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The development of a vaccine specific to severe acute respiratory syndrome coronavirus 2 Omicron has been hampered due to its low immunogenicity. Here, using reverse mutagenesis, we found that a phenylalanine-to-serine mutation at position 375 (F375S) in the spike protein of Omicron to revert it to the sequence found in Delta and other ancestral strains significantly enhanced the immunogenicity of Omicron vaccines. Sequence FAPFFAF at position 371-377 in Omicron spike had a potent inhibitory effect on macrophage uptake of receptor-binding domain (RBD) nanoparticles or spike-pseudovirus particles containing this sequence. Omicron RBD enhanced binding to Siglec-9 on macrophages to impair phagocytosis and antigen presentation and promote immune evasion, which could be abrogated by the F375S mutation. A bivalent F375S Omicron RBD and Delta-RBD nanoparticle vaccine elicited potent and broad nAbs in mice, rabbits and rhesus macaques. Our research suggested that manipulation of the Siglec-9 pathway could be a promising approach to enhance vaccine response.
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COVID-19 , SARS-CoV-2 , Animais , Camundongos , Coelhos , Anticorpos Neutralizantes , Anticorpos Antivirais , Macaca mulatta , Macrófagos , Nanovacinas , Fagocitose , Lectinas Semelhantes a Imunoglobulina de Ligação ao Ácido SiálicoRESUMO
High-acuity vision in primates, including humans, is mediated by a small central retinal region called the fovea. As more accessible organisms lack a fovea, its specialized function and its dysfunction in ocular diseases remain poorly understood. We used 165,000 single-cell RNA-seq profiles to generate comprehensive cellular taxonomies of macaque fovea and peripheral retina. More than 80% of >60 cell types match between the two regions but exhibit substantial differences in proportions and gene expression, some of which we relate to functional differences. Comparison of macaque retinal types with those of mice reveals that interneuron types are tightly conserved. In contrast, projection neuron types and programs diverge, despite exhibiting conserved transcription factor codes. Key macaque types are conserved in humans, allowing mapping of cell-type and region-specific expression of >190 genes associated with 7 human retinal diseases. Our work provides a framework for comparative single-cell analysis across tissue regions and species.
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Fóvea Central/fisiologia , Primatas/fisiologia , Retina/fisiologia , Idoso , Animais , Callithrix , Feminino , Humanos , Macaca , Masculino , Retina/anatomia & histologia , Células Ganglionares da Retina/metabolismoRESUMO
The basic plan of the retina is conserved across vertebrates, yet species differ profoundly in their visual needs1. Retinal cell types may have evolved to accommodate these varied needs, but this has not been systematically studied. Here we generated and integrated single-cell transcriptomic atlases of the retina from 17 species: humans, two non-human primates, four rodents, three ungulates, opossum, ferret, tree shrew, a bird, a reptile, a teleost fish and a lamprey. We found high molecular conservation of the six retinal cell classes (photoreceptors, horizontal cells, bipolar cells, amacrine cells, retinal ganglion cells (RGCs) and Müller glia), with transcriptomic variation across species related to evolutionary distance. Major subclasses were also conserved, whereas variation among cell types within classes or subclasses was more pronounced. However, an integrative analysis revealed that numerous cell types are shared across species, based on conserved gene expression programmes that are likely to trace back to an early ancestral vertebrate. The degree of variation among cell types increased from the outer retina (photoreceptors) to the inner retina (RGCs), suggesting that evolution acts preferentially to shape the retinal output. Finally, we identified rodent orthologues of midget RGCs, which comprise more than 80% of RGCs in the human retina, subserve high-acuity vision, and were previously believed to be restricted to primates2. By contrast, the mouse orthologues have large receptive fields and comprise around 2% of mouse RGCs. Projections of both primate and mouse orthologous types are overrepresented in the thalamus, which supplies the primary visual cortex. We suggest that midget RGCs are not primate innovations, but are descendants of evolutionarily ancient types that decreased in size and increased in number as primates evolved, thereby facilitating high visual acuity and increased cortical processing of visual information.
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Evolução Biológica , Neurônios , Retina , Vertebrados , Visão Ocular , Animais , Humanos , Neurônios/classificação , Neurônios/citologia , Neurônios/fisiologia , Retina/citologia , Retina/fisiologia , Células Ganglionares da Retina/classificação , Análise da Expressão Gênica de Célula Única , Vertebrados/fisiologia , Visão Ocular/fisiologia , Especificidade da Espécie , Células Amácrinas/classificação , Células Fotorreceptoras/classificação , Células Ependimogliais/classificação , Células Bipolares da Retina/classificação , Percepção VisualRESUMO
Macrophages form a major cell population in the tumor microenvironment. They can be activated and polarized into tumor-associated macrophages (TAM) by the tumor-derived soluble molecules to promote tumor progression and metastasis. Here, we used comparative metabolomics coupled with biochemical and animal studies to show that cancer cells release succinate into their microenvironment and activate succinate receptor (SUCNR1) signaling to polarize macrophages into TAM. Furthermore, the results from in vitro and in vivo studies revealed that succinate promotes not only cancer cell migration and invasion but also cancer metastasis. These effects are mediated by SUCNR1-triggered PI3K-hypoxia-inducible factor 1α (HIF-1α) axis. Compared with healthy subjects and tumor-free lung tissues, serum succinate levels and lung cancer SUCNR1 expression were elevated in lung cancer patients, suggesting an important clinical relevance. Collectively, our findings indicate that the secreted tumor-derived succinate belongs to a novel class of cancer progression factors, controlling TAM polarization and promoting tumorigenic signaling.
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Neoplasias Pulmonares/metabolismo , Neoplasias Pulmonares/patologia , Macrófagos/metabolismo , Metástase Neoplásica/patologia , Receptores Acoplados a Proteínas G/metabolismo , Ácido Succínico/metabolismo , Células A549 , Animais , Linhagem Celular Tumoral , Movimento Celular/fisiologia , Células HT29 , Humanos , Subunidade alfa do Fator 1 Induzível por Hipóxia/metabolismo , Células MCF-7 , Macrófagos/patologia , Camundongos Endogâmicos C57BL , Células PC-3 , Transdução de Sinais/fisiologia , Microambiente Tumoral/fisiologiaRESUMO
The ability of neurons to rapidly remodel their synaptic structure and strength in response to neuronal activity is highly conserved across species and crucial for complex brain functions. However, mechanisms required to elicit and coordinate the acute, activity-dependent structural changes across synapses are not well understood, as neurodevelopment and structural plasticity are tightly linked. Here, using an RNAi screen in Drosophila against genes affecting nervous system functions in humans, we uncouple cellular processes important for synaptic plasticity and synapse development. We find mutations associated with neurodegenerative and mental health disorders are 2-times more likely to affect activity-induced synaptic remodeling than synapse development. We report that while both synapse development and activity-induced synaptic remodeling at the fly NMJ require macroautophagy (hereafter referred to as autophagy), bifurcation in the autophagy pathway differentially impacts development and synaptic plasticity. We demonstrate that neuronal activity enhances autophagy activation but diminishes degradative autophagy, thereby driving the pathway towards autophagy-based secretion. Presynaptic knockdown of Snap29, Sec22, or Rab8, proteins implicated in the secretory autophagy pathway, is sufficient to abolish activity-induced synaptic remodeling. This study uncovers secretory autophagy as a transsynaptic signaling mechanism modulating synaptic plasticity.
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Proteínas de Drosophila , Junção Neuromuscular , Animais , Humanos , Junção Neuromuscular/metabolismo , Sinapses/metabolismo , Drosophila/fisiologia , Neurônios/metabolismo , Autofagia/genética , Plasticidade Neuronal/genética , Proteínas de Drosophila/genética , Proteínas de Drosophila/metabolismo , Transmissão Sináptica/fisiologia , GTP Fosfo-Hidrolases/metabolismoRESUMO
In primates, high-acuity vision is mediated by the fovea, a small specialized central region of the retina. The fovea, unique to the anthropoid lineage among mammals, undergoes notable neuronal morphological changes during postnatal maturation. However, the extent of cellular similarity across anthropoid foveas and the molecular underpinnings of foveal maturation remain unclear. Here, we used high-throughput single-cell RNA sequencing to profile retinal cells of the common marmoset (Callithrix jacchus), an early divergent in anthropoid evolution from humans, apes, and macaques. We generated atlases of the marmoset fovea and peripheral retina for both neonates and adults. Our comparative analysis revealed that marmosets share almost all their foveal types with both humans and macaques, highlighting a conserved cellular structure among primate foveas. Furthermore, by tracing the developmental trajectory of cell types in the foveal and peripheral retina, we found distinct maturation paths for each. In-depth analysis of gene expression differences demonstrated that cone photoreceptors and Müller glia (MG), among others, show the greatest molecular divergence between these two regions. Utilizing single-cell ATAC-seq and gene-regulatory network inference, we uncovered distinct transcriptional regulations differentiating foveal cones from their peripheral counterparts. Further analysis of predicted ligand-receptor interactions suggested a potential role for MG in supporting the maturation of foveal cones. Together, these results provide valuable insights into foveal development, structure, and evolution.
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Callithrix , Retina , Humanos , Animais , Recém-Nascido , Callithrix/anatomia & histologia , Retina/metabolismo , Fóvea Central/fisiologia , Células Fotorreceptoras Retinianas Cones , Macaca , MamíferosRESUMO
Several cell types have been proposed to create the required microenvironment for spermatogenesis. However, expression patterns of the key growth factors produced by these somatic cells have not been systematically studied and no such factor has been conditionally deleted from its primary source(s), raising the question of which cell type(s) are the physiological sources of these growth factors. Here, using single-cell RNA sequencing and a series of fluorescent reporter mice, we found that stem cell factor (Scf), one of the essential growth factors for spermatogenesis, was broadly expressed in testicular stromal cells, including Sertoli, endothelial, Leydig, smooth muscle and Tcf21-CreER+ stromal cells. Both undifferentiated and differentiating spermatogonia were associated with Scf-expressing Sertoli cells in the seminiferous tubule. Conditional deletion of Scf from Sertoli cells, but not any other Scf-expressing cells, blocked the differentiation of spermatogonia, leading to complete male infertility. Conditional overexpression of Scf in Sertoli cells, but not endothelial cells, significantly increased spermatogenesis. Our data reveal the importance of anatomical localization for Sertoli cells in regulating spermatogenesis and that SCF produced specifically by Sertoli cells is essential for spermatogenesis.
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Células de Sertoli , Fator de Células-Tronco , Masculino , Animais , Camundongos , Células de Sertoli/metabolismo , Fator de Células-Tronco/genética , Fator de Células-Tronco/metabolismo , Espermatogênese/genética , Testículo/metabolismo , Espermatogônias/metabolismoRESUMO
Strong ultraviolet (UV) radiation at high altitude imposes a serious selective pressure, which may induce skin pigmentation adaptation of indigenous populations. We conducted skin pigmentation phenotyping and genome-wide analysis of Tibetans in order to understand the underlying mechanism of adaptation to UV radiation. We observe that Tibetans have darker baseline skin color compared with lowland Han Chinese, as well as an improved tanning ability, suggesting a two-level adaptation to boost their melanin production. A genome-wide search for the responsible genes identifies GNPAT showing strong signals of positive selection in Tibetans. An enhancer mutation (rs75356281) located in GNPAT intron 2 is enriched in Tibetans (58%) but rare in other world populations (0 to 18%). The adaptive allele of rs75356281 is associated with darker skin in Tibetans and, under UVB treatment, it displays higher enhancer activities compared with the wild-type allele in in vitro luciferase assays. Transcriptome analyses of gene-edited cells clearly show that with UVB treatment, the adaptive variant of GNPAT promotes melanin synthesis, likely through the interactions of CAT and ACAA1 in peroxisomes with other pigmentation genes, and they act synergistically, leading to an improved tanning ability in Tibetans for UV protection.
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Adaptação Fisiológica , Altitude , Pigmentação da Pele , Aciltransferases/genética , Adaptação Fisiológica/genética , Etnicidade , Humanos , Melaninas/genética , Fenótipo , Pigmentação da Pele/genética , Tibet , Transcriptoma , Raios UltravioletaRESUMO
BACKGROUND: Methicillin-resistant Staphylococcus aureus (MRSA) sequence type (ST) 45 is a globally disseminated MRSA lineage. Herein, we investigated whether MRSA ST45 isolates from cellulitis and from osteomyelitis display distinctive phenotypic and genomic characteristics. METHODS: A total of 15 MRSA ST45 isolates from cellulitis (CL-MRSAs; n = 6) or osteomyelitis (OM-MRSAs; n = 9) were collected in a Taiwan hospital. These MRSA ST45 isolates were characterized for their antimicrobial susceptibility, biofilm-forming ability, cellular infectivity in vitro, and pathogenicity in vivo. Four CL-MRSA and six OM-MRSA ST45 isolates were selected for whole-genome sequencing (WGS). RESULTS: Antibiotic resistance tests showed that all OM-MRSA ST45 strains, but not CL-MRSA ST45 strains, were resistant to ciprofloxacin, levofloxacin, gentamicin and doxycycline. Compared to the CL-MRSA ST45 isolates, the OM-MRSA ST45 isolates had stronger biofilm-forming ability and cellular infectivity, and caused more severe disease in mice. WGS analysis revealed that these OM-MRSA ST45 isolates carry multiple common mutations or polymorphisms in genes associated with antibiotic resistance and virulence. Moreover, the transposable elements IS256 and IS257R2 were found only in the OM-MRSA ST45 isolates. CONCLUSIONS: The emergence and spread of the highly pathogenic and multidrug-resistant ST45 MRSAs identified from osteomyelitis may pose a serious threat on public health.
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2D metal-organic frameworks-based (2D MOF-related) materials benefit from variable topological structures, plentiful open active sites, and high specific surface areas, demonstrating promising applications in gas storage, adsorption and separation, energy conversion, and other domains. In recent years, researchers have innovatively designed multiple strategies to avoid the adverse effects of conventional methods on the synthesis of high-quality 2D MOFs. This review focuses on the latest advances in creative synthesis techniques for 2D MOF-related materials from both the top-down and bottom-up perspectives. Subsequently, the strategies are categorized and summarized for synthesizing 2D MOF-related composites and their derivatives. Finally, the current challenges are highlighted faced by 2D MOF-related materials and some targeted recommendations are put forward to inspire researchers to investigate more effective synthesis methods.
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This work reports the nonlinear dynamics of a mid-infrared interband cascade laser (ICL) subject to optical injection. It is shown that the stable locking regime is asymmetric and broadens with increasing injection strength. Outside the locking regime, the ICL mostly produces period-one oscillations. However, three categories of periodic pulse oscillations are observed in the vicinity of the Hopf bifurcation and the saddle-node bifurcation. In particular, it is found that the ICL generates broadband chaos at a near-threshold pump current, and the chaos bandwidth is over 300 MHz.
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Near-infrared semiconductor lasers subject to optical feedback usually produce chaos with a broad bandwidth of a few GHz. However, the reported mid-infrared interband cascade lasers (ICLs) only show chaos with a limited bandwidth below 1â GHz. Here we show that an ICL with optical feedback is able to generate broadband chaos as well. The mid-infrared chaos exhibits a remarkable bandwidth of about 6â GHz, which is comparable to that of the near-infrared counterpart. In addition, the spectral coverage in the electrical domain reaches as high as 17.7â GHz. It is found that the chaos bandwidth generally broadens with increasing feedback ratio and/or increasing pump current of the laser, while it is insensitive to the feedback length.
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Direct mechanical coupling is known to be critical for establishing synchronization among cilia. However, the actual role of the connections is still elusive-partly because controlled experiments in living samples are challenging. Here, we employ an artificial ciliary system to address this issue. Two cilia are formed by chains of self-propelling robots and anchored to a shared base so that they are purely mechanically coupled. The system mimics biological ciliary beating but allows fine control over the beating dynamics. With different schemes of mechanical coupling, artificial cilia exhibit rich motility patterns. Particularly, their synchronous beating display two distinct modes-analogous to those observed in C. reinhardtii, the biciliated model organism for studying synchronization. Close examination suggests that the system evolves towards the most dissipative mode. Using this guideline in both simulations and experiments, we are able to direct the system into a desired state by altering the modes' respective dissipation. Our results have significant implications in understanding the synchronization of cilia.
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Biomimética , Cílios , Robótica , Cílios/fisiologia , Biomimética/métodos , Modelos Biológicos , Chlamydomonas reinhardtii/fisiologiaRESUMO
The tribe-material is the key factor affecting the performance of triboelectric nanogenerators (TENGs). Inorganic materials have higher heat resistance and stability than widely used organic materials. However, the weaker tribe-property limits the application of TENGs. Modulating surface roughness by changing particle shape and size is a simple way to increase performance for TENGs. Polyoxometalates (POMs) have unrivalled structural diversity and can self-assemble to form different nanostructures. In this study, we propose [{(NH4)42[Mo72 VIMo60 VO372(CH3COO)30 (H2O)72] â ca.300H2O â ca.CH3COONH4)}-Mo132] and [{Na8K14(VO)2[{(MoVI) (Mo5 VIO21)(H2O)3]}10{(MoVI)Mo5 VIO21(H2O)3 (SO4)}2{VIVO(H2O)20} {VIVO}10({KSO4}5)2] â 150H2O)}-Mo72V30] with blackberry structure which are cured and prepared into film by spin-coating technique, are used as positive tribe-materials for the first time in the field of TENGs. Keplerate-type POMs can form blackberry structures with higher dispersibility and flexibility, which can be used to control surface roughness by regulating the size of particles. The discovery proves that the particle size influences the surface roughness, which adjusts the output of TENGs. According to our findings, Mo132-h-TENG generates an output voltage of 29.3â V, an output charge of 8 Nc, which is 2-3 folds higher than Mo132-TENG, and a maximum power density of 6.25â mW â m-2 at 300â MΩ. Our research provides that altering the dimensional size can be an available way to raise the output of TENGs.
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OBJECTIVE: To investigate characteristics associated with different COVID-19 outcomes of people with systemic lupus erythematosus (SLE) and COVID-19 during the second pandemic wave of COVID-19 in China. METHODS: In this retrospective study, people with SLE and COVID-19 who visited the First Affiliated Hospital of Nanchang University from December 2022 and February 2023 were subjected to this study. The three possible outcomes were listed in order of ordinal severity: (1) not hospitalized, (2) hospitalized but not receiving oxygenation, and (3) hospitalized with any ventilation or oxygenation. A multivariable ordinal logistic regression model was built to examine the association between COVID-19 severity and demographic traits, medications, comorbidities, and disease activity. Furthermore, among the 301 SLE patients included in our study, only two patients experienced mortality. In order to maintain statistical rigor, we have included these two deceased patients in the outcome measure of hospitalized with any ventilation or oxygenation. RESULTS: A total of 301 patients with SLE were enrolled in this study. The multivariate ordinal logistic regression analyses indicated that high SLE disease activity (vs remission; OR 39.04, 95% CI 3.08 to 494.44, p = .005) was associated with more severe outcomes. Three doses of COVID-19 vaccination (OR 0.19, 95% CI 0.07 to 0.51, p = .001), glucocorticoids dose (1-5 mg/day 0.14, 0.03 to 0.73, p = .020, and 6-9 mg/day 0.12, 0.02 to 0.61, p = .010), and more intensive immunosuppression drugs (0.34, 0.12 to 0.97, p = .044) were associated with better outcomes. In age-adjusted and sex-adjusted models, telitacicept (6.66, 1.35 to 32.86, p = .020) and rituximab (7.81, 1.87 to 32.66, p = .005) were associated with more severe outcomes. Hydroxychloroquine (0.47, 0.25 to 0.88, p = .018) was associated with favorable outcomes. CONCLUSION: Different COVID-19 outcomes in people with SLE are mostly driven by COVID-19 vaccination, medications, and activity SLE. More importantly, three doses of COVID-19 vaccination may be associated with better outcomes.
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COVID-19 , Lúpus Eritematoso Sistêmico , Humanos , Lúpus Eritematoso Sistêmico/tratamento farmacológico , Lúpus Eritematoso Sistêmico/epidemiologia , Lúpus Eritematoso Sistêmico/complicações , Estudos Retrospectivos , Pandemias , Vacinas contra COVID-19 , COVID-19/epidemiologia , COVID-19/complicaçõesRESUMO
The endoplasmic reticulum (ER) plays a pivotal role in protein folding and secretion, Ca2+ storage, and lipid synthesis in eukaryotic cells. When the burden of protein synthesis and folding required to be handled exceeds the processing capacity of the ER, the accumulation of misfolded/unfolded proteins triggers ER stress. In response to short-term ER stress, the unfolded protein response (UPR) is activated to allow cells to survive. When ER stress is severe and sustained, it typically provokes cell death through multiple approaches. It is well documented that ER stress and metabolic deregulation are functionally intertwined, both are considered contributing factors to the pathogenesis of liver diseases, including non-alcoholic fatty liver disease (NAFLD), alcoholic liver disease (ALD), ischemia/reperfusion (I/R) injury, viral hepatitis, liver fibrosis, and hepatocellular carcinoma (HCC). Hepatocytes are rich in smooth and rough ER, which harbor metabolic enzymes that are capable of sensing alterations in various nutritional status and external stimuli. Extensive research has focused on the molecular mechanism linking ER stress with metabolic enzymes. The purpose of this review is to summarize the current knowledge regarding the effects of ER stress on metabolic enzymes in various liver diseases and to provide potential therapeutic strategies for chronic liver diseases via targeting UPR.
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OBJECTIVES: Brain metastases (BMs) are commonly categorized into cystic and solid. However, the difference in the prognosis of patients with either cystic or solid BMs following radiotherapy remains poorly understood. We used a retrospective design to elucidate the disparities in survival between these two patient groups undergoing radiotherapy and to identify factors influencing the overall survival (OS) of patients with BMs. METHODS: This retrospective study encompasses 212 patients diagnosed with BMs. We meticulously analyzed the clinical characteristics, radiation therapy modalities, and risk factors influencing the OS among these patients, categorized by BMs type, post-brain radiation therapy. RESULTS: A statistically significant difference in mOS was observed between the two cohorts (Solid vs Cystic: 23.1 vs 14.6 months). Subgroup analysis unveiled distinctions in mOS, particularly in patients with EGFR-mutant lung adenocarcinoma (Solid vs Cystic: 23.1 vs 6.43 months). The volume of BMs and the biological effective dose (BED) emerged as significantly prognostic factors for patients with cystic BMs. For patients with solid BMs, fraction dose, BED, and the number of BMs were identified as independent prognostic factors for survival. CONCLUSION: Brain radiotherapy shows superior survival benefits for lung cancer patients with solid BMs compared to those with cystic BMs, particularly in EGFR-mutant lung cancer. In particular, patients receiving BED ≥60 Gy have a more favorable prognosis than those receiving BED <60 Gy, regardless of the type of BM (solid or cystic) in lung cancer.
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Neoplasias Encefálicas , Humanos , Neoplasias Encefálicas/secundário , Neoplasias Encefálicas/radioterapia , Neoplasias Encefálicas/mortalidade , Masculino , Feminino , Estudos Retrospectivos , Pessoa de Meia-Idade , Prognóstico , Idoso , Neoplasias Pulmonares/radioterapia , Neoplasias Pulmonares/patologia , Neoplasias Pulmonares/mortalidade , AdultoRESUMO
OBJECTIVES: Computed tomographic perfusion (CTP) can play an auxiliary role in the selection of patients with acute ischemic stroke for endovascular treatment. However, data on CTP in non-stroke patients with intracranial arterial stenosis are scarce. We aimed to investigate images in patients with asymptomatic intracranial arterial stenosis to determine the detection accuracy and interpretation time of large/medium-artery stenosis or occlusion when combining computed tomographic angiography (CTA) and CTP images. METHODS: We retrospectively reviewed 39 patients with asymptomatic intracranial arterial stenosis from our hospital database from January 2021 to August 2023 who underwent head CTP, head CTA, and digital subtraction angiography (DSA). Head CTA images were generated from the CTP data, and the diagnostic performance for each artery was assessed. Two readers independently interpreted the CTA images before and after CTP, and the results were analyzed. RESULTS: After adding CTP maps, the accuracy (area under the curve) of diagnosing internal carotid artery (R1: 0.847 vs. 0.907, R2: 0.776 vs. 0.887), middle cerebral artery (R1: 0.934 vs. 0.933, R2: 0.927 vs. 0.981), anterior cerebral artery (R1: 0.625 vs. 0.750, R2: 0.609 vs. 0.750), vertebral artery (R1: 0.743 vs. 0.764, R2: 0.748 vs. 0.846), and posterior cerebral artery (R1: 0.390 vs. 0.575, R2: 0.390 vs. 0.585) occlusions increased for both readers (p < 0.05). Mean interpretation time (R1: 72.4 ± 6.1 s vs. 67.7 ± 6.4 s, R2: 77.7 ± 3.8 s vs. 72.6 ± 4.7 s) decreased when using a combination of both images both readers (p < 0.001). CONCLUSIONS: The addition of CTP images improved the accuracy of interpreting CTA images and reduced the interpretation time in asymptomatic intracranial arterial stenosis. These findings support the use of CTP imaging in patients with asymptomatic intracranial arterial stenosis.
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AVC Isquêmico , Humanos , Estudos Retrospectivos , Constrição Patológica/diagnóstico por imagem , Tomografia Computadorizada por Raios X/métodos , Angiografia por Tomografia Computadorizada/métodos , Perfusão , Angiografia Cerebral/métodosRESUMO
Sepsis is defined as life-threatening organ dysfunction caused by a dysregulated host response to infection. Studies have indicated that immune dysfunction plays a central role in the pathogenesis of sepsis. Dendritic cells (DCs) play a crucial role in the emergence of immune dysfunction in sepsis. The major manifestations of DCs in the septic state are abnormal functions and depletion in numbers, which are linked to higher mortality and vulnerability to secondary infections in sepsis. Apoptosis is the most widely studied pathway of number reduction in DCs. In the past few years, there has been a surge in studies focusing on regulated cell death (RCD). This emerging field encompasses various forms of cell death, such as necroptosis, pyroptosis, ferroptosis, and autophagy-dependent cell death (ADCD). Regulation of DC's RCD can serve as a possible therapeutic focus for the treatment of sepsis. Throughout time, numerous tactics have been devised and effectively implemented to improve abnormal immune response during sepsis progression, including modifying the functions of DCs and inhibiting DC cell death. In this review, we provide an overview of the functional impairment and RCD of DCs in septic states. Also, we highlight recent advances in targeting DCs to regulate host immune response following septic challenge.
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Células Dendríticas , Sepse , Células Dendríticas/imunologia , Sepse/imunologia , Sepse/patologia , Humanos , Animais , Morte Celular Regulada , Autofagia , Apoptose , PiroptoseRESUMO
In the present work, the taxonomic relationship between Streptomyces coeruleorubidus and Streptomyces bellus was reevaluated by a comprehensive comparison of phenotypic, chemotaxonomic and genomic characteristics, as well as phylogeny. In 1957 and 1960, Streptomyces coeruleorubidus and Streptomyces bellus were described as two novel Streptomyces species. The full-length 16S rRNA gene sequence analysis indicated that Streptomyces bellus JCM 4292T shared highest sequence identity with Streptomyces coerulescens ISP 5146T (100%). Phylogenetic analysis of 16S rRNA gene sequence showed that S. bellus JCM 4292T was most closely related to Streptomyces coerulescens ISP 5146T. Phylogenetic analysis of five housekeeping gene sequences demonstrated that S. bellus JCM 4292T was most closely related to S. coeruleorubidus ATCC 13740T. Nevertheless, the ANIm (average nucleotide identity based on MuMmer ultra-rapid aligning tool) and dDDH (digital DNA-DNA hybridization) values between them were 97.71% and 81.9%, respectively, greater than the threshold of 96.7% and 70% for the delineation of Streptomyces species, suggesting that they represent the same genomic species. In addition, phenotypic and chemotaxonomic characteristics, as well as phylogeny and genomic DNA-DNA correlation analysis also confirmed the above conclusion. Consequently, we proposed that S. bellus Margalith and Beretta 1960 is a later heterotypic synonym of S. coeruleorubidus (Preobrazhenskaya 1957) Pridham et al. 1958.