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1.
Nature ; 618(7964): 287-293, 2023 Jun.
Artículo en Inglés | MEDLINE | ID: mdl-37286650

RESUMEN

All-solid-state batteries with a Li anode and ceramic electrolyte have the potential to deliver a step change in performance compared with today's Li-ion batteries1,2. However, Li dendrites (filaments) form on charging at practical rates and penetrate the ceramic electrolyte, leading to short circuit and cell failure3,4. Previous models of dendrite penetration have generally focused on a single process for dendrite initiation and propagation, with Li driving the crack at its tip5-9. Here we show that initiation and propagation are separate processes. Initiation arises from Li deposition into subsurface pores, by means of microcracks that connect the pores to the surface. Once filled, further charging builds pressure in the pores owing to the slow extrusion of Li (viscoplastic flow) back to the surface, leading to cracking. By contrast, dendrite propagation occurs by wedge opening, with Li driving the dry crack from the rear, not the tip. Whereas initiation is determined by the local (microscopic) fracture strength at the grain boundaries, the pore size, pore population density and current density, propagation depends on the (macroscopic) fracture toughness of the ceramic, the length of the Li dendrite (filament) that partially occupies the dry crack, current density, stack pressure and the charge capacity accessed during each cycle. Lower stack pressures suppress propagation, markedly extending the number of cycles before short circuit in cells in which dendrites have initiated.

2.
Proc Natl Acad Sci U S A ; 121(36): e2406343121, 2024 Sep 03.
Artículo en Inglés | MEDLINE | ID: mdl-39186654

RESUMEN

The extinction risk of the giant panda has been demoted from "endangered" to "vulnerable" on the International Union for Conservation of Nature Red List, but its habitat is more fragmented than ever before, resulting in 33 isolated giant panda populations according to the fourth national survey released by the Chinese government. Further comprehensive investigations of the genetic background and in-depth assessments of the conservation status of wild populations are still necessary and urgently needed. Here, we sequenced the genomes of 612 giant pandas with an average depth of ~26× and generated a high-resolution map of genomic variation with more than 20 million variants covering wild individuals from six mountain ranges and captive representatives in China. We identified distinct genetic clusters within the Minshan population by performing a fine-grained genetic structure. The estimation of inbreeding and genetic load associated with historical population dynamics suggested that future conservation efforts should pay special attention to the Qinling and Liangshan populations. Releasing captive individuals with a genetic background similar to the recipient population appears to be an advantageous genetic rescue strategy for recovering the wild giant panda populations, as this approach introduces fewer deleterious mutations into the wild population than mating with differentiated lineages. These findings emphasize the superiority of large-scale population genomics to provide precise guidelines for future conservation of the giant panda.


Asunto(s)
Conservación de los Recursos Naturales , Genoma , Ursidae , Ursidae/genética , Animales , Conservación de los Recursos Naturales/métodos , Genoma/genética , China , Especies en Peligro de Extinción , Variación Genética , Genética de Población/métodos , Dinámica Poblacional , Secuenciación Completa del Genoma/métodos
3.
Drug Resist Updat ; 76: 101122, 2024 Sep.
Artículo en Inglés | MEDLINE | ID: mdl-39079407

RESUMEN

O6-methylguanine DNA methyltransferase (MGMT) is a crucial determinant of temozolomide (TMZ) sensitivity in patients with glioblastoma (GBM). The therapeutic potential of small interfering RNA (siRNA) targeting MGMT to enhance TMZ sensitivity has been hampered by serum nuclease degradation, off-target effects, poor accumulation at tumor sites, and low circulation in blood stream. In this study, we developed a framework nucleic acid-based nanoparticles (FNN), which is constructed from a six-helix DNA bundle, to encapsulate and protect siMGMT for improving TMZ sensitivity in GBM treatment. For better blood-brain barrier (BBB) penetration and GBM targeting, we conjugated Angiopep-2 (ANG) targeting modules to each end of the FNN. Nucleolin (NCL)-responsive locks were engineered along the sides of the six-helix DNA bundle, which safeguard siMGMT before tumor entry. Upon interaction with tumor-overexpressed NCL, these locks unlock, exposing siMGMT, this allows for effective suppression of MGMT, resulting in a significant improvement of TMZ therapeutic efficacy in GBM. This innovative strategy has the potential to transform the current treatment landscape for GBM.


Asunto(s)
Antineoplásicos Alquilantes , Barrera Hematoencefálica , Neoplasias Encefálicas , Glioblastoma , Nanopartículas , Temozolomida , Glioblastoma/tratamiento farmacológico , Glioblastoma/patología , Temozolomida/farmacología , Temozolomida/administración & dosificación , Temozolomida/uso terapéutico , Humanos , Neoplasias Encefálicas/tratamiento farmacológico , Neoplasias Encefálicas/patología , Neoplasias Encefálicas/genética , Antineoplásicos Alquilantes/farmacología , Antineoplásicos Alquilantes/uso terapéutico , Nanopartículas/química , Animales , Barrera Hematoencefálica/metabolismo , Barrera Hematoencefálica/efectos de los fármacos , Resistencia a Antineoplásicos/efectos de los fármacos , Línea Celular Tumoral , Proteínas de Unión al ARN/metabolismo , Enzimas Reparadoras del ADN/metabolismo , Enzimas Reparadoras del ADN/genética , Metilasas de Modificación del ADN/metabolismo , Nucleolina , Fosfoproteínas/metabolismo , Proteínas Supresoras de Tumor/metabolismo , Proteínas Supresoras de Tumor/genética , ARN Interferente Pequeño/administración & dosificación , Ácidos Nucleicos , Péptidos
4.
Ecotoxicol Environ Saf ; 272: 116105, 2024 Mar 01.
Artículo en Inglés | MEDLINE | ID: mdl-38364760

RESUMEN

2-bromoacetamide (BAcAm) is an emerging class of unregulated disinfection by-products (DBPs), with potent cytogenetic and developmental toxicity in animals. However, whether BAcAm exerts toxic effects on mammalian oocyte quality remains to be elucidate. In this research, we investigated the effect of BAcAm on mouse and human oocyte maturation with an in vitro culture system. Our results revealed that BAcAm exposure hindered the extrusion of the first polar body, disrupted the spindle organization and reduced the competence of embryo development after fertilization in the mouse oocytes. Results of single-cell RNA sequencing (scRNA-seq) showed that 605 differentially expressed genes (DEGs) were identified in the BAcAm exposed mouse oocytes, among which 366 were up-regulated and 239 were down-regulated. Gene Ontology (GO) analysis further revealed that DEGs were mainly enriched in mitochondrial functions, oxidative stress, cytoskeleton, endoplasmic reticulum (ER), Golgi and protein synthesis, DNA damage and apoptosis. We then conducted further tests in these aspects and discovered that BAcAm exposure principally perturbed the function of microtubule and actin cytoskeleton. This finding was confirmed in human oocytes. Overall, our data suggest that BAcAm exposure disturbs the cytoskeleton function, thus impairing oocyte maturation. These data, for the first time, provide a comprehensive view for the toxic effects of BAcAm on oocyte maturation.


Asunto(s)
Citoesqueleto , Oogénesis , Humanos , Animales , Ratones , Citoesqueleto/metabolismo , Oocitos/metabolismo , Mitocondrias/metabolismo , Microtúbulos/metabolismo , Mamíferos
5.
Nano Lett ; 23(5): 1787-1793, 2023 Mar 08.
Artículo en Inglés | MEDLINE | ID: mdl-36802605

RESUMEN

Atomically dispersed metals encapsulated in metal-organic frameworks (MOFs) have attracted extensive attention in catalysis and energy fields. Amino groups were considered conducive to the formation of single atom catalysts (SACs) due to the strong metal-linker interactions. Here, atomic details of Pt1@UiO-66 and Pd1@UiO-66-NH2 are revealed using low-dose integrated differential phase contrast scanning transmission electron microscopy (iDPC-STEM). Single Pt atoms locate on the benzene ring of p-benzenedicarboxylic acid (BDC) linkers in Pt@UiO-66, while single Pd atoms are adsorbed by the amino groups in Pd@UiO-66-NH2. However, Pt@UiO-66-NH2 and Pd@UiO-66 show obvious clusters. Therefore, amino groups do not always favor the formation of SACs, and density functional theory (DFT) calculations indicate that a moderate binding strength between metals and MOFs is preferred. These results directly reveal the adsorption sites of single metal atoms in UiO-66 family, paving the way for understanding the interaction between single metal atoms and the MOFs.

6.
Int J Mol Sci ; 25(4)2024 Feb 15.
Artículo en Inglés | MEDLINE | ID: mdl-38396983

RESUMEN

Oats (Avena sativa) are an important cereal crop and cool-season forage worldwide. Heat shock protein 90 (HSP90) is a protein ubiquitously expressed in response to heat stress in almost all plants. To date, the HSP90 gene family has not been comprehensively reported in oats. Herein, we have identified twenty HSP90 genes in oats and elucidated their evolutionary pathways and responses to five abiotic stresses. The gene structure and motif analyses demonstrated consistency across the phylogenetic tree branches, and the groups exhibited relative structural conservation. Additionally, we identified ten pairs of segmentally duplicated genes in oats. Interspecies synteny analysis and orthologous gene identification indicated that oats share a significant number of orthologous genes with their ancestral species; this implies that the expansion of the oat HSP90 gene family may have occurred through oat polyploidization and large fragment duplication. The analysis of cis-acting elements revealed their influential role in the expression pattern of HSP90 genes under abiotic stresses. Analysis of oat gene expression under high-temperature, salt, cadmium (Cd), polyethylene glycol (PEG), and abscisic acid (ABA) stresses demonstrated that most AsHSP90 genes were significantly up-regulated by heat stress, particularly AsHSP90-7, AsHSP90-8, and AsHSP90-9. This study offers new insights into the amplification and evolutionary processes of the AsHSP90 protein, as well as its potential role in response to abiotic stresses. Furthermore, it lays the groundwork for understanding oat adaptation to abiotic stress, contributing to research and applications in plant breeding.


Asunto(s)
Avena , Grano Comestible , Avena/genética , Avena/metabolismo , Grano Comestible/genética , Filogenia , Genoma de Planta , Fitomejoramiento , Estrés Fisiológico/genética , Proteínas HSP90 de Choque Térmico/metabolismo , Regulación de la Expresión Génica de las Plantas , Proteínas de Plantas/metabolismo
7.
Int J Mol Sci ; 25(17)2024 Aug 29.
Artículo en Inglés | MEDLINE | ID: mdl-39273329

RESUMEN

The alternative oxidase (AOX), a common terminal oxidase in the electron transfer chain (ETC) of plants, plays a crucial role in stress resilience and plant growth and development. Oat (Avena sativa), an important crop with high nutritional value, has not been comprehensively studied regarding the AsAOX gene family. Therefore, this study explored the responses and potential functions of the AsAOX gene family to various abiotic stresses and their potential evolutionary pathways. Additionally, we conducted a genome-wide analysis to explore the evolutionary conservation and divergence of AOX gene families among three Avena species (Avena sativa, Avena insularis, Avena longiglumis) and four Poaceae species (Avena sativa, Oryza sativa, Triticum aestivum, and Brachypodium distachyon). We identified 12 AsAOX, 9 AiAOX, and 4 AlAOX gene family members. Phylogenetic, motif, domain, gene structure, and selective pressure analyses revealed that most AsAOXs, AiAOXs, and AlAOXs are evolutionarily conserved. We also identified 16 AsAOX segmental duplication pairs, suggesting that segmental duplication may have contributed to the expansion of the AsAOX gene family, potentially preserving these genes through subfunctionalization. Chromosome polyploidization, gene structural variations, and gene fragment recombination likely contributed to the evolution and expansion of the AsAOX gene family as well. Additionally, we hypothesize that AsAOX2 may have potential function in resisting wounding and heat stresses, while AsAOX4 could be specifically involved in mitigating wounding stress. AsAOX11 might contribute to resistance against chromium and waterlogging stresses. AsAOX8 may have potential fuction in mitigating ABA-mediated stress. AsAOX12 and AsAOX5 are most likely to have potential function in mitigating salt and drought stresses, respectively. This study elucidates the potential evolutionary pathways of the AsAOXs gene family, explores their responses and potential functions to various abiotic stresses, identifies potential candidate genes for future functional studies, and facilitates molecular breeding applications in A. sativa.


Asunto(s)
Avena , Evolución Molecular , Proteínas Mitocondriales , Familia de Multigenes , Oxidorreductasas , Filogenia , Proteínas de Plantas , Estrés Fisiológico , Avena/genética , Proteínas de Plantas/genética , Proteínas de Plantas/metabolismo , Estrés Fisiológico/genética , Oxidorreductasas/genética , Oxidorreductasas/metabolismo , Proteínas Mitocondriales/genética , Proteínas Mitocondriales/metabolismo , Regulación de la Expresión Génica de las Plantas , Genoma de Planta , Triticum/genética , Triticum/enzimología , Duplicación de Gen
8.
Behav Res Methods ; 56(6): 6363-6388, 2024 09.
Artículo en Inglés | MEDLINE | ID: mdl-38409459

RESUMEN

High-stakes non-cognitive tests frequently employ forced-choice (FC) scales to deter faking. To mitigate the issue of score ipsativity derived, many scoring models have been devised. Among them, the multi-unidimensional pairwise preference (MUPP) framework is a highly flexible and commonly used framework. However, the original MUPP model was developed for unfolding response process and can only handle paired comparisons. The present study proposes the 2PLM-RANK as a generalization of the MUPP model to accommodate dominance RANK format response. In addition, an improved stochastic EM (iStEM) algorithm is devised for more stable and efficient parameter estimation. Simulation results generally supported the efficiency and utility of the new algorithm in estimating the 2PLM-RANK when applied to both triplets and tetrads across various conditions. An empirical illustration with responses to a 24-dimensional personality test further supported the practicality of the proposed model. To further aid in the application of the new model, a user-friendly R package is also provided.


Asunto(s)
Algoritmos , Conducta de Elección , Humanos , Conducta de Elección/fisiología , Simulación por Computador , Modelos Estadísticos , Modelos Psicológicos
9.
Small ; 19(18): e2207248, 2023 05.
Artículo en Inglés | MEDLINE | ID: mdl-36725316

RESUMEN

Glioblastoma (GBM) is the most common lethal brain tumor with dismal treatment outcomes and poor response to chemotherapy. As the regulatory center of cytogenetics and metabolism, most tumor chemotherapeutic molecules exert therapeutic effects in the nucleus. Nanodrugs showing the nuclear aggregation effect are expected to eliminate and fundamentally suppress tumor cells. In this study, a nanodrug delivery system based on polyhedral oligomeric silsesquioxane (POSS) is introduced to deliver drugs into the nuclei of GBM cells, effectively enhancing the therapeutic efficacy of chemotherapy. The nanoparticles are modified with folic acid and iRGD peptides molecules to improve their tumor cell targeting and uptake via receptor-mediated endocytosis. Nuclear aggregation allows for the direct delivery of chemotherapeutic drug temozolomide (TMZ) to the tumor cell nuclei, resulting in more significant DNA damage and inhibition of tumor cell proliferation. Herein, TMZ-loaded POSS nanoparticles can significantly improve the survival of GBM-bearing mice. Therefore, the modified POSS nanoparticles may serve as a promising drug-loaded delivery platform to improve chemotherapy outcomes in GBM patients.


Asunto(s)
Glioblastoma , Nanopartículas , Ratones , Animales , Glioblastoma/patología , Línea Celular Tumoral , Temozolomida/química , Temozolomida/farmacología , Sistemas de Liberación de Medicamentos/métodos , Nanopartículas/química
10.
Clin Genet ; 103(5): 603-608, 2023 05.
Artículo en Inglés | MEDLINE | ID: mdl-36593593

RESUMEN

Total fertilization failure (TFF), which refers to fertilization failure in all mature oocytes, accounting for 5%-10% of in vitro fertilization (IVF) cycles and 1%-3% of intracytoplasmic sperm injection (ICSI) cycles in human. In this study, we recruited three unrelated primary infertile men with repeated cycles of TFF and performed whole-exome sequencing to identify the potential pathogenic variants. We identified homozygous or compound-heterozygous variants of paternal-effect genes ACTL7A and PLCZ1 that followed a Mendelian recessive inheritance pattern. Novel homozygous nonsense variant in ACTL7A [c.C146G: p.S49*] was identified in case 1, who came from a consanguineous family. Ultrastructural observation of ACTL7A-mutated spermatozoa by transmission electron microscopy (TEM) indicated that apparent increased thickness of perinuclear matrix and the acrosome was detached from the nuclear envelop. Besides, two novel compound-heterozygous variants in PLCZ1 were identified in case 2 [c.1174+3A>C:p.?; c.A1274G:p.N425S] and case 3 [c.136-1G>C:p.?; c.G1358A:p.G453D]. Mutated spermatozoa from case 2 with reduced expression of PLCZ1 showed apparent acrosome detachment by TEM analysis. And ICSI with assisted oocyte activation (ICSI-AOA) treatment can partly rescue the TFF. Taken together, our findings revealed that novel biallelic variants in the paternal-effect genes ACTL7A and PLCZ1 were associated with human TFF, which expanding the spectrum of genetic causes and facilitating the genetic diagnosis of male infertility with TFF.


Asunto(s)
Actinas , Infertilidad Masculina , Fosfoinositido Fosfolipasa C , Semen , Femenino , Humanos , Masculino , Embarazo , Fertilización/genética , Fertilización In Vitro , Infertilidad Masculina/genética , Oocitos , Fosfoinositido Fosfolipasa C/genética , Índice de Embarazo , Espermatozoides/metabolismo , Actinas/genética
11.
Opt Express ; 31(12): 20505-20517, 2023 Jun 05.
Artículo en Inglés | MEDLINE | ID: mdl-37381444

RESUMEN

A true-color light-field display system with a large depth-of-field (DOF) is demonstrated. Reducing crosstalk between viewpoints and increasing viewpoint density are the key points to realize light-field display system with large DOF. The aliasing and crosstalk of light beams in the light control unit (LCU) are reduced by adopting collimated backlight and reversely placing the aspheric cylindrical lens array (ACLA). The one-dimensional (1D) light-field encoding of halftone images increases the number of controllable beams within the LCU and improves viewpoint density. The use of 1D light-field encoding leads to a decrease in the color-depth of the light-field display system. The joint modulation for size and arrangement of halftone dots (JMSAHD) is used to increase color-depth. In the experiment, a three-dimensional (3D) model was constructed using halftone images generated by JMSAHD, and a light-field display system with a viewpoint density of 1.45 (i.e. 1.45 viewpoints per degree of view) and a DOF of 50 cm was achieved at a 100 ° viewing angle.

12.
Opt Express ; 31(9): 14945-14953, 2023 Apr 24.
Artículo en Inglés | MEDLINE | ID: mdl-37157347

RESUMEN

AlGaN is an important material for deep ultraviolet optoelectronic devices and electronic devices. The phase separation on the AlGaN surface means small-scale compositional fluctuations of Al, which is prone to degrade the performance of devices. In order to study the mechanism of the surface phase separation, the Al0.3Ga0.7N wafer was investigated by the scanning diffusion microscopy method based on the photo-assisted Kelvin force probe microscope. The response of the surface photovoltage near the bandgap was quite different for the edge and the center of the island on the AlGaN surface. We utilize the theoretical model of scanning diffusion microscopy to fit the local absorption coefficients from the measured surface photovoltage spectrum. During the fitting process, we introduce as and ab parameters (bandgap shift and broadening) to describe the local variation of absorption coefficients α(as, ab, λ). The local bandgap and Al composition can be calculated quantitatively from the absorption coefficients. The results show that there is lower bandgap (about 305 nm) and lower Al composition (about 0.31) at the edge of the island, compared with those at the center of the island (about 300 nm for bandgap and 0.34 for Al composition). Similar to the edge of the island, there is a lower bandgap at the V-pit defect which is about 306 nm corresponding to the Al composition of about 0.30. These results mean Ga enrichment both at the edge of the island and the V-pit defect position. It proves that scanning diffusion microscopy is an effective method to review the micro-mechanism of AlGaN phase separation.

13.
J Neurooncol ; 163(2): 301-311, 2023 Jun.
Artículo en Inglés | MEDLINE | ID: mdl-37231231

RESUMEN

BACKGROUND: Serum albumin has been demonstrated as prognostic parameter in non-Hodgkin lymphoma (NHL). Primary central nervous system lymphoma (PCNSL) is a rare extranodal NHL with highly aggressive behavior. In this study, we aimed at creating a novel prognostic model for PCNSL based on serum albumin levels. METHODS: We compared several commonly used laboratory nutritional parameters for predicting the survival of PCNSL patients using overall survival (OS) for outcome analysis and receiver operating characteristic curve analysis to determine the optimal cut-off values. Parameters associated with OS were evaluated by univariate and multivariate analyses. Independent prognostic parameters for OS were selected for risk stratification, including albumin ≤ 4.1 g/dL, ECOG PS > 1, and LLR > 166.8, which were associated with shorter OS; albumin > 4.1 g/dL, ECOG PS 0-1 and LLR ≤ 166.8, which were associated with longer OS, and five-fold cross-validation was used for evaluating predictive accuracy of identified prognostic model. RESULTS: By univariate analysis, age, ECOG PS, MSKCC score, Lactate dehydrogenase-to-lymphocyte ratio (LLR), total protein, albumin, hemoglobin, and albumin to globulin ratio (AGR) resulted statistically associated with the OS of PCNSL. By multivariate analysis, albumin ≤ 4.1 g/dL, ECOG PS > 1, and LLR > 166.8 were confirmed to be significant predictors of inferior OS. We explored several PCNSL prognostic models based on albumin, ECOG PS and LLR with 1 point assigned to each parameter. Eventually, a novel and effective PCNSL prognostic model based on albumin and ECOG PS successfully classified patients into three risk groups with 5-year survival rates of 47.5%, 36.9%, and 11.9%, respectively. CONCLUSIONS: The novel two-factor prognostic model based on albumin and ECOG PS we propose represents a simple but significant prognostic tool for assessing newly diagnosed patients with PCNSL.


Asunto(s)
Linfoma no Hodgkin , Albúmina Sérica , Humanos , Pronóstico , Albúmina Sérica/metabolismo , Linfoma no Hodgkin/diagnóstico , Linfoma no Hodgkin/terapia , Linfocitos , Estudios Retrospectivos
14.
J Endovasc Ther ; : 15266028231163054, 2023 Mar 30.
Artículo en Inglés | MEDLINE | ID: mdl-36995050

RESUMEN

PURPOSE: Persistent sciatic artery (PSA) is a rare congenital vascular malformation with an incidence of approximately 0.025% to 0.04%. Persistent sciatic artery has major complications, such as aneurysms, thrombosis, and occlusion. Complications may lead to a range of serious clinical problems, and a timely diagnosis of this vascular variant is crucial to avoid life-threatening complications. CASE: A 65-year-old man was admitted to the hospital with pain and chills in the right lower extremity for 2 months, which gradually worsened. This was accompanied by numbness in the right foot for the last 10 days. Computed tomography angiography showed that the right inferior gluteal artery and right popliteal artery of the right internal iliac artery were connected, which is considered a congenital developmental variant. This was complicated by multiple thromboses of the right internal and external iliac arteries, and the right femoral artery. After admission to the hospital, the patient underwent endovascular staging surgery to relieve numbness and pain in the lower extremities. CONCLUSION: Treatment strategies can be selected based on the anatomical characteristics of PSA and superficial femoral artery. Asymptomatic patients with PSA can be closely monitored. Surgery or individualized endovascular treatment plans should be considered for patients with aneurysm formation or vascular occlusion. CLINICAL IMPACT: For the rare vascular variation of the PSA, clinicians must make a timely and accurate diagnosis. Ultrasound screening is essential, which requires experienced ultrasound doctors to be aware of vascular interpretation and develop personalized treatment plans for each patient. In this case, we adopt staged a minimally invasive intervention to solve the problem of lower limb ischemic pain for patients. This operation has the advantages of rapid recovery and less trauma, which has important reference significance for other clinicians.

15.
PLoS Genet ; 16(4): e1008735, 2020 04.
Artículo en Inglés | MEDLINE | ID: mdl-32251417

RESUMEN

The protein phosphatase Cdc25 is a key regulator of the cell cycle by activating Cdk-cyclin complexes. Cdc25 is regulated by its expression levels and post-translational mechanisms. In early Drosophila embryogenesis, Cdc25/Twine drives the fast and synchronous nuclear cycles. A pause in the cell cycle and the remodeling to a more generic cell cycle mode with a gap phase are determined by Twine inactivation and destruction in early interphase 14, in response to zygotic genome activation. Although the pseudokinase Tribbles contributes to the timely degradation of Twine, Twine levels are controlled by additional yet unknown post-translational mechanisms. Here, we apply a non-invasive method based on fluorescence fluctuation analysis (FFA) to record the absolute concentration profiles of Twine with minute-scale resolution in single living embryos. Employing this assay, we found that Protein phosphatase V (PpV), the homologue of the catalytic subunit of human PP6, ensures appropriately low Twine protein levels at the onset of interphase 14. PpV controls directly or indirectly the phosphorylation of Twine at multiple serine and threonine residues as revealed by phosphosite mapping. Mutational analysis confirmed that these sites are involved in control of Twine protein dynamics, and cell cycle remodeling is delayed in a fraction of the phosphosite mutant embryos. Our data reveal a novel mechanism for control of Twine protein levels and their significance for embryonic cell cycle remodeling.


Asunto(s)
Proteínas de Drosophila/genética , Embrión no Mamífero/metabolismo , Proteínas Nucleares/metabolismo , Fosfoproteínas Fosfatasas/metabolismo , Animales , Ciclo Celular , Proteínas de Ciclo Celular/metabolismo , Drosophila , Proteínas de Drosophila/metabolismo , Regulación del Desarrollo de la Expresión Génica , Microscopía Fluorescente/métodos , Fosforilación , Proteínas Serina-Treonina Quinasas/metabolismo , Proteolisis
16.
Medicina (Kaunas) ; 59(3)2023 Feb 23.
Artículo en Inglés | MEDLINE | ID: mdl-36984439

RESUMEN

Dilated cardiomyopathy (DCM) is a common cause of non-ischaemic heart failure, conferring high morbidity and mortality, including sudden cardiac death due to systolic dysfunction or arrhythmic sudden death. Within the DCM cohort exists a group of patients with familial disease. In this article we review the pathophysiology and cardiac imaging findings of familial DCM, with specific attention to known disease subtypes. The role of advanced cardiac imaging cardiovascular magnetic resonance is still accumulating, and there remains much to be elucidated. We discuss its potential clinical roles as currently known, with respect to diagnostic utility and risk stratification. Advances in such risk stratification may help target pharmacological and device therapies to those at highest risk.


Asunto(s)
Cardiomiopatía Dilatada , Insuficiencia Cardíaca , Humanos , Cardiomiopatía Dilatada/diagnóstico por imagen , Cardiomiopatía Dilatada/patología , Imagen por Resonancia Magnética , Muerte Súbita Cardíaca/etiología
17.
J Am Chem Soc ; 144(38): 17477-17486, 2022 Sep 28.
Artículo en Inglés | MEDLINE | ID: mdl-36122375

RESUMEN

Polymers designed with a specific combination of electrochemical, mechanical, and chemical properties could help overcome challenges limiting practical all-solid-state batteries for high-performance next-generation energy storage devices. In composite cathodes, comprising active cathode material, inorganic solid electrolyte, and carbon, battery longevity is limited by active particle volume changes occurring on charge/discharge. To overcome this, impractical high pressures are applied to maintain interfacial contact. Herein, block polymers designed to address these issues combine ionic conductivity, electrochemical stability, and suitable elastomeric mechanical properties, including adhesion. The block polymers have "hard-soft-hard", ABA, block structures, where the soft "B" block is poly(ethylene oxide) (PEO), known to promote ionic conductivity, and the hard "A" block is a CO2-derived polycarbonate, poly(4-vinyl cyclohexene oxide carbonate), which provides mechanical rigidity and enhances oxidative stability. ABA block polymers featuring controllable PEO and polycarbonate lengths are straightforwardly prepared using hydroxyl telechelic PEO as a macroinitiator for CO2/epoxide ring-opening copolymerization and a well-controlled Mg(II)Co(II) catalyst. The influence of block polymer composition upon electrochemical and mechanical properties is investigated, with phosphonic acid functionalities being installed in the polycarbonate domains for adhesive properties. Three lead polymer materials are identified; these materials show an ambient ionic conductivity of 10 -4 S cm-1, lithium-ion transport (tLi+ 0.3-0.62), oxidative stability (>4 V vs Li+/Li), and elastomeric or plastomer properties (G' 0.1-67 MPa). The best block polymers are used in composite cathodes with LiNi0.8Mn0.1Co0.1O2 active material and Li6PS5Cl solid electrolyte-the resulting solid-state batteries demonstrate greater capacity retention than equivalent cells featuring no polymer or commercial polyelectrolytes.

18.
Cancer Sci ; 113(8): 2681-2692, 2022 Aug.
Artículo en Inglés | MEDLINE | ID: mdl-35637600

RESUMEN

The discovery of long noncoding RNAs (lncRNAs) has improved the understanding of development and progression in various cancer subtypes. However, the role of lncRNAs in temozolomide (TMZ) resistance in glioblastoma multiforme (GBM) remains largely undefined. In this present study, the differential expression of lncRNAs was identified between U87 and U87 TMZ-resistant (TR) cells. lncRNA XLOC013218 (XLOC) was drastically upregulated in TR cells and was associated with poor prognosis in glioma. Overexpression of XLOC markedly increased TMZ resistance, promoted proliferation, and inhibited apoptosis in vitro and in vivo. In addition, RNA-seq analysis and gain-of-function or loss-of-function studies revealed that PIK3R2 was the potential target of XLOC. Mechanistically, XLOC recruited specificity protein 1 (Sp1) transcription factor and promoted the binding of Sp1 to the promoters of PIK3R2, which elevated the expression of PIK3R2 in both mRNA and protein levels. Finally, PIK3R2-mediated activation of the PI3K/AKT signaling pathway promoted TMZ resistance and cell proliferation, but inhibited cell apoptosis. In conclusion, these data highlight the vital role of the XLOC/Sp1/PIK3R2/PI3K/AKT axis in GBM TMZ resistance.


Asunto(s)
Neoplasias Encefálicas , Resistencia a Antineoplásicos , Glioblastoma , Glioma , Fosfatidilinositol 3-Quinasas , ARN Largo no Codificante , Neoplasias Encefálicas/tratamiento farmacológico , Neoplasias Encefálicas/genética , Línea Celular Tumoral , Proliferación Celular/genética , Resistencia a Antineoplásicos/genética , Regulación Neoplásica de la Expresión Génica , Glioblastoma/tratamiento farmacológico , Glioblastoma/genética , Glioma/tratamiento farmacológico , Glioma/genética , Humanos , Fosfatidilinositol 3-Quinasas/genética , Fosfatidilinositol 3-Quinasas/metabolismo , Proteínas Proto-Oncogénicas c-akt/metabolismo , ARN Largo no Codificante/genética , Temozolomida/farmacología , Factores de Transcripción/genética
19.
Anal Chem ; 94(12): 5048-5054, 2022 03 29.
Artículo en Inglés | MEDLINE | ID: mdl-35297614

RESUMEN

There is keen research interest in building highly effective semiconductor-based surface-enhanced Raman scattering (SERS) platforms, due to their selectivity for many probe molecules and suitability for complex scenario applications. However, current tuning approaches have not yet been successful in creating semiconductor-based SERS sensors for small inorganic molecules, due to the challenge of creating sufficient SERS enhancement in semiconductors. Here, we demonstrate the use of MoO3·xH2O quantum dots (QDs), to achieve direct and sensitive fingerprinting of the inorganic species hydrazine, which is a first attempt in semiconductor-based SERS research, as well as various other probe molecules. The resulting SERS platform that uses QDs with average size of 2.2 nm could successfully detect the signal of hydrazine with a limit of detection estimated to be around 4 × 10-5 M, significantly lowering the detectable concentration by at least 1000-fold, in sharp contrast to the weak performance of 10 and 100 nm particles, demonstrating that quantum size effect triggered by small particle size below the Bohr radius is crucially responsible for high SERS activity. The significantly enhanced SERS activity is a result of vibronically coupled multipathway, highly efficient charge-transfer resonances induced by the divergence of energy states in quantum-sized MoO3·xH2O. This is a proof-of-concept demonstration of the exploitation of quantum size effect, toward significantly enhanced intrinsic SERS activity in semiconductor-based SERS materials.


Asunto(s)
Puntos Cuánticos , Tamaño de la Partícula , Semiconductores , Espectrometría Raman/métodos
20.
Nat Mater ; 20(8): 1121-1129, 2021 08.
Artículo en Inglés | MEDLINE | ID: mdl-33888903

RESUMEN

Lithium dendrite (filament) propagation through ceramic electrolytes, leading to short circuits at high rates of charge, is one of the greatest barriers to realizing high-energy-density all-solid-state lithium-anode batteries. Utilizing in situ X-ray computed tomography coupled with spatially mapped X-ray diffraction, the propagation of cracks and the propagation of lithium dendrites through the solid electrolyte have been tracked in a Li/Li6PS5Cl/Li cell as a function of the charge passed. On plating, cracking initiates with spallation, conical 'pothole'-like cracks that form in the ceramic electrolyte near the surface with the plated electrode. The spallations form predominantly at the lithium electrode edges where local fields are high. Transverse cracks then propagate from the spallations across the electrolyte from the plated to the stripped electrode. Lithium ingress drives the propagation of the spallation and transverse cracks by widening the crack from the rear; that is, the crack front propagates ahead of the Li. As a result, cracks traverse the entire electrolyte before the Li arrives at the other electrode, and therefore before a short circuit occurs.

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