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1.
J Am Chem Soc ; 146(21): 14493-14504, 2024 May 29.
Artigo em Inglês | MEDLINE | ID: mdl-38743872

RESUMO

High-entropy oxides (HEOs), featuring infinite chemical composition and exceptional physicochemical properties, are attracting much attention. The configurational entropy caused by a component disorder of HEOs is popularly believed to be the main driving force for thermal stability, while the role of vibrational entropy in the thermodynamic landscape has been neglected. In this study, we systematically investigated the vibrational entropy of multicomponent rutile oxides (including Fe0.5Ta0.5O2, Fe0.333Ti0.333Ta0.333O2, Fe0.25Ti0.25Ta0.25Sn0.25O2, and Fe0.21Ti0.21Ta0.21Sn0.21Ge0.16O2) by precise heat capacity measurements. It is found that vibrational entropy gradually decreases with increasing component disorder, beyond what one could expect from an equilibrium thermodynamics perspective. Moreover, all multicomponent rutile oxides exhibit a positive excess vibrational entropy at 298.15 K. Upon examinations of configuration disorder, size mismatch, phase transition, and polyhedral distortions, we demonstrate that the excess vibrational entropy plays a pivotal role in lowering the crystallization temperature of multicomponent rutile oxides. These findings represent the first experimental confirmation of the role of lattice vibrations in the thermodynamic landscape of rutile HEOs. In particular, vibrational entropy could serve as a novel descriptor to guide the predictive design of multicomponent oxide materials.

2.
J Am Chem Soc ; 2024 Oct 23.
Artigo em Inglês | MEDLINE | ID: mdl-39443293

RESUMO

Understanding the fundamental effect of the oxygen vacancy atomic structure in perovskite oxides on catalytic properties remains challenging due to diverse facets, surface sites, defects, etc. in traditional powder catalysts and the inherent structural complexity. Through quantitative synthesis of tetrahedral (LaCoO2.5-T), pyramidal (LaCoO2.5-P), and octahedral (LaCoO3) epitaxial thin films as model catalysts, we demonstrate the reactivity orders of active-site geometrical configurations in oxygen-deficient perovskites during the CO oxidation model reaction: CoO4 tetrahedron > CoO6 octahedron > CoO5 pyramid. Ambient-pressure Co L-edge and O K-edge XAS spectra clarify the dynamic evolutions of active-site electronic structures during realistic catalytic processes and highlight the important roles of defect geometrical structures. In addition, in situ XAS and resonant inelastic X-ray scattering spectra and density functional theory calculations directly reveal the nature of high reactivity for CoO4 sites and that the derived shallow-acceptor defect levels in the band structure facilitate the adsorption and activation of reactive gases, resulting in more than 23-fold enhancement for catalytic reaction rates than CoO5 sites.

3.
New Phytol ; 244(2): 511-527, 2024 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-39060950

RESUMO

The ALMT1 transporter aids malate secretion, chelating Al3+ ions to form nontoxic Al-malate complexes, believed to exclude Al from the roots. However, the extent to which malate secreted by ALMT1 is solely used for the exclusion of Al3+ or can be reutilized by plant roots for internal Al tolerance remains uncertain. In our investigation, we explored the impact of malate secretion on both external and internal Al resistance in Arabidopsis thaliana. Additionally, we delved into the mechanism by which the tonoplast-localized bacterial-type ATP-binding cassette (ABC) transporter complex STAR1/ALS3 promotes the degradation of the Al resistance transcription factor STOP1 to regulate ALMT1 expression. Our study demonstrates that the level of secreted malate influences whether the Al-malate complex is excluded from the roots or transported into root cells. The nodulin 26-like intrinsic protein (NIP) subfamily members NIP1;1 and NIP1;2, located in the plasma membrane, coordinate with STAR1/ALS3 to facilitate Al-malate transport from root apoplasm to the symplasm and eventually to the vacuoles for the internal Al detoxification. ALS3-dependent STAR1 interacts with and promotes the degradation of STOP1, regulating malate exudation. Our findings demonstrate the dual roles of malate exudation in external Al exclusion and Al absorption for internal Al detoxification.


Assuntos
Transportadores de Cassetes de Ligação de ATP , Alumínio , Proteínas de Arabidopsis , Arabidopsis , Malatos , Raízes de Plantas , Alumínio/toxicidade , Proteínas de Arabidopsis/metabolismo , Proteínas de Arabidopsis/genética , Arabidopsis/genética , Arabidopsis/metabolismo , Arabidopsis/efeitos dos fármacos , Malatos/metabolismo , Raízes de Plantas/metabolismo , Transportadores de Cassetes de Ligação de ATP/metabolismo , Transportadores de Cassetes de Ligação de ATP/genética , Regulação da Expressão Gênica de Plantas/efeitos dos fármacos , Proteólise/efeitos dos fármacos , Fatores de Transcrição/metabolismo , Fatores de Transcrição/genética , Transporte Biológico/efeitos dos fármacos , Transportadores de Ânions Orgânicos
4.
New Phytol ; 243(6): 2501-2511, 2024 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-38798233

RESUMO

Gene silencing is crucial in crop breeding for desired trait development. RNA interference (RNAi) has been used widely but is limited by ectopic expression of transgenes and genetic instability. Introducing an upstream start codon (uATG) into the 5'untranslated region (5'UTR) of a target gene may 'silence' the target gene by inhibiting protein translation from the primary start codon (pATG). Here, we report an efficient gene silencing method by introducing a tailor-designed uATG-containing element (ATGE) into the 5'UTR of genes in plants, occupying the original start site to act as a new pATG. Using base editing to introduce new uATGs failed to silence two of the tested three rice genes, indicating complex regulatory mechanisms. Precisely inserting an ATGE adjacent to pATG achieved significant target protein downregulation. Through extensive optimization, we demonstrated this strategy substantially and consistently downregulated target protein expression. By designing a bidirectional multifunctional ATGE4, we enabled tunable knockdown from 19% to 89% and observed expected phenotypes. Introducing ATGE into Waxy, which regulates starch synthesis, generated grains with lower amylose, revealing the value for crop breeding. Together, we have developed a programmable and robust method to knock down gene expression in plants, with potential for biological mechanism exploration and crop enhancement.


Assuntos
Edição de Genes , Inativação Gênica , Oryza , Edição de Genes/métodos , Oryza/genética , Regulação da Expressão Gênica de Plantas , Plantas Geneticamente Modificadas , Loci Gênicos , Genoma de Planta , Regiões 5' não Traduzidas/genética , Genes de Plantas , Sequência de Bases , Proteínas de Plantas/genética , Proteínas de Plantas/metabolismo , Fenótipo
5.
Int J Med Sci ; 21(3): 508-518, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38250613

RESUMO

This study aimed to explore the role of connexin 32 (Cx32) in the directional differentiation of induced pluripotent stem cells (iPSCs) into hepatocytes. Urine-derived epithelial cells were collected from the fresh urine of a healthy donor and transducted with reprogramming plasmid mixture to generate iPSCs. The iPSCs were then directionally differentiated into hepatocytes. During the differentiation, the upregulated and downregulated groups were treated with vitamin K2 (VK2) and 2-aminoethoxyboronate diphenylester (2-APB) to increase and inhibit Cx32 expression, respectively. The control group was not treated with the regulatory factor. Expression of Cx32 and hepatocyte-specific markers, including AFP, hepatocyte nuclear factor 4α (HNF-4α), albumin (ALB) and cytokeratin 18 (CK18) were detected. It indicated that Cx32 expression was not observed in iPSCs, but gradually increased during the process of hepatic differentiation from iPSCs. Upregulation of Cx32 expression by VK2 treatment promoted hepatocyte maturation and enhanced the expression of the aforementioned hepatic specific markers, whereas downregulation of Cx32 expression by 2-APB treatment had the opposite effects. In conclusion, urine-derived iPSCs could be directionally differentiated into hepatocytes. Up-regulation of Cx32 improves the efficiency and maturity of differentiation of iPSCs into hepatocytes, and Cx32 may be a promoting factor during the process of hepatic differentiation from iPSCs.


Assuntos
Diferenciação Celular , Proteína beta-1 de Junções Comunicantes , Hepatócitos , Células-Tronco Pluripotentes Induzidas , Regulação para Baixo , Proteína beta-1 de Junções Comunicantes/genética , Hepatócitos/citologia , Células-Tronco Pluripotentes Induzidas/citologia , Vitamina K 2 , Humanos
6.
Drug Resist Updat ; 68: 100960, 2023 05.
Artigo em Inglês | MEDLINE | ID: mdl-37003125

RESUMO

BACKGROUND: Pancreatic cancer continues to be one of the world's most lethal cancers. Chemotherapy resistance in patients with advanced pancreatic cancer often accompany with dismal prognosis, highlighting the need to investigate mechanisms of drug resistance and develop therapies to overcome chemoresistance. METHODS: This research was filed with the Chinese Clinical Trial Registry (ChiCTR2200061320). In order to isolate primary normal fibroblasts (NFs) and cancer-associated fibroblasts (CAFs) samples of pancreatic ductal adenocarcinoma (PDAC) and paracancerous pancreatic tissue from individuals diagnosed with PDAC were obtained. The exosomes were obtained using ultracentrifugation, and their characteristics were determined by Western blotting, nanoparticle tracking analysis, and transmission electron microscopy. CAF-derived miRNAs were analyzed by RT-qPCR and high-throughput sequencing. Gemcitabine (GEM) was employed to promote ferroptosis, and ferroptosis levels were determined by monitoring lipid reactive oxygen species (ROS), cell survival, and intracellular Fe2+ concentrations. To assess in vivo tumor response to GEM therapy, a xenograft tumor mouse model was utilized. RESULTS: Exosomes derived from CAFs in PDAC did not exhibit innate GEM resistance. CAFs promoted chemoresistance in PDAC cells following GEM treatment by secreting exosomes, and maintaining signaling communication with cancer cells. Mechanistically, miR-3173-5p derived from CAF exosomes sponged ACSL4 and inhibited ferroptosis after uptake by cancer cells. CONCLUSION: This work demonstrates a novel mode of acquired chemoresistance in PDAC and identifies the miR-3173-5p/ACSL4 pathway as a promising treatment target for GEM-resistant pancreatic cancer.


Assuntos
Fibroblastos Associados a Câncer , Carcinoma Ductal Pancreático , Exossomos , Ferroptose , MicroRNAs , Neoplasias Pancreáticas , Humanos , Animais , Camundongos , Gencitabina , MicroRNAs/genética , MicroRNAs/metabolismo , Exossomos/genética , Exossomos/patologia , Ferroptose/genética , Fibroblastos Associados a Câncer/metabolismo , Desoxicitidina/farmacologia , Desoxicitidina/uso terapêutico , Desoxicitidina/metabolismo , Resistencia a Medicamentos Antineoplásicos/genética , Linhagem Celular Tumoral , Neoplasias Pancreáticas/tratamento farmacológico , Neoplasias Pancreáticas/genética , Carcinoma Ductal Pancreático/tratamento farmacológico , Carcinoma Ductal Pancreático/genética , Modelos Animais de Doenças , Proliferação de Células , Coenzima A Ligases/metabolismo , Neoplasias Pancreáticas
7.
J Integr Plant Biol ; 66(6): 1048-1051, 2024 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-38578176

RESUMO

A newly developed rice guanine base editor (OsGTBE) achieves targeted and efficient G-to-T editing (C-to-A in the opposite strand) in rice. Using OsGTBE to edit endogenous herbicide-resistant loci generated several novel alleles conferring herbicide resistance, highlighting its utility in creating valuable germplasm and enhancing genetic diversity..


Assuntos
Alelos , Edição de Genes , Resistência a Herbicidas , Oryza , Oryza/genética , Resistência a Herbicidas/genética , Edição de Genes/métodos , Genes de Plantas , Herbicidas/farmacologia , Sequência de Bases
8.
J Integr Plant Biol ; 65(3): 646-655, 2023 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-36218268

RESUMO

With the widespread use of clustered regularly interspaced palindromic repeats (CRISPR)/CRISPR-associated nuclease (Cas) technologies in plants, large-scale genome editing is increasingly needed. Here, we developed a geminivirus-mediated surrogate system, called Wheat Dwarf Virus-Gate (WDV-surrogate), to facilitate high-throughput genome editing. WDV-Gate has two parts: one is the recipient callus from a transgenic rice line expressing Cas9 and a mutated hygromycin-resistant gene (HygM) for surrogate selection; the other is a WDV-based construct expressing two single guide RNAs (sgRNAs) targeting HygM and a gene of interest, respectively. We evaluated WDV-Gate on six rice loci by producing a total of 874 T0 plants. Compared with the conventional method, the WDV-Gate system, which was characterized by a transient and high level of sgRNA expression, significantly increased editing frequency (66.8% vs. 90.1%), plantlet regeneration efficiency (2.31-fold increase), and numbers of homozygous-edited plants (36.3% vs. 70.7%). Large-scale editing using pooled sgRNAs targeting the SLR1 gene resulted in a high editing frequency of 94.4%, further demonstrating its feasibility. We also tested WDV-Gate on sequence knock-in for protein tagging. By co-delivering a chemically modified donor DNA with the WDV-Gate plasmid, 3xFLAG peptides were successfully fused to three loci with an efficiency of up to 13%. Thus, by combining transiently expressed sgRNAs and a surrogate selection system, WDV-Gate could be useful for high-throughput gene knock-out and sequence knock-in.


Assuntos
Edição de Genes , Oryza , Edição de Genes/métodos , Sistemas CRISPR-Cas , Oryza/genética , Genoma de Planta , Plantas/genética
9.
Biomed Microdevices ; 21(3): 59, 2019 06 21.
Artigo em Inglês | MEDLINE | ID: mdl-31227912

RESUMO

Particle/cell sorting has great potential in medical diagnosis and chemical analysis. Two kinds of microfluidic sorting chips (sequential sorting chip and direct sorting chip) are designed, which combine hydraulic force and acoustic radiation force to achieve continuous sorting of multiple particles. Firstly, the optimal values of the angle (α) between the interdigital transducer (IDT) and the main channel, the peak-to-peak voltage (Vpp), the main flow velocity (Vmax) and the flow ratio (A) are determined by simulation and experiments, the related optimal parameters were obtained that the α = 15°, Vpp = 25 V, Vmax = 4 mm/s, flow ratio A1 = 0.2, and A2 = 0.5, respectively. Then, the corresponding sorting experiments were carried out using two kinds of sorting chips to sort the polystyrene (PS) particles with diameters of 1 µm, 5 µm, and 10 µm, and the sorting rate and purity of particles were calculated and analyzed. Experimental results show that the two kinds of sorting chips can achieve continuous sorting of multiple particles, and the sorting effect of sequential sorting chip (control flow ratio) is better than that of direct sorting chip. In addition, the sorting chips in our research have the advantages of simple structure, high sorting efficiency, and the ability to sort multiple particles, which can be applied in medical and chemical research fields, such as cell sorting and chemical analysis.


Assuntos
Separação Celular/instrumentação , Dispositivos Lab-On-A-Chip , Som , Poliestirenos/isolamento & purificação
10.
Plant J ; 91(6): 1051-1063, 2017 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-28671744

RESUMO

In angiosperms, the first zygotic division usually gives rise to two daughter cells with distinct morphologies and developmental fates, which is critical for embryo pattern formation; however, it is still unclear when and how these distinct cell fates are specified, and whether the cell specification is related to cytoplasmic localization or polarity. Here, we demonstrated that when isolated from both maternal tissues and the apical cell, a single basal cell could only develop into a typical suspensor, but never into an embryo in vitro. Morphological, cytological and gene expression analyses confirmed that the resulting suspensor in vitro is highly similar to its undisturbed in vivo counterpart. We also demonstrated that the isolated apical cell could develop into a small globular embryo, both in vivo and in vitro, after artificial dysfunction of the basal cell; however, these growing apical cell lineages could never generate a new suspensor. These findings suggest that the initial round of cell fate specification occurs at the two-celled proembryo stage, and that the basal cell lineage is autonomously specified towards the suspensor, implying a polar distribution of cytoplasmic contents in the zygote. The cell fate transition of the basal cell lineage to the embryo in vivo is actually a conditional cell specification process, depending on the developmental signals from both the apical cell lineage and maternal tissues connected to the basal cell lineage.


Assuntos
Padronização Corporal , Magnoliopsida/embriologia , Diferenciação Celular , Divisão Celular , Linhagem da Célula , Magnoliopsida/citologia , Magnoliopsida/genética , Sementes/citologia , Sementes/embriologia , Sementes/genética , Nicotiana/citologia , Nicotiana/embriologia , Nicotiana/genética , Zigoto
11.
Eur J Neurosci ; 48(9): 3062-3081, 2018 11.
Artigo em Inglês | MEDLINE | ID: mdl-30295974

RESUMO

Electrical synapses in the mammalian central nervous system (CNS) are increasingly recognized as highly complex structures for mediation of neuronal communication, both with respect to their capacity for dynamic short- and long-term modification in efficacy of synaptic transmission and their multimolecular regulatory and structural components. These two characteristics are inextricably linked, such that understanding of mechanisms that contribute to electrical synaptic plasticity requires knowledge of the molecular composition of electrical synapses and the functions of proteins associated with these synapses. Here, we provide evidence that the key component of gap junctions that form the majority of electrical synapses in the mammalian CNS, namely connexin36 (Cx36), directly interacts with the related E3 ubiquitin ligase proteins Ligand of NUMB protein X1 (LNX1) and Ligand of NUMB protein X2 (LNX2). This is based on immunofluorescence colocalization of LNX1 and LNX2 with Cx36-containing gap junctions in adult mouse brain versus lack of such coassociation in LNX null mice, coimmunoprecipitation of LNX proteins with Cx36, and pull-down of Cx36 with the second PDZ domain of LNX1 and LNX2. Furthermore, cotransfection of cultured cells with Cx36 and E3 ubiquitin ligase-competent LNX1 and LNX2 isoforms led to loss of Cx36-containing gap junctions between cells, whereas these junctions persisted following transfection with isoforms of these proteins that lack ligase activity. Our results suggest that a LNX protein mediates ubiquitination of Cx36 at neuronal gap junctions, with consequent Cx36 internalization, and may thereby contribute to intracellular mechanisms that govern the recently identified modifiability of synaptic transmission at electrical synapses.


Assuntos
Encéfalo/metabolismo , Proteínas de Transporte/metabolismo , Conexinas/metabolismo , Junções Comunicantes/metabolismo , Neurônios/metabolismo , Ubiquitina-Proteína Ligases/metabolismo , Animais , Encéfalo/citologia , Células Cultivadas , Células HEK293 , Células HeLa , Humanos , Peptídeos e Proteínas de Sinalização Intracelular , Camundongos , Camundongos Endogâmicos C57BL , Camundongos Knockout , Ligação Proteica/fisiologia , Ratos , Ratos Sprague-Dawley , Roedores , Ubiquitina-Proteína Ligases/deficiência , Proteína delta-2 de Junções Comunicantes
12.
Proc Natl Acad Sci U S A ; 112(40): 12432-7, 2015 Oct 06.
Artigo em Inglês | MEDLINE | ID: mdl-26396256

RESUMO

The suspensor is a temporary supporting structure of proembryos. It has been proposed that suspensor cells also possess embryogenic potential, which is suppressed by the embryo as an effect of the embryo-suspensor interaction. However, data to support this hypothesis are not yet available. In this report, using an in vivo living cell laser ablation technique, we show that Arabidopsis suspensor cells can develop into embryos after removing the embryo proper. The embryo proper plays a critical role in maintaining suspensor cell identity. However, this depends on the developmental stage; after the globular embryo stage, the suspensors no longer possess the potential to develop into embryos. We also reveal that hypophysis formation may be essential for embryo differentiation. Furthermore, we show that, after removing the embryo, auxin gradually accumulates in the top suspensor cell where cell division occurs to produce an embryo. Auxin redistribution likely reprograms the fate of the suspensor cell and triggers embryogenesis in suspensor cells. Thus, we provide direct evidence that the embryo suppresses the embryogenic potential of suspensor cells.


Assuntos
Arabidopsis/citologia , Arabidopsis/embriologia , Sementes/citologia , Sementes/embriologia , Arabidopsis/genética , Proteínas de Arabidopsis/genética , Proteínas de Arabidopsis/metabolismo , Diferenciação Celular , Divisão Celular , Células Cultivadas , Glucuronidase/genética , Glucuronidase/metabolismo , Proteínas de Fluorescência Verde/genética , Proteínas de Fluorescência Verde/metabolismo , Ácidos Indolacéticos/metabolismo , Microdissecção e Captura a Laser , Microscopia Confocal , Morfogênese , Plantas Geneticamente Modificadas , Sementes/genética , Fatores de Tempo , Técnicas de Cultura de Tecidos , Fatores de Transcrição/genética , Fatores de Transcrição/metabolismo
13.
J Exp Bot ; 67(9): 2829-45, 2016 04.
Artigo em Inglês | MEDLINE | ID: mdl-27162276

RESUMO

The growth and fruit quality of grapevines are widely affected by abnormal climatic conditions such as water deficits, but many of the precise mechanisms by which grapevines respond to drought stress are still largely unknown. Here, we report that VaNAC26, a member of the NAC transcription factor family, was upregulated dramatically during cold, drought and salinity treatments in Vitis amurensis, a cold and drought-hardy wild Vitis species. Heterologous overexpression of VaNAC26 enhanced drought and salt tolerance in transgenic Arabidopsis. Higher activities of antioxidant enzymes and lower concentrations of H2O2 and O2 (-) were found in VaNAC26-OE lines than in wild type plants under drought stress. These results indicated that scavenging by reactive oxygen species (ROS) was enhanced by VaNAC26 in transgenic lines. Microarray-based transcriptome analysis revealed that genes related to jasmonic acid (JA) synthesis and signaling were upregulated in VaNAC26-OE lines under both normal and drought conditions. VaNAC26 showed a specific binding ability on the NAC recognition sequence (NACRS) motif, which broadly exists in the promoter regions of upregulated genes in transgenic lines. Endogenous JA content significantly increased in the VaNAC26-OE lines 2 and 3. Our data suggest that VaNAC26 responds to abiotic stresses and may enhance drought tolerance by transcriptional regulation of JA synthesis in Arabidopsis.


Assuntos
Ciclopentanos/metabolismo , Oxilipinas/metabolismo , Reguladores de Crescimento de Plantas/metabolismo , Fatores de Transcrição/fisiologia , Vitis/metabolismo , Antioxidantes/metabolismo , Arabidopsis/metabolismo , Arabidopsis/fisiologia , Desidratação , Perfilação da Expressão Gênica , Regulação da Expressão Gênica de Plantas/fisiologia , Genes de Plantas/fisiologia , Reguladores de Crescimento de Plantas/fisiologia , Plantas Geneticamente Modificadas , Fatores de Transcrição/metabolismo , Vitis/fisiologia
14.
Stem Cells ; 33(3): 751-61, 2015 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-25377070

RESUMO

Normally, trabecular meshwork (TM) and Schlemm's canal inner wall endothelial cells within the aqueous humor outflow pathway maintain intraocular pressure within a narrow safe range. Elevation in intraocular pressure, because of the loss of homeostatic regulation by these outflow pathway cells, is the primary risk factor for vision loss due to glaucomatous optic neuropathy. A notable feature associated with glaucoma is outflow pathway cell loss. Using controlled cell loss in ex vivo perfused human outflow pathway organ culture, we developed compelling experimental evidence that this level of cell loss compromises intraocular pressure homeostatic function. This function was restored by repopulation of the model with fresh TM cells. We then differentiated induced pluripotent stem cells (iPSCs) and used them to repopulate this cell depletion model. These differentiated cells (TM-like iPSCs) became similar to TM cells in both morphology and expression patterns. When transplanted, they were able to fully restore intraocular pressure homeostatic function. This successful transplantation of TM-like iPSCs establishes the conceptual feasibility of using autologous stem cells to restore intraocular pressure regulatory function in open-angle glaucoma patients, providing a novel alternative treatment option.


Assuntos
Glaucoma de Ângulo Aberto/terapia , Regeneração Tecidual Guiada/métodos , Células-Tronco Pluripotentes Induzidas/fisiologia , Transplante de Células-Tronco/métodos , Diferenciação Celular/fisiologia , Glaucoma de Ângulo Aberto/genética , Glaucoma de Ângulo Aberto/metabolismo , Humanos , Células-Tronco Pluripotentes Induzidas/citologia , Células-Tronco Pluripotentes Induzidas/metabolismo , Transplante Autólogo
15.
Sensors (Basel) ; 15(10): 26198-211, 2015 Oct 16.
Artigo em Inglês | MEDLINE | ID: mdl-26501280

RESUMO

The conventional direction of arrival (DOA) estimation algorithm with static sources assumption usually estimates the source angles of two adjacent moments independently and the correlation of the moments is not considered. In this article, we focus on the DOA estimation of moving sources and a modified particle filtering (MPF) algorithm is proposed with state space model of single acoustic vector sensor. Although the particle filtering (PF) algorithm has been introduced for acoustic vector sensor applications, it is not suitable for the case that one dimension angle of source is estimated with large deviation, the two dimension angles (pitch angle and azimuth angle) cannot be simultaneously employed to update the state through resampling processing of PF algorithm. To solve the problems mentioned above, the MPF algorithm is proposed in which the state estimation of previous moment is introduced to the particle sampling of present moment to improve the importance function. Moreover, the independent relationship of pitch angle and azimuth angle is considered and the two dimension angles are sampled and evaluated, respectively. Then, the MUSIC spectrum function is used as the "likehood" function of the MPF algorithm, and the modified PF-MUSIC (MPF-MUSIC) algorithm is proposed to improve the root mean square error (RMSE) and the probability of convergence. The theoretical analysis and the simulation results validate the effectiveness and feasibility of the two proposed algorithms.

16.
Front Neurol ; 15: 1341252, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38685951

RESUMO

Background: Postoperative pneumonia (POP) is one of the primary complications after aneurysmal subarachnoid hemorrhage (aSAH) and is associated with postoperative mortality, extended hospital stay, and increased medical fee. Early identification of pneumonia and more aggressive treatment can improve patient outcomes. We aimed to develop a model to predict POP in aSAH patients using machine learning (ML) methods. Methods: This internal cohort study included 706 patients with aSAH undergoing intracranial aneurysm embolization or aneurysm clipping. The cohort was randomly split into a train set (80%) and a testing set (20%). Perioperative information was collected from participants to establish 6 machine learning models for predicting POP after surgical treatment. The area under the receiver operating characteristic curve (AUC), precision-recall curve were used to assess the accuracy, discriminative power, and clinical validity of the predictions. The final model was validated using an external validation set of 97 samples from the Medical Information Mart for Intensive Care IV (MIMIC-IV) database. Results: In this study, 15.01% of patients in the training set and 12.06% in the testing set with POP after underwent surgery. Multivariate logistic regression analysis showed that mechanical ventilation time (MVT), Glasgow Coma Scale (GCS), Smoking history, albumin level, neutrophil-to-albumin Ratio (NAR), c-reactive protein (CRP)-to-albumin ratio (CAR) were independent predictors of POP. The logistic regression (LR) model presented significantly better predictive performance (AUC: 0.91) than other models and also performed well in the external validation set (AUC: 0.89). Conclusion: A machine learning model for predicting POP in aSAH patients was successfully developed using a machine learning algorithm based on six perioperative variables, which could guide high-risk POP patients to take appropriate preventive measures.

17.
Front Neurol ; 15: 1305543, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38711558

RESUMO

Objective: Chronic subdural hematoma (CSDH) is a neurological condition with high recurrence rates, primarily observed in the elderly population. Although several risk factors have been identified, predicting CSDH recurrence remains a challenge. Given the potential of machine learning (ML) to extract meaningful insights from complex data sets, our study aims to develop and validate ML models capable of accurately predicting postoperative CSDH recurrence. Methods: Data from 447 CSDH patients treated with consecutive burr-hole irrigations at Wenzhou Medical University's First Affiliated Hospital (December 2014-April 2019) were studied. 312 patients formed the development cohort, while 135 comprised the test cohort. The Least Absolute Shrinkage and Selection Operator (LASSO) method was employed to select crucial features associated with recurrence. Eight machine learning algorithms were used to construct prediction models for hematoma recurrence, using demographic, laboratory, and radiological features. The Border-line Synthetic Minority Over-sampling Technique (SMOTE) was applied to address data imbalance, and Shapley Additive Explanation (SHAP) analysis was utilized to improve model visualization and interpretability. Model performance was assessed using metrics such as AUROC, sensitivity, specificity, F1 score, calibration plots, and decision curve analysis (DCA). Results: Our optimized ML models exhibited prediction accuracies ranging from 61.0% to 86.2% for hematoma recurrence in the validation set. Notably, the Random Forest (RF) model surpassed other algorithms, achieving an accuracy of 86.2%. SHAP analysis confirmed these results, highlighting key clinical predictors for CSDH recurrence risk, including age, alanine aminotransferase level, fibrinogen level, thrombin time, and maximum hematoma diameter. The RF model yielded an accuracy of 92.6% with an AUC value of 0.834 in the test dataset. Conclusion: Our findings underscore the efficacy of machine learning algorithms, notably the integration of the RF model with SMOTE, in forecasting the recurrence of postoperative chronic subdural hematoma. Leveraging the RF model, we devised an online calculator that may serve as a pivotal instrument in tailoring therapeutic strategies and implementing timely preventive interventions for high-risk patients.

18.
Hortic Res ; 11(1): uhad250, 2024 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-38269296

RESUMO

Cytosine and adenosine base editors (CBE and ABE) have been widely used in plants, greatly accelerating gene function research and crop breeding. Current base editors can achieve efficient A-to-G and C-to-T/G/A editing. However, efficient and heritable A-to-Y (A-to-T/C) editing remains to be developed in plants. In this study, a series of A-to-K base editor (AKBE) systems were constructed for monocot and dicot plants. Furthermore, nSpCas9 was replaced with the PAM-less Cas9 variant (nSpRY) to expand the target range of the AKBEs. Analysis of 228 T0 rice plants and 121 T0 tomato plants edited using AKBEs at 18 endogenous loci revealed that, in addition to highly efficient A-to-G substitution (41.0% on average), the plant AKBEs can achieve A-to-T conversion with efficiencies of up to 25.9 and 10.5% in rice and tomato, respectively. Moreover, the rice-optimized AKBE generates A-to-C conversion in rice, with an average efficiency of 1.8%, revealing the significant value of plant-optimized AKBE in creating genetic diversity. Although most of the A-to-T and A-to-C edits were chimeric, desired editing types could be transmitted to the T1 offspring, similar to the edits generated by the traditional ABE8e. Besides, using AKBEs to target tyrosine (Y, TAT) or cysteine (C, TGT) achieved the introduction of an early stop codon (TAG/TAA/TGA) of target genes, demonstrating its potential use in gene disruption.

19.
J Cancer ; 15(16): 5258-5276, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-39247608

RESUMO

Background: Few studies have analyzed the effect of matrix metalloproteinase (MMP) expression patterns on the tumor microenvironment (TME) during development of cervical cancer (CC). Methods: We elucidated the landscape and score of MMP expression in CC using single-cell RNA sequencing (scRNA-seq) and RNA sequencing datasets. Further, we aimed the MMPscore to probe the infiltration of immune cells. Further, MMP expression was measured by quantitative Real-Time Polymerase Chain Reaction (qRT-PCR). Results: We found MMPs were cell-type specific expressed in diverse types of CC cells, regulating the relative pathways of CC progression. Two distinct MMP expression patterns that associated infiltrated tumor microenvironment (TME) were identified. We discovered MMP expression patterns can predict the stage of tumor, subtype, stromal activity in the TME, genetic variation, and patient outcome. Patients with high MMPscore benefited from significantly better treatment and clinical outcomes. Conclusion: These results indicate high MMPscore in diverse cell types may regulate immune response and improve the survival of patients with CC, which assist in developing more effective immunization strategies.

20.
Nat Commun ; 15(1): 7613, 2024 Sep 02.
Artigo em Inglês | MEDLINE | ID: mdl-39223132

RESUMO

Lattice oxygen in metal oxides plays an important role in the reaction of diesel oxidation catalysts, but the atomic-level understanding of structural evolution during the catalytic process remains elusive. Here, we develop a Mn2O3/SmMn2O5 catalyst using a non-stoichiometric exsolution method to explore the roles of lattice oxygen in NO oxidation. The enhanced covalency of Mn-O bond and increased electron density at Mn3+ sites, induced by the interface between exsolved Mn2O3 and mullite, lead to the formation of highly active lattice oxygen adjacent to Mn3+ sites. Near-ambient pressure X-ray photoelectron and absorption spectroscopies show that the activated lattice oxygen enables reversible changes in Mn valence states and Mn-O bond covalency during redox cycles, reducing energy barriers for NO oxidation and promoting NO2 desorption via the cooperative Mars-van Krevelen mechanism. Therefore, the Mn2O3/SmMn2O5 exhibits higher NO oxidation activity and better resistance to hydrothermal aging compared to a commercial Pt/Al2O3 catalyst.

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