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1.
Nature ; 584(7822): 584-588, 2020 08.
Artigo em Inglês | MEDLINE | ID: mdl-32788724

RESUMO

Locust plagues threaten agricultural and environmental safety throughout the world1,2. Aggregation pheromones have a crucial role in the transition of locusts from a solitary form to the devastating gregarious form and the formation of large-scale swarms3,4. However, none of the candidate compounds reported5-7 meet all the criteria for a locust aggregation pheromone. Here, using behavioural assays, electrophysiological recording, olfactory receptor characterization and field experiments, we demonstrate that 4-vinylanisole (4VA) (also known as 4-methoxystyrene) is an aggregation pheromone of the migratory locust (Locusta migratoria). Both gregarious and solitary locusts are strongly attracted to 4VA, regardless of age and sex. Although it is emitted specifically by gregarious locusts, 4VA production can be triggered by aggregation of four to five solitary locusts. It elicits responses specifically from basiconic sensilla on locust antennae. We also identified OR35 as a specific olfactory receptor of 4VA. Knockout of OR35 using CRISPR-Cas9 markedly reduced the electrophysiological responses of the antennae and impaired 4VA behavioural attractiveness. Finally, field trapping experiments verified the attractiveness of 4VA to experimental and wild populations. These findings identify a locust aggregation pheromone and provide insights for the development of novel control strategies for locusts.


Assuntos
Locusta migratoria/efeitos dos fármacos , Locusta migratoria/fisiologia , Feromônios/metabolismo , Feromônios/farmacologia , Estirenos/metabolismo , Estirenos/farmacologia , Envelhecimento , Migração Animal/efeitos dos fármacos , Animais , Ecossistema , Feminino , Controle de Insetos , Locusta migratoria/química , Masculino , Densidade Demográfica , Receptores Odorantes/deficiência , Receptores Odorantes/genética , Receptores Odorantes/metabolismo , Sensilas/fisiologia
2.
Proc Natl Acad Sci U S A ; 120(5): e2216851120, 2023 01 31.
Artigo em Inglês | MEDLINE | ID: mdl-36701367

RESUMO

The phase transition from solitary to gregarious locusts is crucial in outbreaks of locust plague, which threaten agricultural yield and food security. Research on the regulatory mechanisms of phase transition in locusts has focused primarily on the transcriptional or posttranslational level. However, the translational regulation of phase transition is unexplored. Here, we show a phase-dependent pattern at the translation level, which exhibits different polysome profiles between gregarious and solitary locusts. The gregarious locusts exhibit significant increases in 60S and polyribosomes, while solitary locusts possess higher peaks of the monoribosome and a specific "halfmer." The polysome profiles, a molecular phenotype, respond to changes in population density. In gregarious locusts, ten genes involved in the cytosolic ribosome pathway exhibited increased translational efficiency (TE). In solitary locusts, five genes from the mitochondrial ribosome pathway displayed increased TE. The high expression of large ribosomal protein 7 at the translational level promotes accumulation of the free 60S ribosomal subunit in gregarious locusts, while solitary locusts employ mitochondrial small ribosomal protein 18c to induce the assembly of mitochondrial ribosomes, causing divergence of the translational profiles and behavioral transition. This study reveals the translational regulatory mechanism of locust phase transition, in which the locusts employ divergent ribosome pathways to cope with changes in population density.


Assuntos
Gafanhotos , Animais , Gafanhotos/fisiologia , Proteínas Ribossômicas/genética , Proteínas Ribossômicas/metabolismo , Densidade Demográfica , Ribossomos/genética
3.
Proc Natl Acad Sci U S A ; 119(6)2022 02 08.
Artigo em Inglês | MEDLINE | ID: mdl-35110413

RESUMO

Changes in population density lead to phenotypic differentiation of solitary and gregarious locusts, which display different resistance to fungal pathogens; however, how to regulate their cellular immune strategies remains unknown. Here, our stochastic simulation of pathogen proliferation suggested that humoral defense always enhanced resistance to fungal pathogens, while phagocytosis sometimes reduced defense against pathogens. Further experimental data proved that gregarious locusts had significantly decreased phagocytosis of hemocytes compared to solitary locusts. Additionally, transcriptional analysis showed that gregarious locusts promoted immune effector expression (gnbp1 and dfp) and reduced phagocytic gene expression (eater) and the cytokine tumor necrosis factor (TNF). Interestingly, higher expression of the cytokine TNF in solitary locusts simultaneously promoted eater expression and inhibited gnbp1 and dfp expression. Moreover, inhibition of TNF increased the survival of solitary locusts, and injection of TNF decreased the survival of gregarious locusts after fungal infection. Therefore, our results indicate that the alerted expression of TNF regulated the immune strategy of locusts to adapt to environmental changes.


Assuntos
Gafanhotos/imunologia , Gafanhotos/microbiologia , Imunidade Celular/imunologia , Metarhizium/imunologia , Fator de Necrose Tumoral alfa/imunologia , Animais , Expressão Gênica/imunologia , Fagocitose/imunologia , Densidade Demográfica , Transcrição Gênica/imunologia
4.
Molecules ; 29(7)2024 Mar 23.
Artigo em Inglês | MEDLINE | ID: mdl-38611728

RESUMO

The epidermal growth factor receptor (EGFR) plays a pivotal role in cancer therapeutics, with small-molecule EGFR inhibitors emerging as significant agents in combating this disease. This review explores the synthesis and clinical utilization of EGFR inhibitors, starting with the indispensable role of EGFR in oncogenesis and emphasizing the intricate molecular aspects of the EGFR-signaling pathway. It subsequently provides information on the structural characteristics of representative small-molecule EGFR inhibitors in the clinic. The synthetic methods and associated challenges pertaining to these compounds are thoroughly examined, along with innovative strategies to overcome these obstacles. Furthermore, the review discusses the clinical applications of FDA-approved EGFR inhibitors such as erlotinib, gefitinib, afatinib, and osimertinib across various cancer types and their corresponding clinical outcomes. Additionally, it addresses the emergence of resistance mechanisms and potential counterstrategies. Taken together, this review aims to provide valuable insights for researchers, clinicians, and pharmaceutical scientists interested in comprehending the current landscape of small-molecule EGFR inhibitors.


Assuntos
Carcinogênese , Transformação Celular Neoplásica , Humanos , Afatinib , Receptores ErbB , Cloridrato de Erlotinib
5.
Opt Lett ; 48(2): 211-214, 2023 Jan 15.
Artigo em Inglês | MEDLINE | ID: mdl-36638420

RESUMO

Phase retrieval is crucial in phase-shifting interferometry and other phase measurement techniques. However, in noisy wrapped phase maps with high steepness, discontinuities arise and cause phase unwrapping errors. To solve this problem, this Letter presents a phase retrieval method based on a simulated wrapped phase. By establishing the correspondence between the simulated and measured interferograms, the difference in wrapped phases between them can be obtained. The difference in wrapped phase map, which has sparse and wide interference fringes, has a higher reliability of phase unwrapping. The proposed method not only possesses high phase retrieval accuracy but it also simplifies the processing of interferograms. Furthermore, the layout of all interferometric systems, the parameters of optical components, and the model of the measured object are known, so the proposed method can be used as a reference for phase retrieval.

6.
Int J Colorectal Dis ; 38(1): 45, 2023 Feb 16.
Artigo em Inglês | MEDLINE | ID: mdl-36795178

RESUMO

PURPOSE: Identifying the onset age of cancer is essential for its early intervention. The aim of this study was to characterize the features and investigate the variation tendency of first primary colorectal cancer (CRC) onset age in the USA. METHODS: For this retrospective population-based cohort analysis, data on patients diagnosed with first primary CRC (n = 330,977) between 1992 and 2017 were obtained from the Surveillance, Epidemiology, and End Results dataset. Annual percent changes (APC) and average APCs were calculated to examine the changes in average age at CRC diagnosis using the Joinpoint Regression Program. RESULTS: From 1992 to 2017, the average age at CRC diagnosis decreased from 67.0 to 61.2 years, declining by 0.22% and 0.45% annually before and after 2000. The age at diagnosis was lower in the distal than in the proximal CRC cases and the age has the downward trends in all subgroups of sex, race, and stage. Over one-fifth of CRC patients were initially diagnosed with distantly metastatic CRC, with the age lower than that in localized CRC cases (63.5 vs 64.8 years). CONCLUSIONS: The first primary CRC onset age has decreased significantly in the USA over the last 25 years and the modern lifestyle may be responsible for the decline. Specifically, the age of proximal CRC is invariably higher than that of distal CRC. Moreover, the age of advanced stage is lower than that of the early stage. Clinicians should adopt earlier screening age and more effective screening techniques for CRC.


Assuntos
Neoplasias do Colo , Neoplasias Colorretais , Humanos , Estados Unidos/epidemiologia , Pessoa de Meia-Idade , Adulto , Idade de Início , Estudos Retrospectivos , Neoplasias Colorretais/diagnóstico , Neoplasias Colorretais/epidemiologia , Neoplasias Colorretais/patologia , Estudos de Coortes , Incidência
7.
PLoS Genet ; 16(4): e1008675, 2020 04.
Artigo em Inglês | MEDLINE | ID: mdl-32271756

RESUMO

Metarhizium is a group of insect-pathogenic fungi that can produce insecticidal metabolites, such as destruxins. Interestingly, the acridid-specific fungus Metarhizium acridum (MAC) can kill locusts faster than the generalist fungus Metarhizium robertsii (MAA) even without destruxin. However, the underlying mechanisms of different pathogenesis between host-generalist and host-specialist fungi remain unknown. This study compared transcriptomes and metabolite profiles to analyze the difference in responsiveness of locusts to MAA and MAC infections. Results confirmed that the detoxification and tryptamine catabolic pathways were significantly enriched in locusts after MAC infection compared with MAA infection and that high levels of tryptamine could kill locusts. Furthermore, tryptamine was found to be capable of activating the aryl hydrocarbon receptor of locusts (LmAhR) to produce damaging effects by inducing reactive oxygen species production and immune suppression. Therefore, reducing LmAhR expression by RNAi or inhibitor (SR1) attenuates the lethal effects of tryptamine on locusts. In addition, MAA, not MAC, possessed the monoamine oxidase (Mao) genes in tryptamine catabolism. Hence, deleting MrMao-1 could increase the virulence of generalist MAA on locusts and other insects. Therefore, our study provides a rather feasible way to design novel mycoinsecticides by deleting a gene instead of introducing any exogenous gene or domain.


Assuntos
Proteínas Fúngicas/genética , Gafanhotos/metabolismo , Metarhizium/genética , Monoaminoxidase/genética , Triptaminas/metabolismo , Animais , Deleção de Genes , Gafanhotos/microbiologia , Proteínas de Insetos/metabolismo , Metarhizium/patogenicidade , Espécies Reativas de Oxigênio/metabolismo , Receptores de Hidrocarboneto Arílico/metabolismo , Virulência/genética
8.
PLoS Genet ; 16(4): e1008762, 2020 04.
Artigo em Inglês | MEDLINE | ID: mdl-32348297

RESUMO

Animals often exhibit dramatically behavioral plasticity depending on their internal physiological state, yet little is known about the underlying molecular mechanisms. The migratory locust, Locusta migratoria, provides an excellent model for addressing these questions because of their famous phase polyphenism involving remarkably behavioral plasticity between gregarious and solitarious phases. Here, we report that a major insect hormone, juvenile hormone, is involved in the regulation of this behavioral plasticity related to phase change by influencing the expression levels of olfactory-related genes in the migratory locust. We found that the treatment of juvenile hormone analog, methoprene, can significantly shift the olfactory responses of gregarious nymphs from attraction to repulsion to the volatiles released by gregarious nymphs. In contrast, the repulsion behavior of solitarious nymphs significantly decreased when they were treated with precocene or injected with double-stranded RNA of JHAMT, a juvenile hormone acid O-methyltransferase. Further, JH receptor Met or JH-response gene Kr-h1 knockdown phenocopied the JH-deprivation effects on olfactory behavior. RNA-seq analysis identified 122 differentially expressed genes in antennae after methoprene application on gregarious nymphs. Interestingly, several olfactory-related genes were especially enriched, including takeout (TO) and chemosensory protein (CSP) which have key roles in behavioral phase change of locusts. Furthermore, methoprene application and Met or Kr-h1 knockdown resulted in simultaneous changes of both TO1 and CSP3 expression to reverse pattern, which mediated the transition between repulsion and attraction responses to gregarious volatiles. Our results suggest the regulatory roles of a pleiotropic hormone in locust behavioral plasticity through modulating gene expression in the peripheral olfactory system.


Assuntos
Antenas de Artrópodes/metabolismo , Comportamento Animal/efeitos dos fármacos , Hormônios Juvenis/farmacologia , Comportamento Social , Transcriptoma/efeitos dos fármacos , Animais , Antenas de Artrópodes/efeitos dos fármacos , Genes de Insetos , Gafanhotos , Proteínas de Insetos/genética , Proteínas de Insetos/metabolismo , Metoprene/farmacologia , Metiltransferases/genética , Metiltransferases/metabolismo
9.
Sensors (Basel) ; 22(4)2022 Feb 15.
Artigo em Inglês | MEDLINE | ID: mdl-35214411

RESUMO

The research objective of this paper is to propose a new type of ERSD to solve the problem of the uncontrollable velocity of the claw in the current RSD. Firstly, the working characteristics of the RSD in ASIST are analyzed, and the design scheme of the transmission system of the ERSD is provided. The control system is designed by combining the vector control algorithm with the fuzzy adaptive PID control algorithm. On this basis, the trajectory planning of claw capture velocity is completed. Finally, the dynamics model of the transmission system of the ERSD is built by power bond graph theory, and the system simulation is carried out. The results show that the maximum capture time, velocity, and force were reduced by 47%, 53%, and 80%. In addition, when the ERSD is towing the helicopter, the mechanical claw can still provide good velocity tracking performance under a maximum interference load of 34,000 N.

10.
Alzheimers Dement ; 18(6): 1085-1099, 2022 06.
Artigo em Inglês | MEDLINE | ID: mdl-34569690

RESUMO

Speech comprehension in noisy environments depends on central auditory functions, which are vulnerable in Alzheimer's disease (AD). Binaural processing exploits two ear sounds to optimally process degraded sound information; its characteristics are poorly understood in AD. We studied behavioral and electrophysiological alterations in binaural processing among 121 participants (AD = 27; amnestic mild cognitive impairment [aMCI] = 33; subjective cognitive decline [SCD] = 30; cognitively normal [CN] = 31). We observed impairment of binaural processing in AD and aMCI, and detected a U-shaped curve change in phase synchrony (declining from CN to SCD and to aMCI, but increasing from aMCI to AD). This improvement in phase synchrony accompanying more severe cognitive stages could reflect neural adaptation for binaural processing. Moreover, increased phase synchrony is associated with worse memory during the stages when neural adaptation apparently occurs. These findings support a hypothesis that neural adaptation for binaural processing deficit may exacerbate cognitive impairment, which could help identify biomarkers and therapeutic targets in AD.


Assuntos
Doença de Alzheimer , Disfunção Cognitiva , Doença de Alzheimer/psicologia , Biomarcadores , Disfunção Cognitiva/psicologia , Humanos , Transtornos da Memória , Testes Neuropsicológicos
11.
BMC Genomics ; 22(1): 853, 2021 Nov 25.
Artigo em Inglês | MEDLINE | ID: mdl-34819032

RESUMO

BACKGROUND: Alternative splicing is the process of selecting different combinations of splice sites to produce variably spliced mRNAs. However, the relationships between alternative splicing prevalence and level (ASP/L) and variations of intron size and organism complexity (OC) remain vague. Here, we developed a robust protocol to analyze the relationships between ASP/L and variations of intron size and OC. Approximately 8 Tb raw RNA-Seq data from 37 eumetazoan species were divided into three sets of species based on variations in intron size and OC. RESULTS: We found a strong positive correlation between ASP/L and OC, but no correlation between ASP/L and intron size across species. Surprisingly, ASP/L displayed a positive correlation with mean intron size of genes within individual genomes. Moreover, our results revealed that four ASP/L-related pathways contributed to the differences in ASP/L that were associated with OC. In particular, the spliceosome pathway displayed distinct genomic features, such as the highest gene expression level, conservation level, and fraction of disordered regions. Interestingly, lower or no obvious correlations were observed among these genomic features. CONCLUSIONS: The positive correlation between ASP/L and OC ubiquitously exists in eukaryotes, and this correlation is not affected by the mean intron size of these species. ASP/L-related splicing factors may play an important role in the evolution of OC.


Assuntos
Processamento Alternativo , Eucariotos , Eucariotos/genética , Genoma , Íntrons/genética , Splicing de RNA , RNA Mensageiro/metabolismo
12.
BMC Genomics ; 22(1): 257, 2021 Apr 10.
Artigo em Inglês | MEDLINE | ID: mdl-33838645

RESUMO

BACKGROUND: Non-Drosophila insects provide diverse aging types and important complementary systems for studies of aging biology. However, little attention has been paid to the special roles of non-Drosophila insects in aging research. Here, the aging-related features of the migratory locust, Locusta migratoria, were determined at the physiological, cellular, and transcriptional levels. RESULTS: In physiological assessments, the flight performance and sperm state of locusts displayed clear aging-related decline in male adults. Transcriptional analyses demonstrated locusts have similar aging-related genes with model species. However, different from those of Drosophila and mammals, the organ-specific aging transcriptional features of locusts were characterized by intensive expression changes in flight muscle and fat body and little transcriptional changes in brain. The predominant transcriptional characteristics of flight muscle and fat body aging were changes in expression of mitochondrion-related genes and detoxification and phagocytosis genes, respectively. Cellular assessments revealed the incidence of mitochondrial abnormalities significantly increased in aged flight muscle, and apoptotic signals and nuclear abnormalities were enhanced in aged fat body but not in brain. In addition, some well-known aging genes and locust aging-related genes (i.e., IAP1, PGRP-SA, and LIPT1), whose roles in aging regulation were rarely reported, were demonstrated to affect lifespan, metabolism, and flight ability of locusts after RNAi. CONCLUSION: This study revealed multi-level aging signatures of locust, thus laying a foundation for further investigation of aging mechanisms in this famous insect in the future.


Assuntos
Locusta migratoria , Envelhecimento/genética , Animais , Locusta migratoria/genética , Masculino
13.
Cancer Cell Int ; 21(1): 540, 2021 Oct 18.
Artigo em Inglês | MEDLINE | ID: mdl-34663328

RESUMO

BACKGROUND: As the survival rates of cancer patients continue to increase, most cancer patients now die of non-cancer causes. Several studies have been showing elevated suicide rates among patients with cancer. However, no large-scale study has thoroughly assessed the risk of suicide among adolescent and young adult (AYA) patients with cancer. This study was conducted to characterize suicide mortality among AYA patients in the US and identify risk factors associated with a higher risk of suicide. METHODS: Patients aged 15-39 years were residents of the US served by the Surveillance, Epidemiology, and End Results (SEER) program, who were diagnosed with cancers from 1973 to 2015. RESULTS: We report that 981 of the 572,500 AYA patients with cancer committed suicide, for an age-, sex-, and race-adjusted suicide rate of 17.68/100,000 person-years. The rate of suicide was 14.33/100,000 person-years in the corresponding general population, giving a standardized mortality ratio (SMR) of 1.234 [95% confidence interval (CI) 1.159-1.313]. Higher suicide rates were associated with male sex, white race, unmarried state, distant tumor stage, and single primary tumor. AYA patients with otorhinolaryngologic, gonad, stomach, soft tissue, and nasopharyngeal cancer were at the greatest risk of suicide compared with those with other types of cancer. In older patients (≥ 40 years), the risk was highest in those with lung, stomach, oral cavity and pharynx, larynx, and bone malignancies. SMRs were highest in the first 5 years after diagnosis for most types of cancer. CONCLUSION: AYA patients with cancer in the US have over 20% higher the incidence of suicide of the general population, and most suicides occurred in the first 5 years following diagnosis. Suicide rates vary among patients with cancers of different anatomic sites. Further examination of the psychological experience of these young patients with cancer, particularly that of those with certain types of cancer, is warranted.

14.
BMC Cancer ; 21(1): 963, 2021 Aug 27.
Artigo em Inglês | MEDLINE | ID: mdl-34452598

RESUMO

BACKGROUND: Receiving a cancer diagnosis may trigger immediate fatal non-cancer health outcomes in addition to dying of cancer itself. We aim to investigate the full pattern of non-cancer deaths in patients within a year of a cancer diagnosis. METHODS: Patients diagnosed with cancer between 1990 and 2016 were identified from the SEER program. Standardized mortality ratios (SMRs) were calculated to characterize the relative risks of non-cancer deaths compared with the general population. RESULTS: Among 7,366,229 patients, 241,575 non-cancer deaths (15.9%) were recorded in the first year following a cancer diagnosis. The relative risk of non-cancer deaths was 2.34-fold (95% confidence interval (CI): 2.33-2.35) that of the general population. The majority of non-cancer deaths were caused by cardiovascular diseases (21.8%), followed by infectious diseases (7.2%). Significant elevations in mortality risks were observed for nearly all non-cancer causes, particularly in infectious diseases (SMR: 5.08; 95% CI: 5.03-5.13). Patients with liver cancer (SMR: 12.29; 95% CI: 12.06-12.53) were at the highest risk of early non-cancer deaths. The risks of non-cancer deaths were highest within the first month after diagnosis, and decreased rapidly thereafter. CONCLUSIONS: Risks of non-cancer deaths vary by the types of causes and anatomic sites of cancer. Our data underscore the importance of close observation and early multidisciplinary care for noncancer conditions in patients who have recently received a cancer diagnosis.


Assuntos
Doenças Cardiovasculares/mortalidade , Causas de Morte , Doenças Transmissíveis/mortalidade , Neoplasias/diagnóstico , Neoplasias/mortalidade , Programa de SEER/estatística & dados numéricos , Adolescente , Adulto , Idoso , Idoso de 80 Anos ou mais , Criança , Pré-Escolar , Feminino , Seguimentos , Humanos , Lactente , Recém-Nascido , Masculino , Pessoa de Meia-Idade , Prognóstico , Estudos Retrospectivos , Fatores de Risco , Taxa de Sobrevida , Fatores de Tempo , Adulto Jovem
15.
Nanotechnology ; 32(48)2021 Sep 06.
Artigo em Inglês | MEDLINE | ID: mdl-34359060

RESUMO

A new nanomaterial or nano-filler in the form of multiwalled carbon nanotube-zinc oxide (MWCNT-ZnO) was synthesized for the purpose of modifying poly(butylene adipate-co-terephthalate) (PBAT) and its derivative (modified PBAT or MPBAT) through a melt-blending method (MPBAT was obtained by introducing maleic anhydride groups into PBAT). The effect of the new nano-filler on the properties of resultant nanocomposites was determined from the characterization of mechanical properties, morphology, crystallinity, thermal stability, barrier properties, hydrophilicity, conductivity, antibacterial property, and biodegradability. The results showed that MPBAT nanocomposites had stronger mechanical properties, better barrier properties, and higher electrical conductivity than PBAT nanocomposites. Scanning electron microscopy illustrated that MWCNT-ZnO had better compatibility with MPBAT than with PBAT. At 0.2% MWCNT-ZnO, the MPBAT/MWCNT-ZnO nanocomposite film exhibited the greatest mechanical properties (17.74% increase in tensile strength, 22.17% in yield strength, and 14.29% in elongation at break). When the MWCNT-ZnO content was 0.4%, the nanocomposite film demonstrated the best water vapor barrier ability (an increase of 30.4%). The MPBAT/MWCNT-ZnO film with 0.6% MWCNT-ZnO turned out to have the best oxygen barrier performance (an increase of 130% relative to pure PBAT). It was shown from the results of antibacterial evaluation that the new nanomaterial could impart PBAT and MPBAT with antibacterial activity. The biodegradability tests indicated that an MWCNT-ZnO content of 0.2% could slightly reduce the biodegradability, and when the content was higher than 0.2%, the weight loss rate would increase.

16.
Am J Respir Crit Care Med ; 201(11): 1372-1379, 2020 06 01.
Artigo em Inglês | MEDLINE | ID: mdl-32242738

RESUMO

Rationale: The global death toll from coronavirus disease (COVID-19) virus as of May 12, 2020, exceeds 286,000. The risk factors for death were attributed to advanced age and comorbidities but have not been accurately defined.Objectives: To report the clinical features of 85 fatal cases of COVID-19 in two hospitals in Wuhan.Methods: Medical records were collected of 85 fatal cases of COVID-19 between January 9, 2020, and February 15, 2020. Information recorded included medical history, exposure history, comorbidities, symptoms, signs, laboratory findings, computed tomographic scans, and clinical management.Measurements and Main Results: The median age of the patients was 65.8 years, and 72.9% were male. Common symptoms were fever (78 [91.8%]), shortness of breath (50 [58.8%]), fatigue (50 [58.8%]), and dyspnea (60 [70.6%]). Hypertension, diabetes, and coronary heart disease were the most common comorbidities. Notably, 81.2% of patients had very low eosinophil counts on admission. Complications included respiratory failure (80 [94.1%]), shock (69 [81.2%]), acute respiratory distress syndrome (63 [74.1%]), and arrhythmia (51 [60%]), among others. Most patients received antibiotic (77 [90.6%]), antiviral (78 [91.8%]), and glucocorticoid (65 [76.5%]) treatments. A total of 38 (44.7%) and 33 (38.8%) patients received intravenous immunoglobulin and IFN-α2b, respectively.Conclusions: In this depictive study of 85 fatal cases of COVID-19, most cases were males aged over 50 years with noncommunicable chronic diseases. The majority of the patients died of multiple organ failure. Early onset of shortness of breath may be used as an observational symptom for COVID-19 exacerbations. Eosinophilopenia may indicate a poor prognosis. A combination of antimicrobial drugs did not offer considerable benefit to the outcome of this group of patients.


Assuntos
Infecções por Coronavirus/mortalidade , Pneumonia Viral/mortalidade , Adolescente , Adulto , Idoso , Idoso de 80 Anos ou mais , Betacoronavirus , COVID-19 , China/epidemiologia , Comorbidade , Doença das Coronárias/epidemiologia , Diabetes Mellitus/epidemiologia , Feminino , Humanos , Hipertensão/epidemiologia , Masculino , Pessoa de Meia-Idade , Insuficiência de Múltiplos Órgãos/virologia , Pandemias , Estudos Retrospectivos , SARS-CoV-2 , Tomografia Computadorizada por Raios X , Adulto Jovem
17.
Circulation ; 140(5): 390-404, 2019 07 30.
Artigo em Inglês | MEDLINE | ID: mdl-31311300

RESUMO

BACKGROUND: Modeling of human arrhythmias with induced pluripotent stem cell-derived cardiomyocytes has focused on single-cell phenotypes. However, arrhythmias are the emergent properties of cells assembled into tissues, and the impact of inherited arrhythmia mutations on tissue-level properties of human heart tissue has not been reported. METHODS: Here, we report an optogenetically based, human engineered tissue model of catecholaminergic polymorphic ventricular tachycardia (CPVT), an inherited arrhythmia caused by mutation of the cardiac ryanodine channel and triggered by exercise. We developed a human induced pluripotent stem cell-derived cardiomyocyte-based platform to study the tissue-level properties of engineered human myocardium. We investigated pathogenic mechanisms in CPVT by combining this novel platform with genome editing. RESULTS: In our model, CPVT tissues were vulnerable to developing reentrant rhythms when stimulated by rapid pacing and catecholamine, recapitulating hallmark features of the disease. These conditions elevated diastolic Ca2+ levels and increased temporal and spatial dispersion of Ca2+ wave speed, creating a vulnerable arrhythmia substrate. Using Cas9 genome editing, we pinpointed a single catecholamine-driven phosphorylation event, ryanodine receptor-serine 2814 phosphorylation by Ca2+/calmodulin-dependent protein kinase II, that is required to unmask the arrhythmic potential of CPVT tissues. CONCLUSIONS: Our study illuminates the molecular and cellular pathogenesis of CPVT and reveals a critical role of calmodulin-dependent protein kinase II-dependent reentry in the tissue-scale mechanism of this disease. We anticipate that this approach will be useful for modeling other inherited and acquired cardiac arrhythmias.


Assuntos
Células-Tronco Pluripotentes Induzidas/fisiologia , Miócitos Cardíacos/patologia , Miócitos Cardíacos/fisiologia , Taquicardia Ventricular/patologia , Taquicardia Ventricular/fisiopatologia , Engenharia Tecidual/métodos , Potenciais de Ação/fisiologia , Células Cultivadas , Humanos , Células-Tronco Pluripotentes Induzidas/química , Miócitos Cardíacos/química , Optogenética/métodos
18.
Am J Gastroenterol ; 115(5): 766-773, 2020 05.
Artigo em Inglês | MEDLINE | ID: mdl-32287140

RESUMO

OBJECTIVE: Since the outbreak of Coronavirus Disease 2019 (COVID-19) in December 2019, various digestive symptoms have been frequently reported in patients infected with the virus. In this study, we aimed to further investigate the prevalence and outcomes of COVID-19 patients with digestive symptoms. METHODS: In this descriptive, cross-sectional, multicenter study, we enrolled confirmed patients with COVID-19 who presented to 3 hospitals from January 18, 2020, to February 28, 2020. All patients were confirmed by real-time polymerase chain reaction and were analyzed for clinical characteristics, laboratory data, and treatment. Data were followed up until March 18, 2020. RESULTS: In the present study, 204 patients with COVID-19 and full laboratory, imaging, and historical data were analyzed. The average age was 52.9 years (SD ± 16), including 107 men and 97 women. Although most patients presented to the hospital with fever or respiratory symptoms, we found that 103 patients (50.5%) reported a digestive symptom, including lack of appetite (81 [78.6%] cases), diarrhea (35 [34%] cases), vomiting (4 [3.9%] cases), and abdominal pain (2 [1.9%] cases). If lack of appetite is excluded from the analysis (because it is less specific for the gastrointestinal tract), there were 38 total cases (18.6%) where patients presented with a gastrointestinal-specific symptom, including diarrhea, vomiting, or abdominal pain. Patients with digestive symptoms had a significantly longer time from onset to admission than patients without digestive symptoms (9.0 days vs 7.3 days). In 6 cases, there were digestive symptoms, but no respiratory symptoms. As the severity of the disease increased, digestive symptoms became more pronounced. Patients with digestive symptoms had higher mean liver enzyme levels, lower monocyte count, longer prothrombin time, and received more antimicrobial treatment than those without digestive symptoms. DISCUSSION: We found that digestive symptoms are common in patients with COVID-19. Moreover, these patients have a longer time from onset to admission, evidence of longer coagulation, and higher liver enzyme levels. Clinicians should recognize that digestive symptoms, such as diarrhea, are commonly among the presenting features of COVID-19 and that the index of suspicion may need to be raised earlier in at-risk patients presenting with digestive symptoms. However, further large sample studies are needed to confirm these findings.


Assuntos
Infecções por Coronavirus/diagnóstico , Infecções por Coronavirus/epidemiologia , Gastroenteropatias/epidemiologia , Pneumonia Viral/diagnóstico , Pneumonia Viral/epidemiologia , Adulto , Idoso , COVID-19 , China/epidemiologia , Infecções por Coronavirus/terapia , Estudos Transversais , Feminino , Gastroenteropatias/terapia , Gastroenteropatias/virologia , Humanos , Masculino , Pessoa de Meia-Idade , Pandemias , Pneumonia Viral/terapia , Prevalência , Resultado do Tratamento
19.
Phys Rev Lett ; 124(1): 010405, 2020 Jan 10.
Artigo em Inglês | MEDLINE | ID: mdl-31976721

RESUMO

Single-qubit measurements are typically insufficient for inferring arbitrary quantum states of a multiqubit system. We show that, if the system can be fully controlled by driving a single qubit, then utilizing a local random pulse is almost always sufficient for complete quantum-state tomography. Experimental demonstrations of this principle are presented using a nitrogen-vacancy (NV) center in diamond coupled to a nuclear spin, which is not directly accessible. We report the reconstruction of a highly entangled state between the electron and nuclear spin with fidelity above 95% by randomly driving and measuring the NV-center electron spin only. Beyond quantum-state tomography, we outline how this principle can be leveraged to characterize and control quantum processes in cases where the system model is not known.

20.
Scand J Gastroenterol ; 55(9): 1049-1056, 2020 09.
Artigo em Inglês | MEDLINE | ID: mdl-32749177

RESUMO

BACKGROUND AND AIMS: Diarrhea was not uncommon in patients with coronavirus disease 2019 (COVID-19), but the significance remains undetermined. METHODS: This retrospective study included 157 diarrhea cases form 564 hospitalized COVID-19 patients who were admitted to Wuhan Union Hospital from January 20 to February 29, 2020. Clinical characteristics, the course and the outcome of patients with diarrhea were analyzed. The correlation between diarrhea and fecal presence of coronavirus was also determined. RESULTS: The overall morbidity of diarrhea was 27.8% (157/564) in COVID-19 patients. Among them, 38 cases presented only with diarrhea, and 119 cases in both diarrhea and respiratory symptoms. Patients with diarrhea and respiratory symptoms had higher levels of inflammatory activity, longer hospital stay (27.5 vs. 23.0 vs. 22.0 days, p = .029) and higher odds ratio of mortality (3.2 times and 2.2 times, respectively) than those with diarrhea only or respiratory symptoms only. However, patients with diarrhea had longer time from onset to admission (14.5 days vs. 11.0 days, p = .04), higher positive viral RNA in stool (80.0% vs. 52.4%, p = .016) than those with both diarrhea and respiratory symptoms. CONCLUSIONS: Diarrhea caused by high enteric viral burden may lead to long course and poor outcome in COVID-19 patients. The patients with diarrhea and respiratory symptoms were prone to serious condition, and had worse outcomes. However, the patients with diarrhea alone showed mild illness but delayed health-seeking.


Assuntos
Doenças Transmissíveis Emergentes/epidemiologia , Infecções por Coronavirus/epidemiologia , Diarreia/epidemiologia , Surtos de Doenças/estatística & dados numéricos , Mortalidade Hospitalar/tendências , Pneumonia Viral/epidemiologia , Adulto , Idoso , COVID-19 , China/epidemiologia , Estudos de Coortes , Comorbidade , Diarreia/fisiopatologia , Diarreia/virologia , Feminino , Hospitalização/estatística & dados numéricos , Humanos , Incidência , Masculino , Pessoa de Meia-Idade , Pandemias , Estudos Retrospectivos , Medição de Risco , Estatísticas não Paramétricas , Análise de Sobrevida
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