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

RESUMO

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.


Assuntos
Anfíbios , Biodiversidade , Filogenia , Animais , Anfíbios/classificação , China , Conservação dos Recursos Naturais
2.
Proc Natl Acad Sci U S A ; 120(13): e2210796120, 2023 03 28.
Artigo em Inglês | MEDLINE | ID: mdl-36947513

RESUMO

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.


Assuntos
Peróxido de Hidrogênio , Leucemia Mieloide Aguda , Camundongos , Animais , Leucemia Mieloide Aguda/tratamento farmacológico , Leucemia Mieloide Aguda/genética , Leucemia Mieloide Aguda/metabolismo , Oxirredução , Camundongos Transgênicos , Resistencia a Medicamentos Antineoplásicos/genética
3.
Proc Natl Acad Sci U S A ; 119(34): e2203919119, 2022 08 23.
Artigo em Inglês | MEDLINE | ID: mdl-35969783

RESUMO

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.


Assuntos
Vírus da Influenza A Subtipo H1N1 , Infecções por Orthomyxoviridae , RNA Polimerase Dependente de RNA , Doenças dos Suínos , Animais , Furões , Genótipo , Vírus da Influenza A Subtipo H1N1/genética , Vírus da Influenza A Subtipo H1N1/patogenicidade , Camundongos , Mutação , Neuraminidase/genética , Infecções por Orthomyxoviridae/veterinária , Infecções por Orthomyxoviridae/virologia , Filogenia , RNA Polimerase Dependente de RNA/genética , Vírus Reordenados/genética , Suínos , Doenças dos Suínos/virologia , Proteínas Virais/genética
4.
Proc Natl Acad Sci U S A ; 119(13): e2116342119, 2022 03 29.
Artigo em Inglês | MEDLINE | ID: mdl-35286217

RESUMO

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.


Assuntos
Locomoção , Árvores , Adaptação Fisiológica/genética , Animais , Anuros , Evolução Biológica , Fenômenos Biomecânicos , Genômica , Humanos , Locomoção/genética
5.
Proc Natl Acad Sci U S A ; 119(40): e2123030119, 2022 10 04.
Artigo em Inglês | MEDLINE | ID: mdl-36161902

RESUMO

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.


Assuntos
Adaptação Biológica , Evolução Biológica , Lorisidae , Adaptação Biológica/genética , Animais , Demografia , Hibernação , Lorisidae/genética , Metagenômica , Metaloendopeptidases/genética
6.
Proc Natl Acad Sci U S A ; 119(46): e2212406119, 2022 Nov 15.
Artigo em Inglês | MEDLINE | ID: mdl-36346846

RESUMO

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.


Assuntos
Anuros , Raios Ultravioleta , Animais , Anuros/genética , Pele , Perfilação da Expressão Gênica , Antioxidantes
7.
Mol Biol Evol ; 40(1)2023 01 04.
Artigo em Inglês | MEDLINE | ID: mdl-36625089

RESUMO

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.


Assuntos
Cromatina , Genoma , Animais , Bovinos
8.
Mol Biol Evol ; 40(8)2023 08 03.
Artigo em Inglês | MEDLINE | ID: mdl-37433053

RESUMO

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.


Assuntos
Lobos , Cães , Animais , Lobos/genética , Herança Multifatorial , Genoma , Genômica , Sequência de Bases
9.
Radiology ; 312(3): e240885, 2024 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-39287525

RESUMO

Background The specialization and complexity of radiology makes the automatic generation of radiologic impressions (ie, a diagnosis with differential diagnosis and management recommendations) challenging. Purpose To develop a large language model (LLM) that generates impressions based on imaging findings and to evaluate its performance in professional and linguistic dimensions. Materials and Methods Six radiologists recorded imaging examination findings from August 2 to 31, 2023, at Shanghai General Hospital and used the developed LLM before routinely writing report impressions for multiple radiologic modalities (CT, MRI, radiography, mammography) and anatomic sites (cranium and face, neck, chest, upper abdomen, lower abdomen, vessels, bone and joint, spine, breast), making necessary corrections and completing the radiologic impression. A subset was defined to investigate cases where the LLM-generated impressions differed from the final radiologist impressions by excluding identical and highly similar cases. An expert panel scored the LLM-generated impressions on a five-point Likert scale (5 = strongly agree) based on scientific terminology, coherence, specific diagnosis, differential diagnosis, management recommendations, correctness, comprehensiveness, harmlessness, and lack of bias. Results In this retrospective study, an LLM was pretrained using 20 GB of medical and general-purpose text data. The fine-tuning data set comprised 1.5 GB of data, including 800 radiology reports with paired instructions (describing the output task in natural language) and outputs. Test set 2 included data from 3988 patients (median age, 56 years [IQR, 40-68 years]; 2159 male). The median recall, precision, and F1 score of LLM-generated impressions were 0.775 (IQR, 0.56-1), 0.84 (IQR, 0.611-1), and 0.772 (IQR, 0.578-0.957), respectively, using the final impressions as the reference standard. In a subset of 1014 patients (median age, 57 years [IQR, 42-69 years]; 528 male), the overall median expert panel score for LLM-generated impressions was 5 (IQR, 5-5), ranging from 4 (IQR, 3-5) to 5 (IQR, 5-5). Conclusion The developed LLM generated radiologic impressions that were professionally and linguistically appropriate for a full spectrum of radiology examinations. © RSNA, 2024 Supplemental material is available for this article.


Assuntos
Diagnóstico por Imagem , Humanos , Estudos Retrospectivos , Masculino , Feminino , Pessoa de Meia-Idade , Adulto , Idoso , Diagnóstico Diferencial , Diagnóstico por Imagem/métodos , Processamento de Linguagem Natural
10.
Mol Phylogenet Evol ; 201: 108194, 2024 Sep 12.
Artigo em Inglês | MEDLINE | ID: mdl-39276821

RESUMO

Our intensive surveys of wild drosophilids in East and Southeast Asia discovered a great species diversity (more than 100 putatively new species) of the genus Dichaetophora, which is currently comprised of 67 formally described species assigned into five species groups, i.e., agbo, tenuicauda, acutissima, sinensis and trilobita. In the present study, we delimited species from a huge amount of samples of Dichaetophora and allied taxa (the genus Mulgravea and the subgenus Dudaica of Drosophila) collected from a wide range of the Oriental and east Palearctic regions. We first sorted all specimens into morpho-species, and representative specimen(s) selected from each morpho-species were subjected to barcoding of COI (the cytochrome c oxidase subunit I gene) sequences. The applied ASAP (Assemble Species by Automatic Partitioning) analysis estimated a total of 166 to 168 MOTUs (molecular operational taxonomic units). Integrating this result with morphological evidence from re-examined, detailed structures of male terminalia, we recognized a total of 144 (109 new and 35 known) species in our sample. Out of them, 83 species representing the supraspecific taxa of Dichaetophora, Mulgravea and Dudaica were selected, along with 33 species from major genera and subgenera of Drosophila in the tribe Drosophilini, as in-group and four species from the tribe Colocasiomyini as out-group for phylogenetic reconstruction based on 12 nuclear gene markers. In the trees constructed by the maximum likelihood and Bayesian inference methods, the three focal taxa (i.e., Dichaetophora, Mulgravea and Dudaica) formed a clade provisionally called the "pan-Dichaetophora". Within this large clade, the agbo, tenuicauda, sinensis and trilobita groups of Dichaetophora, Mulgravea and Dudaica were recovered as monophyletic groups, but Dichaetophora and its acutissima group were regarded as paraphyletic. In addition, two clusters were recognized among ungrouped species of Dichaetophora. Thus, the present study has uncovered some issues concerning the taxonomy of the pan-Dichaetophora. Such issues will be addressed elsewhere in the phylogenetic reclassification of the pan-Dichaetophora, along with descriptions/redescriptions of a large number of new/known species delimited in the present study.

11.
Blood ; 139(10): 1529-1540, 2022 03 10.
Artigo em Inglês | MEDLINE | ID: mdl-34929029

RESUMO

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.


Assuntos
Proteína 2 Semelhante a Angiopoietina/metabolismo , Medula Óssea , Animais , Medula Óssea/metabolismo , Células da Medula Óssea , Células Endoteliais , Células-Tronco Hematopoéticas/metabolismo , Camundongos , Nicho de Células-Tronco
12.
Opt Lett ; 49(6): 1481-1484, 2024 Mar 15.
Artigo em Inglês | MEDLINE | ID: mdl-38489430

RESUMO

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.

13.
Chemistry ; 30(23): e202304218, 2024 Apr 22.
Artigo em Inglês | MEDLINE | ID: mdl-38362832

RESUMO

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.

14.
Mol Psychiatry ; 28(9): 3739-3750, 2023 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-37848710

RESUMO

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.


Assuntos
Transtorno do Espectro Autista , Animais , Cães , Humanos , Transtorno do Espectro Autista/genética , Sistemas CRISPR-Cas/genética , Modelos Animais de Doenças , Edição de Genes , Proteínas dos Microfilamentos/genética , Proteínas do Tecido Nervoso/genética , Proteínas do Tecido Nervoso/metabolismo
15.
Eur Radiol ; 34(8): 4909-4919, 2024 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-38193925

RESUMO

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.


Assuntos
Inteligência Artificial , Angiografia por Tomografia Computadorizada , Angiografia Coronária , Doença da Artéria Coronariana , Humanos , Masculino , Feminino , Pessoa de Meia-Idade , Angiografia por Tomografia Computadorizada/métodos , Doença da Artéria Coronariana/diagnóstico por imagem , Estudos Prospectivos , Angiografia Coronária/métodos , Medição de Risco , Interpretação de Imagem Radiográfica Assistida por Computador/métodos , Idoso , Fluxo de Trabalho
16.
Microb Cell Fact ; 23(1): 198, 2024 Jul 17.
Artigo em Inglês | MEDLINE | ID: mdl-39014373

RESUMO

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.


Assuntos
Engenharia Metabólica , Metanol , Saccharomycetales , Metanol/metabolismo , Saccharomycetales/metabolismo , Saccharomycetales/genética , Engenharia Metabólica/métodos , Oxirredutases do Álcool/genética , Oxirredutases do Álcool/metabolismo , Formaldeído/metabolismo , Aldeído Oxirredutases/metabolismo , Aldeído Oxirredutases/genética , NAD/metabolismo
17.
BMC Gastroenterol ; 24(1): 239, 2024 Jul 29.
Artigo em Inglês | MEDLINE | ID: mdl-39075342

RESUMO

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.


Assuntos
Movimento Celular , Proliferação de Células , Enzimas Reparadoras do DNA , Invasividade Neoplásica , Monoéster Fosfórico Hidrolases , Neoplasias Gástricas , Ubiquitina Tiolesterase , Humanos , Apoptose , Linhagem Celular Tumoral , Proliferação de Células/genética , Sobrevivência Celular , Enzimas Reparadoras do DNA/metabolismo , Enzimas Reparadoras do DNA/genética , Monoéster Fosfórico Hidrolases/metabolismo , Monoéster Fosfórico Hidrolases/genética , RNA Interferente Pequeno , Neoplasias Gástricas/patologia , Neoplasias Gástricas/metabolismo , Neoplasias Gástricas/genética , Ubiquitina Tiolesterase/metabolismo , Ubiquitina Tiolesterase/genética , Ubiquitinação , Nudix Hidrolases/genética , Nudix Hidrolases/metabolismo
18.
Nanotechnology ; 35(20)2024 Feb 28.
Artigo em Inglês | MEDLINE | ID: mdl-38346336

RESUMO

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.

19.
Environ Res ; 247: 118158, 2024 Apr 15.
Artigo em Inglês | MEDLINE | ID: mdl-38224936

RESUMO

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.


Assuntos
Alginatos , Carvão Vegetal , Águas Residuárias , Microesferas , Sulfadiazina , Fenômenos Magnéticos
20.
J Opt Soc Am A Opt Image Sci Vis ; 41(3): DH1, 2024 Mar 01.
Artigo em Inglês | MEDLINE | ID: mdl-38437447

RESUMO

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.

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