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1.
Biol Reprod ; 108(5): 709-719, 2023 05 10.
Artigo em Inglês | MEDLINE | ID: mdl-36892411

RESUMO

With the development of the embryo, the totipotent blastomere undergoes the first lineage decision to the inner cell mass (ICM) and the trophectoderm (TE). The ICM forms the fetus while the TE forms the placenta, which is one of the unique organs in mammals serving as the interface between maternal and fetal bloodstreams. Proper trophoblast lineage differentiation is crucial for correct placental and fetal development, including the TE progenitor self-renewal and its differentiation toward mononuclear cytotrophoblast, which later either develops into invasive extravillous trophoblast, remodeling the uterine vascular, or fuses into multinuclear syncytiotrophoblast, secreting pregnancy-sustaining hormone. Aberrant differentiation and gene expression of trophoblast lineage is associated with severe pregnancy disorders and fetal growth restriction. This review focuses on the early differentiation and key regulatory factors of trophoblast lineage, which have been poorly elucidated. Meanwhile, the recent development of trophoblast stem cells, trophectoderm stem cells, and blastoids derived from pluripotent stem cells bring the accessible model to investigate the profound mystery of embryo implantation and placentation and were also summarized.


Assuntos
Células-Tronco Pluripotentes , Trofoblastos , Animais , Gravidez , Feminino , Humanos , Trofoblastos/metabolismo , Placenta/metabolismo , Placentação/genética , Diferenciação Celular/genética , Expressão Gênica , Mamíferos
2.
J Environ Manage ; 325(Pt A): 116534, 2023 Jan 01.
Artigo em Inglês | MEDLINE | ID: mdl-36419282

RESUMO

Long-term continuous hourly measurements of ambient volatile organic compounds (VOCs) are scarce at the regional scale. In this study, a one-year hourly measurement campaign of VOCs was performed in Lvliang, Linfen, and Yuncheng in the heavily polluted Fenhe Plain region in China. The VOC average (±standard deviation, std) concentrations in Lvliang, Linfen, and Yuncheng were 44.4 ± 24.9, 45.7 ± 24.9, and 37.5 ± 25.0 ppbv, respectively. Compared to published data from the past two decades in China, the observed VOCs were at high concentration levels. VOCs in the Fenhe Plain cities were significantly impacted by industrial sources according to calculated emission ratios but were less affected by liquefied petroleum gas and natural gas (LPG/NG) and traffic emissions than those in megacities abroad. The emission inventories and observation data were combined for verification and identification of the key VOC species and sources controlling ozone (O3). Industrial emissions were the largest source of VOCs, accounting for 65%-79% of the total VOC emissions, while the coking industry accounted for 45.2%-66.0%. The emission inventories significantly underestimated oxygenated VOC (OVOC) emissions through the verification of VOC emission ratios. O3 control scenarios were analyzed by changing VOC/NOX reduction ratios through a photochemical box model. O3 control strategies were formulated considering local pollution control plans, emission inventories, and O3 formation regimes. The O3 reduction of reactivity-control measures was comparable with emission-control measures, ranging from 16% to 41%, which was contrary to the general perception that ozone formation potential (OFP)-based measures were more efficient for O3 reduction. Sources with high VOC emissions are accompanied by high OFP on the Fenhe Plain, indicating that the control of high-emission sources can effectively mitigate O3 pollution on this region.


Assuntos
Ozônio , Compostos Orgânicos Voláteis , Cidades , China , Poluição Ambiental
3.
Molecules ; 28(2)2023 Jan 09.
Artigo em Inglês | MEDLINE | ID: mdl-36677712

RESUMO

Background: Homocysteine (Hcy) has been found to be closely related to the occurrence of diabetes mellitus (DM) and is considered as one of the risk factors of DM. However, Hcy alone is not enough as a factor to predict DM, and our study analyzed and determined the relationship between the main metabolites involved in the Hcy metabolic pathway and DM. Methods: A total of 48 clinical samples were collected, including 18 health control samples and 30 DM samples. All standards and samples were detected by LC-QTOF-MS. Multivariate statistical analysis and k-means cluster analysis were performed to screen and confirm the metabolites significantly correlated with DM. Results: A total of 13 metabolites of the Hcy metabolic pathway were detected in the samples. The content of Hcy, cysteine, taurine, pyridoxamine, methionine, and choline were significantly increased in the DM group (p < 0.05). Hcy, choline, cystathionine, methionine, and taurine contributed significantly to the probabilistic principal component analysis (PPCA) model. The odds ratios (OR) of Hcy, cysteine, taurine, methionine, and choline were all greater than one. K-means cluster analysis showed that the Hcy, taurine, methionine, and choline were significantly correlated with the distribution of glucose values (divided into four levels: 10.5−11.7 mmol/L, 7.7−9.7 mmol/L, 6.0−6.9 mmol/L, and 5.0−5.9 mmol/L, respectively). Conclusion: Hcy, taurine, methionine, and choline can be used as risk factors for diabetes diagnosis and are expected to be used for the assessment of diabetes severity.


Assuntos
Diabetes Mellitus , Homocisteína , Humanos , Homocisteína/metabolismo , Cisteína/metabolismo , Metionina/metabolismo , Racemetionina/metabolismo , Colina , Redes e Vias Metabólicas , Taurina
4.
Angew Chem Int Ed Engl ; 62(9): e202213606, 2023 Feb 20.
Artigo em Inglês | MEDLINE | ID: mdl-36509706

RESUMO

To optimize the rapid transport of lithium ions (Li+ ) inside lithium metal batteries (LMBs), block copolymer electrolytes (BCPEs) have been fabricated in situ in LMBs via a one-step method combining reversible addition-fragmentation chain transfer (RAFT) polymerization and carboxylic acid-catalyzed ring-opening polymerization (ROP). The BCPEs balanced the Li+ coordination characteristics of the polyether- and polyester-based electrolytes to achieve a rapid Li+ migration in the SPEs. The carboxylic acid played a dual role since it both catalyzed the ROP and stabilized the interface. Furthermore, the in situ assembly of LMBs did effectively enable an efficient intercalation/de-intercalation of Li+ at the electrode/electrolyte interface. The in situ assembled Li/BCPE4/LFP exhibited high-capacity retention of 92 % after 400 cycles at 1 C. The one-step in situ fabrication of BCPEs provides a new direction for the design of polymer electrolytes.

5.
PLoS Biol ; 17(10): e3000187, 2019 10.
Artigo em Inglês | MEDLINE | ID: mdl-31596842

RESUMO

Multipotent trophoblasts undergo dynamic morphological movement and cellular differentiation after conceptus implantation to generate placenta. However, the mechanism controlling trophoblast development and differentiation during peri-implantation development in human remains elusive. In this study, we modeled human conceptus peri-implantation development from blastocyst to early postimplantation stages by using an in vitro coculture system and profiled the transcriptome of 476 individual trophoblast cells from these conceptuses. We revealed the genetic networks regulating peri-implantation trophoblast development. While determining when trophoblast differentiation happens, our bioinformatic analysis identified T-box transcription factor 3 (TBX3) as a key regulator for the differentiation of cytotrophoblast (CT) into syncytiotrophoblast (ST). The function of TBX3 in trophoblast differentiation is then validated by a loss-of-function experiment. In conclusion, our results provided a valuable resource to study the regulation of trophoblasts development and differentiation during human peri-implantation development.


Assuntos
Regulação da Expressão Gênica no Desenvolvimento , Redes Reguladoras de Genes , Modelos Biológicos , Proteínas com Domínio T/genética , Transcriptoma , Trofoblastos/metabolismo , Técnicas de Cultura de Células , Diferenciação Celular , Biologia Computacional/métodos , Implantação do Embrião/genética , Sequenciamento de Nucleotídeos em Larga Escala , Humanos , Análise de Célula Única , Proteínas com Domínio T/metabolismo , Trofoblastos/citologia , Zigoto
6.
Circ Res ; 126(12): 1706-1720, 2020 06 05.
Artigo em Inglês | MEDLINE | ID: mdl-32212953

RESUMO

RATIONALE: The stress response of heart rate, which is determined by the plasticity of the sinoatrial node (SAN), is essential for cardiac function and survival in mammals. As an RNA-binding protein, CIRP (cold-inducible RNA-binding protein) can act as a stress regulator. Previously, we have documented that CIRP regulates cardiac electrophysiology at posttranscriptional level, suggesting its role in SAN plasticity, especially upon stress conditions. OBJECTIVE: Our aim was to clarify the role of CIRP in SAN plasticity and heart rate regulation under stress conditions. METHODS AND RESULTS: Telemetric ECG monitoring demonstrated an excessive acceleration of heart rate under isoprenaline stimulation in conscious CIRP-KO (knockout) rats. Patch-clamp analysis and confocal microscopic Ca2+ imaging of isolated SAN cells demonstrated that isoprenaline stimulation induced a faster spontaneous firing rate in CIRP-KO SAN cells than that in WT (wild type) SAN cells. A higher concentration of cAMP-the key mediator of pacemaker activity-was detected in CIRP-KO SAN tissues than in WT SAN tissues. RNA sequencing and quantitative real-time polymerase chain reaction analyses of single cells revealed that the 4B and 4D subtypes of PDE (phosphodiesterase), which controls cAMP degradation, were significantly decreased in CIRP-KO SAN cells. A PDE4 inhibitor (rolipram) abolished the difference in beating rate resulting from CIRP deficiency. The mechanistic study showed that CIRP stabilized the mRNA of Pde4b and Pde4d by direct mRNA binding, thereby regulating the protein expression of PDE4B and PDE4D at posttranscriptional level. CONCLUSIONS: CIRP acts as an mRNA stabilizer of specific PDEs to control the cAMP concentration in SAN, maintaining the appropriate heart rate stress response.


Assuntos
Proteínas e Peptídeos de Choque Frio/metabolismo , Nucleotídeo Cíclico Fosfodiesterase do Tipo 4/metabolismo , Frequência Cardíaca , Miócitos Cardíacos/metabolismo , Proteínas de Ligação a RNA/metabolismo , Agonistas Adrenérgicos beta/farmacologia , Animais , Células Cultivadas , Proteínas e Peptídeos de Choque Frio/genética , AMP Cíclico/metabolismo , Nucleotídeo Cíclico Fosfodiesterase do Tipo 4/genética , Isoproterenol/farmacologia , Masculino , Miócitos Cardíacos/efeitos dos fármacos , Miócitos Cardíacos/fisiologia , Inibidores de Fosfodiesterase/farmacologia , Estabilidade de RNA , Proteínas de Ligação a RNA/genética , Ratos , Ratos Sprague-Dawley , Rolipram/farmacologia , Nó Sinoatrial/citologia , Nó Sinoatrial/metabolismo , Nó Sinoatrial/fisiologia , Estresse Fisiológico
7.
Macromol Rapid Commun ; 43(18): e2100853, 2022 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-35218088

RESUMO

Structural design is an intriguing strategy to improve the physical and electrochemical performance of polymer electrolytes (PEs) for lithium-ion batteries. However, the complex synthetic process and introduction of nonelectrolyte composition severely limit the development and practical application of PEs. Here, a facile method is reported for the fabrication of a double network polymer electrolyte (DN-PE) through combining the lithium salt-accelerated thiol-Michael addition and lithium salt-catalyzed radical polymerization. By adjusting the reaction temperature, the double network with the cross-linking structure can be in situ formed step by step at room temperature and 80 °C. Notably, using lithium salt as the accelerator and catalyst avoids the addition of extra species and the related side reactions in the electrolyte system. Compared with single network polymer electrolyte (SN-PE), DN-PE has a distinctly improved mechanical strength and a better interfacial compatibility with the electrode, which leads to a stable cycling of the symmetric Li|DN-PE|Li cell over 1000 h at a current density of 0.05 mA cm-2 . In addition, the Li|DN-PE|LiFePO4 cell shows a high discharge specific capacity of 150.3 mAh g-1 at 0.1 C and coulomb efficiency of 99%.

8.
J Biomed Inform ; 136: 104231, 2022 12.
Artigo em Inglês | MEDLINE | ID: mdl-36309196

RESUMO

CircRNAs usually bind to the corresponding RBPs(RNA Binding proteins) and play a key role in gene regulation. Therefore, it is important to identify the binding sites of RBPs on CircRNAs for the regulation of certain diseases. Due to the information provided by the single view feature is limited, the current mainstream methods are mainly to detect the RBP binding sites by constructing multi-view models. However, with the number of view features increases, the invalid information also increases, and the existing methods only simply concatenate together various features from different views, while ignoring the intrinsic connection between multi-view data. To solve this problem, we propose a new multi-view joint representation learning network by improving the consistency of multi-view feature information. First, the network uses different feature encoding methods to fully extract the feature information of RNA, respectively. Then we construct the intrinsic connection between the views by generating a global joint representation of multiple views, and this is used for feature calibration of each view to highlight important features and suppress unimportant ones. Finally, the depth features obtained from the fusion of multiple views are used to detect the binding sites of RNAs. The average AUC of our method is 93.68% in 37 CircRNA-RBP datasets. The experimental results show that the prediction performance of the method is better than existing methods. The code and datasets are obtained at https://github.com/Xuezg/JLCRB. In addition, we also provide a free web server that is freely available at http://82.157.188.204/JLCRB/.


Assuntos
RNA Circular , Proteínas de Ligação a RNA , Sítios de Ligação , Proteínas de Ligação a RNA/química , Proteínas de Ligação a RNA/genética , Proteínas de Ligação a RNA/metabolismo , RNA , Regulação da Expressão Gênica
9.
Mol Cell Neurosci ; 115: 103659, 2021 09.
Artigo em Inglês | MEDLINE | ID: mdl-34400333

RESUMO

Peripheral nerve trauma and regeneration are complex events, and little is known concerning how occurrences in the distal stump affect the cell body's response to injury. Intermediate filament (IF) proteins underpin cellular architecture and take part in nerve cell proliferation, differentiation and axon regeneration, but their role in these processes is not yet fully understood. The present study aimed to investigate the regulation and interrelationship of major neural IFs in adult dorsal root ganglion (DRG) neurons and satellite glial cells (SGCs) following sciatic nerve injury. We demonstrated that the expression of neural IFs in DRG neurons and SGCs after axotomy depends on vimentin activity. In intact DRGs, synemin M and peripherin proteins are detected in small neurons while neurofilament L (NFL) and synemin L characterize large neurons. Both neuronal populations are surrounded by vimentin positive- and glial fibrillary acidic protein (GFAP)-negative SGCs. In response to axotomy, synemin M and peripherin were upregulated in large wild-type DRG neurons and, to a lesser extent, in vim-/- and synm-/- DRG neurons, suggesting the role for these IFs in axon regeneration. However, an increase in the number of NFL-positive small neurons was observed in vim-/- mice, accompanied by a decrease of peripherin-positive small neurons. These findings suggest that vimentin is required for injury-induced neuronal IF remodeling. We further show that vimentin is also indispensable for nerve injury-induced GFAP upregulation in perineuronal SGCs and that inactivation of vimentin and synemin appears to accelerate the rate of DRG neurite regeneration at early stages in vitro.


Assuntos
Gânglios Espinais , Filamentos Intermediários , Animais , Axônios , Camundongos , Regeneração Nervosa , Neuroglia , Neurônios , Vimentina
10.
Dev Dyn ; 250(7): 974-985, 2021 07.
Artigo em Inglês | MEDLINE | ID: mdl-33449399

RESUMO

BACKGROUND: Genetic programs underlying preimplantation development and early lineage segregation are highly conserved across mammals. It has been suggested that nonhuman primates would be better model organisms for human embryogenesis, but a limited number of studies have investigated the monkey preimplantation development. In this study, we collect single cells from cynomolgus monkey preimplantation embryos for transcriptome profiling and compare with single-cell RNA-seq data derived from human and mouse embryos. RESULTS: By weighted gene-coexpression network analysis, we found that cynomolgus gene networks have greater conservation with human embryos including a greater number of conserved hub genes than that of mouse embryos. Consistently, we found that early ICM/TE lineage-segregating genes in monkeys exhibit greater similarity with human when compared to mouse, so are the genes in signaling pathways such as LRP1 and TCF7 involving in WNT pathway. Last, we tested the role of one conserved pre-EGA hub gene, SIN3A, using a morpholino knockdown of maternal RNA transcripts in monkey embryos followed by single-cell RNA-seq. We found that SIN3A knockdown disrupts the gene-silencing program during the embryonic genome activation transition and results in developmental delay of cynomolgus embryos. CONCLUSION: Taken together, our study provided new insight into evolutionarily conserved and divergent transcriptome dynamics during mammalian preimplantation development.


Assuntos
Blastômeros/metabolismo , Desenvolvimento Embrionário/genética , Macaca fascicularis/embriologia , Adulto , Animais , Blastocisto , Blastômeros/citologia , Linhagem da Célula/genética , Células Cultivadas , Embrião de Mamíferos , Desenvolvimento Embrionário/fisiologia , Feminino , Perfilação da Expressão Gênica , Regulação da Expressão Gênica no Desenvolvimento , Redes Reguladoras de Genes/fisiologia , Humanos , Macaca fascicularis/genética , Macaca mulatta , Masculino , Camundongos , Gravidez , Complexo Correpressor Histona Desacetilase e Sin3/genética , Complexo Correpressor Histona Desacetilase e Sin3/fisiologia , Análise de Célula Única/veterinária , Transcriptoma/genética
11.
Langmuir ; 37(27): 8270-8280, 2021 Jul 13.
Artigo em Inglês | MEDLINE | ID: mdl-34210143

RESUMO

Herein, composite membranes based on a single-ion conducting polymer electrolyte (SIPE) and poly(vinylidene fluoride-hexafluoropropylene) (PVDF-HFP) were prepared by an electrospinning technology. The SIPE with hydrogen bonding was obtained via reversible addition-fragmentation chain transfer (RAFT) copolymerization of 2-(3-(6-methyl-4-oxo-1,4-dihydropyrimidin-2-yl)ureido)ethyl methacrylate (UPyMA), poly(ethylene glycol) methyl ether methacrylate (PEGMA), and lithium 4-styrenesulfonyl (phenylsulfonyl) imide (SSPSILi). The obtained composite membrane exhibited a highly porous network structure, superior thermal stability (>300 °C), and high mechanical strength (17.3 MPa). The fabricated SIPE/PVDF-HFP composite membrane without lithium salts possessed a high ionic conductivity of 2.78 × 10-5 S cm-1 at 30 °C, excellent compatibility with the lithium metal electrode, and high lithium-ion transference number (0.89). The symmetric Li//Li cell exhibited a superior cycle performance without short circuit, indicating the generation of a stable interface between SIPE and the lithium metal electrode during the process of lithium plating/stripping, which could inhibit lithium dendrite growth in lithium metal batteries (LMBs). The Li//LiFePO4 cell also exhibited superior cycle life and excellent rate capability at 60 or 25 °C. In consequence, the composite membrane exhibits a considerable future prospect for advanced LMBs.

12.
Thromb J ; 19(1): 8, 2021 Feb 10.
Artigo em Inglês | MEDLINE | ID: mdl-33568153

RESUMO

BACKGROUND: The progression of coagulation in COVID-19 patients with confirmed discharge status and the combination of autopsy with complete hemostasis parameters have not been well studied. OBJECTIVE: To clarify the thrombotic phenomena and hemostasis state in COVID-19 patients based on epidemiological statistics combining autopsy and statistical analysis. METHODS: Using autopsy results from 9 patients with COVID-19 pneumonia and the medical records of 407 patients, including 39 deceased patients whose discharge status was certain, time-sequential changes in 11 relevant indices within mild, severe and critical infection throughout hospitalization according to the Chinese National Health Commission (NHC) guidelines were evaluated. Statistical tools were applied to calculate the importance of 11 indices and the correlation between those indices and the severity of COVID-19. RESULTS: At the beginning of hospitalization, platelet (PLT) counts were significantly reduced in critically ill patients compared with severely or mildly ill patients. Blood glucose (GLU), prothrombin time (PT), activated partial thromboplastin time (APTT), and D-dimer levels in critical patients were increased compared with mild and severe patients during the entire admission period. The International Society on Thrombosis and Haemostasis (ISTH) disseminated intravascular coagulation (DIC) score was also high in critical patients. In the relatively late stage of nonsurvivors, the temporal changes in PLT count, PT, and D-dimer levels were significantly different from those in survivors. A random forest model indicated that the most important feature was PT followed by D-dimer, indicating their positive associations with disease severity. Autopsy of deceased patients fulfilling diagnostic criteria for DIC revealed microthromboses in multiple organs. CONCLUSIONS: Combining autopsy data, time-sequential changes and statistical methods to explore hemostasis-relevant indices among the different severities of the disease helps guide therapy and detect prognosis in COVID-19 infection.

13.
J Hum Nutr Diet ; 34(3): 585-594, 2021 06.
Artigo em Inglês | MEDLINE | ID: mdl-33491826

RESUMO

BACKGROUND: The influence of body composition changes during neoadjuvant treatment (NT) on long-term survival in patients with gastric cancer (GC) undergoing radical gastrectomy remains unclear. The present study aimed to explore the association between changes in body composition during NT and survival in patients with GC. METHODS: GC patients treated with NT and radical gastrectomy between 2015 and 2018 were included in this retrospective study. Skeletal muscle mass, visceral adipose tissue (VAT) and subcutaneous adipose tissue (SAT) were measured by computer tomography before and after NT. Body composition changes during NT were compared with Kaplan-Meier curves. Univariate and multivariate regression analyses were applied to determine the predictors of overall survival (OS) and disease-free survival (DFS). RESULTS: In total, 157 GC patients were studied. A marked loss of adipose tissue was associated with poor nutritional status. The median follow-up time for all patients was 25 months. Patients with marked VAT loss (≥ 35.7%) during NT had significantly shorter OS (p = 0.028) and DFS (p = 0.03). Similarly, poorer OS (p = 0.033) and DFS (p = 0.003) were observed in patients with marked SAT loss (≥ 30.1%) during NT. Changes in skeletal muscle mass and body weight during NT were not associated with survival. Marked VAT loss accompanied by marked SAT loss was an independent predictor of OS (hazards ratio = 2.447; p = 0.045) and DFS (hazards ratio = 2.674; p = 0.018). CONCLUSIONS: Patients with locally advanced GC have a worse survival when they experienced marked loss of adipose tissue during NT.


Assuntos
Adenocarcinoma/terapia , Tecido Adiposo/fisiopatologia , Composição Corporal , Terapia Neoadjuvante/efeitos adversos , Neoplasias Gástricas/terapia , Idoso , China/epidemiologia , Estudos de Coortes , Feminino , Gastrectomia/efeitos adversos , Humanos , Gordura Intra-Abdominal/fisiopatologia , Masculino , Pessoa de Meia-Idade , Estado Nutricional , Prognóstico , Estudos Retrospectivos , Gordura Subcutânea/fisiopatologia , Análise de Sobrevida
14.
Chaos ; 31(3): 031104, 2021 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-33810718

RESUMO

Increasing atmospheric carbon dioxide (CO2) is expected to be the main factor of global warming. The relation between CO2 concentrations and surface air temperature (SAT) has been found related to Rossby waves based on a multi-layer complex network approach. However, the significant relations between CO2 and SAT occur in the South Hemisphere that is not that much influenced by human activities may offer not enough information to formulate targeted carbon reduction policies. Here, we address it by removing the effects of the Rossby waves to reconstruct CO2 concentrations and SAT multi-layer complex network. We uncover that the CO2 concentrations are strongly associated with the surrounding SAT regions. The influential regions of CO2 on SAT occur over eastern Asia, West Asia, North Africa, the coast of North American, and Western Europe. It is shown that CO2 over Siberia in phase with the SAT variability in eastern East Asia. Indeed, CO2 concentration variability is causing effects on the recent warming of SAT in some middle latitude regions. Furthermore, sensitive parameters that CO2 impacts SAT of top 15 carbon emissions countries have been identified. These countries are significantly responsible for global warming, giving implications for carbon emissions reductions. The methodology and results presented here not only facilitate further research in regions of increased sensitivity to the warming resulting from CO2 concentrations but also can formulate strategies and countermeasures for carbon emission and carbon reduction.

15.
Am J Physiol Cell Physiol ; 318(4): C709-C718, 2020 04 01.
Artigo em Inglês | MEDLINE | ID: mdl-32023076

RESUMO

This review analyzes data concerning patients with cardiomyopathies or skeletal myopathies associated with a variation in the intermediate filament (IF) synemin gene (SYNM), also referred to as desmuslin (DMN). Molecular studies demonstrate that synemin copolymerizes with desmin and vimentin IF and interacts with vinculin, α-actinin, α-dystrobrevin, dystrophin, talin, and zyxin. It has been found that synemin is an A-kinase-anchoring protein (AKAP) that anchors protein kinase A (PKA) and modulates the PKA-dependent phosphorylation of several cytoskeletal substrates such as desmin. Because several IF proteins, including desmin, have been implicated in human genetic disorders such as dominant or recessive congenital and adult-onset myopathy, synemin becomes a significant candidate for cardiac and skeletal myopathies of unknown etiology. Because SYNM is a new candidate gene that displays numerous sequence polymorphisms, in this review, we summarize the genetic and clinical literature about SYNM mutations. Protein-changing variants (missense, frameshifts, nonsense) were further evaluated based on structural modifications and amino acid interactions. We present in silico modeling of helical salt-bridges between residues to evaluate the impact of the synemin networks crucial to interactions with cytoskeletal proteins. Finally, a discussion is featured regarding certain variants that may contribute to the disease state.


Assuntos
Citoesqueleto/patologia , Proteínas de Filamentos Intermediários/metabolismo , Proteínas Musculares/metabolismo , Doenças Musculares/metabolismo , Animais , Citoesqueleto/metabolismo , Coração/fisiopatologia , Humanos , Filamentos Intermediários/metabolismo , Doenças Musculares/patologia
16.
FASEB J ; 33(1): 140-150, 2019 01.
Artigo em Inglês | MEDLINE | ID: mdl-29944447

RESUMO

Patient-derived xenograft (PDX) animal models allow the exogenous growth of human tumors, offering an irreplaceable preclinical tool for oncology research. Mice are the most commonly used host for human PDX models, however their small body size limits the xenograft growth, sample collection, and drug evaluation. Therefore, we sought to develop a novel rat model that could overcome many of these limitations. We knocked out Rag1, Rag2, and Il2rg in Sprague Dawley (SD) rats by clustered regularly interspaced short palindromic repeats (CRISPR)-CRISPR-associated protein 9 technology. The development of lymphoid organs is significantly impaired in Rag1-/-Rag2-/-Il2rg-/Y (designated as SD-RG) rats. Consequently, SD-RG rats are severely immunodeficient with an absence of mature T, B, and NK cells in the immune system. After subcutaneous injection of tumor cell lines of different origin, such as NCI-H460, U-87MG, and MDA-MB-231, the tumors grow significantly faster and larger in SD-RG rats than in nonobese diabetic- Cg-Prkdcscid Il2rgtm1Wjl/SzJ mice. Most important of all, we successfully established a PDX model of lung squamous cell carcinoma in which the grafts recapitulate the histopathologic features of the primary tumor for several passages. In conclusion, the severely immunodeficient SD-RG rats support fast growth of PDX compared with mice, thus holding great potential to serve as a new model for oncology research.-He, D., Zhang, J., Wu, W., Yi, N., He, W., Lu, P., Li, B., Yang, N., Wang, D., Xue, Z., Zhang, P., Fan, G., Zhu, X. A novel immunodeficient rat model supports human lung cancer xenografts.


Assuntos
Modelos Animais de Doenças , Neoplasias Pulmonares/imunologia , Neoplasias Pulmonares/patologia , Animais , Apoptose , Proliferação de Células , Feminino , Humanos , Masculino , Camundongos , Camundongos Endogâmicos NOD , Camundongos SCID , Ratos , Ratos Sprague-Dawley , Células Tumorais Cultivadas , Ensaios Antitumorais Modelo de Xenoenxerto
17.
Langmuir ; 36(32): 9616-9625, 2020 Aug 18.
Artigo em Inglês | MEDLINE | ID: mdl-32787134

RESUMO

Porous membranes fabricated from poly(vinylidene fluoride) (PVDF) and a star polymer with linear poly(ethylene glycol) (PEG) arms and cycloPEG cores were fabricated via the phase-separation method. The porous gel polymer electrolytes (PGPEs) were obtained by immersing the porous membranes in the electrolyte solution. When the additive amount of star polymer was up to 20 wt %, the prepared membrane had the largest porosity and the pores were uniformly distributed in the membrane. The star polymer can not only decrease the crystallization of PVDF and enhance the absorption of liquid electrolyte but also offer ion conduction channels (cycloPEG cores). Therefore, the PGPE with 20 wt % star polymers exhibited competitive ionic conductivities of 1.27 mS cm-1 at 30 °C and 2.89 mS cm-1 at 80 °C. To stabilize the liquid electrolyte in the holes of porous membranes, a gelator was introduced in the liquid electrolyte to form gelled porous gel polymer electrolytes (GPGPEs), and the leakage of liquid electrolytes was thus remarkably reduced. The ionic conductivity of GPGPEs with 20 wt % star polymer and 1.5 wt % gelator was importantly improved at high temperatures (6.02 mS cm-1 at 80 °C). We systematically investigated the electrochemical performances of PGPEs without star polymer, PGPEs with star polymer, and GPGPEs with star polymer. The incorporation of star polymers with linear PEG arms and cycloPEG cores into the PGPEs and GPGPEs significantly improved the electrochemical performances of the lithium metal/LiFePO4 cell assembled with the PGPEs or GPGPEs.

18.
Environ Sci Technol ; 54(24): 15660-15670, 2020 12 15.
Artigo em Inglês | MEDLINE | ID: mdl-33225703

RESUMO

The COVID-19 outbreak greatly limited human activities and reduced primary emissions particularly from urban on-road vehicles but coincided with Beijing experiencing "pandemic haze," raising the public concerns about the effectiveness of imposed traffic policies to improve the air quality. This paper explores the relationship between local vehicle emissions and the winter haze in Beijing before and during the COVID-19 lockdown based on an integrated analysis framework, which combines a real-time on-road emission inventory, in situ air quality observations, and a localized numerical modeling system. We found that traffic emissions decreased substantially during the COVID-19 pandemic, but its imbalanced emission abatement of NOx (76%, 125.3 Mg/day) and volatile organic compounds (VOCs, 53%, 52.9 Mg/day) led to a significant rise of atmospheric oxidants in urban areas, resulting in a modest increase in secondary aerosols due to inadequate precursors, which still offset reduced primary emissions. Moreover, the enhanced oxidizing capacity in the surrounding regions greatly increased the secondary particles with relatively abundant precursors, which was transported into Beijing and mainly responsible for the aggravated haze pollution. We recommend that mitigation policies should focus on accelerating VOC emission reduction and synchronously controlling regional sources to release the benefits of local traffic emission control.


Assuntos
Poluentes Atmosféricos , Poluição do Ar , COVID-19 , Poluentes Atmosféricos/análise , Poluição do Ar/análise , Pequim , China , Monitoramento Ambiental , Humanos , Pandemias , Material Particulado/análise , SARS-CoV-2 , Emissões de Veículos/análise
19.
J Environ Sci (China) ; 95: 183-189, 2020 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-32653178

RESUMO

Coking industry is an important volatile organic compounds (VOCs) emission source in China, however, detailed information on VOCs emissions is lacking. Therefore, we selected a typical mechanized coking plant and collected air samples according to the Emission Standard of Pollutants for Coking Chemical Industry (GB16171-2012). Using gas chromatography-mass spectrometry method, we analyzed the VOCs in the air samples, and applied maximum increment reactivity (MIR) rule to estimate ozone formation potential (OFP) of the VOCs emitted from the coke production. More than 90 VOCs species were detected from the coking plant, including alkanes, alkenes, alkynes, aromatic hydrocarbons, halogenated hydrocarbons and oxygenated VOCs. The concentrations of VOCs (ρ(VOCs)) generated at different stages of the coking process are significantly different. ρ(VOCs) from coke oven chimney had the highest concentration (87.1 mg/m3), followed by coke pushing (4.0 mg/m3), coal charging (3.3 mg/m3) and coke oven tops (1.1 mg/m3). VOCs species emitted from the coke production processes were dominated by alkanes and alkenes, but the composition proportions were different at the different stages. Alkenes were the most abundant emission species in flue gases of the coke oven chimney accounting for up to 66% of the total VOCs, while the VOCs emissions from coke pushing and coal charging were dominated by alkanes (36% and 42%, respectively), and the alkanes and alkenes emitted from coke oven top were similar (31% and 29%, respectively). Based on above results, reduction of VOCs emissions from coke oven chimney flue gases is suggested to be an effective measure, especially for alkenes.


Assuntos
Poluentes Atmosféricos/análise , Coque , Ozônio/análise , Compostos Orgânicos Voláteis/análise , China , Monitoramento Ambiental
20.
Nature ; 500(7464): 593-7, 2013 Aug 29.
Artigo em Inglês | MEDLINE | ID: mdl-23892778

RESUMO

Mammalian pre-implantation development is a complex process involving dramatic changes in the transcriptional architecture. We report here a comprehensive analysis of transcriptome dynamics from oocyte to morula in both human and mouse embryos, using single-cell RNA sequencing. Based on single-nucleotide variants in human blastomere messenger RNAs and paternal-specific single-nucleotide polymorphisms, we identify novel stage-specific monoallelic expression patterns for a significant portion of polymorphic gene transcripts (25 to 53%). By weighted gene co-expression network analysis, we find that each developmental stage can be delineated concisely by a small number of functional modules of co-expressed genes. This result indicates a sequential order of transcriptional changes in pathways of cell cycle, gene regulation, translation and metabolism, acting in a step-wise fashion from cleavage to morula. Cross-species comparisons with mouse pre-implantation embryos reveal that the majority of human stage-specific modules (7 out of 9) are notably preserved, but developmental specificity and timing differ between human and mouse. Furthermore, we identify conserved key members (or hub genes) of the human and mouse networks. These genes represent novel candidates that are likely to be key in driving mammalian pre-implantation development. Together, the results provide a valuable resource to dissect gene regulatory mechanisms underlying progressive development of early mammalian embryos.


Assuntos
Embrião de Mamíferos/embriologia , Embrião de Mamíferos/metabolismo , Desenvolvimento Embrionário/genética , Regulação da Expressão Gênica no Desenvolvimento , Análise de Sequência de RNA , Análise de Célula Única , Alelos , Animais , Blastocisto/citologia , Blastocisto/metabolismo , Ciclo Celular/genética , Embrião de Mamíferos/citologia , Perfilação da Expressão Gênica , Humanos , Camundongos , Mórula/citologia , Mórula/metabolismo , Oócitos/citologia , Oócitos/metabolismo
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