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1.
Ann Clin Transl Neurol ; 8(11): 2174-2183, 2021 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-34716746

RESUMO

OBJECTIVE: New subtyping classification systems of Parkinson's disease (PD) have been proposed for phenotyping patients into three different subtypes: mild motor-predominant (PD-MMP), intermediate (PD-IM) and diffuse malignant (PD-DM). The quality of life (QoL) underlying the novel PD clinical subtypes is unknown. This study aimed explore the feasibility of the classification in Chinese PD patients and to investigate the potential heterogeneous determinants of QoL among the three subtypes. METHODS: 298 PD patients were enrolled, including 129 PD-MMP patients, 121 PD-IM patients and 48 PD-DM patients. All patients completed the QoL assessment, clinical evaluations and neuropsychological tests. Univariate linear analysis and multiple stepwise regression analysis were performed to identify determinants of QoL. RESULTS: Compared to PD-MMP patients, PD-IM and PD-DM patients had more impaired QoL. The Geriatric Depression Rating Scale (GDS) score, Non-Motor Symptoms Questionnaire (NMSQ) score, Unified Parkinson's Disease Rating Scale part III (UPDRS-III) score and Epworth Sleepiness Score (ESS) were independent contributors to QoL in PD-MMP patients. The GDS score, ESS and sniffin' sticks screening 12 test score were independent contributors to QoL in PD-IM patients. The GDS score and Mini Mental State Examination score were independent contributors to QoL in PD-DM patients. INTERPRETATION: The new novel subtyping classification is feasible for Chinese PD patients. Although depression was the most crucial determinant for QoL in PD-MMP, PD-IM and PD-DM patients, the other contributors of QoL in the three subtypes were heterogeneous. These findings may prompt clinicians to target specific factors for improving QoL depending on PD subtypes.

2.
Ann Clin Transl Neurol ; 8(10): 2096-2104, 2021 10.
Artigo em Inglês | MEDLINE | ID: mdl-34595848

RESUMO

OBJECTIVE: Little is known about the disease progression of Parkinson's disease patients with subjective cognitive complaint (PD-SCC). This longitudinal cohort study aims to compare the progression of clinical features and quality of life (QoL) in PD patients with normal cognition (NC), SCC, and mild cognitive impairment (MCI). METHODS: A total of 383 PD patients were enrolled, including 189 PD-NC patients, 59 PD-SCC patients, and 135 PD-MCI patients, with 1-7 years of follow-up. Linear mixed models were applied to evaluate longitudinal changes in motor symptoms, nonmotor features (cognitive impairment, depression, and excessive daytime sleepiness), and QoL in PD. RESULTS: At baseline, PD-SCC patients had lower Beck Depression Inventory (BDI) scores and Parkinson's Disease Questionnaire-39 (PDQ-39) scores than PD-NC patients (all p < 0.05). Longitudinal analyses revealed that the PD-SCC group exhibited faster progression in terms of BDI scores (p = 0.042) and PDQ-39 scores (p = 0.035) than the PD-NC group. The PD-MCI group exhibited faster progression rates in the Epworth Sleepiness Scale scores (p = 0.001) and PDQ-39 scores (p = 0.005) than the PD-NC group. In addition, the PD-SCC group exhibited a greater reduction in attention (Trail Making Test Part A, p = 0.047) and executive function (Stroop Color-Word Test, p = 0.037) than the PD-NC group. INTERPRETATION: PD-SCC patients exhibited faster deterioration of depression and QoL than PD-NC patients, and SCC may be an indicator of initial attention and executive function decline in PD. Our findings provided a more accurate prognosis in PD-SCC patients.

3.
Front Immunol ; 12: 738697, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34659231

RESUMO

The severe respiratory consequences of the coronavirus disease 2019 (COVID-19) pandemic have prompted the urgent need for novel therapies. Cell-based therapies, primarily using mesenchymal stromal cells (MSCs), have demonstrated safety and potential efficacy in the treatment of critical illness, particularly sepsis and acute respiratory distress syndrome (ARDS). However, there are limited preclinical data for MSCs in COVID-19. Recent studies have shown that MSCs could decrease inflammation, improve lung permeability, enhance microbe and alveolar fluid clearance, and promote lung epithelial and endothelial repair. In addition, MSC-based therapy has shown promising effects in preclinical studies and phase 1 clinical trials in sepsis and ARDS. Here, we review recent advances related to MSC-based therapy in the context of sepsis and ARDS and evaluate the potential value of MSCs as a therapeutic strategy for COVID-19.


Assuntos
COVID-19/terapia , Terapia Baseada em Transplante de Células e Tecidos/métodos , Síndrome da Liberação de Citocina/terapia , Transplante de Células-Tronco Mesenquimais/métodos , Síndrome da Liberação de Citocina/patologia , Humanos , Inflamação/terapia , Células-Tronco Mesenquimais/imunologia , SARS-CoV-2 , Sepse/terapia
4.
Huan Jing Ke Xue ; 42(10): 4753-4760, 2021 Oct 08.
Artigo em Chinês | MEDLINE | ID: mdl-34581117

RESUMO

This study quantified an integron gene intI1 and 19 antibiotic resistance genes(ARGs) to identify the ARGs pollution characteristics in 11 drinking water reservoirs of central China. The results indicated that the ARGs abundance did not change significantly over time in the studied reservoir waterbodies. Tetracycline, sulfonamide, and ß-lactam ARGs were dominant. The high abundance and detection rate of two sulfonamide ARGs(sul1 and sul2) suggested that they were the predominant ARGs. No polymyxin resistance genes(mcr-1) were detected, which indicated that the antibiotic restriction policy of China has achieved positive outcomes. Compared with that in other environmental media, the ARGs abundance in the reservoir environment was low. The correlation analysis showed relevance between the water quality indicators and the ARGs, which suggested that the water quality indexes can be used as ARGs pollution indicators in the reservoir environment. The abundance and detection rate of carbapenem ARGs were low owing to their dosage restriction and high degradability. Tetracycline ARGs were closely related to the other resistance gene types, which might have been due to horizontal gene transfer. Although the overall correlation between intI1 and ARGs was modest, it might be the main reason for the spread of several individual ARGs in the reservoir environment.


Assuntos
Antibacterianos , Genes Bacterianos , Antibacterianos/análise , China , Resistência Microbiana a Medicamentos/genética , Monitoramento Ambiental , Análise Fatorial , Genes Bacterianos/genética , Estações do Ano , Abastecimento de Água
5.
Nat Metab ; 3(8): 1109-1124, 2021 08.
Artigo em Inglês | MEDLINE | ID: mdl-34385701

RESUMO

Zika virus (ZIKV) infection during pregnancy can cause microcephaly in newborns, yet the underlying mechanisms remain largely unexplored. Here, we reveal extensive and large-scale metabolic reprogramming events in ZIKV-infected mouse brains by performing a multi-omics study comprising transcriptomics, proteomics, phosphoproteomics and metabolomics approaches. Our proteomics and metabolomics analyses uncover dramatic alteration of nicotinamide adenine dinucleotide (NAD+)-related metabolic pathways, including oxidative phosphorylation, TCA cycle and tryptophan metabolism. Phosphoproteomics analysis indicates that MAPK and cyclic GMP-protein kinase G signaling may be associated with ZIKV-induced microcephaly. Notably, we demonstrate the utility of our rich multi-omics datasets with follow-up in vivo experiments, which confirm that boosting NAD+ by NAD+ or nicotinamide riboside supplementation alleviates cell death and increases cortex thickness in ZIKV-infected mouse brains. Nicotinamide riboside supplementation increases the brain and body weight as well as improves the survival in ZIKV-infected mice. Our study provides a comprehensive resource of biological data to support future investigations of ZIKV-induced microcephaly and demonstrates that metabolic alterations can be potentially exploited for developing therapeutic strategies.


Assuntos
Microcefalia/etiologia , Microcefalia/metabolismo , NAD/metabolismo , Infecção por Zika virus/complicações , Infecção por Zika virus/virologia , Zika virus/fisiologia , Animais , Encéfalo/metabolismo , Encéfalo/patologia , Encéfalo/virologia , Células Cultivadas , Cromatografia Líquida , Modelos Animais de Doenças , Suscetibilidade a Doenças , Feminino , Metabolômica , Camundongos , Microcefalia/patologia , Neurônios/metabolismo , Gravidez , Proteômica/métodos , Espectrometria de Massas em Tandem
6.
Front Med (Lausanne) ; 8: 681548, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34422856

RESUMO

Venovenous extracorporeal membrane oxygenation (VV-ECMO) may be a lifesaving rescue therapy for patients with severe coronavirus disease 2019 (COVID-19). However, little is known regarding the efficacy of prolonged ECMO (duration longer than 14 days) in patients with COVID-19. In this case report, we report the successful use of prolonged VV-ECMO (111 days) in a 61-year-old man with severe COVID-19. Given the high mortality rate of severe COVID-19, this case provided evidence for use of prolonged VV-ECMO as supportive care in patients with severe COVID-19.

7.
Langmuir ; 37(29): 8776-8788, 2021 07 27.
Artigo em Inglês | MEDLINE | ID: mdl-34266237

RESUMO

With the purpose of oil energy recovery as well as achieving efficiency of oil/water separation, hydrophobic mesh materials have attracted extensive attention. However, fabrication of the current methods is not environmentally friendly, has high energy consumption, and creates serious pollution. Inspired by lotus leaves and rose petals, a biomimetic superhydrophobic surface was fabricated prepared on a stainless steel mesh by an in situ chemical reduction method with simple operation and mild conditions. The results of SEM, XRD, and XPS demonstrated that the mesh shows a stable and uniform moss-like rough structured surface. The SSM/Ag/ODA mesh, which was modified by moss-like Ag nanoclusters and low surface energy agents, has excellent superhydrophobicity with an excellent oil/water separation efficiency that reached up to 99.8%. The silver mirror phenomenon formed by the Ag nanoclusters further confirmed that silver ions were reduced and attached to the surface of the mesh. Moreover, the mesh can maintain superhydrophobicity under harsh conditions, such as a high concentration of a salty solution, organic solvents, alkaline, acidic solution, and even long-time UV irradiation, etc. More importantly, the modified mesh has excellent physical stability, in which the water contact angle on the mesh can be maintained above 150° after harsh mechanical wear. The hydrophobic mesh showed great potential to be applied for highly efficient oil/water separation and oil energy recovery even under complex and harsh conditions.


Assuntos
Óleos , Prata , Biomimética , Interações Hidrofóbicas e Hidrofílicas , Telas Cirúrgicas
8.
Biosens Bioelectron ; 192: 113498, 2021 Nov 15.
Artigo em Inglês | MEDLINE | ID: mdl-34280652

RESUMO

DNA detection plays an important role in the rapid screening of cancers and early diagnosis of infectious diseases. Here, we developed a simple, versatile, electric field-enhanced (EFE), electrochemical CRISPR biosensor to detect DNA targets in a homogeneous solution phase. To improve the detection sensitivity, we applied a pulsed electric field to enrich nucleic acids on the electrode surface. The EFE electrochemical CRISPR biosensor takes advantage of the diffusivity difference between electrochemical oligonucleotide probes and CRISPR-cleaved probes toward a negatively charged working electrode, enabling simple and sensitive electrochemical detection of DNA without the need for complicated immobilization processing of electrochemical probes. Our developed CRISPR biosensor directly detects unamplified human papillomavirus-16 (HPV-16) DNA with a sensitivity of 1 pM. Further, the EFE electrochemical CRISPR biosensor coupled with recombinase polymerase amplification (RPA) successfully detects HPV-16 DNA in clinical samples. Thus, the EFE electrochemical CRISPR biosensor provides a simple, robust, and sensitive detection method for nucleic acid-based molecular diagnostics.


Assuntos
Técnicas Biossensoriais , Ácidos Nucleicos , Sistemas CRISPR-Cas , Repetições Palindrômicas Curtas Agrupadas e Regularmente Espaçadas , DNA/genética , Técnicas Eletroquímicas , Humanos
9.
ACS Sens ; 6(7): 2497-2522, 2021 07 23.
Artigo em Inglês | MEDLINE | ID: mdl-34143608

RESUMO

Clustered regularly interspaced short palindromic repeats, CRISPR, has recently emerged as a powerful molecular biosensing tool for nucleic acids and other biomarkers due to its unique properties such as collateral cleavage nature, room temperature reaction conditions, and high target-recognition specificity. Numerous platforms have been developed to leverage the CRISPR assay for ultrasensitive biosensing applications. However, to be considered as a new gold standard, several key challenges for CRISPR molecular biosensing must be addressed. In this paper, we briefly review the history of biosensors, followed by the current status of nucleic acid-based detection methods. We then discuss the current challenges pertaining to CRISPR-based nucleic acid detection, followed by the recent breakthroughs addressing these challenges. We focus upon future advancements required to enable rapid, simple, sensitive, specific, multiplexed, amplification-free, and shelf-stable CRISPR-based molecular biosensors.


Assuntos
Técnicas Biossensoriais , Ácidos Nucleicos , Bioensaio , Sistemas CRISPR-Cas , Repetições Palindrômicas Curtas Agrupadas e Regularmente Espaçadas , Ácidos Nucleicos/genética
10.
Sens Actuators B Chem ; 344: 130242, 2021 Oct 01.
Artigo em Inglês | MEDLINE | ID: mdl-34121812

RESUMO

Severe acute respiratory coronavirus 2 (SARS-CoV-2) pandemic has become a global public health emergency. The detection of SARS-CoV-2 and human enteric pathogens in wastewater can provide an early warning of disease outbreak. Herein, a sensitive, multiplexed, colorimetric detection (termed "SMCD") method was established for pathogen detection in wastewater samples. The SMCD method integrated on-chip nucleic acid extraction, two-stage isothermal amplification, and colorimetric detection on a 3D printed microfluidic chip. The colorimetric signal during nucleic acid amplification was recorded in real-time and analyzed by a programmed smartphone without the need for complicated equipment. By combining two-stage isothermal amplification assay into the integrated microfluidic platform, we detected SARS-CoV-2 and human enteric pathogens with sensitivities of 100 genome equivalent (GE)/mL and 500 colony-forming units (CFU)/mL, respectively, in wastewater within one hour. Additionally, we realized smart, connected, on-site detection with a reporting framework embedded in a portable detection platform, which exhibited potential for rapid spatiotemporal epidemiologic data collection regarding the environmental dynamics, transmission, and persistence of infectious diseases.

11.
Front Cell Dev Biol ; 9: 640753, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-33937237

RESUMO

The c-Jun N-terminal kinase (JNK) is highly evolutionarily conserved and plays important roles in a broad range of physiological and pathological processes. The WD40-repeat protein 62 (WDR62) is a scaffold protein that recruits different components of the JNK signaling pathway to regulate several human diseases including neurological disorders, infertility, and tumorigenesis. Recent studies revealed that WDR62 regulates the process of neural stem cell mitosis and germ cell meiosis through JNK signaling. In this review we summarize the roles of WDR62 and JNK signaling in neuronal and non-neuronal contexts and discuss how JNK-dependent signaling regulates both processes. WDR62 is involved in various human disorders via JNK signaling regulation, and may represent a promising therapeutic strategy for the treatment of related diseases.

12.
Biosens Bioelectron ; 186: 113306, 2021 May 07.
Artigo em Inglês | MEDLINE | ID: mdl-33991846

RESUMO

A simple, disposable, and integrated electronic-tube cap (E-tube cap) for DNA detection at the point-of-care was designed, fabricated, and tested. The E-tube cap contains a 3D printed electrode substrate for DNA extraction and label-free pH sensing detection. One Flinders Technology Associates (Whatman FTA) membrane was incorporated into the 3D printed electrode substrate for the isolation, concentration, and purification of DNA. The E-tube cap with captured DNA by the membrane was inserted directly into a reaction tube for loop-mediated isothermal amplification (LAMP). The isothermal amplification process was monitored in real-time by a 3D printed electrochemical electrode coated with pH-sensitive material (carbon/iridium oxide layer). The pH sensing electrode showed an excellent linear response within the pH range of 6-9 with a slope of -31.32 ± 0.5 mV/pH at room temperature. The utility of the integrated E-tube cap was demonstrated by detecting the presence of lambda DNA spiked in saliva samples with a sensitivity of 100 copies per mL sample within 30 min. Such a simple, rapid, and affordable diagnostic device is particularly suitable for point-of-care molecular diagnostics of infectious diseases.

13.
Appl Radiat Isot ; 173: 109703, 2021 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-33799002

RESUMO

This paper presents a novel monitoring method for gamma irradiation facility, which has the advantages of big view, accurate and working in event of a power outage. The state of radioactive source is monitored based on the property of electrical signal curves from photovoltaic devices when they are facing the source frame, and these electrical signals are generated by radio-voltaic and photovoltaic effects. GaAs based photovoltaic device was selected as the module to convert the rays near the radioactive source into electrical signals by the two above effects, and a Co-60 facility for irradiation processing was used as monitored object in this work. The influence of parameters such as the distance between the Co-60 frame and the photovoltaic device array, better electrical signals for forming curves on the monitoring effect were analyzed by Geant4. And the monitoring effect of the Co-60 frame in many cases was studied by Geant4 and experiment. Simulation results show that there are optimal parameters to achieve best monitoring effect, and the distribution of the Co-60 rods on the frame, the working condition and integrity of the Co-60 frame can be clearly reflected with this method. The consistency of the tendency of the electrical signal curves in verification experiment and Geant4 simulation verified the feasibility of this monitoring method. This method may provide new ideas for monitoring system designed for irradiation facility, nuclear power plants and other scenarios with rays.

14.
Sci Total Environ ; 782: 146549, 2021 Aug 15.
Artigo em Inglês | MEDLINE | ID: mdl-33839652

RESUMO

Oil spills near natural water bodies pose considerable threats to aquatic ecosystem and drinking water system. Various detection techniques have been developed to identify the oil pollution in natural waters. These techniques mainly focus on large and major oil spills involving significant changes in environmental characteristics. However, monitoring of minor oil spills (from seepage and dripping) in waters remains a bottleneck, allowing inconspicuous and persistent oil contamination. To overcome this drawback, a sediment microbial fuel cell (SMFC) sensor equipped with a vertical floating cathode is developed for on-line and in-situ monitoring of minor oil spills in natural waters. The vertical floating cathode was intended for recognizing oil on water surface. Oil on the cathode will trigger current drop. Two kinds of natural sediments were adopted in two sensors (SMFC1 from a lake and SMFC2 from an urban stream) for comparison. Both showed linear relationship between net steady-state current decrease and oil dose (30.78 and 27.29 µA/mL of sensitivity, respectively). The current change process was fitted well to a pseudo-first order kinetic equation. A one-point/two-point dynamic identification methods were derived from the kinetic equation. Therefore, the detection time was shortened from 10 h to 10/30 min. The triggered current decrease was mainly attributed to the increase in internal resistance related to charge and mass transfer. Despite the power loss after oil contamination, results implied SMFC sensor could still achieve self-sustainability. This study shows that the SMFC sensor with vertical floating cathodes is applicable to monitoring the unnoticeable minor oil pollutions in natural waters.


Assuntos
Fontes de Energia Bioelétrica , Poluição por Petróleo , Ecossistema , Eletrodos , Sedimentos Geológicos
15.
Cell Death Dis ; 12(1): 75, 2021 01 12.
Artigo em Inglês | MEDLINE | ID: mdl-33436552

RESUMO

Mutations of WD40 repeat domain 60 (WDR60) have been identified in short-rib polydactyly syndromes (SRPS I-V), a group of lethal congenital disorders characterized by short ribs, polydactyly, and a range of extraskeletal phenotypes. However, the underlying mechanism is still unclear. Here, we report that WDR60 is essential for embryonic development and plays a critical role in the multipolar-bipolar transition and migration of newborn neurons during brain development. Mechanically, we found that WDR60 was located at the microtubule-organizing center to control microtubule organization and possibly, the trafficking of cellular components. Importantly, the migration defect caused by Wdr60 knockdown could be rescued by the stable form of α-Tubulin, α-TubulinK40Q (an acetylation-mimicking mutant). These findings identified a non-cilia function of WDR60 and provided insight into its biological function, as well as the pathogenesis of WDR60 deficiency associated with SRPS.


Assuntos
Proteínas Adaptadoras de Transdução de Sinal/metabolismo , Neurogênese/genética , Neurônios/metabolismo , Síndrome de Costela Curta e Polidactilia/genética , Animais , Movimento Celular , Feminino , Humanos , Camundongos , Ratos
16.
J Biopharm Stat ; 31(1): 37-46, 2021 01 02.
Artigo em Inglês | MEDLINE | ID: mdl-32594849

RESUMO

Signal detection methods have been used extensively in post-market surveillance to identify elevated risks of adverse events. However, these statistical methods have not been widely used in detecting AE signals for medical devices. In this paper, we focused on the use of a likelihood ratio test (LRT)-based method in identifying adverse event (AE) signals associated with left ventricular assist devices (LVADs) using Medical Device Reporting (MDR) data. Among 110,927 adverse event entries identified in MDR data for LVADs, the LRT method detected 18 AE signals which included seven bleeding-related AEs such as hemolysis, thrombosis, hematuria, thrombus, blood loss, and hemorrhage. The LRT method was also applied to longitudinal data from 2007 to 2019 where a monotone alpha-spending function was used to ensure the control of type I error at each look and overall for trend analysis. Furthermore, the LRT method was compared to proportional reporting ratios (PRRs), Bayesian confidence propagation neural network (BCPNN), and simplified Bayes methods and found to be the most conservative method when examining the total number of detected signals, given its ability to control type-I error and the false discovery rate.

17.
J Biopharm Stat ; 31(1): 47-54, 2021 01 02.
Artigo em Inglês | MEDLINE | ID: mdl-32589494

RESUMO

Effective post-market safety surveillance of medical devices is critical for public health. However, many current statistical methods for safety signal detection do not control for type I error when assessing multiple device and adverse event (AE) combinations. This can result in increased false signals, underscoring the need for more robust statistical methods. Moreover, the duration of medical device use can be an important factor to consider in safety surveillance. In this study, we adapted a likelihood ratio test (LRT) based method, which was initially developed and applied to drugs, to identify safety signals for left ventricular assist devices (LVAD). Among patients with chronic, advanced left ventricular failure, we analyzed AE data for HeartWare and HeartMate II patients during a two-year period and further incorporated person-years (henceforth exposure-time). The novel modified LRT and conventional Z-test with p-values adjusted by the Benjamini-Hochberg (BH) procedure were used to explore safety signals by comparing HeartWare and HeartMate II patients in the presence of multiple adverse events. Both methods identified greater incidence of stroke among HeartWare as compared to HeartMate II patients without exposure-time (p = .025 for LRT and p = .027 for Z-test with BH) and with exposure-time (p = .002 for LRT and p = .005 for Z-test with BH). By using improved statistical methods for safety signal detection, potential safety issues can be identified and addressed in a more timely manner to enhance public safety.

18.
Front Public Health ; 8: 576528, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-33262968

RESUMO

In December 2019, human infection with a novel coronavirus, known as SARS-CoV-2, was confirmed in Wuhan, China, and spread rapidly beyond Wuhan and around the world. By 7 May 2020, a total of 84,409 patients were infected in mainland China, with 4,643 deaths, according to a Chinese Center for Disease Control and Prevention report. Recent studies reported that critically ill patients were presented with high mortality. However, the clinical experiences of patients with coronavirus disease 2019 (COVID-19) have not been described in Guangdong Province, where by 7 May 2020, 1,589 people had been confirmed as having COVID-19 but with a very low mortality of 8 death (0.5%). Here, we describe the experience of critical care response to the outbreak of SARS-CoV-2 in Guangdong Province in the following points: Early intervention by the government, Establishment of a Multidisciplinary Working Group, Prompt intensive care interventions, Adequate ICU beds and Human resource in ICU, Infection control practices.


Assuntos
COVID-19 , China/epidemiologia , Cuidados Críticos , Surtos de Doenças/prevenção & controle , Humanos , SARS-CoV-2
19.
Cell Rep ; 33(11): 108495, 2020 12 15.
Artigo em Inglês | MEDLINE | ID: mdl-33326788

RESUMO

Neurogenesis in the developing neocortex relies on extensive mitosis of radial glial cells (RGCs) in the apical surface. The nuclear migration of epithelial-like RGCs is fundamentally important for proper mitosis, but how the apical processes of RGCs are anchored to ensure the nucleokinetic behavior of RGCs remains unclear. Here we find that Talpid3, related to Joubert syndrome, is localized to the mother centriole of RGCs and is required for their apical mitosis. Genetic silencing of Talpid3 causes abnormal RGC delamination and thereby impairs their interkinetic nuclear migration in both cell-autonomous and non-autonomous manners. Further analyses reveal that Talpid3 associates with Ninein to regulate microtubule organization and maintain the integrity of adherens junctions to anchor RGCs. Moreover, genetic ablation of Talpid3 results in synchronized, ectopic mitosis of neural progenitors and dysregulated neurogenesis. Our study provides an intriguing perspective for the non-ciliogenic role of centriolar proteins in mediating cortical neurogenesis.

20.
Front Med (Lausanne) ; 7: 576457, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-33195325

RESUMO

Background: Information about critically ill patients with coronavirus disease 2019 (COVID-19) in China but outside of Wuhan is scarce. We aimed to describe the clinical features, treatment, and outcomes of patients with COVID-19 admitted to the intensive care unit (ICU) in Guangdong Province. Methods: In this multicenter, retrospective, observational study, we enrolled consecutive patients with COVID-19 who were admitted to seven ICUs in Guangdong Province. Demographic data, symptoms, laboratory findings, comorbidities, treatment, and outcomes were collected. Data were compared between patients with and without intubation. Results: A total of 45 COVID-19 patients required ICU admission in the study hospitals [mean age 56.7 ± 15.4 years, 29 males (64.4%)]. The most common symptoms at onset were fever and cough. Most patients presented with lymphopenia and elevated lactate dehydrogenase. Treatment with antiviral drugs was initiated in all patients. Thirty-six patients (80%) developed acute respiratory distress syndrome at ICU admission, and 15 (33.3%) septic shock. Twenty patients (44.4%) were intubated, and 10 (22.2%) received extracorporeal membrane oxygenation. The 60-day mortality was 4.4% (2 of 45). Conclusion: COVID-19 patients admitted to ICU were characterized by fever, lymphopenia, acute respiratory failure, and multiple organ dysfunction. The mortality of ICU patients in Guangdong Province was relatively low with a small sample size.

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