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1.
Neural Regen Res ; 20(3): 821-835, 2025 Mar 01.
Artigo em Inglês | MEDLINE | ID: mdl-38886955

RESUMO

JOURNAL/nrgr/04.03/01300535-202503000-00027/figure1/v/2024-06-17T092413Z/r/image-tiff Repetitive traumatic brain injury impacts adult neurogenesis in the hippocampal dentate gyrus, leading to long-term cognitive impairment. However, the mechanism underlying this neurogenesis impairment remains unknown. In this study, we established a male mouse model of repetitive traumatic brain injury and performed long-term evaluation of neurogenesis of the hippocampal dentate gyrus after repetitive traumatic brain injury. Our results showed that repetitive traumatic brain injury inhibited neural stem cell proliferation and development, delayed neuronal maturation, and reduced the complexity of neuronal dendrites and spines. Mice with repetitive traumatic brain injuryalso showed deficits in spatial memory retrieval. Moreover, following repetitive traumatic brain injury, neuroinflammation was enhanced in the neurogenesis microenvironment where C1q levels were increased, C1q binding protein levels were decreased, and canonical Wnt/ß-catenin signaling was downregulated. An inhibitor of C1 reversed the long-term impairment of neurogenesis induced by repetitive traumatic brain injury and improved neurological function. These findings suggest that repetitive traumatic brain injury-induced C1-related inflammation impairs long-term neurogenesis in the dentate gyrus and contributes to spatial memory retrieval dysfunction.

2.
Int Immunopharmacol ; 142(Pt A): 113075, 2024 Sep 10.
Artigo em Inglês | MEDLINE | ID: mdl-39260312

RESUMO

Medulloblastoma (MB) is the most common malignant brain tumor in children. Within MB, tumors driven by the Sonic Hedgehog (SHH) pathway represent the most heterogeneous subtype, known as SHH subtype medulloblastoma (SHH-MB). Tenovin-6, a recognized p53 activator, has been demonstrated to inhibit autophagy and modulate sirtuin activity, underscoring its potential as a novel therapeutic agent across various malignancies. However, its efficacy in treating SHH-MB remains unexplored. This study aims to investigate the inhibitory effects of tenovin-6 on SHH-MB and elucidate its underlying signaling pathways. We assessed the impact of tenovin-6 on cell proliferation through the CCK-8 and colony formation assays. The scratch and transwell invasion assays were utilized to evaluate the drug's effects on metastasis. Apoptosis and reactive oxygen species (ROS) levels were measured using flow cytometry. Potential signaling pathways were identified via transcriptomics and quantitative PCR (qPCR). Our in vivo studies involved a mouse xenograft model to explore tenovin-6's anticancer efficacy against SHH-MB. The findings indicate that tenovin-6 not only inhibits cell proliferation and metastasis in SHH-MB cell lines but also promotes apoptosis, which is closely linked to its proliferation-inhibiting properties. Additionally, animal experiments confirmed that tenovin-6 suppresses MB growth in vivo. We discovered that tenovin-6 reduces intracellular ROS levels and inhibits autophagy in SHH-MB by disrupting the fusion of autophagosomes with lysosomes, likely through inducing autophagosome formation.

3.
BMC Biol ; 22(1): 185, 2024 Sep 02.
Artigo em Inglês | MEDLINE | ID: mdl-39218872

RESUMO

BACKGROUND: Scutellaria, a sub-cosmopolitan genus, stands as one of the Lamiaceae family's largest genera, encompassing approximately 500 species found in both temperate and tropical montane regions. Recognized for its significant medicinal properties, this genus has garnered attention as a research focus, showcasing anti-cancer, anti-inflammatory, antioxidant, and hepatoprotective qualities. Additionally, it finds application in agriculture and horticulture. Comprehending Scutellaria's taxonomy is pivotal for its effective utilization and conservation. However, the current taxonomic frameworks, primarily based on morphological characteristics, are inadequate. Despite several phylogenetic studies, the species relationships and delimitations remain ambiguous, leaving the genus without a stable and reliable classification system. RESULTS: This study analyzed 234 complete chloroplast genomes, comprising 220 new and 14 previously published sequences across 206 species, subspecies, and varieties worldwide. Phylogenetic analysis was conducted using six data matrices through Maximum Likelihood and Bayesian Inference, resulting in a robustly supported phylogenetic framework for Scutellaria. We propose three subgenera, recommending the elevation of Section Anaspis to subgeneric rank and the merging of Sections Lupulinaria and Apeltanthus. The circumscription of Subgenus Apeltanthus and Section Perilomia needs to be reconsidered. Comparative analysis of chloroplast genomes highlighted the IR/SC boundary feature as a significant taxonomic indicator. We identified a total of 758 SSRs, 558 longer repetitive sequences, and ten highly variable regions, including trnK-rps16, trnC-petN, petN-psbM, accD-psaI, petA-psbJ, rpl32-trnL, ccsA-ndhD, rps15-ycf1, ndhF, and ycf1. These findings serve as valuable references for future research on species identification, phylogeny, and population genetics. CONCLUSIONS: The phylogeny of Scutellaria, based on the most comprehensive sample collection to date and complete chloroplast genome analysis, has significantly enhanced our understanding of its infrageneric relationships. The extensive examination of chloroplast genome characteristics establishes a solid foundation for the future development and utilization of Scutellaria, an important medicinal plant globally.


Assuntos
Genoma de Cloroplastos , Filogenia , Scutellaria , Scutellaria/genética
4.
New Phytol ; 2024 Sep 05.
Artigo em Inglês | MEDLINE | ID: mdl-39238152

RESUMO

Long terminal repeat retroelements (LTR-REs) have profound effects on DNA methylation and gene regulation. Despite the vast abundance of LTR-REs in the genome of Moso bamboo (Phyllostachys edulis), an industrial crop in underdeveloped countries, their precise implication of the LTR-RE mobility in stress response and development remains unknown. We investigated the RNA and DNA products of LTR-REs in Moso bamboo under various developmental stages and stressful conditions. Surprisingly, our analyses identified thousands of active LTR-REs, particularly those located near genes involved in stress response and developmental regulation. These genes adjacent to active LTR-REs exhibited an increased expression under stress and are associated with reduced DNA methylation that is likely affected by the induced LTR-REs. Moreover, the analyses of simultaneous mapping of insertions and DNA methylation showed that the LTR-REs effectively alter the epigenetic status of the genomic regions where they inserted, and concomitantly their transcriptional competence which might impact the stress resilience and growth of the host. Our work unveils the unusually strong LTR-RE mobility in Moso bamboo and its close association with (epi)genetic changes, which supports the co-evolution of the parasitic DNAs and host genome in attaining stress tolerance and developmental robustness.

5.
PLoS One ; 19(9): e0307839, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-39226282

RESUMO

The Guangdong-Hong Kong-Macao Greater Bay Area has attracted attention for its extraordinary pace of economic development and is considered to be leading the way in China's transformation from a manufacturing to an innovation cluster. However, due to rapid economic expansion and rapid urbanization, the Great Bay Area still struggles with low energy efficiency and environmental degradation, which has slowed down the pace of development. Therefore, in order to alleviate energy pressure, promote the country's sustainable development and gain a competitive advantage in the global market, researching energy efficiency and improving energy utilization efficiency is crucial. In this study, macro-level energy efficiency indicators are constructed using energy consumption data from various cities in the Greater Bay Area for the period from 2000 to 2020, and the spatio-temporal evolution of energy efficiency is analysed. The results show that all cities in the Greater Bay Area experienced an increasing trend in energy efficiency from 2000 to 2019, with significant variation in growth rates and magnitudes between cities. Compared to the nine cities in Guangdong province, Hong Kong and Macao exhibited significantly superior energy efficiency, with Foshan recording the highest growth rate of 14%. In 2020, most cities experienced a decline in energy efficiency due to the COVID-19 pandemic, with Macao experiencing the greatest decrease at 57%. Hong Kong and Macao are both in the "low consumption and high efficiency" target region, while Guangzhou, Shenzhen and Zhuhai are consistently in the "both high" region. Changes in the industrial upgrading index correspond significantly with changes in energy efficiency trajectories, with the transition from primary to secondary and tertiary industries playing a more substantial role. There is no significant association found between the strength of environmental regulation and changes in energy efficiency. The study's findings indicate that the most effective way to achieve economic transformation in the majority of China's regions is to combine adequate environmental legislation with industrial structural adjustment.


Assuntos
Desenvolvimento Econômico , China , Hong Kong , Humanos , COVID-19/epidemiologia , Baías , Urbanização , Cidades , Macau , Fontes Geradoras de Energia , Análise Espaço-Temporal
6.
Nat Commun ; 15(1): 7680, 2024 Sep 03.
Artigo em Inglês | MEDLINE | ID: mdl-39227604

RESUMO

Intraluminal epithelial abnormalities, potential precursors to significant conditions like cancer, necessitate early detection for improved prognosis. We present a motor-free telerobotic optical coherence tomography (OCT) endoscope that offers high-resolution intraluminal imaging and overcomes the limitations of traditional systems in navigating curved lumens. This system incorporates a compact magnetic rotor with a rotatable diametrically magnetized cylinder permanent magnet (RDPM) and a reflector, effectively mitigating thermal and electrical risks by utilizing an external magnetic field to maintain temperature increases below 0.5 °C and generated voltage under 0.02 mV. Additionally, a learning-based method corrects imaging distortions resulting from nonuniform rotational speeds. Demonstrating superior maneuverability, the device achieves steerable angles up to 110° and operates effectively in vivo, providing distortion-free 3D programmable imaging in mouse colons. This advancement represents a significant step towards guidewire-independent endomicroscopy, enhancing both safety and potential patient outcomes.


Assuntos
Tomografia de Coerência Óptica , Animais , Tomografia de Coerência Óptica/métodos , Tomografia de Coerência Óptica/instrumentação , Camundongos , Imageamento Tridimensional/métodos , Imageamento Tridimensional/instrumentação , Endoscópios , Humanos , Desenho de Equipamento , Microscopia/métodos , Microscopia/instrumentação , Endoscopia/métodos , Endoscopia/instrumentação
7.
Theranostics ; 14(12): 4683-4700, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-39239525

RESUMO

N6-methyladenosine (m6A) is the most abundant post-transcriptional dynamic RNA modification process in eukaryotes, extensively implicated in cellular growth, embryonic development and immune homeostasis. One of the most profound biological functions of m6A is to regulate RNA metabolism, thereby determining the fate of RNA. Notably, the regulation of m6A-mediated organized RNA metabolism critically relies on the assembly of membraneless organelles (MLOs) in both the nucleus and cytoplasm, such as nuclear speckles, stress granules and processing bodies. In addition, m6A-associated MLOs exert a pivotal role in governing diverse RNA metabolic processes encompassing transcription, splicing, transport, decay and translation. However, emerging evidence suggests that dysregulated m6A levels contribute to the formation of pathological condensates in a range of human diseases, including tumorigenesis, reproductive diseases, neurological diseases and respiratory diseases. To date, the molecular mechanism by which m6A regulates the aggregation of biomolecular condensates associated with RNA metabolism is unclear. In this review, we comprehensively summarize the updated biochemical processes of m6A-associated MLOs, particularly focusing on their impact on RNA metabolism and their pivotal role in disease development and related biological mechanisms. Furthermore, we propose that m6A-associated MLOs could serve as predictive markers for disease progression and potential drug targets in the future.


Assuntos
Adenosina , RNA , Humanos , Adenosina/metabolismo , Adenosina/análogos & derivados , RNA/metabolismo , Organelas/metabolismo , Animais , Processamento Pós-Transcricional do RNA , Neoplasias/metabolismo , Neoplasias/genética , Neoplasias/patologia , Núcleo Celular/metabolismo , Citoplasma/metabolismo
8.
Skin Res Technol ; 30(9): e70042, 2024 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-39233331

RESUMO

BACKGROUND: Value analysis of a small-molecule fluorescent probe for methylation detection in different cervical lesions. MATERIALS AND METHODS: (1) The grayscale values of distinct lesion tissues were remarkably distinct among the four groups (p < 0.05). The comparison of the grayscale value between the two groups showed that the CA group noticeably exceeded the LSIL and cervicitis groups, and the HSIL group was apparently higher than the LSIL and cervicitis groups (p < 0.05); (2) The mean grayscale values of the enrolled subjects were calculated with 55.21 as the midline, with >55.21 as positive and ≤55.21 as negative. RESULTS: The results showed that the positive rate of the cervicitis group was 0.00%, the LSIL group 67.74%, the HSIL group 83.33%, and the CA group 100.00%. The results among the four groups were notably distinct (p < 0.05); (3) The comparison among DAPI, probe, bright, and merged images of cervicitis, LSIL, HSIL, and CA indicated that different cervical lesions were with quite various stains. CONCLUSION: The grayscale value, positive rate, and stained picture of distinct cervical lesions were remarkably different. The small-molecule fluorescent probe has a good value in differentiating cervical lesions and can be considered for popularization and application.


Assuntos
DNA (Citosina-5-)-Metiltransferase 1 , Metilação de DNA , Corantes Fluorescentes , Neoplasias do Colo do Útero , Humanos , Feminino , Neoplasias do Colo do Útero/genética , Adulto , Pessoa de Meia-Idade , DNA (Citosina-5-)-Metiltransferase 1/metabolismo , DNA (Citosina-5-)-Metiltransferase 1/genética , Idoso , Sensibilidade e Especificidade , Cervicite Uterina/metabolismo , Displasia do Colo do Útero/diagnóstico
9.
Int J Cardiol ; 414: 132417, 2024 Aug 03.
Artigo em Inglês | MEDLINE | ID: mdl-39098611

RESUMO

BACKGROUND: Immune thrombocytopenia (ITP) is a prevalent autoimmune bleeding disorder, with the primary objective of treatment being the prevention of bleeding. Clinical investigations have indicated that individuals with ITP face an elevated risk of thrombosis, and the occurrence of thromboembolic events in ITP patients can be attributed to a multitude of factors. However, establishing a definitive causal relationship between ITP and thrombosis remains challenging. METHODS: A two-sample Mendelian randomization (MR) study utilizing summary data from FinnGen consortium and UK Biobank was undertaken to investigate the causal association between ITP and thrombosis. The primary analysis employed the inverse-variance weighted (IVW) method, while supplementary analyses were conducted using the MR-Egger, weighted median, and MR-PRESSO approaches. RESULTS: Based on IVW method, there was a statistically significant but small positive correlation between ITP and thrombosis. Specifically, ITP patients exhibited a suggestive positive correlation with myocardial infarction and deep-vein thrombosis. However, our investigation did not identify any causal relationship between ITP and cerebral infarction, arterial embolism, other arterial embolisms, pulmonary embolism, thrombophlebitis, or portal vein thrombosis. Sensitivity analyses further confirmed the accuracy and robustness of these findings. CONCLUSIONS: This study presents empirical support for the causal relationship between ITP and thrombosis. It is important to note that a diminished platelet count does not serve as a preventive measure against thrombus formation. Consequently, when managing a newly diagnosed ITP patient, clinicians need to be aware that there is a slight elevation in the risk of thrombosis during treatment.

10.
Animals (Basel) ; 14(15)2024 Jul 28.
Artigo em Inglês | MEDLINE | ID: mdl-39123722

RESUMO

Inappropriate substitution of dietary fishmeal (FM) can adversely affect the growth, health, and metabolism of carnivorous fish species. To effectively reduce the amount of dietary FM in carnivorous largemouth bass (Micropterus salmoides), a terrestrial compound protein (Cpro) with chicken meal, bone meal, and black soldier fly protein was used to formulate four isoproteic (52%) and isolipidic (12%) diets, namely T1 (36% FM), T2 (30% FM), T3 (24% FM), and T4 (18% FM), for feeding juveniles (initial weight: ~12 g) for 81 days. Results indicated that the growth performance, feed efficiency, and morphological indicators, as well as muscle texture and edible quality of fish, did not differ significantly among the four groups. However, the muscle protein contents and ATP/AMP ratio of fish in the T4 group were significantly increased in comparison with those of fish in the T1 group, while the opposite was true for muscle glycogen. Compared with the T1 group, high serum total amino acid and MDA contents, as well as low AST activities, were observed in the T3 and T4 groups, and relatively high intestinal trypsin and lipase activities were found in the T2-T4 groups. The transcripts of intestinal proinflammatory cytokines (il-1ß, il-6, and tnf-α) were downregulated in the T2-T4 groups compared with T1 group, while the expression of anti-inflammatory cytokines (il-10) and tight junction (zo-1 and occludin) showed the reverse trend. The mRNA expression of positive regulators related to protein synthesis (sirt1, pgc1-α, pi3k, and akt) were significantly upregulated in the muscle of fish fed diets T3 and T4, while their negative regulators (4e-bp1) mRNA levels were downregulated. The results indicate that the dietary FM of largemouth bass could be effectively reduced to at least 18% by the Cpro, which is beneficial to health, digestion, and protein synthesis for maintaining accelerated growth.

11.
Commun Biol ; 7(1): 1002, 2024 Aug 16.
Artigo em Inglês | MEDLINE | ID: mdl-39152250

RESUMO

The processes of forming lineages undergoing widespread radiations remain a knowledge gap that is fundamental to our understanding of the geographic distributions of species. Although early studies emphasized the importance of dispersal ability and historical migration events, key innovations that promote rapid diversification and/or adaptation to new habitats may also strongly influence distribution ranges. Juniperus is the second largest genus of conifers and is widely distributed throughout the Northern Hemisphere. Here, we used phylogenetic, phenotypic, and climatic data to investigate the contributions of these processes to the wide distribution and rapid diversification of Juniperus. Combining a time-scaled phylogeny and macroevolutionary theory, we show that the key innovations of berry-like seed cones and dioecy promoted the rapid diversification of Juniperus and that increased dispersal ability promoted allopatric speciation. Ecological niches had significant divergence among different clades of Juniperus. Biogeographic results supported multiple long-distance dispersal events and niche variation that contributed to the modern range of Juniperus, while both phenotypic adaptation and ecological opportunity probably drove its distribution range. Our findings suggest that the current widespread distribution is likely the result of significant divergence driven by niche variation in which ecological opportunities from key innovation and phenotypic divergence.


Assuntos
Ecossistema , Juniperus , Filogenia , Juniperus/genética , Evolução Biológica , Fenótipo , Filogeografia , Biodiversidade
12.
J Food Sci ; 2024 Aug 16.
Artigo em Inglês | MEDLINE | ID: mdl-39150685

RESUMO

Ara h1 was the highest content of peanut allergen protein, identified as a biomarker of peanut allergen. In this study, Ara h1 was covalently complexed with caffeic acid (CA) to research the effects of covalent conjugation on the antigenicity and protein structural properties of Ara h1. After the covalent complexing of Ara h1 and CA, the IgG-binding capacity of Ara h1 was reduced compared with that of control Ara h1. Moreover, the structure of Ara h1 changed from ordered to disordered, the number of intermolecular hydrogen bonds decreased, and some hydrophobic groups were exposed or hydrophobic peptides were released. The carboxyl group in CA reacted with the amino group in Ara h1. The digestibility of Ara h1-CA was increased. The antigenicity of Ara h1-CA was undetectable after 30 min of digestion in vitro. These findings can serve as a reference for further research on hypoallergenic peanut products.

13.
Chem Commun (Camb) ; 60(68): 9050-9053, 2024 Aug 20.
Artigo em Inglês | MEDLINE | ID: mdl-39099533

RESUMO

In situ growth of intertwined trinuclear copper complexes (nCu3) on a cellulose-derived carbon support (CMC) produced a high-performance electrocatalyst (CMC-nCu3) for the oxygen reduction reaction (ORR), which demonstrated superior performance in zinc-air batteries compared to a commercial Pt/C catalyst. This work highlights the importance of copper-based molecular catalysts with rich and intertwined tricopper structures for boosting both ORR activity and stability.

14.
Sci Prog ; 107(3): 368504241262902, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-39096043

RESUMO

OBJECTIVE: We sought to characterize the clinical prognostic factors in veterans with amyotrophic lateral sclerosis (ALS) followed in our ALS clinic. BACKGROUND: ALS is a rare, progressive neurodegenerative condition associated with decreased survival compared to that in the normal population. METHOD: The electronic medical records of 105 veterans diagnosed with ALS who are followed in our ALS clinic between 2010 and 2021 were reviewed. Approval from the institutional review board was obtained from the study protocol. Demographic and clinical variables included age at symptom onset, age at initial evaluation, survival (from symptom onset to death), gender, site of onset (appendicular, bulbar, and respiratory), initial amyotrophic lateral sclerosis functional-related score-revised (ALSFRS-R), total functional independence measure (TFIM) scores, initial forced vital capacity (FVC), and interventions (Riluzole, gastrostomy, noninvasive ventilation [NIV], and tracheostomy). Normally distributed data was expressed as mean ± standard deviation. Fischer's exact analysis of the distribution differences of categorical data. The Kaplan-Meier plot analyzed the time-to-event. RESULTS: The mean (SD) age at symptom onset was 62.0 (11.1) years, age at diagnosis was 65 (11) years, with 72% of the patients being over 60 years at diagnosis. The median survival time from symptom onset was 4.12 (3) years. Limb-onset ALS (appendicular) was the most frequent (52%) followed by bulbar-onset ALS (43%). The mean ALSFRS-R and TFIM scores were 31 (8) and 91 (25), respectively. Family history (familial), bulbar, and respiratory presentation at diagnosis were associated with shorter survival times. CONCLUSION: This study suggests that of the clinical prognostic factors veterans with familial ALS, bulbar, and respiratory onset at presentations had shorter survival. The presence of Agent Orange, PEG placement, and NIV did not affect survival.


Assuntos
Esclerose Lateral Amiotrófica , Veteranos , Humanos , Esclerose Lateral Amiotrófica/mortalidade , Esclerose Lateral Amiotrófica/fisiopatologia , Esclerose Lateral Amiotrófica/genética , Esclerose Lateral Amiotrófica/diagnóstico , Pessoa de Meia-Idade , Masculino , Veteranos/estatística & dados numéricos , Feminino , Idoso , Idade de Início , Prognóstico , Estimativa de Kaplan-Meier
15.
Sci Data ; 11(1): 844, 2024 Aug 03.
Artigo em Inglês | MEDLINE | ID: mdl-39097648

RESUMO

Episyrphus balteatus can provide dual ecosystem services including pest control and pollination, which the larvae are excellent predators of aphid pest whereas adults are efficient pollinator. In this study, we assembled a high-quality genome of E. balteatus from northern China geographical population at the chromosome level by using Illumina, PacBio long reads, and Hi-C technologies. The 467.42 Mb genome was obtained from 723 contigs, with a contig N50 of 9.16 Mb and Scaffold N50 of 118.85 Mb, and 90.25% (431.75 Mb) of the assembly was anchored to 4 pseudo-autosomes and one pseudo-heterosome. In total, 14,848 protein-coding genes were annotated, and 95.14% of genes were fully represented in NR, GO, KEGG databases. Besides, we also obtained the mitochondrial genome of E. balteatus of 16, 837 bp in length with 37 typical mitochondrial genes. Overall, this high-quality genome is valuable for evolutionary and genetic studies of E. balteatus and other Syrphidae hoverfly species.


Assuntos
Dípteros , Genoma de Inseto , Genoma Mitocondrial , Animais , Dípteros/genética , China , Cromossomos de Insetos/genética
16.
Cancer Res ; 2024 Aug 13.
Artigo em Inglês | MEDLINE | ID: mdl-39137404

RESUMO

Prostate cancer (PCa) rarely responds to immune-checkpoint blockade (ICB) therapies. Cancer-associated fibroblasts (CAFs) are critical components of the immunologically "cold" tumor microenvironment and are considered a promising target to enhance the immunotherapy response. In this study, we aimed to reveal the mechanisms regulating CAF plasticity to identify potential strategies to switch CAFs from pro-tumorigenic to anti-tumor phenotypes and enhance ICB efficacy in PCa. Integration of four PCa single-cell RNA-sequencing datasets defined pro-tumorigenic and anti-tumor CAFs, and RNA-seq, flow cytometry, and a PCa organoid model demonstrated the functions of two CAF subtypes. Extracellular matrix-associated CAFs (ECM-CAF) promoted collagen deposition and cancer cell progression, and lymphocyte-associated CAFs (Lym-CAF) exhibited an anti-tumor phenotype and induced the infiltration and activation of CD8+ T cells. YAP1 activity regulated the ECM-CAF phenotype, and YAP1 silencing promoted switching to Lym-CAFs. NF-κB p65 was the core transcription factor in the Lym-CAF subset, and YAP1 inhibited nuclear translocation of p65. Selective depletion of YAP1 in ECM-CAFs in vivo promoted CD8+ T-cell infiltration and activation and enhanced the therapeutic effects of anti- PD-1 treatment in PCa. Overall, this study revealed a mechanism regulating CAF identity in PCa and highlighted a therapeutic strategy for altering the CAF subtype to suppress tumor growth and increase sensitivity to ICB.

17.
Angew Chem Int Ed Engl ; : e202412712, 2024 Aug 21.
Artigo em Inglês | MEDLINE | ID: mdl-39168820

RESUMO

Organic heterostructures (OHs) with multi-segments exhibit special optoelectronic properties compared with monomeric structures. Nevertheless, the synthesis of multi-block heterostructures remains challenging due to compatibility issues between segment parts, which restricts their application in optical waveguides and integrated optics. Herein, we demonstrate programmable in-situ co-assembly engineering, combining multi-step spontaneous self-assembly processes to promote the synthesis of multi-block heterostructures with a rational arrangement of three or more segments. The rational design of segments enables exciton manipulation and ensures optical waveguides and proper output among the multi-segment OHs. This work enables the controllable growth of segments within multi-block OHs, providing a pathway to construct complex OHs for the rational development of future optical applications.

18.
Chemosphere ; 364: 143121, 2024 Aug 20.
Artigo em Inglês | MEDLINE | ID: mdl-39154768

RESUMO

INTRODUCTION: Benzo[a]pyrene (B[a]P) is a carcinogenic polycyclic aromatic hydrocarbon that poses significant risks to human health. B[a]P influences cellular processes via intricate interactions; however, a comprehensive understanding of B[a]P's effects on the transcriptome remains elusive. This study aimed to conduct a comprehensive analysis focused on identifying relevant genes and signaling pathways affected by B[a]P exposure and their impact on human gene expression. METHODS: We searched the Gene Expression Omnibus database and identified four studies involving B[a]P exposure in human cells (T lymphocytes, hepatocellular carcinoma cells, and C3A cells). We utilized two approaches for differential expression analysis: the LIMMA package and linear regression. A meta-analysis was utilized to combine log fold changes (FC) and p-values from the identified studies using a random effects model. We identified significant genes at a Bonferroni-adjusted significance level of 0.05 and determined overlapping genes across datasets. Pathway enrichment analysis elucidated key cellular processes modulated by B[a]P exposure. RESULTS: The meta-analysis revealed significant upregulation of CYP1B1 (log FC = 1.15, 95% CI: 0.51-1.79, P < 0.05, I2 = 82%) and ASB2 (log FC = 0.44, 95% CI: 0.20-0.67, P < 0.05, I2 = 40%) in response to B[a]P exposure. Pathway analyses identified 26 significantly regulated pathways, with the top including Aryl Hydrocarbon Receptor Signaling (P = 0.00214) and Xenobiotic Metabolism Signaling (P = 0.00550). Key genes CYP1A1, CYP1B1, and CDKN1A were implicated in multiple pathways, highlighting their roles in xenobiotic metabolism, oxidative stress response, and cell cycle regulation. CONCLUSION: The results provided insights into the mechanisms of B[a]P toxicity, highlighting CYP1B1's key role in B[a]P bioactivation. The findings underscored the complexity of B[a]P's mechanisms of action and their potential implications for human health. The identified genes and pathways provided a foundation for further exploration and enhanced our understanding of the multifaceted biological activities associated with B[a]P exposure.

19.
J Colloid Interface Sci ; 677(Pt B): 1075-1083, 2024 Aug 13.
Artigo em Inglês | MEDLINE | ID: mdl-39180842

RESUMO

Pancreatic and colon cancer are malignant tumors of the digestive system that currently lack effective treatments. In cancer cells, a high level of glutathione (GSH) is indispensable to scavenge excessive reactive oxygen species (ROS) and detoxify xenobiotics, which make it a potential target for cancer therapy. GSH depletion has been proved to improve the therapeutic efficacy of photodynamic therapy. Here, we reported that naked mesoporous rhodium nanospheres (Rh MNs), prepared by soft template redox method, can act as GSH depletion agent and photothermal conversion agent to achieve synergistic therapy respectively. Different from conventional nanoagents, Rh MNs with the characteristics of easy synthesis, simple structure and multiple functions can decrease the GSH level in tumor and depict excellent photothermal ability with a high photothermal conversion efficiency (PTCE) up to 39%. Notably, multiple anti-tumor mechanisms in CT26 and BxPC-3 tumor models, include inhibited anti-apoptosis, DNA replication repair, and GSH synthesis are revealed, and the pancreatic tumor cure rate of the cooperative treatment group is 80%. Collectively, we developed Rh MNs to combine GSH depletion with photothermal therapy for cancer treatment.

20.
Sci Adv ; 10(35): eadp3145, 2024 Aug 30.
Artigo em Inglês | MEDLINE | ID: mdl-39196931

RESUMO

The complex anatomy of internal luminal organs, like bronchioles, poses challenges for endoscopic optical coherence tomography (OCT). These challenges include limited steerability for targeted imaging and nonuniform rotation distortion (NURD) with proximal scanning. Using rotary micromotors for distal scanning could address NURD but raises concerns about electrical safety and costs. We present pneumaOCT, the first pneumatic OCT endoscope, comprising a steerable catheter with a soft pneumatic actuator and an imaging probe with a miniature pneumatic turbine. With a diameter of 2.8 mm, pneumaOCT allows for a bending angle of up to 237°, facilitating navigation through narrow turns. The pneumatic turbine enables adjustable imaging speeds from 51 to 446 revolutions per second. We demonstrate the pneumaOCT in vivo imaging of mouse esophagus and colon, as well as targeted and distortion-free imaging of peripheral bronchioles in a bronchial phantom and a porcine lung. This advancement substantially improves endoscopic OCT for navigational imaging in curved and narrow lumens.


Assuntos
Tomografia de Coerência Óptica , Tomografia de Coerência Óptica/métodos , Animais , Camundongos , Suínos , Imagens de Fantasmas , Esôfago/diagnóstico por imagem , Colo/diagnóstico por imagem , Endoscopia/métodos , Bronquíolos/diagnóstico por imagem
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