules, including sphingomyelin (SM)(d40:4), SM(d38:5) and monoglyceride(33:5), were depleted, and 122 lipid molecules, including phosphatidylcholine(36:4p), phosphatidylethanolamine (PE)(16:0p/20:5) and diglyceride(20:1/18:2), were enriched in confirmed patients recovery. CONCLUSION: This study is the first to characterise the oral microbiome in COVID-19, and oral microbiomes and lipid alterations in recovered patients, to explore their correlations and to report the successful establishment and validation of a diagnostic model for COVID-19.


Assuntos
COVID-19/sangue , COVID-19/microbiologia , Fezes/microbiologia , Lipídeos/sangue , Boca/microbiologia , Adulto , COVID-19/diagnóstico , Estudos de Casos e Controles , China , Estudos de Coortes , Feminino , Microbioma Gastrointestinal , Humanos , Lipidômica , Masculino , Pessoa de Meia-Idade
14.
Mol Biol Evol ; 37(4): 1007-1019, 2020 04 01.
Artigo em Inglês | MEDLINE | ID: mdl-31778175

RESUMO

The rapidity with which the mutation rate evolves could greatly impact evolutionary patterns. Nevertheless, most studies simply assume a constant rate in the time scale of interest (Kimura 1983; Drake 1991; Kumar 2005; Li 2007; Lynch 2010). In contrast, recent studies of somatic mutations suggest that the mutation rate may vary by several orders of magnitude within a lifetime (Kandoth et al. 2013; Lawrence et al. 2013). To resolve the discrepancy, we now propose a runaway model, applicable to both the germline and soma, whereby mutator mutations form a positive-feedback loop. In this loop, any mutator mutation would increase the rate of acquiring the next mutator, thus triggering a runaway escalation in mutation rate. The process can be initiated more readily if there are many weak mutators than a few strong ones. Interestingly, even a small increase in the mutation rate at birth could trigger the runaway process, resulting in unfit progeny. In slowly reproducing species, the need to minimize the risk of this uncontrolled accumulation would thus favor setting the mutation rate low. In comparison, species that starts and ends reproduction sooner do not face the risk and may set the baseline mutation rate higher. The mutation rate would evolve in response to the risk of runaway mutation, in particular, when the generation time changes. A rapidly evolving mutation rate may shed new lights on many evolutionary phenomena (Elango et al. 2006; Thomas et al. 2010, 2018; Langergraber et al. 2012; Besenbacher et al. 2019).


Assuntos
Modelos Genéticos , Acúmulo de Mutações , Taxa de Mutação , Carcinogênese/genética , Evolução Molecular , Humanos
15.
J Hepatol ; 74(3): 584-592, 2021 03.
Artigo em Inglês | MEDLINE | ID: mdl-33039403

RESUMO

BACKGROUND & AIMS: There are no data validating the performance of spleen stiffness measurement in ruling out high-risk varices in patients with HBV-related cirrhosis under maintained viral suppression. Thus, we aimed to prospectively validate the performance of spleen stiffness measurement (cut-off 46 kPa) combined with Baveno VI criteria in ruling out high-risk varices in these patients. METHODS: Patients with cirrhosis were enrolled from April to December 2019 at the hepatology unit of the Nanfang Hospital, China. Liver and spleen transient elastography and esophagogastroduodenoscopy were performed at enrollment. Antiviral regimen(s) and virological responses, evaluated every 3-6 months, were recorded. RESULTS: Overall 341 patients with HBV-related cirrhosis under maintained viral suppression were enrolled, and the prevalence of high-risk varices was 20.5% (70/341). Baveno VI criteria spared 37.0% (126/341) esophagogastroduodenoscopies and no high-risk varices were missed (0/70). Eight cases of high-risk varices (8/70, 11.4%) were misclassified in patients (208/341, 61.0%) within the expanded Baveno VI criteria. The spleen stiffness measurement cut-off (≤46.0 kPa) was shown to safely rule out high-risk varices in these patients (the percentage of missed high-risk varices was 4.3%). Over half (61.6%, 210/341) of patients met the combined model (Baveno VI criteria and spleen stiffness measurement cut-off ≤46 kPa) and 4.3% (3/70) of high-risk varices cases were misclassified. This combined model exhibited a sensitivity of 95.71%, specificity of 76.38%, negative predictive value of 98.57%, and negative likelihood ratio of 0.06 for ruling out high-risk varices. CONCLUSIONS: We validated the excellent performance of Baveno VI criteria combined with spleen stiffness measurement (cut-off 46 kPa) for safely ruling out high-risk varices in patients with HBV-related cirrhosis under viral suppression; more than half of esophagogastroduodenoscopy procedures were spared using this combination. CLINICAL TRIAL NUMBER: NCT04123509 LAY SUMMARY: Esophageal varices have important prognostic implications in patients with cirrhosis. Thus, their timely identification is important so that treatment can be initiated early. Herein, we validated the excellent performance of the combination of Baveno VI criteria with spleen stiffness measurement (cut-off 46 kPa) for ruling out high-risk esophageal varices in patients with HBV-related cirrhosis under maintained viral suppression (with antiviral treatment). This combined model was able to safely rule out high-risk varices (missed/total <5%) and over half (61.6%) of esophagogastroduodenoscopy procedures were spared.


Assuntos
Antivirais/uso terapêutico , Elasticidade , Varizes Esofágicas e Gástricas/epidemiologia , Varizes Esofágicas e Gástricas/etiologia , Vírus da Hepatite B/genética , Hepatite B/complicações , Hepatite B/tratamento farmacológico , Cirrose Hepática/complicações , Baço/patologia , Adulto , China/epidemiologia , DNA Viral/genética , Técnicas de Imagem por Elasticidade , Feminino , Hepatite B/virologia , Humanos , Masculino , Pessoa de Meia-Idade , Contagem de Plaquetas , Valor Preditivo dos Testes , Prevalência , Estudos Prospectivos , Resposta Viral Sustentada
16.
Intervirology ; 64(2): 69-80, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-33709967

RESUMO

OBJECTIVE: To investigate the relationship between hematologic tumors and Epstein-Barr virus (EBV)-encoded small noncoding RNA (EBER) variations as well as latent membrane protein 1 (LMP1) variations. METHODS: Patients with leukemia and myelodysplastic syndrome (MDS) were selected as subjects. Genotypes 1/2 and genotypes F/f were analyzed using the nested PCR technology, while EBER and LMP1 subtypes were analyzed by the nested PCR and DNA sequencing. RESULTS: Type 1 was more dominant than type 2, found in 59 out of 82 (72%) leukemia and in 31 out of 35 (88.6%) MDS, while type F was more prevalent than type f in leukemia (83/85, 97.6%) and MDS (29/31, 93.5%) samples. The distribution of EBV genotypes 1/2 was not significantly different among leukemia, MDS, and healthy donor groups, neither was that of EBV genotypes F/f. EB-6m prototype was the dominant subtype of EBER in leukemia and MDS (73.2% [30/41] and 83.3% [10/12], respectively). The frequency of EB-6m was lower than that of healthy people (96.7%, 89/92), and the difference was significant (p < 0.05). China 1 subtype was the dominant subtype of LMP1 in leukemia and MDS (70% [28/40] and 90% [9/10], respectively), and there was no significant difference in the distribution of LMP1 subtypes among the 3 groups (p > 0.05). CONCLUSION: The distribution of EBV 1/2, F/f, EBER, and LMP1 subtypes in leukemia and MDS was similar to that in the background population in Northern China, which means that these subtypes may be rather region-restricted but not associated with leukemia and MDS pathogenesis.


Assuntos
Infecções por Vírus Epstein-Barr , Neoplasias Hematológicas , Pequeno RNA não Traduzido , China/epidemiologia , Infecções por Vírus Epstein-Barr/epidemiologia , Herpesvirus Humano 4/genética , Humanos , Proteínas de Membrana , RNA Viral , Proteínas da Matriz Viral
17.
Nanotechnology ; 32(13)2021 Jan 08.
Artigo em Inglês | MEDLINE | ID: mdl-33427201

RESUMO

Band renormalization effects play a significant role for two-dimensional (2D) materials in designing a device structure and customizing their optoelectronic performance. However, the intrinsic physical mechanism about the influence of these effects cannot be revealed by general steady-state studies. Here, band renormalization effects in organic superacid treated monolayer MoS2, untreated monolayer MoS2and few-layer MoS2are quantitatively analyzed by using broadband femtosecond transient absorption spectroscopy. In comparison with the untreated monolayer, organic superacid treated monolayer MoS2maintains a direct bandgap structure with two thirds of carriers populated at K valley, even when the initial exciton density is as high as 2.05 × 1014cm-2(under 400 nm excitations). While for untreated monolayer and few-layer MoS2, many-particle induced band renormalizations lead to a stronger imbalance for the carrier population between K and Q valleys inkspace, and the former experiences a direct-to-indirect bandgap transition when the initial exciton density exceeds 5.0 × 1013cm-2(under 400 nm excitations). Those many-particle induced band renormalization processes further suggest a band-structure-controlling method in practical 2D devices.

18.
Phys Chem Chem Phys ; 23(39): 22430-22436, 2021 Oct 13.
Artigo em Inglês | MEDLINE | ID: mdl-34585679

RESUMO

Since excitonic quasiparticles, including excitons, trions and charges, have a great influence on the photoelectric characteristics of two-dimensional (2D) transition metal dichalcogenides (TMDs), systematic explorations of the trion dynamics and charge photogeneration in 2D TMDs are important for their future optoelectronic applications. Here, broadband femtosecond transient absorption spectroscopic experiments are performed first to investigate the peak shifting and broadening kinetics in MoS2 nanosheets in solution prepared by liquid phase exfoliation (LPE-MoS2, ∼9 layers, 9L), which reveal that the binding energies for the A-, B-, and C-exciton states are ∼77 meV, ∼76 meV, and -70 meV (the energy difference between free charges and excitons; the negative sign for C-excitons means a spontaneous dissociation nature in band-nesting regions), respectively. Then, the trion dynamics and charge photogeneration in LPE-MoS2 nanosheets have been studied in detail, demonstrating that they are comparable to those in chemical vapor deposition grown MoS2 films (1L-, 3L- and 7L-MoS2). These experimental results suggest that LPE-TMD nanosheets also have the potential for use in charge-related optoelectronic devices based on 2D TMDs.

19.
Prenat Diagn ; 41(6): 766-771, 2021 May.
Artigo em Inglês | MEDLINE | ID: mdl-33782977

RESUMO

OBJECTIVE: To review the prenatal and postnatal clinical characteristics and pathological subtypes, as well as the surgical outcome for congenital mesoblastic nephroma (CMN) cases. METHOD: A retrospective review was performed in 11 cases with CMN prenatally diagnosed at a single center between 2015 and 2019. The clinical characteristics, surgical outcome, histopathology, and follow-up were retrospectively obtained and reviewed. RESULTS: The median gestational age at which the sonographic diagnosis was made was 35 weeks. Polyhydramnios was found in four (36.4%) cases, and all resulted in a preterm birth. Nine infants had hypertension. Ten cases underwent radical nephrectomy, and one underwent radical nephrectomy and partial adrenalectomy. The pathological results showed that six tumors were classical variants, four mixed variants, and one was a cellular variant. Three cases presented as a stage I, eight as stage II, and no stage III or IV cases were diagnosed. All patients are alive so far. At a median follow-up of 14 months, no local recurrence, or remote metastases were found. CONCLUSION: The prognosis of prenatal CMN cases is excellent after early surgery.


Assuntos
Nefroma Mesoblástico/diagnóstico , Nefroma Mesoblástico/terapia , Adulto , China/epidemiologia , Feminino , Humanos , Recém-Nascido , Rim/patologia , Rim/fisiopatologia , Imageamento por Ressonância Magnética/métodos , Nefroma Mesoblástico/epidemiologia , Gravidez , Diagnóstico Pré-Natal/métodos , Diagnóstico Pré-Natal/estatística & dados numéricos , Prognóstico , Estudos Retrospectivos
20.
Int J Biometeorol ; 64(10): 1699-1708, 2020 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-32564191

RESUMO

Measured leaf photosynthetic light response (PLR) curves at different positions were fitted by non-rectangular hyperbola (NRH) equation to characterize vertical profile of parameters in NRH equation, namely maximum net photosynthetic rate Pnmax, initial quantum yield of assimilation φ, dark respiration rate Rd, and convexity of the curve k, at both jointing and heading stages within rice canopy. And leaf-position-specific and canopy average NRH equations were constructed respectively based on measured PLR curves at each specific leaf position and all measured PLR curves within rice canopy. The results showed that the Pnmax, φ, and Rd reached the maximum at the top second leaf and then decreased at jointing stage and decreased in downward leaves at heading stage. The k increased with lowering leaf position at both stages. The leaf-position-specific NRH equation performed well in estimating net photosynthetic rate Pn for all leaves at different positions and stages, while the canopy average NRH equation underestimated leaf Pn at upper canopy and overestimated Pn at lower canopy. The top fourth leaf was suitable for estimating photosynthetic parameters at canopy scale, as the Pnmax, φ, Rd, and k of the top fourth leaf were near to these parameters of rice canopy, and the canopy average NRH equation performed well in estimating leaf Pn for the top fourth leaf. The results will provide basic information for upscaling leaf photosynthesis to canopy scale.


Assuntos
Oryza , Fotossíntese , Luz , Folhas de Planta
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