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1.
Tohoku J Exp Med ; 255(2): 111-121, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34629365

RESUMO

Gastric cancer is the one of the most lethal malignancies of digestive system. Identifying molecular biomarkers is invaluable in help predicting clinical outcomes and developing targeted chemotherapies. GINS complex subunit 2 (GINS2) plays an essential role in the initiation and elongation of DNA replication. Although there have been studies revealing the prognostic significance of GINS2 in breast cancer and lung cancer, its involvement and function in gastric cancer need to be elucidated. We retrospectively enrolled a cohort of gastric adenocarcinoma patients after surgical resection (n = 123). By analyzing the mRNA and protein levels of GINS2 in tissue samples, we found that GINS2 presented a higher expression in tumor tissues than in adjacent normal stomach tissues. Besides, GINS2 level was positively correlated with tumor size and gastric adenocarcinoma tumor stage, implying its potential role as a tumor promoter. Univariate and multivariate analyses identified that patients with lower GINS2 showed a better overall survival compared to those with higher GINS2 expression. In addition, cellular and xenograft experiments confirmed the role of GINS2 in facilitating tumor proliferation both in vitro and in vivo. To our knowledge, this is the initial finding on GINS2 in promoting gastric adenocarcinoma progression. In conclusion, our study revealed a pro-oncogenic role of GINS2 in gastric cancer.

2.
J Affect Disord ; 296: 418-427, 2021 Oct 02.
Artigo em Inglês | MEDLINE | ID: mdl-34606805

RESUMO

BACKGROUND: Depression is a psychiatric disorder with a high comorbidity burden; however, previous comorbidity studies predominately focused on a few common diseases and relied on self-reported data. We aimed to investigate the comorbid status of depression concerning the entire spectrum of chronic diseases using network analysis. METHOD: Totally, 22,872 depressed inpatients and one-to-one matched controls were enrolled in the retrospective study. Hospital discharge records were aggregated to measure the comorbidities, where those with a prevalence ≥ 1% were selected for further analysis. Based on the co-occurrence frequency, sex- and age-specific comorbidity networks in depressed patients were constructed and the results were compared with the controls. Louvain algorithm was used to detect the highly interlinked communities. RESULTS: Depressed patients had 4 comorbidities on average, and 84.4% had at least one comorbidity. The comorbidity network in depression cases was more complex than controls (connections of 839 vs. 369). Intricate but distinct communities appeared within the comorbidity network in depressed patients, where the largest community included cerebrovascular diseases, chronic ischaemia heart disease, atherosclerosis and osteoporosis. Sex-specific central diseases existed, and cardiovascular diseases were the major central diseases to both gender. The older the depressed patients, the more severe the central diseases in the comorbidity network. LIMITATIONS: The causality of the observed interactions could not be determined. CONCLUSIONS: The application of network analysis on longitudinal healthcare datasets to assess comorbidity patterns can supplement the traditional clinical study approaches. The findings would improve our understanding of depression-related comorbidities and enhance the integrated management of depression.

3.
BMC Vet Res ; 17(1): 316, 2021 Sep 27.
Artigo em Inglês | MEDLINE | ID: mdl-34579716

RESUMO

BACKGROUND: Thymidine kinase 1 (TK1) catalyzes the initial phosphorylation of thymidine in the salvage pathway synthesis of dTTP, an essential building block of DNA. TK1 is a cytosolic enzyme with its highest level during the S-phase of the cell cycle. In cancer cells TK1 is upregulated and excess TK1 is leaked into the blood. Therefore, serum TK1 has been used as biomarker for cancer diagnosis and prognosis in human medicine. Feline TK1 shows high sequence similarity to TK1 from other species. The aim of this study was to characterize feline TK1 and evaluate if serum TK1 can be used as a diagnostic biomarker. RESULTS: Feline TK1 was cloned, expressed and affinity purified. The purified feline TK1 phosphorylated not only pyrimidine deoxyribonucleosides but also pyrimidine ribonucleosides and to some extent purine deoxynucleosides. A number of anticancer and antiviral nucleoside analogs also served as substrates with fairly high efficiency. ATP and dATP were the preferred phosphate donor. Serum TK1 activity in felines with malignant diseases was significantly higher than that in healthy individuals. ROC analysis revealed an area under the curve (AUC) of 0.98 with a sensitivity of 0.83 and a specificity of 0.95 for felines with lymphoma. Serum TK1 activity in felines with IBD or inflammatory disease was within the same range as healthy ones. Furthermore, in felines with lymphoma serum TK1 activity returned to normal levels in response to treatment. CONCLUSION: Feline TK1 has high specific activity and a broader substrate specificity in comparison with TK1 from other species. Serum TK1 activity in felines with malignant diseases is significantly higher than that in normal felines and in felines with inflammatory diseases. These results suggest that serum TK1 may be a promising biomarker for the diagnosis and monitoring of malignant diseases and for the differential diagnosis of certain inflammatory disease.

4.
J Colloid Interface Sci ; 607(Pt 1): 281-289, 2021 Aug 27.
Artigo em Inglês | MEDLINE | ID: mdl-34507000

RESUMO

Exploring innovation strategies has huge potential to significantly improving both activity and stability of current catalysts. Here, a chainmail design is proposed to enable the electronic interaction of ultrathin nitrogen-doped carbon shell with Ni2P nanorod core arrayed on nickel foam (Ni2P@NC/NF) for simultaneously promoting the activity and stability in both alkaline and neutral hydrogen evolution reaction (HER). The easy penetration of valence electrons from active Ni2P core to NC shell enables the obvious improvement of HER performance compared to pure Ni2P. In 1 M KOH and 1 M PBS solution, the resultant Ni2P@NC/NF requires the ultralow overpotentials of only 93 and 96 mV to drive the current density of 10 mA cm-2 with the Faradaic efficiency of 96% and 94%, respectively. Remarkably, such a chainmail design also reveals an obviously improved stability with almost negligible performance degradation under the current density of 20 mA cm-2 for 30 h. Theoretical calculations confirm that the nitrogen-doped carbon shell improves the durability of transition metal phosphides by increasing the dissolution resistance of Ni atoms. The proposed concept may create a new pathway for synchronizing high activity and robust stability in manipulating heterogeneous catalytic properties.

5.
Reprod Biol ; 21(3): 100542, 2021 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-34388417

RESUMO

ADAMTSs (A disintegrin and metalloproteinase with thrombospondin motifs) are a family of 19 secreted zinc metalloproteinases that play a major role in the assembly and degradation of the extracellular matrix (ECM) during development, morphogenesis, tissue repair, and remodeling. ADAMTS18 is a poorly characterized member of the ADAMTS family. Previously, ADAMTS18 was found to participate in the development of female reproductive tract in mice. However, whether ADAMTS18 also plays a role in the development of male reproductive system remains unclear. In this study, Adamts18 mRNA was found to be highly expressed in the basal cells of the developing preputial gland. Male Adamts18 knockout (Adamts18-/-) mice exhibit abnormal preputial gland morphogenesis, including reduced size and sharp outline. Histological analyses of preputial gland from 2-week-old male Adamts18-/- mice showed significant atrophy of the whole gland. Preputial glands from 7 months and older Adamts18-/- mice appeared macroscopic swelling on their surface. Histologically, preputial gland swelling is characterized by tissue fibrosis and thicker keratinized squamous cell layer. Preputial gland lesions in age-matched male Adamts18+/+ mice were barely detected. ADAMTS18 deficiency does not lead to significant changes in morphogenesis of prostate and testis in male mice. These results indicate that ADAMTS18 is required for normal morphogenesis and homeostasis of the preputial gland in male mice.

6.
Environ Res ; 204(Pt A): 111928, 2021 Aug 23.
Artigo em Inglês | MEDLINE | ID: mdl-34437848

RESUMO

The short-term morbidity effects of gaseous air pollutants on mental disorders (MDs), and the corresponding morbidity and economic burdens have not been well studied. We aimed to explore the associations of ambient sulfur dioxide (SO2), nitrogen dioxide (NO2), ozone (O3) and carbon monoxide (CO) with MDs hospitalizations in 17 Chinese cities during 2015-2018, and estimate the attributable risk and economic costs of MDs hospitalizations associated with gaseous pollutants. City-specific relationships between gaseous pollutants and MDs hospitalizations were evaluated using over-dispersed generalized additive models, then combined to obtain the pooled effect. Concentration-response (C-R) curves of gaseous pollutants with MDs from each city were pooled to allow regional estimates to be derived. The morbidity and economic burdens of MDs hospitalizations attributable to gaseous pollutants were further assessed. A total of 171,939 MDs hospitalizations were included. We observed insignificant association of O3 with MDs. An interquartile range increase in SO2 at lag0 (9.1 µg/m³), NO2 at lag0 (16.7 µg/m³) and CO at lag2 (0.4 mg/m³) corresponded to a 3.02% (95%CI: 0.72%, 5.38%), 5.03% (95%CI: 1.84%, 8.32%) and 2.18% (95%CI: 0.40%, 4.00%) increase in daily MDs hospitalizations, respectively. These effects were modified by sex, season and cause-specific MDs. The C-R curves of SO2 and NO2 with MDs indicated nonlinearity and the slops were steeper at lower concentrations. Overall, using current standards as reference concentrations, 0.27% (95%CI: 0.07%, 0.48%) and 0.06% (95%CI: 0.02%, 0.10%) of MDs hospitalizations could be attributable to extra SO2 and NO2 exposures, and the corresponding economic costs accounted for 0.34% (95%CI: 0.08%, 0.60%) and 0.07% (95%CI: 0.03%, 0.11%) of hospitalization expenses, respectively. Moreover, using threshold values detected from C-R curves as reference concentrations, the above mentioned morbidity and economic burdens increased a lot. These findings suggest more strict emission control regulations are needed to protect mental health from gaseous pollutants.

7.
J Nanosci Nanotechnol ; 21(12): 6007-6015, 2021 12 01.
Artigo em Inglês | MEDLINE | ID: mdl-34229798

RESUMO

Occupational exposure to indium oxide and indium containing particles has been associated with the development of severe lung diseases called "indium lung." According to the survey of occupational hygiene, indium oxide nanoparticles have been identified in the workplaces and the lungs of workers. To date, the potential mechanism of the pneumotoxicity has been poorly understood and no effective therapies are available against "indium lung." Our present study reported that the exposure of indium oxide nanoparticles damaged lung epithelial cells and alveolar macrophages and induced pulmonary alveolar proteinosis and inflammation in rats. In the 8-week post-exposure period, the indium oxide nanoparticles still mostly accumulated in the lungs and then persistently release indium ions in two months after exposure. In vitro, the epithelial cells show the greater potential for release of indium ions from indium oxide nanoparticles compared with the macrophages. EDTA-2Na, a metal chelating agent expected to remove the indium ions, was found to significantly reduced the cytotoxicity of indium oxide nanoparticles. Herein, the pneumotoxicity may be attributed to the slow and incremental release of indium ions from indium oxide nanoparticles primary dissolved by epithelial cells and macrophages, at least partially. The study may provide some insights to the pathogenicity mechanisms of "indium lung" and some clues against the health hazards of occupational inhaled indium oxide nanoparticles at the workplaces.


Assuntos
Índio , Nanopartículas , Animais , Células Epiteliais , Índio/toxicidade , Íons , Pulmão , Macrófagos , Nanopartículas/toxicidade , Ratos
8.
ACS Appl Mater Interfaces ; 13(27): 32316-32331, 2021 Jul 14.
Artigo em Inglês | MEDLINE | ID: mdl-34210131

RESUMO

Pathogenic bacterial infection has become a serious medical threat to global public health. Once the skin has serious defects, bacterial invasion and the following chain reactions will be a thorny clinical conundrum, which takes a long time to heal. Although various strategies have been used to eradicate bacteria, the treatment which can simultaneously disinfect and regulate the infection-related host responses is rarely reported. Herein, inspired by the host microenvironment, a photoenhanced dual-functional nanomedicine is constructed (Hemin@Phmg-TA-MSN) for localized bacterial ablation and host microenvironment modulation. The "NIR-triggered local microthermal therapy" and positively charged surface endow the nanomedicine with excellent bacterial capture and killing activities. Meanwhile, the nanomedicine exhibits broad-spectrum reactive oxygen species (ROS) scavenging activity via the synergistic effect of hemin and tannic acid with photoenhanced electron and hydrogen transfers. Furthermore, the in vivo experiments demonstrate that the dual-functional nanomedicine not only presents robust bacterial eradication capability, but also triggers the oxidative stress and inflammatory microenvironment regulation. The work not only shows a facile and effective way for infected wound management but also provides a new horizon for designing novel and efficient anti-infection therapy shifting focus from bacteria treatment to host microenvironment modulation.


Assuntos
Microambiente Celular/efeitos dos fármacos , Interações Hospedeiro-Patógeno/efeitos dos fármacos , Raios Infravermelhos , Nanomedicina/métodos , Cicatrização/efeitos da radiação , Animais , Feminino , Camundongos
9.
Adv Sci (Weinh) ; 8(18): e2101498, 2021 09.
Artigo em Inglês | MEDLINE | ID: mdl-34272933

RESUMO

Acute kidney injury (AKI), as a common oxidative stress-related renal disease, causes high mortality in clinics annually, and many other clinical diseases, including the pandemic COVID-19, have a high potential to cause AKI, yet only rehydration, renal dialysis, and other supportive therapies are available for AKI in the clinics. Nanotechnology-mediated antioxidant therapy represents a promising therapeutic strategy for AKI treatment. However, current enzyme-mimicking nanoantioxidants show poor biocompatibility and biodegradability, as well as non-specific ROS level regulation, further potentially causing deleterious adverse effects. Herein, the authors report a novel non-enzymatic antioxidant strategy based on ultrathin Ti3 C2 -PVP nanosheets (TPNS) with excellent biocompatibility and great chemical reactivity toward multiple ROS for AKI treatment. These TPNS nanosheets exhibit enzyme/ROS-triggered biodegradability and broad-spectrum ROS scavenging ability through the readily occurring redox reaction between Ti3 C2 and various ROS, as verified by theoretical calculations. Furthermore, both in vivo and in vitro experiments demonstrate that TPNS can serve as efficient antioxidant platforms to scavenge the overexpressed ROS and subsequently suppress oxidative stress-induced inflammatory response through inhibition of NF-κB signal pathway for AKI treatment. This study highlights a new type of therapeutic agent, that is, the redox-mediated non-enzymatic antioxidant MXene nanoplatforms in treatment of AKI and other ROS-associated diseases.


Assuntos
Injúria Renal Aguda/tratamento farmacológico , Antioxidantes/farmacologia , Oxirredução/efeitos dos fármacos , Polivinil/farmacologia , Pirrolidinas/farmacologia , Titânio/farmacologia , Injúria Renal Aguda/metabolismo , Apoptose/efeitos dos fármacos , Humanos , Rim/efeitos dos fármacos , Rim/metabolismo , Estresse Oxidativo/efeitos dos fármacos , Espécies Reativas de Oxigênio/metabolismo , Transdução de Sinais/efeitos dos fármacos
10.
Hum Mutat ; 42(11): 1429-1442, 2021 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-34273908

RESUMO

Xq28 duplication syndrome (MIM# 300815) is a severe neurodevelopmental disorder in males due to MeCP2 overexpression. Most females with MECP2 duplication are asymptomatic carriers, but there are phenotypic heterogeneities. Skewed X-chromosome inactivation (XCI) can protect females from exhibiting clinical phenotypes. Herein we reported two asymptomatic females (mother and grandmother) with interstitial Xq28 duplication. AR and RP2 assays showed that both had extremely skewed XCI, the Xq28 duplicated chromosome was inactivated in the mother, but was surprisingly activated in the grandmother. Interestingly, by combining RNA sequencing and whole-exome sequencing, we confirmed that XIST only expressed in the Xq28 duplication chromosomes of the two females, indicating that the Xq28 duplication chromosomes were inactive. Meanwhile, MECP2 and most XCI genes in the duplicated X-chromosomes were not transcriptionally expressed or upregulated, precluding major clinical phenotypes in the two females, especially the grandmother. We showed that XCI status detected using RNA sequencing was more relevant for establishing the clinical phenotype of MECP2 duplication in females. It suggested that there were other factors maintaining the XCI status in addition to DNA methylation, a possible additional inhibition mechanism occurred at the transcriptional level in the unmethylated X-chromosome, counter balancing the MECP2 duplication's detrimental phenotype effects.

11.
Cell Death Dis ; 12(6): 590, 2021 06 08.
Artigo em Inglês | MEDLINE | ID: mdl-34103477

RESUMO

Prostate cancer is one of the most prevalent forms of cancer around the world. Androgen-deprivation treatment and chemotherapy are the curative approaches used to suppress prostate cancer progression. However, drug resistance is extensively and hard to overcome even though remarkable progress has been made in recent decades. Noncoding RNAs, such as miRNAs, lncRNAs, and circRNAs, are a group of cellular RNAs which participate in various cellular processes and diseases. Recently, accumulating evidence has highlighted the vital role of non-coding RNA in the development of drug resistance in prostate cancer. In this review, we summarize the important roles of these three classes of noncoding RNA in drug resistance and the potential therapeutic applications in this disease.

12.
Methods Mol Biol ; 2276: 143-151, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34060038

RESUMO

Deoxynucleoside 5'-triphosphates (dNTPs) are the molecular building blocks for DNA synthesis, and their balanced concentration in the cell is fundamental for health. dNTP imbalance can lead to genomic instability and other metabolic disturbances, resulting in devastating mitochondrial diseases.The accurate and efficient measurement of dNTPs from different biological samples and cellular compartments is vital to understand the mechanisms behind these diseases and develop and scrutinize their possible treatments. This chapter describes an update on the most recent development of the traditional radiolabeled polymerase extension method and its adaptation for the measurement of whole-cell and mitochondrial dNTP pools from cultured cells and tissue samples. The solid-phase reaction setting enables an increase in efficiency, accuracy, and measurement scale.


Assuntos
Bioensaio/métodos , Fracionamento Celular/métodos , Células/metabolismo , Desoxirribonucleotídeos/metabolismo , Mitocôndrias/metabolismo , Animais , Células Cultivadas , DNA Mitocondrial/genética , DNA Mitocondrial/metabolismo , Humanos , Camundongos , Mitocôndrias/genética
13.
Nanotechnology ; 32(34)2021 May 31.
Artigo em Inglês | MEDLINE | ID: mdl-33975285

RESUMO

Graphite possessing extraordinary frictional properties has been widely used as solid lubricants. Interesting frictional characteristics have been observed for pristine graphene layers, for defective graphene, the frictional signal shows richer behaviors such as those found in topological defective graphene and graphene step edges. Recently discovered nanoporous graphene represents a new category of defect in graphene and its impact on graphene frictional properties has not yet been explored. In this work, we perform molecular dynamics simulations on the frictional responses of nanoporous graphene layers when slid using a silicon tip. We show that the buried nanopore raises maximum friction signal amplitude while preserving the stick-slip character, the size of the nanopore plays a key role in determining the maximum frictional force. Negative friction is observed when the silicon tip scanned towards the center of the nanopore, this phenomenon originates from the asymmetrical variation of the in-plane strain and the out-of-plane deformation when indented by the silicon tip. Moreover, the layer dependent frictional character is examined for the buried graphene nanopores, showing that increasing graphene layers weakens the effect of nanopore on the frictional signal.

14.
JMIR Cancer ; 7(2): e23161, 2021 Apr 12.
Artigo em Inglês | MEDLINE | ID: mdl-33843600

RESUMO

BACKGROUND: The integration of data from disparate sources could help alleviate data insufficiency in real-world studies and compensate for the inadequacies of single data sources and short-duration, small sample size studies while improving the utility of data for research. OBJECTIVE: This study aims to describe and evaluate a process of integrating data from several complementary sources to conduct health outcomes research in patients with non-small cell lung cancer (NSCLC). The integrated data set is also used to describe patient demographics, clinical characteristics, treatment patterns, and mortality rates. METHODS: This retrospective cohort study integrated data from 4 sources: administrative claims from the HealthCore Integrated Research Database, clinical data from a Cancer Care Quality Program (CCQP), clinical data from abstracted medical records (MRs), and mortality data from the US Social Security Administration. Patients with lung cancer who initiated second-line (2L) therapy between November 01, 2015, and April 13, 2018, were identified in the claims and CCQP data. Eligible patients were 18 years or older and received atezolizumab, docetaxel, erlotinib, nivolumab, pembrolizumab, pemetrexed, or ramucirumab in the 2L setting. The main analysis cohort included patients with claims data and data from at least one additional data source (CCQP or MR). Patients without integrated data (claims only) were reported separately. Descriptive and univariate statistics were reported. RESULTS: Data integration resulted in a main analysis cohort of 2195 patients with NSCLC; 2106 patients had CCQP and 407 patients had MR data. The claims-only cohort included 931 eligible patients. For the main analysis cohort, the mean age was 62.1 (SD 9.27) years, 48.56% (1066/2195) were female, the median length of follow-up was 6.8 months, and for 37.77% (829/2195), death was observed. For the claims-only cohort, the mean age was 66.6 (SD 12.69) years, 52.1% (485/931) were female, the median length of follow-up was 8.6 months, and for 29.3% (273/931), death was observed. The most frequent 2L treatment was immunotherapy (1094/2195, 49.84%), followed by platinum-based regimens (472/2195, 21.50%) and single-agent chemotherapy (441/2195, 20.09%); mean duration of 2L therapy was 5.6 (SD 4.9, median 4) months. We describe challenges and learnings from the data integration process, and the benefits of the integrated data set, which includes a richer set of clinical and outcome data to supplement the utilization metrics available in administrative claims. CONCLUSIONS: The management of patients with NSCLC requires care from a multidisciplinary team, leading to a lack of a single aggregated data source in real-world settings. The availability of integrated clinical data from MRs, health plan claims, and other sources of clinical care may improve the ability to assess emerging treatments.

15.
NMR Biomed ; 34(6): e4497, 2021 06.
Artigo em Inglês | MEDLINE | ID: mdl-33751691

RESUMO

Magnetic resonance spectroscopy (MRS) is capable of revealing important biochemical and metabolic information of tissues noninvasively. However, the low concentrations of metabolites often lead to poor signal-to-noise ratio (SNR) and a long acquisition time. Therefore, the applications of MRS in detection and quantitative measurements of metabolites in vivo remain limited. Reducing or even eliminating noise can improve SNR sufficiently to obtain high quality spectra in addition to increasing the number of signal averaging (NSA) or the field strength, both of which are limited in clinical applications. We present a Spectral Wavelet-feature ANalysis and Classification Assisted Denoising (SWANCAD) approach to differentiate signal and noise peaks in magnetic resonance spectra based on their respective wavelet features, followed by removing the identified noise components to improve SNR. The performance of this new denoising approach was evaluated by measuring and comparing SNRs and quantified metabolite levels of low NSA spectra (e.g. NSA = 8) before and after denoising using the SWANCAD approach or by conventional spectral fitting and denoising methods, such as LCModel and wavelet threshold methods, as well as the high NSA spectra (e.g. NSA = 192) recorded in the same sampling volumes. The results demonstrated that SWANCAD offers a more effective way to detect the signals and improve SNR by removing noise from the noisy spectra collected with low NSA or in the subminute scan time (e.g. NSA = 8 or 16 s). The potential applications of SWANCAD include using low NSA to accelerate MRS acquisition while maintaining adequate spectroscopic information for detection and quantification of the metabolites of interest when a limited time is available for an MRS examination in the clinical setting.

16.
Reprod Toxicol ; 101: 28-32, 2021 04.
Artigo em Inglês | MEDLINE | ID: mdl-33610732

RESUMO

miRNAs play a critical role in the regulation of highly orchestrated gene expression profiles during spermatogenesis and early human embryonic development. However, there is much less information available on the effects of sperm-borne miRNAs on human embryonic development than on spermatogenesis. This study was designed to assess the relationship between two sperm-borne miRNAs (miR-34c and miR-149) and preimplantation embryo development in conventional in vitro fertilization treatment. A positive correlation was seen between a decreased level of miR-149 and a higher percentage of good-quality embryos on day 3 in conventional in vitro fertilization treatment (P < 0.0001), but no correlation was seen between miR-34c and a higher percentage of good-quality embryos (P = 0.1084). Receiver-operating characteristic curve analysis and logistic regression analysis showed that sperm-borne miR-149 with decreased expression was significantly associated with a high rate of good-quality embryos (area under the curve 0.781) (odds ratio: 0.078, 95 % confidence interval: 0.024-0.259, P < 0.0001). Our results demonstrate that the expression profile of miR-149 with significantly decreased expression could be used as a first indication of early embryonic development and may provide novel insight into the biological background of idiopathic infertile males.

17.
Dev Cell ; 56(4): 557-568.e6, 2021 02 22.
Artigo em Inglês | MEDLINE | ID: mdl-33400914

RESUMO

Crop productivity depends on activity of meristems that produce optimized plant architectures, including that of the maize ear. A comprehensive understanding of development requires insight into the full diversity of cell types and developmental domains and the gene networks required to specify them. Until now, these were identified primarily by morphology and insights from classical genetics, which are limited by genetic redundancy and pleiotropy. Here, we investigated the transcriptional profiles of 12,525 single cells from developing maize ears. The resulting developmental atlas provides a single-cell RNA sequencing (scRNA-seq) map of an inflorescence. We validated our results by mRNA in situ hybridization and by fluorescence-activated cell sorting (FACS) RNA-seq, and we show how these data may facilitate genetic studies by predicting genetic redundancy, integrating transcriptional networks, and identifying candidate genes associated with crop yield traits.


Assuntos
Estudos de Associação Genética , Locos de Características Quantitativas/genética , Análise de Sequência de RNA , Análise de Célula Única , Zea mays/crescimento & desenvolvimento , Zea mays/genética , Sequência de Bases , Regulação da Expressão Gênica no Desenvolvimento , Regulação da Expressão Gênica de Plantas , Redes Reguladoras de Genes , Protoplastos/metabolismo , Reprodutibilidade dos Testes , Transcriptoma/genética
18.
Bioinformatics ; 37(3): 382-387, 2021 04 20.
Artigo em Inglês | MEDLINE | ID: mdl-32777814

RESUMO

SUMMARY: With the advance of next-generation sequencing technologies and reductions in the costs of these techniques, bulked segregant analysis (BSA) has become not only a powerful tool for mapping quantitative trait loci but also a useful way to identify causal gene mutations underlying phenotypes of interest. However, due to the presence of background mutations and errors in sequencing, genotyping, and reference assembly, it is often difficult to distinguish true causal mutations from background mutations. In this study, we developed the BSAseq workflow, which includes an automated bioinformatics analysis pipeline with a probabilistic model for estimating the linked region (the region linked to the causal mutation) and an interactive Shiny web application for visualizing the results. We deeply sequenced a sorghum male-sterile parental line (ms8) to capture the majority of background mutations in our bulked F2 data. We applied the workflow to 11 bulked sorghum F2 populations and 1 rice F2 population and identified the true causal mutation in each population. The workflow is intuitive and straightforward, facilitating its adoption by users without bioinformatics analysis skills. We anticipate that the BSAseq workflow will be broadly applicable to the identification of causal mutations for many phenotypes of interest. AVAILABILITY AND IMPLEMENTATION: BSAseq is freely available on https://www.sciapps.org/page/bsa. SUPPLEMENTARY INFORMATION: Supplementary data are available at Bioinformatics online.


Assuntos
Sequenciamento de Nucleotídeos em Larga Escala , Locos de Características Quantitativas , Internet , Mutação , Sorghum/genética , Fluxo de Trabalho
19.
Int J Artif Organs ; 44(5): 302-309, 2021 May.
Artigo em Inglês | MEDLINE | ID: mdl-33016167

RESUMO

OBJECTIVES: Examine the impacts of age, diabetes, gender, and access type on vascular access (VA) associated costs among Chinese hemodialysis (HD) patients. METHODS: We retrospectively included patients whose first permanent VA was created at the West China Hospital. Clinical characteristics, maturation, intervention, utilization, and exchange of every VA, as well as VA-related infection were collected. The study period for each patient was from HD initiation to the last follow-up. VA-related costs, including those for placement and intervention procedures, were calculated according to the standards set in 2019 for Chinese tertiary hospitals. Mann-Whitney U and Chi-square tests were conducted for comparisons between groups. RESULTS: A total of 358 Chinese HD patients experienced functionally 143 arteriovenous fistula (AVF), 22 arteriovenous graft (AVG), and 439 tunneled cuffed central venous catheter (tcCVC) during a median study period of 26 (IQR 13-44) months, of which 42.5% used more than one permanent VA. The median annual VA-related cost in the groups of age >75 years and ⩽75 years, diabetes and non-diabetes, male and female, was $525 and $397 (p = 0.016), $459 and $462 (p = 0.64), $476 and $445 (p = 0.94), respectively. The median monthly costs for AVF ($18), AVG ($289), and tcCVC ($37) were significantly different. CONCLUSION: HD patients aged >75 years had significantly higher annual VA-related costs. However, the annual VA-related costs did not differ across the diabetes groups or the gender groups. AVF was the most cost-effective permanent VA type in China, partly due to the inexpensive materials used compared to AVG or tcCVC.

20.
J Ren Nutr ; 31(3): 306-312, 2021 05.
Artigo em Inglês | MEDLINE | ID: mdl-32981835

RESUMO

OBJECTIVES: The aim of this study is to compare the prognostic effects of visceral fat area (VFA) with coronary artery calcification score (CACs) in patients on maintenance hemodialysis. DESIGN AND METHODS: In the prospective study with no intervention, clinical characteristics and serum biochemical indexes at baseline for each patient were collected through the electronic medical records. Body composition assessment using bioelectrical impedance analysis, computed tomography examination with the Agatston scoring method, and echocardiographic measurements were performed at enrollment. Primary endpoints included cardiovascular events (CVEs), cardiovascular death (CVD), and all-cause death. RESULTS: A total of 97 Chinese patients aged 48 (35-62) years were enrolled from our Hemodialysis Center, of which 61.9% were male and 20.6% had diabetes. The median of VFA and CACs at baseline was 64.5 (43.5-88.7) cm2 and 0.9 (0-467.6), respectively. CVEs occurred in 20 (20.6%) patients during a median follow-up of 26.4 (13-27.7) months. The cardiovascular and all-cause mortality was 8.2% (8 patients) and 11.3% (11 patients), respectively. VFA was associated with CVEs (hazard ratio [HR] = 9.21 for VFA ≥71.3 cm2 vs. VFA <71.3 cm2, P = .017), CVD (HR = 1.11 for 1 cm2 increase, P = .035), and all-cause mortality (HR = 1.08 for 1 cm2 increase, P = .011). Also, VFA was significantly correlated with cardiac structure parameters and the development of left ventricular hypertrophy (odds ratio = 1.02 for 1 cm2 increase, P = .03). Yet, CACs were not correlated with CVEs, CVD, or all-cause mortality. CONCLUSIONS: Increased VFA can be used as an independent predictor for CVEs, CVD, and all-cause mortality. The effect VFA exerts on cardiac reconstruction might be the underlying mechanism. Further studies are warranted for the management of VFA in the hemodialysis population.

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