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1.
Nat Methods ; 21(4): 712-722, 2024 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-38491270

RESUMO

Spatial clustering, which shares an analogy with single-cell clustering, has expanded the scope of tissue physiology studies from cell-centroid to structure-centroid with spatially resolved transcriptomics (SRT) data. Computational methods have undergone remarkable development in recent years, but a comprehensive benchmark study is still lacking. Here we present a benchmark study of 13 computational methods on 34 SRT data (7 datasets). The performance was evaluated on the basis of accuracy, spatial continuity, marker genes detection, scalability, and robustness. We found existing methods were complementary in terms of their performance and functionality, and we provide guidance for selecting appropriate methods for given scenarios. On testing additional 22 challenging datasets, we identified challenges in identifying noncontinuous spatial domains and limitations of existing methods, highlighting their inadequacies in handling recent large-scale tasks. Furthermore, with 145 simulated data, we examined the robustness of these methods against four different factors, and assessed the impact of pre- and postprocessing approaches. Our study offers a comprehensive evaluation of existing spatial clustering methods with SRT data, paving the way for future advancements in this rapidly evolving field.


Assuntos
Benchmarking , Perfilação da Expressão Gênica , Análise por Conglomerados , Análise Espacial , Transcriptoma
2.
Plant Cell ; 2024 Jun 25.
Artigo em Inglês | MEDLINE | ID: mdl-38916914

RESUMO

Alternative splicing (AS) plays crucial roles in regulating various biological processes in plants. However, the genetic mechanisms underlying AS and its role in controlling important agronomic traits in rice (Oryza sativa) remain poorly understood. In this study, we explored AS in rice leaves and panicles using the rice minicore collection. Our analysis revealed a high level of transcript isoform diversity, with approximately one fifth of potential isoforms acting as major transcripts in both tissues. Regarding the genetic mechanism of AS, we found that the splicing of 833 genes in the leaf and 1,230 genes in the panicle was affected by cis-genetic variation. Twenty-one percent of these AS events could only be explained by large structural variations. Approximately 77.5% of genes with significant splicing quantitative trait loci (sGenes) exhibited tissue-specific regulation, and AS can cause 26.9% (leaf) and 23.6% (panicle) of sGenes to have altered, lost or gained functional domains. Additionally, through splicing-phenotype association analysis, we identified phosphate-starvation induced RING-type E3 ligase (OsPIE1; LOC_Os01g72480), whose splicing ratio was significantly associated with plant height. In summary, this study provides an understanding of AS in rice and its contribution to the regulation of important agronomic traits.

3.
Immunity ; 48(1): 91-106.e6, 2018 01 16.
Artigo em Inglês | MEDLINE | ID: mdl-29343444

RESUMO

CD103+ dendritic cells are critical for cross-presentation of tumor antigens. Here we have shown that during immunotherapy, large numbers of cells expressing CD103 arose in murine tumors via direct differentiation of Ly6c+ monocytic precursors. These Ly6c+CD103+ cells could derive from bone-marrow monocytic progenitors (cMoPs) or from peripheral cells present within the myeloid-derived suppressor cell (MDSC) population. Differentiation was controlled by inflammation-induced activation of the transcription factor p53, which drove upregulation of Batf3 and acquisition of the Ly6c+CD103+ phenotype. Mice with a targeted deletion of p53 in myeloid cells selectively lost the Ly6c+CD103+ population and became unable to respond to multiple forms of immunotherapy and immunogenic chemotherapy. Conversely, increasing p53 expression using a p53-agonist drug caused a sustained increase in Ly6c+CD103+ cells in tumors during immunotherapy, which markedly enhanced the efficacy and duration of response. Thus, p53-driven differentiation of Ly6c+CD103+ monocytic cells represents a potent and previously unrecognized target for immunotherapy.


Assuntos
Células Apresentadoras de Antígenos/fisiologia , Monócitos/fisiologia , Células Mieloides/metabolismo , Neoplasias/imunologia , Proteína Supressora de Tumor p53/metabolismo , Animais , Células Apresentadoras de Antígenos/imunologia , Antígenos CD/metabolismo , Antígenos Ly/metabolismo , Diferenciação Celular/genética , Diferenciação Celular/fisiologia , Linhagem Celular , Citometria de Fluxo , Humanos , Imunoterapia/métodos , Cadeias alfa de Integrinas/metabolismo , Camundongos , Monócitos/imunologia , Células Mieloides/fisiologia
4.
Plant Cell ; 35(12): 4199-4216, 2023 Nov 30.
Artigo em Inglês | MEDLINE | ID: mdl-37647532

RESUMO

Breeding has dramatically changed the plant architecture of wheat (Triticum aestivum), resulting in the development of high-yielding varieties adapted to modern farming systems. However, how wheat breeding shaped the genomic architecture of this crop remains poorly understood. Here, we performed a comprehensive comparative analysis of a whole-genome resequencing panel of 355 common wheat accessions (representing diverse landraces and modern cultivars from China and the United States) at the phenotypic and genomic levels. The genetic diversity of modern wheat cultivars was clearly reduced compared to landraces. Consistent with these genetic changes, most phenotypes of cultivars from China and the United States were significantly altered. Of the 21 agronomic traits investigated, 8 showed convergent changes between the 2 countries. Moreover, of the 207 loci associated with these 21 traits, more than half overlapped with genomic regions that showed evidence of selection. The distribution of selected loci between the Chinese and American cultivars suggests that breeding for increased productivity in these 2 regions was accomplished by pyramiding both shared and region-specific variants. This work provides a framework to understand the genetic architecture of the adaptation of wheat to diverse agricultural production environments, as well as guidelines for optimizing breeding strategies to design better wheat varieties.


Assuntos
Genoma de Planta , Triticum , Estados Unidos , Triticum/genética , Genoma de Planta/genética , Melhoramento Vegetal , Fenótipo , China , Variação Genética
5.
J Immunol ; 212(8): 1345-1356, 2024 Apr 15.
Artigo em Inglês | MEDLINE | ID: mdl-38407485

RESUMO

The one-carbon metabolism enzyme methylenetetrahydrofolate dehydrogenase 2 (MTHFD2) is critical for cancer cell proliferation and immune cell phenotypes, but whether it can contribute to macrophage inflammatory responses remains unclear. In this study, we show that MTHFD2 was upregulated by LPS in murine macrophages upon activation of the TLR4-MyD88-IKKα/ß-NF-κB signaling pathway. MTHFD2 significantly attenuated LPS-induced macrophage proinflammatory cytokine production through its enzymatic activity. Notably, ablation of myeloid MTHFD2 rendered mice more sensitive to septic shock and CCl4-induced acute hepatitis. Mechanistically, MTHFD2 restrained IKKα/ß-NF-κB activation and macrophage inflammatory phenotype by scavenging reactive oxygen species through the generation of NADPH. Our study reveals MTHFD2 as a "self-control" mechanism in macrophage-mediated inflammatory responses.


Assuntos
Quinase I-kappa B , NF-kappa B , Camundongos , Animais , NF-kappa B/metabolismo , Espécies Reativas de Oxigênio , Quinase I-kappa B/metabolismo , Lipopolissacarídeos , Transdução de Sinais , Macrófagos
6.
Brief Bioinform ; 24(6)2023 09 22.
Artigo em Inglês | MEDLINE | ID: mdl-37950905

RESUMO

Cancer genomics is dedicated to elucidating the genes and pathways that contribute to cancer progression and development. Identifying cancer genes (CGs) associated with the initiation and progression of cancer is critical for characterization of molecular-level mechanism in cancer research. In recent years, the growing availability of high-throughput molecular data and advancements in deep learning technologies has enabled the modelling of complex interactions and topological information within genomic data. Nevertheless, because of the limited labelled data, pinpointing CGs from a multitude of potential mutations remains an exceptionally challenging task. To address this, we propose a novel deep learning framework, termed self-supervised masked graph learning (SMG), which comprises SMG reconstruction (pretext task) and task-specific fine-tuning (downstream task). In the pretext task, the nodes of multi-omic featured protein-protein interaction (PPI) networks are randomly substituted with a defined mask token. The PPI networks are then reconstructed using the graph neural network (GNN)-based autoencoder, which explores the node correlations in a self-prediction manner. In the downstream tasks, the pre-trained GNN encoder embeds the input networks into feature graphs, whereas a task-specific layer proceeds with the final prediction. To assess the performance of the proposed SMG method, benchmarking experiments are performed on three node-level tasks (identification of CGs, essential genes and healthy driver genes) and one graph-level task (identification of disease subnetwork) across eight PPI networks. Benchmarking experiments and performance comparison with existing state-of-the-art methods demonstrate the superiority of SMG on multi-omic feature engineering.


Assuntos
Neoplasias , Oncogenes , Mutação , Benchmarking , Genes Essenciais , Genômica , Neoplasias/genética
7.
Plant Physiol ; 194(4): 2354-2371, 2024 Mar 29.
Artigo em Inglês | MEDLINE | ID: mdl-38060676

RESUMO

Temperature-sensitive male sterility is one of the core components for hybrid rice (Oryza sativa) breeding based on the 2-line system. We previously found that knockout of ARGONAUTE 1d (AGO1d) causes temperature-sensitive male sterility in rice by influencing phased small interfering RNA (phasiRNA) biogenesis and function. However, the specific phasiRNAs and their targets underlying the temperature-sensitive male sterility in the ago1d mutant remain unknown. Here, we demonstrate that the ago1d mutant displays normal female fertility but complete male sterility at low temperature. Through a multiomics analysis of small RNA (sRNA), degradome, and transcriptome, we found that 21-nt phasiRNAs account for the greatest proportion of the 21-nt sRNA species in rice anthers and are sensitive to low temperature and markedly downregulated in the ago1d mutant. Moreover, we found that 21-nt phasiRNAs are essential for the mRNA cleavage of a set of fertility- and cold tolerance-associated genes, such as Earlier Degraded Tapetum 1 (EDT1), Tapetum Degeneration Retardation (TDR), OsPCF5, and OsTCP21, directly or indirectly determined by AGO1d-mediated gene silencing. The loss of function of 21-nt phasiRNAs can result in upregulation of their targets and causes varying degrees of defects in male fertility and grain setting. Our results highlight the essential functions of 21-nt phasiRNAs in temperature-sensitive male sterility in rice and suggest their promising application in 2-line hybrid rice breeding in the future.


Assuntos
Infertilidade Masculina , Oryza , Masculino , Humanos , Oryza/genética , Oryza/metabolismo , Nucleotídeos/metabolismo , RNA Mensageiro/genética , RNA Mensageiro/metabolismo , Temperatura , RNA de Plantas/genética , Melhoramento Vegetal , RNA Interferente Pequeno/genética , Regulação da Expressão Gênica de Plantas
8.
EMBO Rep ; 24(8): e56335, 2023 08 03.
Artigo em Inglês | MEDLINE | ID: mdl-37341560

RESUMO

While there is growing evidence that many epigenetically silenced genes in cancer are tumour suppressor candidates, their significance in cancer biology remains unclear. Here, we identify human Neuralized (NEURL), which acts as a novel tumour suppressor targeting oncogenic Wnt/ß-catenin signalling in human cancers. The expression of NEURL is epigenetically regulated and markedly suppressed in human colorectal cancer. We, therefore, considered NEURL to be a bona fide tumour suppressor in colorectal cancer and demonstrate that this tumour suppressive function depends on NEURL-mediated oncogenic ß-catenin degradation. We find that NEURL acts as an E3 ubiquitin ligase, interacting directly with oncogenic ß-catenin, and reducing its cytoplasmic levels in a GSK3ß- and ß-TrCP-independent manner, indicating that NEURL-ß-catenin interactions can lead to a disruption of the canonical Wnt/ß-catenin pathway. This study suggests that NEURL is a therapeutic target against human cancers and that it acts by regulating oncogenic Wnt/ß-catenin signalling.


Assuntos
Neoplasias do Colo , beta Catenina , Humanos , beta Catenina/genética , beta Catenina/metabolismo , Via de Sinalização Wnt , Neoplasias do Colo/genética , Ubiquitina-Proteína Ligases/metabolismo , Proteínas Contendo Repetições de beta-Transducina/genética , Proteínas Contendo Repetições de beta-Transducina/metabolismo , Linhagem Celular Tumoral
9.
Cereb Cortex ; 34(5)2024 May 02.
Artigo em Inglês | MEDLINE | ID: mdl-38725292

RESUMO

The local field potential (LFP) is an extracellular electrical signal associated with neural ensemble input and dendritic signaling. Previous studies have linked gamma band oscillations of the LFP in cortical circuits to sensory stimuli encoding, attention, memory, and perception. Inconsistent results regarding gamma tuning for visual features were reported, but it remains unclear whether these discrepancies are due to variations in electrode properties. Specifically, the surface area and impedance of the electrode are important characteristics in LFP recording. To comprehensively address these issues, we conducted an electrophysiological study in the V1 region of lightly anesthetized mice using two types of electrodes: one with higher impedance (1 MΩ) and a sharp tip (10 µm), while the other had lower impedance (100 KΩ) but a thicker tip (200 µm). Our findings demonstrate that gamma oscillations acquired by sharp-tip electrodes were significantly stronger than those obtained from thick-tip electrodes. Regarding size tuning, most gamma power exhibited surround suppression at larger gratings when recorded from sharp-tip electrodes. However, the majority showed enhanced gamma power at larger gratings when recorded from thick-tip electrodes. Therefore, our study suggests that microelectrode parameters play a significant role in accurately recording gamma oscillations and responsive tuning to sensory stimuli.


Assuntos
Ritmo Gama , Camundongos Endogâmicos C57BL , Estimulação Luminosa , Córtex Visual Primário , Animais , Ritmo Gama/fisiologia , Camundongos , Estimulação Luminosa/métodos , Córtex Visual Primário/fisiologia , Masculino , Microeletrodos , Córtex Visual/fisiologia , Eletrodos
10.
Nucleic Acids Res ; 51(20): 10924-10933, 2023 11 10.
Artigo em Inglês | MEDLINE | ID: mdl-37843097

RESUMO

Detailed knowledge of the genetic variations in diverse crop populations forms the basis for genetic crop improvement and gene functional studies. In the present study, we analyzed a large rice population with a total of 10 548 accessions to construct a rice super-population variation map (RSPVM), consisting of 54 378 986 single nucleotide polymorphisms, 11 119 947 insertion/deletion mutations and 184 736 presence/absence variations. Assessment of variation detection efficiency for different population sizes revealed a sharp increase of all types of variation as the population size increased and a gradual saturation of that after the population size reached 10 000. Variant frequency analysis indicated that ∼90% of the obtained variants were rare, and would therefore likely be difficult to detect in a relatively small population. Among the rare variants, only 2.7% were predicted to be deleterious. Population structure, genetic diversity and gene functional polymorphism of this large population were evaluated based on different subsets of RSPVM, demonstrating the great potential of RSPVM for use in downstream applications. Our study provides both a rich genetic basis for understanding natural rice variations and a powerful tool for exploiting great potential of rare variants in future rice research, including population genetics and functional genomics.


Assuntos
Variação Genética , Oryza , Genética Populacional , Genômica , Oryza/genética , Polimorfismo de Nucleotídeo Único
11.
Physiol Genomics ; 56(8): 544-554, 2024 Aug 01.
Artigo em Inglês | MEDLINE | ID: mdl-38808774

RESUMO

The intratumoral microbiota can modulate the tumor immune microenvironment (TIME); however, the underlying mechanism by which intratumoral microbiota influences the TIME in urothelial carcinoma of the bladder (UCB) remains unclear. To address this, we collected samples from 402 patients with UCB, including paired host transcriptome and tumor microbiome data, from The Cancer Genome Atlas (TCGA). We found that the intratumoral microbiome profiles were significantly correlated with the expression pattern of epithelial-mesenchymal transition (EMT)-related genes. Furthermore, we detected that the genera Lachnoclostridium and Sutterella in tumors could indirectly promote the EMT program by inducing an inflammatory response. Moreover, the inflammatory response induced by these two intratumoral bacteria further enhanced intratumoral immune infiltration, affecting patient survival and response to immunotherapy. In addition, an independent immunotherapy cohort of 348 patients with bladder cancer was used to validate our results. Collectively, our study elucidates the potential mechanism by which the intratumoral microbiota influences the TIME of UCB and provides a new guiding strategy for the targeted therapy of UCB.NEW & NOTEWORTHY The intratumoral microbiota may mediate the bladder tumor inflammatory response, thereby promoting the epithelial-mesenchymal transition program and influencing tumor immune infiltration.


Assuntos
Transição Epitelial-Mesenquimal , Inflamação , Microbiota , Microambiente Tumoral , Neoplasias da Bexiga Urinária , Transição Epitelial-Mesenquimal/genética , Neoplasias da Bexiga Urinária/imunologia , Neoplasias da Bexiga Urinária/microbiologia , Neoplasias da Bexiga Urinária/genética , Neoplasias da Bexiga Urinária/patologia , Humanos , Inflamação/imunologia , Inflamação/microbiologia , Microambiente Tumoral/imunologia , Imunoterapia/métodos , Masculino , Feminino , Clostridiales/genética , Transcriptoma/genética , Regulação Neoplásica da Expressão Gênica , Pessoa de Meia-Idade
12.
J Am Chem Soc ; 146(21): 14734-14744, 2024 May 29.
Artigo em Inglês | MEDLINE | ID: mdl-38748980

RESUMO

Symmetry breaking is prevalent in nature and provides distinctive access to hierarchical structures for artificial materials. However, it is rarely explored in two-dimensional (2D) entities, especially for lateral asymmetry. Herein, we describe a unique symmetry breaking process in surface-initiated 2D living crystallization-driven self-assembly. The 2D epitaxial growth occurs only at one lateral side of the immobilized cylindrical micelle seeds, accessing unilateral platelets with the yield increasing with the seed length, the growth temperature, and poly(2-vinylpyridine) corona length (maximum = 92%). Generally, the tilted immobilization of seeds blocks one lateral side and triggers the lateral symmetry breaking, where the intensity and spatial arrangement of seed-surface interactions dictate the regulation. Segmented unilateral platelets with segmented corona regions are further fabricated with the addition of different blended unimers. Remarkably, discrete slope-like and dense blade-like platelet arrays grow off the surface when seeds are compactly aligned either with spherical micelles or themselves. This strategy provides nanoscale insights into the symmetry breaking in long-range self-assembly and would be promising for the design of innovative colloids and smart surfaces.

13.
Cancer Sci ; 115(5): 1492-1504, 2024 May.
Artigo em Inglês | MEDLINE | ID: mdl-38476086

RESUMO

Long noncoding RNAs (lncRNAs) have emerged as important molecules and potential new targets for human cancers. This study investigates the function of lncRNA CTBP1 antisense RNA (CTBP1-AS) in prostate cancer (PCa) and explores the entailed molecular mechanism. Aberrantly expressed genes potentially correlated with PCa progression were probed using integrated bioinformatics analyses. A cohort of 68 patients with PCa was included, and their tumor and para-cancerous tissues were collected. CTBP1-AS was highly expressed in PCa tissues and cells and associated with poor patient prognosis. By contrast, tumor protein p63 (TP63) and S100 calcium binding protein A14 (S100A14) were poorly expressed in the PCa tissues and cells. CTBP1-AS did not affect TP63 expression; however it blocked the TP63-mediated transcriptional activation of S100A14, thereby reducing its expression. CTBP1-AS silencing suppressed proliferation, apoptosis resistance, migration, invasion, and tumorigenicity of PCa cell lines, while its overexpression led to inverse results. The malignant phenotype of cells was further weakened by TP63 overexpression but restored following artificial S100A14 silencing. In conclusion, this study demonstrates that CTBP1-AS plays an oncogenic role in PCa by blocking TP63-mediated transcriptional activation of S100A14. This may provide insight into the management of PCa.


Assuntos
Proliferação de Células , Progressão da Doença , Regulação Neoplásica da Expressão Gênica , Neoplasias da Próstata , RNA Longo não Codificante , Fatores de Transcrição , Proteínas Supressoras de Tumor , Animais , Humanos , Masculino , Camundongos , Oxirredutases do Álcool/genética , Oxirredutases do Álcool/metabolismo , Apoptose/genética , Linhagem Celular Tumoral , Movimento Celular/genética , Proliferação de Células/genética , Prognóstico , Neoplasias da Próstata/genética , Neoplasias da Próstata/patologia , Neoplasias da Próstata/metabolismo , RNA Antissenso/genética , RNA Longo não Codificante/genética , RNA Longo não Codificante/metabolismo , Fatores de Transcrição/genética , Fatores de Transcrição/metabolismo , Ativação Transcricional , Proteínas Supressoras de Tumor/genética , Proteínas Supressoras de Tumor/metabolismo
14.
Clin Immunol ; 263: 110206, 2024 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-38599263

RESUMO

Patients suffering from sepsis-induced acute lung injury (ALI) exhibit a high mortality rate, and their prognosis is closely associated with infiltration of neutrophils into the lungs. In this study, we found a significant elevation of CD64+ neutrophils, which highly expressed p75 neurotrophin receptor (p75NTR) in peripheral blood of mice and patients with sepsis-induced ALI. p75NTR+CD64+ neutrophils were also abundantly expressed in the lung of ALI mice induced by lipopolysaccharide. Conditional knock-out of the myeloid lineage's p75NTR gene improved the survival rates, attenuated lung tissue inflammation, reduced neutrophil infiltration and enhanced the phagocytic functions of CD64+ neutrophils. In vitro, p75NTR+CD64+ neutrophils exhibited an upregulation and compromised phagocytic activity in blood samples of ALI patients. Blocking p75NTR activity by soluble p75NTR extracellular domain peptide (p75ECD-Fc) boosted CD64+ neutrophils phagocytic activity and reduced inflammatory cytokine production via regulation of the NF-κB activity. The findings strongly indicate that p75NTR+CD64+ neutrophils are a novel pathogenic neutrophil subpopulation promoting sepsis-induced ALI.


Assuntos
Lesão Pulmonar Aguda , Camundongos Endogâmicos C57BL , Neutrófilos , Fagocitose , Receptores de IgG , Receptores de Fator de Crescimento Neural , Sepse , Animais , Lesão Pulmonar Aguda/imunologia , Lesão Pulmonar Aguda/etiologia , Neutrófilos/imunologia , Neutrófilos/metabolismo , Sepse/imunologia , Sepse/complicações , Humanos , Receptores de IgG/metabolismo , Receptores de IgG/genética , Receptores de IgG/imunologia , Camundongos , Masculino , Fagocitose/imunologia , Receptores de Fator de Crescimento Neural/metabolismo , Receptores de Fator de Crescimento Neural/genética , Receptores de Fator de Crescimento Neural/imunologia , Camundongos Knockout , Lipopolissacarídeos , Citocinas/metabolismo , Citocinas/imunologia , Pulmão/imunologia , Pulmão/patologia , Feminino , NF-kappa B/metabolismo , NF-kappa B/imunologia , Proteínas do Tecido Nervoso
15.
Eur J Immunol ; 53(10): e2250071, 2023 10.
Artigo em Inglês | MEDLINE | ID: mdl-37379419

RESUMO

Disulfide bond A oxidoreductase-like protein (DsbA-L) drives acute kidney injury (AKI) by directly upregulating the expression of voltage-dependent anion-selective channels in proximal tubular cells. However, the role of DsbA-L in immune cells remains unclear. In this study, we used an LPS-induced AKI mouse model to assess the hypothesis that DsbA-L deletion attenuates LPS-induced AKI and explore the potential mechanism of DsbA-L action. After 24 hours of LPS exposure, the DsbA-L knockout group exhibited lower serum creatinine levels compared to the WT group. Furthermore, peripheral levels of the inflammatory cytokine IL-6 were decreased. Transcriptomic data analysis revealed a significant down-regulation in the IL-17 and tumor necrosis factor pathways in DsbA-L knockout mice following LPS induction. Metabolomic analysis suggested that arginine metabolism was significantly different between the WT and DsbA-L knockout groups after LPS treatment. Notably, the M1 polarization of macrophages in the kidneys of DsbA-L knockout AKI mice was significantly reduced. Expression of the transcription factors NF-κB and AP-1 was downregulated after DsbA-L knockout. Our results suggest that DsbA-L regulates LPS-mediated oxidative stress, promotes M1 polarization of macrophages, and induces expression of inflammatory factors via the NF-κB/AP-1 pathway.


Assuntos
Injúria Renal Aguda , NF-kappa B , Animais , Camundongos , Injúria Renal Aguda/induzido quimicamente , Injúria Renal Aguda/genética , Rim/patologia , Lipopolissacarídeos/farmacologia , Macrófagos , NF-kappa B/metabolismo , Fator de Transcrição AP-1
16.
Small ; : e2401432, 2024 May 31.
Artigo em Inglês | MEDLINE | ID: mdl-38818686

RESUMO

Colloidal composites, translating the great potential of nanoscale building bricks into macroscopic dimensions, have emerged as an appealing candidate for new materials with applications in optics, energy storage, and biomedicines. However, it remains a key challenge to bridge the size regimes from nanoscopic colloidal particles to macroscale composites possessing mechanical robustness. Herein, a bottom-up approach is demonstrated to manufacture colloidal composites with customized macroscopic forms by virtue of the co-assembly of nanosized soft polymeric micelles and hard inorganic nanoparticles. Upon association, the hairy micellar corona can bind with the hard nanoparticles, linking individual hard constituents together in a soft-hard alternating manner to form a collective entity. This permits the integration of block copolymer micelles with controlled amounts of hard nanoparticles into macroscopic colloidal composites featuring diverse internal microstructures. The resultant composites showed tunable microscale mechanical strength in a range of 90-270 MPa and macroscale mechanical strength in a range of 7-42 MPa for compression and 2-24 MPa for bending. Notably, the incorporation of soft polymeric micelles also imparts time- and temperature-dependent dynamic deformability and versatile capacity to the resulting composites, allowing their application in the low-temperature plastic processing for functional fused silica glass.

17.
Metabolomics ; 20(4): 74, 2024 Jul 09.
Artigo em Inglês | MEDLINE | ID: mdl-38980520

RESUMO

BACKGROUND AND AIMS: Biopterins, including tetrahydrobiopterin (BH4), dihydrobiopterin (BH2), and biopterin (B), were crucial enzyme cofactors in vivo. Despite their recognized clinical significance, there remain notable research gaps and controversies surrounding experimental outcomes. This study aims to clarify the biopterins-related issues, including analytical art, physiological intervals, and pathophysiological implications. MATERIALS AND METHODS: A novel LC-MS/MS method was developed to comprehensively profile biopterins in plasma, utilizing chemical derivatization and cold-induced phase separation. Subsequently, apparently healthy individuals were enrolled to investigate the physiological ranges. And the relationships between biopterins and biochemical indicators were analyzed to explore the pathophysiological implications. RESULTS: The developed method was validated as reliable for detecting biopterins across the entire physiological range. Timely anti-oxidation was found to be essential for accurate assessment of biopterins. The observed overall mean ± SDs levels were 3.51 ± 0.94, 1.54 ± 0.48, 2.45 ± 0.84 and 5.05 ± 1.14 ng/mL for BH4, BH2, BH4/BH2 and total biopterins. The status of biopterins showed interesting correlations with age, gender, hyperuricemia and overweight. CONCLUSION: In conjunction with proper anti-oxidation, the newly developed method enables accurate determination of biopterins status in plasma. The observed physiological intervals and pathophysiological implications provide fundamental yet inspiring support for further clinical researches.


Assuntos
Biopterinas , Espectrometria de Massas em Tandem , Humanos , Biopterinas/análogos & derivados , Biopterinas/sangue , Biopterinas/metabolismo , Feminino , Masculino , Adulto , Espectrometria de Massas em Tandem/métodos , Pessoa de Meia-Idade , Cromatografia Líquida/métodos , Adulto Jovem , Idoso , Biomarcadores/sangue
18.
Respir Res ; 25(1): 226, 2024 May 29.
Artigo em Inglês | MEDLINE | ID: mdl-38811960

RESUMO

BACKGROUND: This study aimed to explore the incidence of occult lymph node metastasis (OLM) in clinical T1 - 2N0M0 (cT1 - 2N0M0) small cell lung cancer (SCLC) patients and develop machine learning prediction models using preoperative intratumoral and peritumoral contrast-enhanced CT-based radiomic data. METHODS: By conducting a retrospective analysis involving 242 eligible patients from 4 centeres, we determined the incidence of OLM in cT1 - 2N0M0 SCLC patients. For each lesion, two ROIs were defined using the gross tumour volume (GTV) and peritumoral volume 15 mm around the tumour (PTV). By extracting a comprehensive set of 1595 enhanced CT-based radiomic features individually from the GTV and PTV, five models were constucted and we rigorously evaluated the model performance using various metrics, including the area under the curve (AUC), accuracy, sensitivity, specificity, calibration curve, and decision curve analysis (DCA). For enhanced clinical applicability, we formulated a nomogram that integrates clinical parameters and the rad_score (GTV and PTV). RESULTS: The initial investigation revealed a 33.9% OLM positivity rate in cT1 - 2N0M0 SCLC patients. Our combined model, which incorporates three radiomic features from the GTV and PTV, along with two clinical parameters (smoking status and shape), exhibited robust predictive capabilities. With a peak AUC value of 0.772 in the external validation cohort, the model outperformed the alternative models. The nomogram significantly enhanced diagnostic precision for radiologists and added substantial value to the clinical decision-making process for cT1 - 2N0M0 SCLC patients. CONCLUSIONS: The incidence of OLM in SCLC patients surpassed that in non-small cell lung cancer patients. The combined model demonstrated a notable generalization effect, effectively distinguishing between positive and negative OLMs in a noninvasive manner, thereby guiding individualized clinical decisions for patients with cT1 - 2N0M0 SCLC.


Assuntos
Neoplasias Pulmonares , Metástase Linfática , Carcinoma de Pequenas Células do Pulmão , Tomografia Computadorizada por Raios X , Humanos , Neoplasias Pulmonares/epidemiologia , Neoplasias Pulmonares/patologia , Neoplasias Pulmonares/diagnóstico por imagem , Carcinoma de Pequenas Células do Pulmão/diagnóstico por imagem , Carcinoma de Pequenas Células do Pulmão/epidemiologia , Carcinoma de Pequenas Células do Pulmão/patologia , Masculino , Feminino , Pessoa de Meia-Idade , Estudos Retrospectivos , Idoso , Metástase Linfática/diagnóstico por imagem , Incidência , Tomografia Computadorizada por Raios X/métodos , Valor Preditivo dos Testes , Meios de Contraste , Estadiamento de Neoplasias/métodos , Adulto , Linfonodos/patologia , Linfonodos/diagnóstico por imagem , Idoso de 80 Anos ou mais , Radiômica
19.
Biomacromolecules ; 25(7): 4449-4468, 2024 Jul 08.
Artigo em Inglês | MEDLINE | ID: mdl-38819927

RESUMO

The γ-cyclodextrin (γ-CD) metal-organic frameworks (CD-MOF-1) consist of γ-CD and potassium (K+) ions through coordinating an eight-coordinated K+ ion with two C5-linked oxygen and C6-linked hydroxyl (C5-O/C6-OH) groups in the primary faces of adjacent γ-CD units and two C2- and C3-linked hydroxyl (C2-OH/C3-OH) groups in the secondary faces. Herein, we found polysaccharide gels with only C2-OH/C3-OH or C5-O/C6-OH groups in pyranoid rings can form four-coordinated K+ ions and then coordinate γ-CD in a KOH solution for CD-MOF-1 growth. Exposure of C2-OH/C3-OH or C5-O/C6-OH groups in polysaccharide gels is important to form active four-coordinated K+ ions. Mechanism supporting this work is that four-coordinated K+ ion sites are first formed after coordinating C2-OH/C3-OH groups in pectin and then coordinating C5-O/C6-OH groups in the primary faces of γ-CD units. Alternatively, four-coordinated K+ ions with C5-O/C6-OH groups in chitosan can coordinate the C2-OH/C3-OH groups in the secondary faces of γ-CD units. Mechanism of CD-MOF-1 growing on pectin and chitosan gels through the proposed four-coordinated K+ ions is also universally applicable to other polysaccharide gels with similar C2-OH/C3-OH or C5-O/C6-OH groups such as alginate gel. Based on this mechanism, we developed pectin and chitosan gel-based CD-MOF-1 composites and exemplified applications of them in antibacterial and organic dye removal. To help future research and applications of this mechanism, we share our theoretical assumption for further investigations that any matrices with an ortho-hydroxyl carbon chain or ortho-hydroxyl ether structures may form four-coordinated K+ ions for CD-MOF-1 growth. The proposed mechanism will broaden the development of novel CD-MOF-1 composites in various fields.


Assuntos
Géis , Potássio , Potássio/química , Géis/química , Porosidade , gama-Ciclodextrinas/química , Estruturas Metalorgânicas/química , Polissacarídeos/química , Pectinas/química , Íons/química
20.
Int J Geriatr Psychiatry ; 39(6): e6110, 2024 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-38831201

RESUMO

OBJECTIVES: To explore the association between drinking water sources and cognitive functioning among older adults residing in rural China. METHODS: Data were extracted from the 2008-2018 Chinese Longitudinal Healthy Longevity Survey. Drinking water sources were categorized according to whether purification measures were employed. The Chinese version of the Mini-Mental State Examination was used for cognitive functioning assessment, and the score of <24 was considered as having cognitive dysfunction. Cox regression analyses were conducted to derive hazard ratios (HRs) and 95% confidence intervals (CIs) for the effects of various drinking water sources, changes in such sources, and its interaction with exercise on cognition dysfunction. RESULTS: We included 2304 respondents aged 79.67 ± 10.02 years; of them, 1084 (44.49%) were men. Our adjusted model revealed that respondents consistently drinking tap water were 21% less likely to experience cognitive dysfunction compared with those drinking untreated water (HR = 0.79, 95% CI: 0.70-0.90). Respondents transitioning from natural to tap water showed were 33% less likely to experience cognitive dysfunction (HR = 0.67, 95% CI: 0.58-0.78). Moreover, the HR (95% CI) for the interaction between drinking tap water and exercising was 0.86 (0.75-1.00) when compared with that between drinking untreated water and not exercising. All results adjusted for age, occupation, exercise, and body mass index. CONCLUSIONS: Prolonged tap water consumption and switching from untreated water to tap water were associated with a decreased risk of cognitive dysfunction in older individuals. Additionally, exercising and drinking tap water was synergistically associated with the low incidence of cognitive dysfunction. These findings demonstrate the importance of prioritizing drinking water health in rural areas, indicating that purified tap water can enhance cognitive function among older adults.


Assuntos
Disfunção Cognitiva , Água Potável , População Rural , Humanos , Masculino , Idoso , Feminino , China/epidemiologia , População Rural/estatística & dados numéricos , Idoso de 80 Anos ou mais , Disfunção Cognitiva/epidemiologia , Disfunção Cognitiva/etiologia , Estudos Longitudinais , Exercício Físico , Cognição/fisiologia , Modelos de Riscos Proporcionais , Abastecimento de Água
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