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1.
Proc Natl Acad Sci U S A ; 121(20): e2320674121, 2024 May 14.
Artículo en Inglés | MEDLINE | ID: mdl-38684007

RESUMEN

Identifying and protecting hotspots of endemism and species richness is crucial for mitigating the global biodiversity crisis. However, our understanding of spatial diversity patterns is far from complete, which severely limits our ability to conserve biodiversity hotspots. Here, we report a comprehensive analysis of amphibian species diversity in China, one of the most species-rich countries on Earth. Our study combines 20 y of field surveys with new molecular analyses of 521 described species and also identifies 100 potential cryptic species. We identify 10 hotspots of amphibian diversity in China, each with exceptional species richness and endemism and with exceptional phylogenetic diversity and phylogenetic endemism (based on a new time-calibrated, species-level phylogeny for Chinese amphibians). These 10 hotspots encompass 59.6% of China's described amphibian species, 49.0% of cryptic species, and 55.6% of species endemic to China. Only four of these 10 hotspots correspond to previously recognized biodiversity hotspots. The six new hotspots include the Nanling Mountains and other mountain ranges in South China. Among the 186 species in the six new hotspots, only 9.7% are well covered by protected areas and most (88.2%) are exposed to high human impacts. Five of the six new hotspots are under very high human pressure and are in urgent need of protection. We also find that patterns of richness in cryptic species are significantly related to those in described species but are not identical.


Asunto(s)
Anfibios , Biodiversidad , Filogenia , Animales , Anfibios/clasificación , China , Conservación de los Recursos Naturales
2.
Proc Natl Acad Sci U S A ; 120(13): e2210796120, 2023 03 28.
Artículo en Inglés | MEDLINE | ID: mdl-36947513

RESUMEN

Rewiring of redox metabolism has a profound impact on tumor development, but how the cellular heterogeneity of redox balance affects leukemogenesis remains unknown. To precisely characterize the dynamic change in redox metabolism in vivo, we developed a bright genetically encoded biosensor for H2O2 (named HyPerion) and tracked the redox state of leukemic cells in situ in a transgenic sensor mouse. A H2O2-low (HyPerion-low) subset of acute myeloid leukemia (AML) cells was enriched with leukemia-initiating cells, which were endowed with high colony-forming ability, potent drug resistance, endosteal rather than vascular localization, and short survival. Significantly high expression of malic enzymes, including ME1/3, accounted for nicotinamide adenine dinucleotide phosphate (NADPH) production and the subsequent low abundance of H2O2. Deletion of malic enzymes decreased the population size of leukemia-initiating cells and impaired their leukemogenic capacity and drug resistance. In summary, by establishing an in vivo redox monitoring tool at single-cell resolution, this work reveals a critical role of redox metabolism in leukemogenesis and a potential therapeutic target.


Asunto(s)
Peróxido de Hidrógeno , Leucemia Mieloide Aguda , Ratones , Animales , Leucemia Mieloide Aguda/tratamiento farmacológico , Leucemia Mieloide Aguda/genética , Leucemia Mieloide Aguda/metabolismo , Oxidación-Reducción , Ratones Transgénicos , Resistencia a Antineoplásicos/genética
3.
Proc Natl Acad Sci U S A ; 119(34): e2203919119, 2022 08 23.
Artículo en Inglés | MEDLINE | ID: mdl-35969783

RESUMEN

Previous studies have shown that the Eurasian avian-like H1N1 (EA H1N1) swine influenza viruses circulated widely in pigs around the world and formed multiple genotypes by acquiring non-hemagglutinin and neuraminidase segments derived from other swine influenza viruses. Swine influenza control is not a priority for the pig industry in many countries, and it is worrisome that some strains may become more pathogenic and/or transmissible during their circulation in nature. Our routine surveillance indicated that the EA H1N1 viruses obtained different internal genes from different swine influenza viruses and formed various new genotypes. In this study, we found that a naturally isolated swine influenza reassortant, A/swine/Liaoning/265/2017 (LN265), a representative strain of one of the predominant genotypes in recent years, is lethal in mice and transmissible in ferrets. LN265 contains the hemagglutinin, neuraminidase, and matrix of the EA H1N1 virus; the basic polymerase 2, basic polymerase 1, acidic polymerase (PA), and nucleoprotein of the 2009 H1N1 pandemic virus; and the nonstructural protein of the North American triple-reassortment H1N2 virus. By generating and testing a series of reassortants and mutants, we found that four gradually accumulated mutations in PA are responsible for the increased pathogenicity and transmissibility of LN265. We further revealed that these mutations increase the messenger RNA transcription of viral proteins by enhancing the endonuclease cleavage activity and viral RNA-binding ability of the PA protein. Our study demonstrates that EA H1N1 swine influenza virus became pathogenic and transmissible in ferrets by acquiring key mutations in PA and provides important insights for monitoring field strains with pandemic potential.


Asunto(s)
Subtipo H1N1 del Virus de la Influenza A , Infecciones por Orthomyxoviridae , ARN Polimerasa Dependiente del ARN , Enfermedades de los Porcinos , Animales , Hurones , Genotipo , Subtipo H1N1 del Virus de la Influenza A/genética , Subtipo H1N1 del Virus de la Influenza A/patogenicidad , Ratones , Mutación , Neuraminidasa/genética , Infecciones por Orthomyxoviridae/veterinaria , Infecciones por Orthomyxoviridae/virología , Filogenia , ARN Polimerasa Dependiente del ARN/genética , Virus Reordenados/genética , Porcinos , Enfermedades de los Porcinos/virología , Proteínas Virales/genética
4.
Proc Natl Acad Sci U S A ; 119(13): e2116342119, 2022 03 29.
Artículo en Inglés | MEDLINE | ID: mdl-35286217

RESUMEN

SignificanceTo adapt to arboreal lifestyles, treefrogs have evolved a suite of complex traits that support vertical movement and gliding, thus presenting a unique case for studying the genetic basis for traits causally linked to vertical niche expansion. Here, based on two de novo-assembled Asian treefrog genomes, we determined that genes involved in limb development and keratin cytoskeleton likely played a role in the evolution of their climbing systems. Behavioral and morphological evaluation and time-ordered gene coexpression network analysis revealed the developmental patterns and regulatory pathways of the webbed feet used for gliding in Rhacophorus kio.


Asunto(s)
Locomoción , Árboles , Adaptación Fisiológica/genética , Animales , Anuros , Evolución Biológica , Fenómenos Biomecánicos , Genómica , Humanos , Locomoción/genética
5.
Proc Natl Acad Sci U S A ; 119(40): e2123030119, 2022 10 04.
Artículo en Inglés | MEDLINE | ID: mdl-36161902

RESUMEN

Lorises are a group of globally threatened strepsirrhine primates that exhibit many unusual physiological and behavioral features, including a low metabolic rate, slow movement, and hibernation. Here, we assembled a chromosome-level genome sequence of the pygmy loris (Xanthonycticebus pygmaeus) and resequenced whole genomes from 50 pygmy lorises and 6 Bengal slow lorises (Nycticebus bengalensis). We found that many gene families involved in detoxification have been specifically expanded in the pygmy loris, including the GSTA gene family, with many newly derived copies functioning specifically in the liver. We detected many genes displaying evolutionary convergence between pygmy loris and koala, including PITRM1. Significant decreases in PITRM1 enzymatic activity in these two species may have contributed to their characteristic low rate of metabolism. We also detected many evolutionarily convergent genes and positively selected genes in the pygmy loris that are involved in muscle development. Functional assays demonstrated the decreased ability of one positively selected gene, MYOF, to up-regulate the fast-type muscle fiber, consistent with the lower proportion of fast-twitch muscle fibers in the pygmy loris. The protein product of another positively selected gene in the pygmy loris, PER2, exhibited weaker binding to the key circadian core protein CRY, a finding that may be related to this species' unusual circadian rhythm. Finally, population genomics analysis revealed that these two extant loris species, which coexist in the same habitat, have exhibited an inverse relationship in terms of their demography over the past 1 million years, implying strong interspecies competition after speciation.


Asunto(s)
Adaptación Biológica , Evolución Biológica , Lorisidae , Adaptación Biológica/genética , Animales , Demografía , Hibernación , Lorisidae/genética , Metagenómica , Metaloendopeptidasas/genética
6.
Proc Natl Acad Sci U S A ; 119(46): e2212406119, 2022 Nov 15.
Artículo en Inglés | MEDLINE | ID: mdl-36346846

RESUMEN

Defense against ultraviolet (UV) radiation exposure is essential for survival, especially in high-elevation species. Although some specific genes involved in UV response have been reported, the full view of UV defense mechanisms remains largely unexplored. Herein, we used integrated approaches to analyze UV responses in the highest-elevation frog, Nanorana parkeri. We show less damage and more efficient antioxidant activity in skin of this frog than those of its lower-elevation relatives after UV exposure. We also reveal genes related to UV defense and a corresponding temporal expression pattern in N. parkeri. Genomic and metabolomic analysis along with large-scale transcriptomic profiling revealed a time-dependent coordinated defense mechanism in N. parkeri. We also identified several microRNAs that play important regulatory roles, especially in decreasing the expression levels of cell cycle genes. Moreover, multiple defense genes (i.e., TYR for melanogenesis) exhibit positive selection with function-enhancing substitutions. Thus, both expression shifts and gene mutations contribute to UV adaptation in N. parkeri. Our work demonstrates a genetic framework for evolution of UV defense in a natural environment.


Asunto(s)
Anuros , Rayos Ultravioleta , Animales , Anuros/genética , Piel , Perfilación de la Expresión Génica , Antioxidantes
7.
Mol Biol Evol ; 40(1)2023 01 04.
Artículo en Inglés | MEDLINE | ID: mdl-36625089

RESUMEN

Determining the functional consequences of karyotypic changes is invariably challenging because evolution tends to obscure many of its own footprints, such as accumulated mutations, recombination events, and demographic perturbations. Here, we describe the assembly of a chromosome-level reference genome of the gayal (Bos frontalis) thereby revealing the structure, at base-pair-level resolution, of a telo/acrocentric-to-telo/acrocentric Robertsonian translocation (2;28) (T/A-to-T/A rob[2;28]). The absence of any reduction in the recombination rate or genetic introgression within the fusion region of gayal served to challenge the long-standing view of a role for fusion-induced meiotic dysfunction in speciation. The disproportionate increase noted in the distant interactions across pro-chr2 and pro-chr28, and the change in open-chromatin accessibility following rob(2;28), may, however, have led to the various gene expression irregularities observed in the gayal. Indeed, we found that many muscle-related genes, located synthetically on pro-chr2 and pro-chr28, exhibited significant changes in expression. This, combined with genome-scale structural variants and expression alterations in genes involved in myofibril composition, may have driven the rapid sarcomere adaptation of gayal to its rugged mountain habitat. Our findings not only suggest that large-scale chromosomal changes can lead to alterations in genome-level expression, thereby promoting both adaptation and speciation, but also illuminate novel avenues for studying the relationship between karyotype evolution and speciation.


Asunto(s)
Cromatina , Genoma , Animales , Bovinos
8.
Mol Biol Evol ; 40(8)2023 08 03.
Artículo en Inglés | MEDLINE | ID: mdl-37433053

RESUMEN

Sighthounds, a distinctive group of hounds comprising numerous breeds, have their origins rooted in ancient artificial selection of dogs. In this study, we performed genome sequencing for 123 sighthounds, including one breed from Africa, six breeds from Europe, two breeds from Russia, and four breeds and 12 village dogs from the Middle East. We gathered public genome data of five sighthounds and 98 other dogs as well as 31 gray wolves to pinpoint the origin and genes influencing the morphology of the sighthound genome. Population genomic analysis suggested that sighthounds originated from native dogs independently and were comprehensively admixed among breeds, supporting the multiple origins hypothesis of sighthounds. An additional 67 published ancient wolf genomes were added for gene flow detection. Results showed dramatic admixture of ancient wolves in African sighthounds, even more than with modern wolves. Whole-genome scan analysis identified 17 positively selected genes (PSGs) in the African population, 27 PSGs in the European population, and 54 PSGs in the Middle Eastern population. None of the PSGs overlapped in the three populations. Pooled PSGs of the three populations were significantly enriched in "regulation of release of sequestered calcium ion into cytosol" (gene ontology: 0051279), which is related to blood circulation and heart contraction. In addition, ESR1, JAK2, ADRB1, PRKCE, and CAMK2D were under positive selection in all three selected groups. This suggests that different PSGs in the same pathway contributed to the similar phenotype of sighthounds. We identified an ESR1 mutation (chr1: g.42,177,149 T > C) in the transcription factor (TF) binding site of Stat5a and a JAK2 mutation (chr1: g.93,277,007 T > A) in the TF binding site of Sox5. Functional experiments confirmed that the ESR1 and JAK2 mutation reduced their expression. Our results provide new insights into the domestication history and genomic basis of sighthounds.


Asunto(s)
Lobos , Perros , Animales , Lobos/genética , Herencia Multifactorial , Genoma , Genómica , Secuencia de Bases
9.
Blood ; 139(10): 1529-1540, 2022 03 10.
Artículo en Inglés | MEDLINE | ID: mdl-34929029

RESUMEN

Bone marrow niche cells have been reported to fine-tune hematopoietic stem cell (HSC) stemness via direct interaction or secreted components. Nevertheless, how niche cells control HSC activities remains largely unknown. We previously showed that angiopoietin-like protein 2 (ANGPTL2) can support the ex vivo expansion of HSCs by binding to human leukocyte immunoglobulin-like receptor B2. However, how ANGPTL2 from specific niche cell types regulates HSC activities under physiological conditions is still not clear. Herein, we generated an Angptl2-flox/flox transgenic mouse line and conditionally deleted Angptl2 expression in several niche cells, including Cdh5+ or Tie2+ endothelial cells, Prx1+ mesenchymal stem cells, and Pf4+ megakaryocytes, to evaluate its role in the regulation of HSC fate. Interestingly, we demonstrated that only endothelial cell-derived ANGPTL2 and not ANGPTL2 from other niche cell types plays important roles in supporting repopulation capacity, quiescent status, and niche localization. Mechanistically, ANGPTL2 enhances peroxisome-proliferator-activated receptor D (PPARD) expression to transactivate G0s2 to sustain the perinuclear localization of nucleolin to prevent HSCs from entering the cell cycle. These findings reveal that endothelial cell-derived ANGPTL2 serves as a critical niche component to maintain HSC stemness, which may benefit the understanding of stem cell biology in bone marrow niches and the development of a unique strategy for the ex vivo expansion of HSCs.


Asunto(s)
Proteína 2 Similar a la Angiopoyetina/metabolismo , Médula Ósea , Animales , Médula Ósea/metabolismo , Células de la Médula Ósea , Células Endoteliales , Células Madre Hematopoyéticas/metabolismo , Ratones , Nicho de Células Madre
10.
Opt Lett ; 49(6): 1481-1484, 2024 Mar 15.
Artículo en Inglés | MEDLINE | ID: mdl-38489430

RESUMEN

We propose a novel, to the best of our knowledge, and fast adaptive layer-based (ALB) method for generating a computer-generated hologram (CGH) with accurate depth information. A complex three-dimensional (3D) object is adaptively divided into layers along the depth direction according to its own non-uniformly distributed depth coordinates, which reduces the depth error caused by the conventional layer-based method. Each adaptive layer generates a single-layer hologram using the angular spectrum method for diffraction, and the final hologram of a complex three-dimensional object is obtained by superimposing all the adaptive layer holograms. A hologram derived with the proposed method is referred to as an adaptive layer-based hologram (ALBH). Our demonstration shows that the desired reconstruction can be achieved with 52 adaptive layers in 8.7 s, whereas the conventional method requires 397 layers in 74.9 s.

11.
Chemistry ; 30(23): e202304218, 2024 Apr 22.
Artículo en Inglés | MEDLINE | ID: mdl-38362832

RESUMEN

Based on our previous study in chemical subtleties of the proton tunneling distance for metal hydride formation (PTD-MH) to regulate the selectivity of CO2 reduction reaction (CO2RR), we have developed a family of Mn terpyridine derivatives, in which urea groups functions as multipoint hydrogen-bonding hangman to accelerate the reaction rate. We found that such changes to the second coordination sphere significantly increased the turnover frequency (TOF) for CO2 reduction to ca. 360 s - 1 ${{s}^{-1}}$ with this family of molecular catalysts while maintaining high selectivity (ca. 100 %±3) for CO even in the presence of a large amount of phenol as proton source. Notably, the compounds studied in this manuscript all exhibit large value for i c a t / i p ${{{\bf i}}_{{\bf c a t}}/{{\bf i}}_{{\bf p}}}$ as that achieved by Fe porphyrins derivates, while saving up to 0.55 V in overpotential with respect to the latter.

12.
Mol Psychiatry ; 28(9): 3739-3750, 2023 Sep.
Artículo en Inglés | MEDLINE | ID: mdl-37848710

RESUMEN

Despite intensive studies in modeling neuropsychiatric disorders especially autism spectrum disorder (ASD) in animals, many challenges remain. Genetic mutant mice have contributed substantially to the current understanding of the molecular and neural circuit mechanisms underlying ASD. However, the translational value of ASD mouse models in preclinical studies is limited to certain aspects of the disease due to the apparent differences in brain and behavior between rodents and humans. Non-human primates have been used to model ASD in recent years. However, a low reproduction rate due to a long reproductive cycle and a single birth per pregnancy, and an extremely high cost prohibit a wide use of them in preclinical studies. Canine model is an appealing alternative because of its complex and effective dog-human social interactions. In contrast to non-human primates, dog has comparable drug metabolism as humans and a high reproduction rate. In this study, we aimed to model ASD in experimental dogs by manipulating the Shank3 gene as SHANK3 mutations are one of most replicated genetic defects identified from ASD patients. Using CRISPR/Cas9 gene editing, we successfully generated and characterized multiple lines of Beagle Shank3 (bShank3) mutants that have been propagated for a few generations. We developed and validated a battery of behavioral assays that can be used in controlled experimental setting for mutant dogs. bShank3 mutants exhibited distinct and robust social behavior deficits including social withdrawal and reduced social interactions with humans, and heightened anxiety in different experimental settings (n = 27 for wild-type controls and n = 44 for mutants). We demonstrate the feasibility of producing a large number of mutant animals in a reasonable time frame. The robust and unique behavioral findings support the validity and value of a canine model to investigate the pathophysiology and develop treatments for ASD and potentially other psychiatric disorders.


Asunto(s)
Trastorno del Espectro Autista , Animales , Perros , Humanos , Trastorno del Espectro Autista/genética , Sistemas CRISPR-Cas/genética , Modelos Animales de Enfermedad , Edición Génica , Proteínas de Microfilamentos/genética , Proteínas del Tejido Nervioso/genética , Proteínas del Tejido Nervioso/metabolismo
13.
Eur Radiol ; 34(8): 4909-4919, 2024 Aug.
Artículo en Inglés | MEDLINE | ID: mdl-38193925

RESUMEN

OBJECTIVES: To prospectively investigate whether fully automated artificial intelligence (FAAI)-based coronary CT angiography (CCTA) image processing is non-inferior to semi-automated mode in efficiency, diagnostic ability, and risk stratification of coronary artery disease (CAD). MATERIALS AND METHODS: Adults with indications for CCTA were prospectively and consecutively enrolled at two hospitals and randomly assigned to either FAAI-based or semi-automated image processing using equipment workstations. Outcome measures were workflow efficiency, diagnostic accuracy for obstructive CAD (≥ 50% stenosis), and cardiovascular events at 2-year follow-up. The endpoints included major adverse cardiovascular events, hospitalization for unstable angina, and recurrence of cardiac symptoms. The non-inferiority margin was 3 percentage difference in diagnostic accuracy and C-index. RESULTS: In total, 1801 subjects (62.7 ± 11.1 years) were included, of whom 893 and 908 were assigned to the FAAI-based and semi-automated modes, respectively. Image processing times were 121.0 ± 18.6 and 433.5 ± 68.4 s, respectively (p <0.001). Scan-to-report release times were 6.4 ± 2.7 and 10.5 ± 3.8 h, respectively (p < 0.001). Of all subjects, 152 and 159 in the FAAI-based and semi-automated modes, respectively, subsequently underwent invasive coronary angiography. The diagnostic accuracies for obstructive CAD were 94.7% (89.9-97.7%) and 94.3% (89.5-97.4%), respectively (difference 0.4%). Of all subjects, 779 and 784 in the FAAI-based and semi-automated modes were followed for 589 ± 182 days, respectively, and the C-statistic for cardiovascular events were 0.75 (0.67 to 0.83) and 0.74 (0.66 to 0.82) (difference 1%). CONCLUSIONS: FAAI-based CCTA image processing significantly improves workflow efficiency than semi-automated mode, and is non-inferior in diagnosing obstructive CAD and risk stratification for cardiovascular events. CLINICAL RELEVANCE STATEMENT: Conventional coronary CT angiography image processing is semi-automated. This observation shows that fully automated artificial intelligence-based image processing greatly improves efficiency, and maintains high diagnostic accuracy and the effectiveness in stratifying patients for cardiovascular events. KEY POINTS: • Coronary CT angiography (CCTA) relies heavily on high-quality and fast image processing. • Full-automation CCTA image processing is clinically non-inferior to the semi-automated mode. • Full automation can facilitate the application of CCTA in early detection of coronary artery disease.


Asunto(s)
Inteligencia Artificial , Angiografía por Tomografía Computarizada , Angiografía Coronaria , Enfermedad de la Arteria Coronaria , Humanos , Masculino , Femenino , Persona de Mediana Edad , Angiografía por Tomografía Computarizada/métodos , Enfermedad de la Arteria Coronaria/diagnóstico por imagen , Estudios Prospectivos , Angiografía Coronaria/métodos , Medición de Riesgo , Interpretación de Imagen Radiográfica Asistida por Computador/métodos , Anciano , Flujo de Trabajo
14.
Microb Cell Fact ; 23(1): 198, 2024 Jul 17.
Artículo en Inglés | MEDLINE | ID: mdl-39014373

RESUMEN

BACKGROUND: Komagataella phaffii, a type of methanotrophic yeast, can use methanol, a favorable non-sugar substrate in eco-friendly bio-manufacturing. The dissimilation pathway in K. phaffii leads to the loss of carbon atoms in the form of CO2. However, the ΔFLD strain, engineered to lack formaldehyde dehydrogenase-an essential enzyme in the dissimilation pathway-displayed growth defects when exposed to a methanol-containing medium. RESULTS: Inhibiting the dissimilation pathway triggers an excessive accumulation of formaldehyde and a decline in the intracellular NAD+/NADH ratio. Here, we designed dual-enzyme complex with the alcohol oxidase1/dihydroxyacetone synthase1 (Aox1/Das1), enhancing the regeneration of the formaldehyde receptor xylulose-5-phosphate (Xu5P). This strategy mitigated the harmful effects of formaldehyde accumulation and associated toxicity to cells. Concurrently, we elevated the NAD+/NADH ratio by overexpressing isocitrate dehydrogenase in the TCA cycle, promoting intracellular redox homeostasis. The OD600 of the optimized combination of the above strategies, strain DF02-1, was 4.28 times higher than that of the control strain DF00 (ΔFLD, HIS4+) under 1% methanol. Subsequently, the heterologous expression of methanol oxidase Mox from Hansenula polymorpha in strain DF02-1 resulted in the recombinant strain DF02-4, which displayed a growth at an OD600 4.08 times higher than that the control strain DF00 in medium containing 3% methanol. CONCLUSIONS: The reduction of formaldehyde accumulation, the increase of NAD+/NADH ratio, and the enhancement of methanol oxidation effectively improved the efficient utilization of a high methanol concentration by strain ΔFLD strain lacking formaldehyde dehydrogenase. The modification strategies implemented in this study collectively serve as a foundational framework for advancing the efficient utilization of methanol in K. phaffii.


Asunto(s)
Ingeniería Metabólica , Metanol , Saccharomycetales , Metanol/metabolismo , Saccharomycetales/metabolismo , Saccharomycetales/genética , Ingeniería Metabólica/métodos , Oxidorreductasas de Alcohol/genética , Oxidorreductasas de Alcohol/metabolismo , Formaldehído/metabolismo , Aldehído Oxidorreductasas/metabolismo , Aldehído Oxidorreductasas/genética , NAD/metabolismo
15.
BMC Gastroenterol ; 24(1): 239, 2024 Jul 29.
Artículo en Inglés | MEDLINE | ID: mdl-39075342

RESUMEN

BACKGROUND: MutT homolog 1 (MTH1) sanitizes oxidized dNTP pools to promote the survival of cancer cells and its expression is frequently upregulated in cancers. Polyubiquitination stabilizes MTH1 to facilitate the proliferation of melanoma cells, suggesting the ubiquitin system controls the stability and function of MTH1. However, whether ubiquitination regulates MTH1 in gastric cancers has not been well defined. This study aims to investigate the interaction between MTH1 and a deubiquitinase, USP9X, in regulating the proliferation, survival, migration, and invasion of gastric cancer cells. METHODS: The interaction between USP9X and MTH1 was evaluated by co-immunoprecipitation (co-IP) in HGC-27 gastric cancer cells. siRNAs were used to interfere with USP9X expression in gastric cancer cell lines HGC-27 and MKN-45. MTT assays were carried out to examine the proliferation, propidium iodide (PI) and 7-AAD staining assays were performed to assess the cell cycle, Annexin V/PI staining assays were conducted to examine the apoptosis, and transwell assays were used to determine the migration and invasion of control, USP9X-deficient, and USP9X-deficient plus MTH1-overexpressing HGC-27 and MKN-45 gastric cancer cells. RESULTS: Co-IP data show that USP9X interacts with and deubiquitinates MTH1. Overexpression of USP9X elevates MTH1 protein level by downregulating its ubiquitination, while knockdown of USP9X has the opposite effect on MTH1. USP9X deficiency in HGC-27 and MKN-45 cells causes decreased proliferation, cell cycle arrest, extra apoptosis, and defective migration and invasion, which could be rescued by excessive MTH1. CONCLUSION: USP9X interacts with and stabilizes MTH1 to promote the proliferation, survival, migration and invasion of gastric cancer cells.


Asunto(s)
Movimiento Celular , Proliferación Celular , Enzimas Reparadoras del ADN , Invasividad Neoplásica , Monoéster Fosfórico Hidrolasas , Neoplasias Gástricas , Ubiquitina Tiolesterasa , Humanos , Apoptosis , Línea Celular Tumoral , Proliferación Celular/genética , Supervivencia Celular , Enzimas Reparadoras del ADN/metabolismo , Enzimas Reparadoras del ADN/genética , Monoéster Fosfórico Hidrolasas/metabolismo , Monoéster Fosfórico Hidrolasas/genética , ARN Interferente Pequeño , Neoplasias Gástricas/patología , Neoplasias Gástricas/metabolismo , Neoplasias Gástricas/genética , Ubiquitina Tiolesterasa/metabolismo , Ubiquitina Tiolesterasa/genética , Ubiquitinación , Hidrolasas Nudix/genética , Hidrolasas Nudix/metabolismo
16.
Nanotechnology ; 35(20)2024 Feb 28.
Artículo en Inglés | MEDLINE | ID: mdl-38346336

RESUMEN

All-inorganic CsPbI2Br, as a promising photovoltaic (PV) material, have attracted extensive research attention in society for its outstanding thermal stability and appropriate trade-offs. Carbon-based perovskite solar cells (C-PSCs) without hole transporting layer (HTL) have shown great potential in terms of cost-effectiveness and stability. However, the inevitable defects on the surface of CsPbI2Br films severely hampers the development of high-efficiency CsPbI2Br C-PSCs. Surface engineering has emerged an effective approach to overcome this challenge. Herein, 1-decyl-3-methylimidazolium tetrafluoroborate (DMTT) ionic liquid was introduced between CsPbI2Br and carbon electrode to reduce non-recombination of charges, decrease defect states, minimize the energy-level mismatch, and greatly enhance the device stability. As a result, the HTL-free CsPbI2Br C-PSCs combined with DMTT as an interface modification achieved a higher power conversion efficiency (PCE) of 12.47% than that of the control devices with a PCE of 11.32%. Furthermore, without any encapsulation, the DMTT-optimized C-PSC remained approximately 84% of its initial PCE after over 700 h under room temperature and 25% relative humidity (RH) conditions. Additionally, when exposed to a temperature of 65 °C for over 400 h, the device still retained 74% of the initial PCE, demonstrating its thermal stability.

17.
Environ Res ; 247: 118158, 2024 Apr 15.
Artículo en Inglés | MEDLINE | ID: mdl-38224936

RESUMEN

Existing wastewater treatment technologies face the key challenge of simultaneously removing emerging contaminants and nutrients from wastewater efficiently, with a simplified technological process and minimized operational costs. In this study, a novel alginate-embedded magnetic biochar-anoxygenic photosynthetic bacteria composite microspheres (CA-MBC-PSB microspheres) was prepared for efficient, cost-effective and one-step removal of antibiotics and NH4+-N from wastewater. Our results demonstrated that the CA-MBC-PSB microspheres removed 97.23% of sulfadiazine (SDZ) within 7 h and 91% of NH4+-N within 12 h, which were 21.23% and 38% higher than those achieved by pure calcium alginate-Rhodopseudomonas palustris microspheres (53% and 45.7%), respectively. The enhanced SDZ and NH4+-N removal were attributed to the enhanced photoheterotrophic metabolism and excretion of extracellular photosensitive active substances from R. Palustris through the photo-bioelectrochemical interaction between R. Palustris and magnetic biochar. The long-term pollutants removal performance of the CA-MBC-PSB microspheres was not deteriorated but continuously improved with increasing ruse cycles with a simultaneous removal efficiency of 99% for SDZ and 92% for NH4+-N after three cycles. The excellent stability and reusability were due to the fact that calcium alginate acts as an encapsulating agent preventing the loss and contamination of R. palustris biomass. The CA-MBC-PSB microspheres also exhibited excellent performance for simultaneous removal of SDZ (89% in 7 h) and NH4+-N (90.7% in 12 h) from the secondary effluent of wastewater treatment plant, indicating the stable and efficient performance of CA-MBC-PSB microspheres in practical wastewater treatment.


Asunto(s)
Alginatos , Carbón Orgánico , Aguas Residuales , Microesferas , Sulfadiazina , Fenómenos Magnéticos
18.
J Opt Soc Am A Opt Image Sci Vis ; 41(3): DH1, 2024 Mar 01.
Artículo en Inglés | MEDLINE | ID: mdl-38437447

RESUMEN

The Optica Topical Meeting on Digital Holography and 3D Imaging (DH) was held 14-17 August 2023 in Boston, Massachusetts. The meeting was organized co-jointly with the Optica Imaging Congress. Feature issues based on the DH meeting series have been released by Applied Optics (AO) since 2007. Since 2017, AO and the Journal of the Optical Society of America A (JOSA A) have presented a feature issue in each journal. This feature issues includes 17 papers in AO and 9 in JOSA A. Together they cover a large range of topics, reflecting the rapidly expanding techniques and applications of digital holography and 3D imaging. The upcoming DH Conference (DH 2024) will be held from 3 to 6 June in Paestum, Italy.

19.
J Opt Soc Am A Opt Image Sci Vis ; 41(3): A32-A39, 2024 Mar 01.
Artículo en Inglés | MEDLINE | ID: mdl-38437421

RESUMEN

A computer-generated hologram (CGH) is a technique that generates an object light field by superimposing elementary holograms. Unlike traditional holography, this technique does not require the generation of an additional reference light to interfere with the calculated object light field. Texture mapping is a method that enhances the realism of 3D scenes. A fast method is presented that allows users to render holograms of 3D scenes consisting of triangular meshes with texture mapping. All calculations are performed with analytical expressions to ensure that the holograms generated by this method are fast and can reconstruct three-dimensional scenes with high quality. Using this method, a hologram of a three-dimensional scene consisting of thousands of triangles is generated. Our algorithm generates the same reconstruction results as those of Kim et al. [Appl. Opt.47, D117 (2008)APOPAI0003-693510.1364/AO.47.00D117], but significantly reduces the computation time (the computation time of our algorithm is only one-third of that of Kim et al.'s algorithm). The results show that the proposed method is computationally efficient as compared to a previous work. The proposed method is verified by simulations and optical experiments.

20.
Mol Cell Proteomics ; 21(8): 100261, 2022 08.
Artículo en Inglés | MEDLINE | ID: mdl-35738554

RESUMEN

Brain development and function are governed by precisely regulated protein expressions in different regions. To date, multiregional brain proteomes have been systematically analyzed only for adult human and mouse brains. To understand the underpinnings of brain development and function, we generated proteomes from six regions of the postnatal brain at three developmental stages of domestic dogs (Canis familiaris), which are special among animals in terms of their remarkable human-like social cognitive abilities. Quantitative analysis of the spatiotemporal proteomes identified region-enriched synapse types at different developmental stages and differential myelination progression in different brain regions. Through integrative analysis of inter-regional expression patterns of orthologous proteins and genome-wide cis-regulatory element frequencies, we found that proteins related with myelination and hippocampus were highly correlated between dog and human but not between mouse and human, although mouse is phylogenetically closer to human. Moreover, the global expression patterns of neurodegenerative disease and autism spectrum disorder-associated proteins in dog brain more resemble human brain than in mouse brain. The high similarity of myelination and hippocampus-related pathways in dog and human at both proteomic and genetic levels may contribute to their shared social cognitive abilities. The inter-regional expression patterns of disease-associated proteins in the brain of different species provide important information to guide mechanistic and translational study using appropriate animal models.


Asunto(s)
Trastorno del Espectro Autista , Enfermedades Neurodegenerativas , Adulto , Animales , Encéfalo , Perros , Humanos , Ratones , Proteoma , Proteómica
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