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1.
Genes (Basel) ; 12(5)2021 Apr 29.
Artigo em Inglês | MEDLINE | ID: mdl-33947140

RESUMO

Parkinson's disease (PD) is a neurodegenerative disease with the pathological hallmark of Lewy bodies and Lewy neurites composed of α-synuclein. The SNP rs591323 is one of the risk loci located near the FGF20 gene that has been implicated in PD. The variation of FGF20 in the 3' untranslated region was shown to increase α-synuclein expression. We examined the association of rs591323 with the risk of PD in a Taiwanese population and conducted a meta-analysis, including our study and two other studies from China, to further confirm the role of this SNP in Taiwanese/Chinese populations. A total of 586 patients with PD and 586 health controls (HCs) were included in our study. We found that the minor allele (A) and the AA + GA genotype under the dominant model are significantly less frequent in PD than in controls. The meta-analysis consisted of 1950 patients with PD and 2073 healthy controls from three studies. There was significant association between rs591323 and the risk of PD in the additive (Z = -3.96; p < 0.0001) and the dominant models (Z = -4.01; p < 0.0001). Our study results and the meta-analysis support the possible protective role of the rs591323 A allele in PD in Taiwanese/Chinese populations.

2.
J Endocrinol ; 2021 Apr 01.
Artigo em Inglês | MEDLINE | ID: mdl-33847279

RESUMO

Currently, there are no conventional treatments for stress-induced cardiomyopathy (SCM, also known as Takotsubo syndrome), and the existing therapies are not effective. The recently discovered G protein- coupled estrogen receptor (GPER) executes the rapid effects of estrogen (E2). In this study, we investigated the effects and mechanism of GPER on epinephrine (Epi)-induced cardiac stress. SCM was developed with a high dose of Epi in adult rats and human-induced pluripotent stem cells-derived cardiomyocytes(hiPSC-CMs). (1) GPER activation with agonist G1/ E2 prevented an increase in left ventricular internal diameter at end-systole, the decrease both in ejection fraction and cardiomyocyte shortening amplitude elicited by Epi. (2) G1/ E2 mitigated heart injury induced by Epi, as revealed by reduced plasma brain natriuretic peptide and lactate dehydrogenase release into culture supernatant. (3) G1/E2 prevented the raised phosphorylation and internalization of ß2-adrenergic receptors(ß2AR). (4) Blocking Gαi abolished the cardiomyocyte contractile inhibition by Epi. G1/E2 downregulated Gαi activity of cardiomyocytes and further upregulated cyclic adenosine monophosphate concentration in culture supernatant treated with Epi. (5) G1/E2 rescued decreased Ca2+ amplitude and Ca2+ channel current (ICa-L) in rat cardiomyocytes. Notably, the above effects of E2 were blocked by the GPER antagonist, G15. In hiPSC-CM (which expressed GPER, ß1AR and ß2ARs), knockdown of GPER by siRNA abolished E2 effects on increasing ICa-L and action potential duration in the stress state. In conclusion, GPER played a protective role against SCM. Mechanistically, this effect was mediated by balancing the coupling of ß2AR to the Gαs and Gαi signalling pathways.

3.
Protein Cell ; 2021 Apr 17.
Artigo em Inglês | MEDLINE | ID: mdl-33864621

RESUMO

A new coronavirus (SARS-CoV-2) has been identified as the etiologic agent for the COVID-19 outbreak. Currently, effective treatment options remain very limited for this disease; therefore, there is an urgent need to identify new anti-COVID-19 agents. In this study, we screened over 6,000 compounds that included approved drugs, drug candidates in clinical trials, and pharmacologically active compounds to identify leads that target the SARS-CoV-2 papain-like protease (PLpro). Together with main protease (Mpro), PLpro is responsible for processing the viral replicase polyprotein into functional units. Therefore, it is an attractive target for antiviral drug development. Here we discovered four compounds, YM155, cryptotanshinone, tanshinone I and GRL0617 that inhibit SARS-CoV-2 PLpro with IC50 values ranging from 1.39 to 5.63 µmol/L. These compounds also exhibit strong antiviral activities in cell-based assays. YM155, an anticancer drug candidate in clinical trials, has the most potent antiviral activity with an EC50 value of 170 nmol/L. In addition, we have determined the crystal structures of this enzyme and its complex with YM155, revealing a unique binding mode. YM155 simultaneously targets three "hot" spots on PLpro, including the substrate-binding pocket, the interferon stimulating gene product 15 (ISG15) binding site and zinc finger motif. Our results demonstrate the efficacy of this screening and repurposing strategy, which has led to the discovery of new drug leads with clinical potential for COVID-19 treatments.

4.
Syst Rev ; 10(1): 99, 2021 Apr 05.
Artigo em Inglês | MEDLINE | ID: mdl-33820557

RESUMO

BACKGROUND: The Reporting Items for Practice Guidelines in Healthcare (RIGHT) checklist was used to assess the reporting quality of 2009-2019 clinical practice guidelines (CPGs) regarding gout and hyperuricemia, aimed to improve the reporting quality of future guidelines. METHODS: We searched PubMed, the Chinese Biomedical Literature database, the Wanfang Database, and the China National Knowledge Infrastructure from January 2009 to June 2019 for guidelines regarding gout and hyperuricemia. We also searched the websites of guideline development organizations (the Guidelines International Network, the National Institute for Health and Clinical Excellence, the American College of Rheumatology, and the European League Against Rheumatism (EULAR)). Furthermore, supplementary guidelines reported in included articles were systematically searched, as well as Google Scholar. RESULTS: Seventeen guidelines were included, of which one was in Chinese and 16 were in English. The mean reporting rate of the 35 items specified was 14.9 (42.5%); only five CPGs (29.4%) had a reporting rate >50%. Of the 35 items, three were very frequently reported. The reporting proportion of the seven domains (basic information, background, evidence, recommendations, review and quality assurance, funding and declaration and management of interests, and other information) were 64.7%, 36.8%, 50.6%, 42.9%, 8.82%, 33.8%, and 31.4%, respectively. CONCLUSION: The reporting quality of the present guidelines for gout and hyperuricemia is relatively poor. We suggest that the RIGHT reporting checklist should be used by CPG developers to ensure higher reporting quality of future guidelines.

5.
Nat Prod Res ; : 1-7, 2021 Apr 26.
Artigo em Inglês | MEDLINE | ID: mdl-33899597

RESUMO

Four new phenylspirodrimanes, stachybotranes A-D (1-4), along with seven known analogues (5-11), were isolated from the extract of a wetland fungal strain Stachybotrys chartarum DTH12-9. The structures of new compounds were determined by spectroscopic analyses, X-ray crystallographic analysis, and the CD analysis of the in situ formed [Rh2(OCOCF3)4] complex. Compounds 1-3, 5-8, and 10 were evaluated for in vitro cytotoxicity against five human cancer cell lines, HL-60, SMMC-7721, A-549, MCF-7, and SW-480. Compounds 1, 2, and 7 exhibited moderate cytotoxic potency against various human cancer cell lines.

6.
Artigo em Inglês | MEDLINE | ID: mdl-33915295

RESUMO

OBJECTIVE: To delineate the activities of decorin and biglycan in the progression of post-traumatic osteoarthritis (PTOA). DESIGN: Three-month-old inducible biglycan (BgniKO) and decorin/biglycan compound (Dcn/BgniKO) knockout mice were subjected to the destabilization of the medial meniscus (DMM) surgery to induce PTOA. The OA phenotype was evaluated by assessing joint structure and sulfated glycosaminoglycan (sGAG) staining via histology, surface collagen fibril nanostructure and calcium content via scanning electron microscopy, tissue modulus via atomic force microscopy-nanoindentation, as well as subchondral bone structure and meniscus ossification via micro-computed tomography. Outcomes were compared with previous findings in the inducible decorin (DcniKO) knockout mice. RESULTS: In the DMM model, BgniKO mice developed similar degree of OA as the control (0.44 [-0.18 1.05] difference in modified Mankin score), different from the more severe OA phenotype observed in DcniKO mice (1.38 [0.91 1.85] difference). Dcn/BgniKO mice exhibited similar histological OA phenotype as DcniKO mice (1.51 [0.97 2.04] difference versus control), including aggravated loss of sGAGs, salient surface fibrillation and formation of osteophyte. Meanwhile, Dcn/BgniKO mice showed further cartilage thinning than DcniKO mice, resulting in the exposure of underlying calcified tissues and aberrantly high surface modulus. BgniKO and Dcn/BgniKO mice developed altered subchondral trabecular bone structure in both Sham and DMM groups, while DcniKO and control mice did not. CONCLUSION: In PTOA, decorin plays a more crucial role than biglycan in regulating cartilage degeneration, while biglycan is more important in regulating subchondral bone structure. The two have distinct activities and modest synergy in the pathogenesis of PTOA.

7.
Artigo em Inglês | MEDLINE | ID: mdl-33909408

RESUMO

The CRISPR/Cas9 gene-editing system has become a promising strategy for tumor therapy with its powerful oncogene-editing ability. However, the efficient delivery of sgRNA/Cas9 complex into target tumor cells remains a challenge. Herein, we report a facile strategy for the construction of an sgRNA/Cas9 complex co-assembled nanoplatform for targeted gene editing and combined tumor therapy. In our design, the TAT peptide and thiolated DNA linker functionalized gold nanorod can efficiently load the sgRNA/Cas9 complex through the hybridization between the 3' overhang of sgRNA and the DNA linker. Due to the integration of an active cell targeting group (aptamer) and nuclear targeting peptide (TAT), the multifunctional nanoplatform can elicit the targeted cellular internalization and efficient nuclear targeting transportation to realize endogenous RNase H activated gene editing of the tumor-associated gene polo-like kinase 1 (PLK1). With mild photothermal treatment, this sgRNA/Cas9 complex loaded nanoplatform achieved efficient inhibition of tumor cell proliferation. This multifunctional nanocarrier provides a new strategy for the development of combined tumor therapy.

8.
Anal Chim Acta ; 1154: 338330, 2021 Apr 15.
Artigo em Inglês | MEDLINE | ID: mdl-33736792

RESUMO

The recent outbreak of coronavirus disease 2019 (COVID-19) is highly infectious, which threatens human health and has received increasing attention. So far, there is no specific drug or vaccine for COVID-19. Therefore, it is urgent to establish a rapid and sensitive early diagnosis platform, which is of great significance for physical separation of infected persons after rapid diagnosis. Here, we propose a colorimetric/SERS/fluorescence triple-mode biosensor based on AuNPs for the fast selective detection of viral RNA in 40 min. AuNPs with average size of 17 nm were synthesized, and colorimetric, surface enhanced Raman scattering (SERS), and fluorescence signals of sensors are simultaneously detected based on their basic aggregation property and affinity energy to different bio-molecules. The sensor achieves a limit detection of femtomole level in all triple modes, which is 160 fM in absorbance mode, 259 fM in fluorescence mode, and 395 fM in SERS mode. The triple-mode signals of the sensor are verified with each other to make the experimental results more accurate, and the capacity to recognize single-base mismatch in each working mode minimizes the false negative/positive reading of SARS-CoV-2. The proposed sensing platform provides a new way for the fast, sensitive, and selective detection of COVID-19 and other diseases.


Assuntos
Técnicas Biossensoriais/métodos , Nanopartículas Metálicas/química , RNA Viral/análise , /genética , /virologia , Ouro/química , Humanos , Limite de Detecção , Tamanho da Partícula , RNA Viral/química , Análise Espectral Raman , Glicoproteína da Espícula de Coronavírus/genética
9.
Acta Pharmacol Sin ; 2021 Mar 29.
Artigo em Inglês | MEDLINE | ID: mdl-33782542

RESUMO

Checkpoint kinase 1 inhibitors (CHK1i) have shown impressive single-agent efficacy in treatment of certain tumors, as monotherapy or potentiators of chemotherapy in clinical trials, but the sensitive tumor types and downstream effectors to dictate the therapeutic responses to CHK1i remains unclear. In this study we first analyzed GDSC (Genomics of Drug Sensitivity in Cancer) and DepMap database and disclosed that hematologic malignancies (HMs) were relatively sensitive to CHK1i or CHK1 knockdown. This notion was confirmed by examining PY34, a new and potent in-house selective CHK1i, which exhibited potent anti-HM effect in vitro and in vivo, as single agent. We demonstrated that the downregulation of c-Myc and its signaling pathway was the common transcriptomic profiling response of sensitive HM cell lines to PY34, whereas overexpressing c-Myc could partially rescue the anticancer effect of PY34. Strikingly, we revealed the significant correlations between downregulation of c-Myc and cell sensitivity to PY34 in 17 HM cell lines and 39 patient-derived cell (PDC) samples. Thus, our results demonstrate that HMs are more sensitive to CHK1i than solid tumors, and c-Myc downregulation could represent the CHK1i efficacy in HMs.

10.
J Popul Res (Canberra) ; : 1-9, 2021 Mar 06.
Artigo em Inglês | MEDLINE | ID: mdl-33758578

RESUMO

Emerging at the end of 2019, COVID-19 has become a public health threat to people worldwide. Apart from deaths with a positive COVID-19 test, many others have died from causes indirectly related to COVID-19. Therefore, the COVID-19 confirmed deaths underestimate the influence of the pandemic on society; instead, the measure of 'excess deaths' is a more objective and comparable way to assess the scale of the epidemic and formulate lessons. One common practical issue in analysing the impact of COVID-19 is to determine the 'pre-COVID-19' period and the 'post-COVID-19' period. We apply a change point detection method to identify any change points using excess deaths in Belgium.

11.
Haematologica ; 2021 Mar 11.
Artigo em Inglês | MEDLINE | ID: mdl-33691379

RESUMO

Recurrent loss-of-function mutations of spliceosome gene, ZRSR2, occur in myelodysplastic syndromes (MDS). Mutation/loss of ZRSR2 in human myeloid cells primarily causes impaired splicing of the U12-type introns. To investigate further the role of this splice factor in splicing and hematopoietic development, we generated mice lacking ZRSR2. Unexpectedly, Zrsr2-deficient mice developed normal hematopoiesis with no abnormalities in myeloid differentiation evident in either young or ≥1-year old knockout mice. Repopulation ability of Zrsr2-deficient hematopoietic stem cells was also unaffected in both competitive and non-competitive reconstitution assays. Myeloid progenitors lacking ZRSR2 exhibited mis-splicing of U12-type introns, however, this phenotype was moderate compared to the ZRSR2- deficient human cells. Our investigations revealed that a closely related homolog, Zrsr1, expressed in the murine hematopoietic cells, but not human, contributes to splicing of U12-type introns. Depletion of Zrsr1 in Zrsr2 KO myeloid cells exacerbated retention of the U12-type introns, thus highlighting a collective role of ZRSR1 and ZRSR2 in murine U12-spliceosome. We also demonstrate that aberrant retention of U12-type introns of MAPK9 and MAPK14 leads to their reduced protein expression. Overall, our findings highlight that both ZRSR1 and ZRSR2 are functional components of the murine U12-spliceosome, and depletion of both proteins is required to model accurately ZRSR2-mutant MDS in mice.

12.
Artigo em Inglês | MEDLINE | ID: mdl-33704429

RESUMO

OBJECTIVE: To investigate the incidence and potential risk factors for development of fenofibrate-associated nephrotoxicity in gout patients. METHODS: 983 gout patients with fenofibrate treatment were retrospectively enrolled from the electronic record system who visited the dedicated Gout Clinic at the Affiliated Hospital of Qingdao University between September 2016 and June 2020. Fenofibrate-associated nephrotoxicity was defined as an increase in serum creatinine (SCr) ≥0.3 mg/dL within 6 months of fenofibrate initiation. The change trend of SCr and uric acid levels during treatment period were assessed by generalised additive mixed model (GAMM). Multivariate analysis was performed for risk factors affecting elevated SCr. RESULTS: 100 (10.2%) patients experienced an increase in SCr ≥0.3 mg/dL within 6 months after fenofibrate initiation. The median (quartile) change of SCr in the whole cohort was 0.11 (0.03-0.20) mg/dL, whereas it was 0.36 (0.33-0.45) mg/dL in the fenofibrate-associated nephrotoxicity group. In a multivariable regression model, chronic kidney disease (CKD) (OR, 2.39, 95% CI,1.48-3.86) and tophus (OR, 2.29, 95% CI, 1.39-3.78) were identified to be risk predictors, independent of measured covariates, of fenofibrate-associated nephrotoxicity. During the treatment period, although SCr temporarily elevated, serum urate and triglyceride concentrations decreased resulted from the interaction analysis of GAMM. Of those with fenofibrate withdrawal records, 65% of patients' SCr was reversible after an average of 49 days off the drug. CONCLUSIONS: This observational study implied that fenofibrate-associated nephrotoxicity occurs frequently in gout patients, especially in patients with tophi or CKD. The potential renal risks of fenofibrate usage in gout need additional focus.

13.
JMIR Med Inform ; 9(3): e25704, 2021 Mar 10.
Artigo em Inglês | MEDLINE | ID: mdl-33688846

RESUMO

BACKGROUND: Pressure injury (PI) is a common and preventable problem, yet it is a challenge for at least two reasons. First, the nurse shortage is a worldwide phenomenon. Second, the majority of nurses have insufficient PI-related knowledge. Machine learning (ML) technologies can contribute to lessening the burden on medical staff by improving the prognosis and diagnostic accuracy of PI. To the best of our knowledge, there is no existing systematic review that evaluates how the current ML technologies are being used in PI management. OBJECTIVE: The objective of this review was to synthesize and evaluate the literature regarding the use of ML technologies in PI management, and identify their strengths and weaknesses, as well as to identify improvement opportunities for future research and practice. METHODS: We conducted an extensive search on PubMed, EMBASE, Web of Science, Cumulative Index to Nursing and Allied Health Literature (CINAHL), Cochrane Library, China National Knowledge Infrastructure (CNKI), the Wanfang database, the VIP database, and the China Biomedical Literature Database (CBM) to identify relevant articles. Searches were performed in June 2020. Two independent investigators conducted study selection, data extraction, and quality appraisal. Risk of bias was assessed using the Prediction model Risk Of Bias ASsessment Tool (PROBAST). RESULTS: A total of 32 articles met the inclusion criteria. Twelve of those articles (38%) reported using ML technologies to develop predictive models to identify risk factors, 11 (34%) reported using them in posture detection and recognition, and 9 (28%) reported using them in image analysis for tissue classification and measurement of PI wounds. These articles presented various algorithms and measured outcomes. The overall risk of bias was judged as high. CONCLUSIONS: There is an array of emerging ML technologies being used in PI management, and their results in the laboratory show great promise. Future research should apply these technologies on a large scale with clinical data to further verify and improve their effectiveness, as well as to improve the methodological quality.

14.
Nurs Open ; 2021 Mar 30.
Artigo em Inglês | MEDLINE | ID: mdl-33784439

RESUMO

AIM: To examine the interrelationship between professional identity, clinical teaching behaviour and transition shock for new nurses in Western China. DESIGN: A cross-sectional design. METHODS: A total of 779 new nurses were recruited in Gansu province and Lanzhou city from June to July 2019. Each patient was given three questionnaires to complete, and structural equation modelling was used to identify the relationships. RESULTS: The overall mean scores for the transition shock, professional identity and clinical teaching behaviour were 92.53(SD = 22.17), 89.74(SD = 16.57) 80.12(SD = 12.38), respectively. The most important aspects identified were the Physical aspect, the Sense of Mastery and Committing to Teaching. Professional identity and clinical teaching behaviour were negatively related to transition shock, a better sense of identity coupled with supportive clinical teaching were keys to a smoother journey from new to experienced nurses.

15.
Anal Chem ; 93(11): 4697-4706, 2021 03 23.
Artigo em Inglês | MEDLINE | ID: mdl-33710854

RESUMO

Enrichment-detection integrated biosensors for exosome profiling have shown great potential in noninvasive diagnosis and point-of-care testing with the advantage of multifunctions. This Feature focuses on the enrichment-detection integrated exosome profiling biosensors emphasizing (i) the underlying working fundamentals of these sorts of biosensors, (ii) four advanced strategies developed for exosome analysis, and (iii) future outlook and present challenges of exosome profiling systems.

16.
Anal Chem ; 93(12): 5129-5136, 2021 03 30.
Artigo em Inglês | MEDLINE | ID: mdl-33720706

RESUMO

Non-invasive early diagnosis is of great significance in disease pathologic development and subsequent medical treatments, and microRNA (miRNA) detection has attracted critical attention in early cancer screening and diagnosis. High-throughput, sensitive, economic, and fast miRNA sensing platforms are necessary to realize the low-concentration miRNA detection in clinical diagnosis and biological studies. Here, we developed an attomolar-level ultrasensitive, rapid, and multiple-miRNA simultaneous detection platform enabled by nanomaterial locally assembled microfluidic biochips. This platform presents a large linear detection regime of 1 aM-10 nM, an ultralow detection limit of 0.146 aM with no amplification, a short detection time of 35 min with multiplex miRNA sensing capability, and a small sample volume consumption of 2 µL. The detection results of five miRNAs in real samples from breast cancer patients and healthy humans indicate its excellent capacity for practical applications in early cancer diagnosis. The proposed ultrasensitive, rapid, and multiple-miRNA detection microfluidic biochip platform is a universal miRNA detection approach and an important and valuable tool in early cancer screening and diagnosis as well as biological studies.

17.
Medicine (Baltimore) ; 100(10): e24072, 2021 Mar 12.
Artigo em Inglês | MEDLINE | ID: mdl-33725818

RESUMO

BACKGROUND: Blood pressure lowering treatments can help prevent cardiovascular disease. However, little is known about the possibility of home visiting programs for hypertension. This study aims to evaluate the effectiveness of home visiting programs on hypertensive patients. METHODS: We systematically reviewed the medical literature and performed a meta-analysis. Five electronic databases were systematically searched from their inception to September 2019. Two reviewers independently assessed the risk of bias of the studies included in the review using tools developed by the Cochrane Collaboration. The meta-analysis was performed using Review Manager software (version 5.3). RESULTS: Thirteen RCTs with 2674 participants were identified. The home visiting program demonstrated a greater reduction in systolic blood pressure (MD = -5.63, 95% confidence interval (CI): -8.32 to -2.94), diastolic blood pressure (MD = -4.14, 95% CI: -6.72 to -1.56) and waist circumference (MD = -2.61, 95% CI: -3.5, -1.72) during a 6 month intervention. However, there were no significant differences between the groups in terms of body mass index, weight, or blood lipids. CONCLUSION: Home visiting programs were associated with improved BP control and reduced blood pressure, which indicate that it might be an effective method for management of hypertension.


Assuntos
Assistência ao Convalescente/métodos , Visita Domiciliar , Hipertensão/terapia , Cuidados de Enfermagem/métodos , Determinação da Pressão Arterial/estatística & dados numéricos , Humanos , Hipertensão/diagnóstico , Ensaios Clínicos Controlados Aleatórios como Assunto , Resultado do Tratamento
18.
Nanomedicine (Lond) ; 16(6): 441-452, 2021 03.
Artigo em Inglês | MEDLINE | ID: mdl-33599549

RESUMO

Background: Due to the noninvasive nature of boron neutron capture therapy (BNCT), it is considered a promising cancer treatment method. Aim: To investigate whether polyvinyl alcohol/boric acid crosslinked nanoparticles (PVA/BA NPs) are an efficient delivery system for BNCT. Materials & methods: PVA/BA NPs were synthesized and cocultured with brain and oral cancers cells for BNCT. Results: PVA/BA NPs had a boron-loading capacity of 7.83 ± 1.75 w/w%. They accumulated in brain and oral cancers cells at least threefold more than in fibroblasts and macrophages. The IC50 values of the brain and oral cancers cells were at least ninefold and sixfold lower than those of fibroblasts and macrophages, respectively. Conclusion: Theoretically, PVA/BA NPs target brain and oral cancers cells and could offer improved therapeutic outcomes of BNCT.

19.
J Cardiovasc Electrophysiol ; 32(4): 1095-1102, 2021 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-33565217

RESUMO

OBJECTIVE: This study aims to develop an artificial intelligence-based method to screen patients with left ventricular ejection fraction (LVEF) of 50% or lesser using electrocardiogram (ECG) data alone. METHODS: Convolutional neural network (CNN) is a class of deep neural networks, which has been widely used in medical image recognition. We collected standard 12-lead ECG and transthoracic echocardiogram (TTE) data including the LVEF value. Then, we paired the ECG and TTE data from the same individual. For multiple ECG-TTE pairs from a single individual, only the earliest data pair was included. All the ECG-TTE pairs were randomly divided into the training, validation, or testing data set in a ratio of 9:1:1 to create or evaluate the CNN model. Finally, we assessed the screening performance by overall accuracy, sensitivity, specificity, positive predictive value, and negative predictive value. RESULTS: We retrospectively enrolled a total of 26 786 ECG-TTE pairs and randomly divided them into training (n = 21 732), validation (n = 2 530), and testing data set (n = 2 530). In the testing set, the CNN algorithm showed an overall accuracy of 73.9%, sensitivity of 69.2%, specificity of 70.5%, positive predictive value of 70.1%, and negative predictive value of 69.9%. CONCLUSION: Our results demonstrate that a well-trained CNN algorithm may be used as a low-cost and noninvasive method to identify patients with left ventricular dysfunction.

20.
PLoS Biol ; 19(2): e3001044, 2021 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-33529193

RESUMO

Evolutionarily conserved microRNAs (miRNAs) usually have high copy numbers in the genome. The redundant and specific roles of each member of a multimember miRNA gene family are poorly understood. Previous studies have shown that the miR156-SPL-miR172 axis constitutes a signaling cascade in regulating plant developmental transitions. Here, we report the feasibility and utility of CRISPR-Cas9 technology to investigate the functions of all 5 MIR172 family members in Arabidopsis. We show that an Arabidopsis plant devoid of miR172 is viable, although it displays pleiotropic morphological defects. MIR172 family members exhibit distinct expression pattern and exert functional specificity in regulating meristem size, trichome initiation, stem elongation, shoot branching, and floral competence. In particular, we find that the miR156-SPL-miR172 cascade is bifurcated into specific flowering responses by matching pairs of coexpressed SPL and MIR172 genes in different tissues. Our results thus highlight the spatiotemporal changes in gene expression that underlie evolutionary novelties of a miRNA gene family in nature. The expansion of MIR172 genes in the Arabidopsis genome provides molecular substrates for the integration of diverse floral inductive cues, which ensures that plants flower at the optimal time to maximize seed yields.

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