Your browser doesn't support javascript.
loading
Mostrar: 20 | 50 | 100
Resultados 1 - 20 de 292
Filtrar
Mais filtros

Base de dados
Tipo de documento
Intervalo de ano de publicação
1.
EMBO J ; 42(21): e113975, 2023 11 02.
Artigo em Inglês | MEDLINE | ID: mdl-37718683

RESUMO

Paneth cells (PCs), a specialized secretory cell type in the small intestine, are increasingly recognized as having an essential role in host responses to microbiome and environmental stresses. Whether and how commensal and pathogenic microbes modify PC composition to modulate inflammation remain unclear. Using newly developed PC-reporter mice under conventional and gnotobiotic conditions, we determined PC transcriptomic heterogeneity in response to commensal and invasive microbes at single cell level. Infection expands the pool of CD74+ PCs, whose number correlates with auto or allogeneic inflammatory disease progressions in mice. Similar correlation was found in human inflammatory disease tissues. Infection-stimulated cytokines increase production of reactive oxygen species (ROS) and expression of a PC-specific mucosal pentraxin (Mptx2) in activated PCs. A PC-specific ablation of MyD88 reduced CD74+ PC population, thus ameliorating pathogen-induced systemic disease. A similar phenotype was also observed in mice lacking Mptx2. Thus, infection stimulates expansion of a PC subset that influences disease progression.


Assuntos
Microbiota , Celulas de Paneth , Humanos , Animais , Camundongos , Celulas de Paneth/metabolismo , Celulas de Paneth/patologia , Intestino Delgado , Inflamação/patologia , Citocinas/metabolismo
2.
Proc Natl Acad Sci U S A ; 121(5): e2318265121, 2024 Jan 30.
Artigo em Inglês | MEDLINE | ID: mdl-38261618

RESUMO

Surgical resections of solid tumors guided by visual inspection of tumor margins have been performed for over a century to treat cancer. Near-infrared (NIR) fluorescence labeling/imaging of tumor in the NIR-I (800 to 900 nm) range with systemically administrated fluorophore/tumor-targeting antibody conjugates have been introduced to improve tumor margin delineation, tumor removal accuracy, and patient survival. Here, we show Au25 molecular clusters functionalized with phosphorylcholine ligands (AuPC, ~2 nm in size) as a preclinical intratumorally injectable agent for NIR-II/SWIR (1,000 to 3,000 nm) fluorescence imaging-guided tumor resection. The AuPC clusters were found to be uniformly distributed in the 4T1 murine breast cancer tumor upon intratumor (i.t.) injection. The phosphocholine coating afforded highly stealth clusters, allowing a high percentage of AuPC to fill the tumor interstitial fluid space homogeneously. Intra-operative surgical navigation guided by imaging of the NIR-II fluorescence of AuPC allowed for complete and non-excessive tumor resection. The AuPC in tumors were also employed as a photothermal therapy (PTT) agent to uniformly heat up and eradicate tumors. Further, we performed in vivo NIR-IIb (1,500 to 1,700 nm) molecular imaging of the treated tumor using a quantum dot-Annexin V (QD-P3-Anx V) conjugate, revealing cancer cell apoptosis following PTT. The therapeutic functionalities of AuPC clusters combined with rapid renal excretion, high biocompatibility, and safety make them promising for clinical translation.


Assuntos
Neoplasias da Mama , Neoplasias Mamárias Animais , Humanos , Animais , Camundongos , Feminino , Imagem Óptica , Anexina A5 , Apoptose , Ouro
3.
PLoS Genet ; 20(1): e1011107, 2024 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-38181050

RESUMO

Eukaryotic chromatin is organized into either silenced heterochromatin or relaxed euchromatin regions, which controls the accessibility of transcriptional machinery and thus regulates gene expression. In fission yeast, Schizosaccharomyces pombe, Set1 is the sole H3K4 methyltransferase and is mainly enriched at the promoters of actively transcribed genes. In contrast, Clr4 methyltransferase initiates H3K9 methylation, which has long been regarded as a hallmark of heterochromatic silencing. Lsd1 and Lsd2 are two highly conserved H3K4 and H3K9 demethylases. As these histone-modifying enzymes perform critical roles in maintaining histone methylation patterns and, consequently, gene expression profiles, cross-regulations among these enzymes are part of the complex regulatory networks. Thus, elucidating the mechanisms that govern their signaling and mutual regulations remains crucial. Here, we demonstrated that C-terminal truncation mutants, lsd1-ΔHMG and lsd2-ΔC, do not compromise the integrity of the Lsd1/2 complex but impair their chromatin-binding capacity at the promoter region of target genomic loci. We identified protein-protein interactions between Lsd1/2 and Raf2 or Swd2, which are the subunits of the Clr4 complex (CLRC) and Set1-associated complex (COMPASS), respectively. We showed that Clr4 and Set1 modulate the protein levels of Lsd1 and Lsd2 in opposite ways through the ubiquitin-proteasome-dependent pathway. During heat stress, the protein levels of Lsd1 and Lsd2 are upregulated in a Set1-dependent manner. The increase in protein levels is crucial for differential gene expression under stress conditions. Together, our results support a cross-regulatory model by which Set1 and Clr4 methyltransferases control the protein levels of Lsd1/2 demethylases to shape the dynamic chromatin landscape.


Assuntos
Proteínas de Schizosaccharomyces pombe , Schizosaccharomyces , Schizosaccharomyces/metabolismo , Proteínas de Schizosaccharomyces pombe/genética , Proteínas de Schizosaccharomyces pombe/metabolismo , Histonas/genética , Histonas/metabolismo , Histona-Lisina N-Metiltransferase/genética , Histona-Lisina N-Metiltransferase/metabolismo , Proteínas de Ciclo Celular/genética , Proteínas de Ciclo Celular/metabolismo , Heterocromatina/metabolismo , Fatores de Transcrição/genética
4.
Development ; 149(1)2022 01 01.
Artigo em Inglês | MEDLINE | ID: mdl-34910127

RESUMO

Although Wnt signaling is clearly important for the intestinal epithelial homeostasis, the relevance of various sources of Wnt ligands themselves remains incompletely understood. Blocking the release of Wnt in distinct stromal cell types suggests obligatory functions of several stromal cell sources and yields different observations. The physiological contribution of epithelial Wnt to tissue homeostasis remains unclear. We show here that blocking epithelial Wnts affects colonic Reg4+ epithelial cell differentiation and impairs colonic epithelial regeneration after injury in mice. Single-cell RNA analysis of intestinal stroma showed that the majority of Wnt-producing cells were contained in transgelin (Tagln+) and smooth muscle actin α2 (Acta2+) expressing populations. We genetically attenuated Wnt production from these stromal cells using Tagln-Cre and Acta2-CreER drivers, and found that blockage of Wnt release from either epithelium or Tagln+ and Acta2+ stromal cells impaired colonic epithelial healing after chemical-induced injury. Aggregated blockage of Wnt release from both epithelium and Tagln+ or Acta2+ stromal cells drastically diminished epithelial repair, increasing morbidity and mortality. These results from two uncharacterized stromal populations suggested that colonic recovery from colitis-like injury depends on multiple Wnt-producing sources.


Assuntos
Actinas/metabolismo , Colite Ulcerativa/metabolismo , Mucosa Intestinal/metabolismo , Proteínas dos Microfilamentos/metabolismo , Proteínas Musculares/metabolismo , Proteína Wnt3A/metabolismo , Cicatrização , Actinas/genética , Animais , Células Cultivadas , Colo/citologia , Colo/metabolismo , Colo/fisiologia , Mucosa Intestinal/citologia , Camundongos , Camundongos Endogâmicos C57BL , Proteínas dos Microfilamentos/genética , Proteínas Musculares/genética , Proteínas Associadas a Pancreatite/genética , Proteínas Associadas a Pancreatite/metabolismo , Receptores Acoplados a Proteínas G/genética , Receptores Acoplados a Proteínas G/metabolismo , Células-Tronco/metabolismo , Proteína Wnt3A/genética
5.
J Cell Mol Med ; 28(4): e18113, 2024 02.
Artigo em Inglês | MEDLINE | ID: mdl-38332530

RESUMO

The resistance to anoikis plays a critical role in the metastatic progression of various types of malignancies, including gastric cancer (GC). Nevertheless, the precise mechanism behind anoikis resistance is not fully understood. Here, our primary focus was to examine the function and underlying molecular mechanism of Integrin beta-like 1 (ITGBL1) in the modulation of anoikis resistance and metastasis in GC. The findings of our investigation have demonstrated that the overexpression of ITGBL1 significantly augmented the resistance of GC cells to anoikis and promoted their metastatic potential, while knockdown of ITGBL1 had a suppressive effect on both cellular processes in vitro and in vivo. Mechanistically, we proved that ITGBL1 has a role in enhancing the resistance of GC cells to anoikis and promoting metastasis through the AKT/Fibulin-2 (FBLN2) axis. The inhibition of AKT/FBLN2 signalling was able to reverse the impact of ITGBL1 on the resistance of GC cells to anoikis and their metastatic capability. Moreover, the expression levels of ITGBL1 were found to be significantly elevated in the cancerous tissues of patients diagnosed with GC, and there was a strong correlation observed between high expression levels of ITGBL1 and worse prognosis among individuals diagnosed with GC. Significantly, it was revealed that within our cohort of GC patients, individuals exhibiting elevated ITGBL1 expression and diminished FBLN2 expression experienced the worst prognosis. In conclusion, the findings of our study indicate that ITGBL1 may serve as a possible modulator of resistance to anoikis and the metastatic process in GC.


Assuntos
Anoikis , Proteínas de Ligação ao Cálcio , Neoplasias Gástricas , Humanos , Anoikis/genética , Neoplasias Gástricas/patologia , Proteínas Proto-Oncogênicas c-akt/genética , Proteínas Proto-Oncogênicas c-akt/metabolismo , Proteínas da Matriz Extracelular , Linhagem Celular Tumoral , Metástase Neoplásica , Integrina beta1/genética
6.
Anal Chem ; 96(21): 8657-8664, 2024 May 28.
Artigo em Inglês | MEDLINE | ID: mdl-38738643

RESUMO

Online analysis of the composition and evolution of complex oligomeric intermediates in biomass degradation is highly desirable to elucidate the mechanism of bond cleavage and study the effect of conditions on the selective conversion of feedstocks. However, harsh reaction conditions and complicated conversion systems pose tremendous challenges for conventional, state-of-the-art analytical techniques. Herein, we introduce a continuous and rapid compositional analysis strategy coupling a high-pressure flow-through reactor with online high-resolution mass spectrometry, which enables the molecular-level characterization of most biomass-related products throughout the conversion for over 2 h. Catalytic depolymerization of one model compound was studied, and temperature-dependent data of over 50 intermediates as well as recondensation dimers and oligomers were obtained, which have rarely been reported in the literature. Thousands of products during the flow-through conversion of birch wood with molecular weights up to 1000 Da were presented, and 8 typical lignin dimers and oligomers with various interunit linkages were identified at the molecular level, demonstrating the potential to analyze more complicated systems far beyond conventional methods, especially for complex oligomers. The continuous evolutions of different components and typical products were unveiled for the first time, providing valuable insights into the investigation of the structure, composition, and decomposition mechanism of lignocellulose as well as the influence of reaction conditions. This method leads to the previously unattained ability to probe and reveal complicated chemical compositions in high-pressure reactions and can be applied to all other high-pressure heterogeneous aqueous reactions.

7.
Small ; 20(26): e2306916, 2024 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-38221813

RESUMO

Ferroptosis, a novel form of nonapoptotic cell death, can effectively enhance photodynamic therapy (PDT) performance by disrupting intracellular redox homeostasis and promoting apoptosis. However, the extremely hypoxic tumor microenvironment (TME) together with highly expressed hypoxia-inducible factor-1α (HIF-1α) presents a considerable challenge for clinical PDT against osteosarcoma (OS). Hence, an innovative nanoplatform that enhances antitumor PDT by inducing ferroptosis and alleviating hypoxia is fabricated. Capsaicin (CAP) is widely reported to specifically activate transient receptor potential vanilloid 1 (TRPV1) channel, trigger an increase in intracellular Ca2+ concentration, which is closely linked with ferroptosis, and participate in decreased oxygen consumption by inhibiting HIF-1α in tumor cells, potentiating PDT antitumor efficiency. Thus, CAP and the photosensitizer IR780 are coencapsulated into highly biocompatible human serum albumin (HSA) to construct a nanoplatform (CI@HSA NPs) for synergistic tumor treatment under near-infrared (NIR) irradiation. Furthermore, the potential underlying signaling pathways of the combination therapy are investigated. CI@HSA NPs achieve real-time dynamic distribution monitoring and exhibit excellent antitumor efficacy with superior biosafety in vivo. Overall, this work highlights a promising NIR imaging-guided "pro-death" strategy to overcome the limitations of PDT for OS by promoting ferroptosis and alleviating hypoxia, providing inspiration and support for future innovative tumor therapy approaches.


Assuntos
Capsaicina , Ferroptose , Osteossarcoma , Fotoquimioterapia , Ferroptose/efeitos dos fármacos , Osteossarcoma/tratamento farmacológico , Osteossarcoma/patologia , Osteossarcoma/metabolismo , Fotoquimioterapia/métodos , Humanos , Capsaicina/farmacologia , Linhagem Celular Tumoral , Animais , Nanopartículas/química , Camundongos , Subunidade alfa do Fator 1 Induzível por Hipóxia/metabolismo , Hipóxia/tratamento farmacológico , Hipóxia/metabolismo , Fármacos Fotossensibilizantes/farmacologia , Fármacos Fotossensibilizantes/uso terapêutico
8.
New Phytol ; 243(1): 111-131, 2024 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-38708434

RESUMO

Leaf traits are essential for understanding many physiological and ecological processes. Partial least squares regression (PLSR) models with leaf spectroscopy are widely applied for trait estimation, but their transferability across space, time, and plant functional types (PFTs) remains unclear. We compiled a novel dataset of paired leaf traits and spectra, with 47 393 records for > 700 species and eight PFTs at 101 globally distributed locations across multiple seasons. Using this dataset, we conducted an unprecedented comprehensive analysis to assess the transferability of PLSR models in estimating leaf traits. While PLSR models demonstrate commendable performance in predicting chlorophyll content, carotenoid, leaf water, and leaf mass per area prediction within their training data space, their efficacy diminishes when extrapolating to new contexts. Specifically, extrapolating to locations, seasons, and PFTs beyond the training data leads to reduced R2 (0.12-0.49, 0.15-0.42, and 0.25-0.56) and increased NRMSE (3.58-18.24%, 6.27-11.55%, and 7.0-33.12%) compared with nonspatial random cross-validation. The results underscore the importance of incorporating greater spectral diversity in model training to boost its transferability. These findings highlight potential errors in estimating leaf traits across large spatial domains, diverse PFTs, and time due to biased validation schemes, and provide guidance for future field sampling strategies and remote sensing applications.


Assuntos
Folhas de Planta , Folhas de Planta/fisiologia , Folhas de Planta/anatomia & histologia , Análise dos Mínimos Quadrados , Característica Quantitativa Herdável , Clorofila/metabolismo , Estações do Ano , Modelos Biológicos , Água , Carotenoides/metabolismo
9.
J Exp Bot ; 75(3): 935-946, 2024 Feb 02.
Artigo em Inglês | MEDLINE | ID: mdl-37904595

RESUMO

Tea (Camellia sinensis) is a highly important beverage crop renowned for its unique flavour and health benefits. Chlorotic mutants of tea, known worldwide for their umami taste and economic value, have gained global popularity. However, the genetic basis of this chlorosis trait remains unclear. In this study, we identified a major-effect quantitative trait locus (QTL), qChl-3, responsible for the chlorosis trait in tea leaves, linked to a non-synonymous polymorphism (G1199A) in the magnesium chelatase I subunit (CsCHLI). Homozygous CsCHLIA plants exhibited an albino phenotype due to defects in magnesium protoporphyrin IX and chlorophylls in the leaves. Biochemical assays revealed that CsCHLI mutations did not affect subcellular localization or interactions with CsCHLIG and CsCHLD. However, combining CsCHLIA with CsCHLIG significantly reduced ATPase activity. RNA-seq analysis tentatively indicated that CsCHLI inhibited photosynthesis and enhanced photoinhibition, which in turn promoted protein degradation and increased the amino acid levels in chlorotic leaves. RT-qPCR and enzyme activity assays confirmed the crucial role of asparagine synthetase and arginase in asparagine and arginine accumulation, with levels increasing over 90-fold in chlorotic leaves. Therefore, this study provides insights into the genetic mechanism underlying tea chlorosis and the relationship between chlorophyll biosynthesis and amino acid metabolism.


Assuntos
Anemia Hipocrômica , Camellia sinensis , Liases , Camellia sinensis/genética , Camellia sinensis/metabolismo , Clorofila/metabolismo , Chá/metabolismo , Aminoácidos/metabolismo , Mutação , Anemia Hipocrômica/metabolismo , Folhas de Planta/genética , Folhas de Planta/metabolismo
10.
BMC Gastroenterol ; 24(1): 7, 2024 Jan 02.
Artigo em Inglês | MEDLINE | ID: mdl-38166603

RESUMO

Gallbladder polyps are a common biliary tract disease whose treatment options have yet to be fully established. The indication of "polyps ≥ 10 mm in diameter" for cholecystectomy increases the possibility of gallbladder excision due to benign polyps. Compared to enumeration of risk factors in clinical guidelines, predictive models based on statistical methods and artificial intelligence provide a more intuitive representation of the malignancy degree of gallbladder polyps. Minimally invasive gallbladder-preserving polypectomy procedures, as a combination of checking and therapeutic approaches that allow for eradication of lesions and preservation of a functional gallbladder at the same time, have been shown to maximize the benefits to patients with benign polyps. Despite the reported good outcomes of predictive models and gallbladder-preserving polypectomy procedures, the studies were associated with various limitations, including small sample sizes, insufficient data types, and unknown long-term efficacy, thereby enhancing the need for multicenter and large-scale clinical studies. In conclusion, the emergence of predictive models and minimally invasive gallbladder-preserving polypectomy procedures has signaled an ever increasing attention to the role of the gallbladder and clinical management of gallbladder polyps.


Assuntos
Doenças da Vesícula Biliar , Neoplasias da Vesícula Biliar , Pólipos , Humanos , Neoplasias da Vesícula Biliar/cirurgia , Neoplasias da Vesícula Biliar/patologia , Inteligência Artificial , Doenças da Vesícula Biliar/cirurgia , Colecistectomia , Pólipos/cirurgia , Pólipos/patologia , Estudos Retrospectivos , Estudos Multicêntricos como Assunto
11.
Environ Sci Technol ; 58(9): 4291-4301, 2024 Mar 05.
Artigo em Inglês | MEDLINE | ID: mdl-38385161

RESUMO

Photochemical ozone (O3) formation in the atmospheric boundary layer occurs at both the surface and elevated altitudes. Therefore, the O3 formation sensitivity is needed to be evaluated at different altitudes before formulating an effective O3 pollution prevention and control strategy. Herein, we explore the vertical evolution of O3 formation sensitivity via synchronous observations of the vertical profiles of O3 and proxies for its precursors, formaldehyde (HCHO) and nitrogen dioxide (NO2), using multi-axis differential optical absorption spectroscopy (MAX-DOAS) in urban areas of the Beijing-Tianjin-Hebei (BTH), Yangtze River Delta (YRD), and Pearl River Delta (PRD) regions in China. The sensitivity thresholds indicated by the HCHO/NO2 ratio (FNR) varied with altitude. The VOC-limited regime dominated at the ground level, whereas the contribution of the NOx-limited regime increased with altitude, particularly on heavily polluted days. The NOx-limited and transition regimes played more important roles throughout the entire boundary layer than at the surface. The feasibility of extreme NOx reduction to mitigate the extent of the O3 pollution was evaluated using the FNR-O3 curve. Based on the surface sensitivity, the critical NOx reduction percentage for the transition from a VOC-limited to a NOx-limited regime is 45-72%, which will decrease to 27-61% when vertical evolution is considered. With the combined effects of clean air action and carbon neutrality, O3 pollution in the YRD and PRD regions will transition to the NOx-limited regime before 2030 and be mitigated with further NOx reduction.


Assuntos
Poluentes Atmosféricos , Ozônio , Compostos Orgânicos Voláteis , Ozônio/análise , Poluentes Atmosféricos/análise , Dióxido de Nitrogênio/análise , Compostos Orgânicos Voláteis/análise , Monitoramento Ambiental/métodos , China
12.
J Fluoresc ; 2024 Apr 27.
Artigo em Inglês | MEDLINE | ID: mdl-38676771

RESUMO

As one of the most significant parameters in cellular microenvironment, viscosity levels could be used to determine the metabolic process of bioactive substances within cells. Abnormal viscosity levels are closely associated with a series of diseases. Therefore, the design and synthesis of fluorescent probes that can monitor changes of intracellular viscosity in real-time is of great significance for the study of disease development process. Here, a new viscosity-recognized NIR fluorescence probe W1 based on quinoline-malonitrile is synthesized, and it is not susceptible to interference substances. Besides, AIE probe W1 shows fast response, excellent photostability, low cytotoxicity, good linear relationship between fluorescence intensity value and viscosity. Based on the above advantages, probe W1 is used to image the change of viscosity level in the cell model induced by nystatin.

13.
Mol Biol Rep ; 51(1): 673, 2024 May 24.
Artigo em Inglês | MEDLINE | ID: mdl-38787479

RESUMO

BACKGROUND: T-type calcium channels, characterized as low-voltage activated (LVA) calcium channels, play crucial physiological roles across a wide range of tissues, including both the neuronal and nonneuronal systems. Using in situ hybridization and RNA interference (RNAi) techniques in vitro, we previously identified the tissue distribution and physiological function of the T-type calcium channel α1 subunit (DdCα1G) in the plant-parasitic nematode Ditylenchus destructor. METHODS AND RESULTS: To further characterize the functional role of DdCα1G, we employed a combination of immunohistochemistry and fungus-mediated RNAi and found that DdCα1G was clearly distributed in stylet-related tissue, oesophageal gland-related tissue, secretory-excretory duct-related tissue and male spicule-related tissue. Silencing DdCα1G led to impairments in the locomotion, feeding, reproductive ability and protein secretion of nematodes. To confirm the defects in behavior, we used phalloidin staining to examine muscle changes in DdCα1G-RNAi nematodes. Our observations demonstrated that defective behaviors are associated with related muscular atrophy. CONCLUSION: Our findings provide a deeper understanding of the physiological functions of T-type calcium channels in plant-parasitic nematodes. The T-type calcium channel can be considered a promising target for sustainable nematode management practices.


Assuntos
Actinas , Canais de Cálcio Tipo T , Interferência de RNA , Animais , Canais de Cálcio Tipo T/metabolismo , Canais de Cálcio Tipo T/genética , Actinas/metabolismo , Actinas/genética , Masculino , Fungos/genética , Inativação Gênica
14.
J Nat Prod ; 87(2): 381-387, 2024 02 23.
Artigo em Inglês | MEDLINE | ID: mdl-38289330

RESUMO

Tryptoquivalines are highly toxic metabolites initially isolated from the fungus Aspergillus clavatus. The relative and absolute configuration of tryptoquivaline derivates was primarily established by comparison of the chemical shifts, NOE data, and ECD calculations. A de novo determination of the complete relative configuration using NMR spectroscopy was challenging due to multiple spatially separated stereocenters, including one nonprotonated carbon. In this study, we isolated a new tryptoquivaline derivative, 12S-deoxynortryptoquivaline (1), from the marine ascidian-derived fungus Aspergillus clavatus AS-107. The correct assignment of the relative configuration of 1 was accomplished using anisotropic NMR spectroscopy, while the absolute configuration was determined by comparing calculated and experimental ECD spectra. This case study highlights the effectiveness of anisotropic NMR parameters over isotropic NMR parameters in determining the relative configuration of complex natural products without the need for crystallization.


Assuntos
Urocordados , Animais , Espectroscopia de Ressonância Magnética/métodos , Aspergillus/química , Fungos , Estrutura Molecular
15.
Int J Hyperthermia ; 41(1): 2316085, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38346911

RESUMO

OBJECTIVE: This study aimed to evaluate the combined efficacy of hyperthermia and chemotherapy using a bladder cancer organoid model and to explore hyperthermia-related molecular pathways. METHOD: Tumor organoids were generated by embedding RT4 bladder cancer cells into Matrigel. The resulting organoids were treated with pirarubicin or gemcitabine at 37 °C or 42 °C. Proliferation was determined by Ki67 immunofluorescence staining, and apoptosis was assessed using a TdT-mediated dUTP nick end labeling (TUNEL) assay. RNA sequencing was used to identify the differentially expressed genes. RESULTS: Bladder cancer organoids were successfully established and exhibited robust proliferative abilities. Treatment with gemcitabine or pirarubicin under hyperthermic conditions caused pronounced structural damage to the organoids and increased cell death compared to that in the normothermically treated group. Furthermore, Ki67 labeling and TUNEL assays showed that the hyperthermia chemotherapy group showed a significantly reduced proliferation rate and high level of apoptosis. Finally, RNA sequencing revealed the IFN-γ signaling pathway to be associated with hyperthermia. CONCLUSION: Overall, hyperthermia combined with chemotherapy exerted better therapeutic effects than those of normothermic chemotherapy in grade 1-2 non-muscle-invasive bladder cancer, potentially through activation of the IFN-γ-JAK-STAT pathway.


Assuntos
Doxorrubicina/análogos & derivados , Hipertermia Induzida , Neoplasias da Bexiga Urinária , Humanos , Gencitabina , Janus Quinases/uso terapêutico , Antígeno Ki-67 , Fatores de Transcrição STAT/uso terapêutico , Transdução de Sinais , Neoplasias da Bexiga Urinária/tratamento farmacológico , Neoplasias da Bexiga Urinária/patologia , Hipertermia , Hipertermia Induzida/métodos , Organoides/patologia
16.
Antonie Van Leeuwenhoek ; 117(1): 81, 2024 May 22.
Artigo em Inglês | MEDLINE | ID: mdl-38777900

RESUMO

A Gram-stain-negative, aerobic, non-motile, catalase- and oxidase-positive, pale orange, rod-shaped strain EF6T, was isolated from a natural wetland reserve in Hebei province, China. The strain grew at 25-37 °C (optimum, 30 °C), pH 5-9 (optimum, pH 7), and in the presence of 1.0-4.0% (w/v) NaCl (optimum, 2%). A phylogenetic analysis based on 16S rRNA gene sequence revealed that strain EF6T belongs to the genus Paracoccus, and the closest members were Paracoccus shandongensis wg2T with 98.1% similarity, Paracoccus fontiphilus MVW-1 T (97.9%), Paracoccus everestensis S8-55 T (97.7%), Paracoccus subflavus GY0581T (97.6%), Paracoccus sediminis CMB17T (97.3%), Paracoccus caeni MJ17T (97.0%), and Paracoccus angustae E6T (97.0%). The genome size of strain EF6T was 4.88 Mb, and the DNA G + C content was 65.3%. The digital DNA-DNA hybridization, average nucleotide identity, and average amino acid identity values between strain EF6T and the reference strains were all below the threshold limit for species delineation (< 32.8%, < 88.0%, and < 86.7%, respectively). The major fatty acids (≥ 5.0%) were summed feature 8 (86.3%, C18:1 ω6c and/or C18:1 ω7c) and C18:1 (5.0%) and the only isoprenoid quinone was Q-10. The polar lipids consisted of diphosphatidylglycerol, phosphatidylglycerol, two unidentified glycolipids, five unidentified phospholipids, and an unidentified aminolipid. Strain EF6T displays notable resistance to benzoate and selenite, with higher tolerance levels (25 g/L for benzoate and 150 mM for selenite) compared to the closely related species. Genomic analysis identified six benzoate resistance genes (acdA, pcaF, fadA, pcaC, purB, and catA) and twenty selenite resistance and reduction-related genes (iscR, ssuB, ssuD, selA, selD and so on). Additionally, EF6T possesses unique genes (catA, ssuB, and ssuC) absent in the closely related species for benzoate and selenite resistance. Its robust resistance to benzoate and selenite, coupled with its genomic makeup, make EF6T a promising candidate for the remediation of both organic and inorganic pollutants. It is worth noting that the specific resistance phenotypes described above were not reported in other novel species in Paracoccus. Based on the results of biochemical, physiological, phylogenetic, and chemotaxonomic analyses, combined with comparisons of the 16S rRNA gene sequence and the whole genome sequence, strain EF6T is considered to represent a novel species of the genus Paracoccus within the family Rhodobacteraceae, for which the name Paracoccus benzoatiresistens sp. nov. is proposed. The type strain is EF6T (= GDMCC 1.3400 T = JCM 35642 T = MCCC 1K08702T).


Assuntos
Composição de Bases , DNA Bacteriano , Ácidos Graxos , Paracoccus , Filogenia , RNA Ribossômico 16S , Áreas Alagadas , Paracoccus/genética , Paracoccus/classificação , Paracoccus/isolamento & purificação , Paracoccus/metabolismo , Paracoccus/efeitos dos fármacos , RNA Ribossômico 16S/genética , Ácidos Graxos/metabolismo , Ácidos Graxos/química , DNA Bacteriano/genética , China , Selenito de Sódio/metabolismo , Técnicas de Tipagem Bacteriana , Fosfolipídeos/análise , Análise de Sequência de DNA , Hibridização de Ácido Nucleico , Oxirredução , Farmacorresistência Bacteriana
17.
Appl Opt ; 63(1): 210-220, 2024 Jan 01.
Artigo em Inglês | MEDLINE | ID: mdl-38175023

RESUMO

Fringe projection profilometry (FPP) is widely used in 3D vision measurement because of its high robustness and measurement accuracy. In the case of HDR objects, due to the problem of surface reflectivity, the obtained image will be overexposed. This will cause the sinusoidality of the fringes projected on the surface of the object in the acquired image to be interfered, resulting in a phase error in the calculated wrapped phase. Therefore, a polarization-encoded sinusoidal structured light is proposed to enhance the sinusoidality of the fringe. The phase information contained in the polarized sinusoidal structured light fringe is only related to the polarization state, not to the light intensity. A polarization coding assisted structured light measurement strategy (PASM) is proposed. This method uses polarization coding assisted polarization phase-shifting fringes for phase unwrapping. The angle of the linear polarizer is set to zero in this method, and it does not require rotating the polarizer. It only needs a single exposure to improve the fringe quality and obtain a more stable unwrapping phase. The experimental results show that the obtained polarization fringes have better sinusoidality, and the phase unwrapping can be more accurate. The reconstructed 3D point cloud also does not appear missing and has better accuracy. It is a reliable method for vision measurement of HDR objects.

18.
Appl Opt ; 63(4): 1094-1104, 2024 Feb 01.
Artigo em Inglês | MEDLINE | ID: mdl-38437408

RESUMO

High-speed tracking technology has wide applications in the military and aerospace industry. However, existing approaches, such as camera arrays or Doppler radar systems, suffer from high cost and inconvenience. This paper reports a high-speed target tracking control system based on short-time rotational reflection imaging, specifically aimed at overcoming certain limitations. In the system we designed, a high-speed camera coupled with a rotating reflector is used to achieve reliable high-speed target tracking. This paper first introduces the working principle and mathematical model of the system, then analyzes the key technologies, including motor response delay time and rotational speed curve fitting, and, finally, verifies the feasibility of the system and the correctness of the theory based on a series of experiments. Experimental results demonstrated that our work is efficient and accurate in target tracking and image clarity. The developed system demonstrates significant potential for widespread use across military and aerospace sectors. Furthermore, the insights gained from our investigation into key technologies could act as a reference point for fellow researchers in related scientific areas.

19.
Appl Opt ; 63(11): 2981-2993, 2024 Apr 10.
Artigo em Inglês | MEDLINE | ID: mdl-38856397

RESUMO

The imaging quality of a rotational reflection high-speed tracking system is greatly affected by the optical characteristics of the reflector and the depth of field limitations of the imaging system, especially for tracking systems working in small distances. In order to improve the imaging quality, this paper focused on two factors that affect the imaging quality: double vision caused by the optical characteristics of reflectors and blurring caused by the depth of field of imaging systems. This paper quantified the impact of these two factors on imaging through theoretical analysis, proposed a method of changing the hardware position, and conducted a simulation and experiments. The results show that the proposed solution in this paper can effectively improve the imaging quality of the system. The content studied in this paper has certain significance in the field of high-speed tracking of rotating reflectors and can provide reference for relevant researchers.

20.
Nucleic Acids Res ; 50(D1): D1340-D1347, 2022 01 07.
Artigo em Inglês | MEDLINE | ID: mdl-34554251

RESUMO

Alternative splicing (AS) represents a crucial method in mRNA level to regulate gene expression and contributes to the protein complexity. Abnormal splicing has been reported to play roles in several diseases, including cancers. We developed the OncoSplicing database for visualization of survival-associated and differential alternative splicing in 2019. Here, we provide an updated version of OncoSplicing for an integrative view of clinically relevant alternative splicing based on 122 423 AS events across 33 cancers in the TCGA SpliceSeq project and 238 558 AS events across 32 cancers in the TCGA SplAdder project. The new version of the database contains several useful features, such as annotation of alternative splicing-associated transcripts, survival analysis based on median and optimal cut-offs, differential analysis between TCGA tumour samples and adjacent normal samples or GTEx normal samples, pan-cancer views of alternative splicing, splicing differences and results of Cox'PH regression, identification of clinical indicator-relevant and cancer-specific splicing events, and downloadable splicing data in the SplAdder project. Overall, the substantially updated version of OncoSplicing (www.oncosplicing.com) is a user-friendly and registration-free database for browsing and searching clinically relevant alternative splicing in human cancers.


Assuntos
Processamento Alternativo/genética , Bases de Dados Genéticas , Neoplasias/genética , Software , Regulação Neoplásica da Expressão Gênica/genética , Redes Reguladoras de Genes/genética , Humanos , Neoplasias/patologia , Splicing de RNA
SELEÇÃO DE REFERÊNCIAS
DETALHE DA PESQUISA