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1.
Food Chem ; 462: 141063, 2025 Jan 01.
Artículo en Inglés | MEDLINE | ID: mdl-39226640

RESUMEN

In this research, the TT-COF(Fe)@NH2-CNTs was innovatively prepared through a post-modification synthetic process functionalized TT-COF@NH2-CNTs with active site (Fe), where TT-COF@NH2-CNTs was prepared via a one-pot strategy using 5,10,15,20-tetrakis (para-aminophenyl) porphyrin (TTAP), 2,3,6,7-tetra (4-formylphenyl) tetrathiafulvalene (TTF) and aminated carbon nanotubes (NH2-CNTs) as raw materials. The complex TT-COF(Fe)@NH2-CNTs material possessed porous structures, outstanding conductivity and rich catalytic sites. Thus, it can be adopted to construct electrochemical sensor with glassy carbon electrode (GCE). The TT-COF(Fe)@NH2-CNTs/GCE can selectively detect luteolin (Lu) with a wide linear plot ranging from 0.005 to 3 µM and a low limit of detection (LOD) of 1.45 nM (S/N = 3). The Lu residues in carrot samples were determined using TT-COF(Fe)@NH2-CNTs sensor and UV-visible (UV-Vis) approach. This TT-COF(Fe)@NH2-CNTs/GCE sensor paves the way for the quantification of Lu through a cost-efficient and sensitive electrochemical approach, which can make a significant step in the sensing field based on crystalline COFs.


Asunto(s)
Técnicas Electroquímicas , Luteolina , Nanotubos de Carbono , Nanotubos de Carbono/química , Luteolina/química , Luteolina/análisis , Técnicas Electroquímicas/instrumentación , Límite de Detección , Estructuras Metalorgánicas/química , Contaminación de Alimentos/análisis , Dominio Catalítico
2.
Exp Neurol ; 382: 114950, 2024 Sep 13.
Artículo en Inglés | MEDLINE | ID: mdl-39278588

RESUMEN

Intracerebral hemorrhage (ICH) is a severe disease that often leads to disability and death. Neuroinflammatory response is a key causative factor of early secondary brain injury after ICH. AIM2 is a DNA-sensing protein that recognizes cytosolic double-stranded DNA and take a significant part in neuroinflammation. Mitochondrial DNA participates in the translation of proteins such as the respiratory chain in the mitochondria. Whether mtDNA is involved in forming AIM2 inflammasome after ICH remains unclear. We used mice to construct ICH model in vivo and we used BV2 microglial cells treated with oxyhemoglobin to simulate ICH in vitro. Following lentiviral transfection to overexpress AIM2 antagonist P202, a notable decrease was observed in the levels of AIM2 inflammasome-associated proteins, leading to a reduction in dead neurons surrounding the hematoma and an enhancement in long-term and short-term behavior of neurological deficits. We further explored whether mtDNA took part in the AIM2 activation after ICH. The cytosolic mtDNA level was down-regulated by the mitochondrial division protector Mdivi-1 and up-regulated by transfection of mtDNA into cytoplasm. We found the expression level of AIM2 inflammasome-related proteins and inflammatory cytokines release were regulated by the cytosolic mtDNA level. In conclusion, after ICH, the mtDNA content in the cytoplasm of microglia around the hematoma rises, causing AIM2 inflammation leading to neuronal apoptosis, which leads to neurological deficits in mice. On the other hand, P202 was able to block inflammatory vesicle activation and improve neurological function by preventing the interaction between AIM2 protein and mitochondrial DNA.

3.
Front Microbiol ; 15: 1422941, 2024.
Artículo en Inglés | MEDLINE | ID: mdl-39318431

RESUMEN

The McMurdo Dry Valleys (MDVs) of Antarctica are a mosaic of extreme habitats which are dominated by microbial life. The MDVs include glacial melt holes, streams, lakes, and soils, which are interconnected through the transfer of energy and flux of inorganic and organic material via wind and hydrology. For the first time, we provide new data on the viral community structure and function in the MDVs through metagenomics of the planktonic and benthic mat communities of Lakes Bonney and Fryxell. Viral taxonomic diversity was compared across lakes and ecological function was investigated by characterizing auxiliary metabolic genes (AMGs) and predicting viral hosts. Our data suggest that viral communities differed between the lakes and among sites: these differences were connected to microbial host communities. AMGs were associated with the potential augmentation of multiple biogeochemical processes in host, most notably with phosphorus acquisition, organic nitrogen acquisition, sulfur oxidation, and photosynthesis. Viral genome abundances containing AMGs differed between the lakes and microbial mats, indicating site specialization. Using procrustes analysis, we also identified significant coupling between viral and bacterial communities (p = 0.001). Finally, host predictions indicate viral host preference among the assembled viromes. Collectively, our data show that: (i) viruses are uniquely distributed through the McMurdo Dry Valley lakes, (ii) their AMGs can contribute to overcoming host nutrient limitation and, (iii) viral and bacterial MDV communities are tightly coupled.

4.
J Exp Med ; 221(10)2024 Oct 07.
Artículo en Inglés | MEDLINE | ID: mdl-39321257

RESUMEN

Upon antigenic stimulation, naïve CD4+ T cells can give rise to phenotypically distinct effector T helper cells and long-lived memory T cells. We computationally reconstructed the in vivo trajectory of CD4+ T cell differentiation during a type I inflammatory immune response and identified two distinct differentiation paths for effector and precursor central memory T cells arising directly from naïve CD4+ T cells. Unexpectedly, our studies revealed heterogeneity among naïve CD4+ T cells, which are typically considered homogeneous save for their diverse T cell receptor usage. Specifically, a previously unappreciated population of naïve CD4+ T cells sensing environmental type I IFN exhibited distinct activation thresholds, suggesting that naïve CD4+ T cell differentiation potential may be influenced by environmental cues. This population was expanded in human viral infection and type I IFN response-lined autoimmunity. Understanding the relevance of naïve T cell heterogeneity to beneficial and maladaptive T cell responses may have therapeutic implications for adoptive T cell therapies in cancer immunotherapy and vaccination.


Asunto(s)
Linfocitos T CD4-Positivos , Diferenciación Celular , Memoria Inmunológica , Células T de Memoria , Humanos , Linfocitos T CD4-Positivos/inmunología , Diferenciación Celular/inmunología , Animales , Memoria Inmunológica/inmunología , Células T de Memoria/inmunología , Ratones , Interferón Tipo I/metabolismo , Interferón Tipo I/inmunología , Activación de Linfocitos/inmunología
5.
J Phys Chem Lett ; 15(38): 9575-9584, 2024 Sep 26.
Artículo en Inglés | MEDLINE | ID: mdl-39269336

RESUMEN

Ligand engineering of aromatic heterocyclic cations in two-dimensional (2D) Dion-Jacobson (DJ) perovskites has been widely explored in recent years. In this study, how the positional isomers of aromatic heterocyclic cations tune the lattice of 2D perovskites, thereby influencing the transport and recombination dynamics of charge carriers, has been investigated through nonadiabatic molecular dynamics simulations. We demonstrate that the meta-substituted 3-(aminomethyl)pyridinium (3AMPY) cations greatly reduce the strength of electron-vibration coupling since the strong hydrogen-bonding network introduced by the changes in the arrangement of spacer cations significantly suppresses the structural thermal fluctuations. Compared to the para-substituted 4-(aminomethyl)pyridinium (4AMPY) cation, using the asymmetric 3AMPY as a spacer cation can achieve improved in-plane transport performance, enhanced thermal stability, and suppressed charge carrier recombination through weakening electron-vibration interactions. Our results explain the observed lifetime difference between the two types of DJ-phase perovskites in experiments and provide new guidance for optimizing the performance of perovskite devices.

6.
Chem Commun (Camb) ; 60(78): 10962-10965, 2024 Sep 26.
Artículo en Inglés | MEDLINE | ID: mdl-39259168

RESUMEN

We develop a novel electrochemiluminescence (ECL) emitter of aqueous-based perovskite quantum dots, with long-term stable ECL emission in aqueous media. Moreover, an electron transfer annihilation mechanism of ECL generation is proposed, revealed by the experimental results. This study opens a door for exploring efficient perovskite-based ECL emitters.

7.
Brief Bioinform ; 25(6)2024 Sep 23.
Artículo en Inglés | MEDLINE | ID: mdl-39316943

RESUMEN

Histone modifications (HMs) are pivotal in various biological processes, including transcription, replication, and DNA repair, significantly impacting chromatin structure. These modifications underpin the molecular mechanisms of cell-type-specific gene expression and complex diseases. However, annotating HMs across different cell types solely using experimental approaches is impractical due to cost and time constraints. Herein, we present dHICA (deep histone imputation using chromatin accessibility), a novel deep learning framework that integrates DNA sequences and chromatin accessibility data to predict multiple HM tracks. Employing the transformer architecture alongside dilated convolutions, dHICA boasts an extensive receptive field and captures more cell-type-specific information. dHICA outperforms state-of-the-art baselines and achieves superior performance in cell-type-specific loci and gene elements, aligning with biological expectations. Furthermore, dHICA's imputations hold significant potential for downstream applications, including chromatin state segmentation and elucidating the functional implications of SNPs (Single Nucleotide Polymorphisms). In conclusion, dHICA serves as a valuable tool for advancing the understanding of chromatin dynamics, offering enhanced predictive capabilities and interpretability.


Asunto(s)
Cromatina , Histonas , Cromatina/metabolismo , Cromatina/genética , Histonas/metabolismo , Histonas/genética , Humanos , Polimorfismo de Nucleótido Simple , Aprendizaje Profundo , Biología Computacional/métodos , Código de Histonas
9.
Int J Surg ; 2024 Sep 18.
Artículo en Inglés | MEDLINE | ID: mdl-39291970

RESUMEN

BACKGROUND: Fever is a common side effect following thermal ablation in patients with hepatocellular carcinoma (HCC), yet its impact on prognosis remains unclear. MATERIALS AND METHODS: This retrospective study included initial HCC patients who underwent US-guided percutaneous microwave ablation at 13 hospitals between January 2006 and February 2021. All patients were categorized into afebrile, transient low-grade fever (TLF), and prolonged or high-grade fever (PHF) groups. Primary outcomes included very early recurrence (VER) and early recurrence (ER), secondary outcomes were disease-free survival (DFS) and overall survival (OS). Fever cut-offs for VER/ER were established using restrictive cubic splines and adjusted Cox model. Survival analyses used the Kaplan-Meier method. RESULTS: A total of 1458 initial HCC patients (mean age, 59±11[SD]; 1146 men). Compared to afebrile individuals, patients with TLF (temperatures ranging 37.0-38.8°C for 1-2 d), showed independent protective effects against VER (HR, 0.73; 95% CI: 0.57,0.95; P=0.02) and ER (HR, 0.66; 95% CI: 0.54,0.81; P<0.001), however, PHF showed no differences in VER (HR, 0.99; 95% CI: 0.76,1.30; P=0.96) and ER (HR, 0.86; 95% CI: 0.69,1.07; P=0.17). With a median follow-up of 47 months (IQR:26-79), the median DFS for TLF patients was 40 months, superior to afebrile (30 mo, P=0.019) and PHF patients (33 mo, P=0.049). The 5-year OS rate for TLF patients was 73.2%, higher than afebrile (69.3%, P=0.02) and PHF patients (66.7%, P=0.03). No significant difference was found in DFS and OS between afebrile and PHF patients (P=0.90 and 0.71). Notably, TLF patients exhibited the highest lymphocyte counts increasing median 7 days after ablation (P<0.001 vs. afebrile and P=0.01 vs. PHF). CONCLUSION: Transient low-grade fever following percutaneous microwave ablation in hepatocellular carcinoma patients demonstrated protection against early recurrence, possibly attributed to the short-term activation of lymphocytes.

10.
Spectrochim Acta A Mol Biomol Spectrosc ; 325: 125147, 2024 Sep 15.
Artículo en Inglés | MEDLINE | ID: mdl-39299065

RESUMEN

To investigate the effects of steric hindrance fluorene and heavy-atom bromine on the general optoelectronic properties of star-shaped organic emitters based on 9-(2-cyanophenyl) carbazole (OCzPhCN) frameworks, heavy element of bromine and steric hindrance fluorene were introduced into OCzPhCN to produce four derivatives of 2-(3-bromo-9H-carbazol-9-yl)benzonitrile (BrCzPhCN), 2-(3-bromo-6-(9-(4-ethoxyphenyl)-9H-fluoren-9-yl)-9H-carbazol-9-yl)benzonitrile (BrFCzPhCN), 2-(3-(9-(4-ethoxyphenyl)-9H-fluoren-9-yl)-9H-carbazol-9-yl)benzonitrile (FCzPhCN) and 2-(3,6-bis(9-(4-ethoxyphenyl)-9H-fluoren-9-yl)-9H-carbazol-9-yl)benzonitrile (2FCzPhCN). The fluorene units obviously improve the thermal stability of the obtained compounds, and 2FCzPhCN has the highest thermal stability with 5 % mass heat loss temperature reaching 447 °C. In different polar solvents, the absorption peaks wavelength of OCzPhCN, FCzPhCN and 2FCzPhCN are basically unchanged, and the redshifted emission peaks are positively correlated with solvent polarity. The photoluminescence quantum yields (PLQYs) of OCzPhCN, BrCzPhCN, FCzPhCN, BrFCzPhCN and 2FCzPhCN powders were 20.17 %, 5.43 %, 30.75 %, 3.27 % and 23.56 %. The fluorescence and phosphorescent quantum efficiencies of OCzPhCN, BrCzPhCN, FCzPhCN, BrFCzPhCN and 2FCzPhCN powders are 9.76 % and 10.41 %, 1.2 % and 3.23 %, 28.45 % and 2.3 %, 3.27 % and 0 %, 23.56 % and 0 %. OCzPhCN, BrCzPhCN and FCzPhCN powders show obvious room temperature phosphorescent emission, and the phosphorescent emission lifetime of OCzPhCN, BrCzPhCN and FCzPhCN powders at 561 nm, 576 nm and 568 nm are 193.17 ms, 18.65 ms and 7.25 ms. Compared with OCzPhCN, the introduction of bromine decreases the PLQY and the phosphorescent lifetime of BrCzPhCN powder, while the fluorescence quantum efficiency of the compound FCzPhCN powder has been improved. The corresponding single-triplet energy splitting (ΔEST) of OCzPhCN, FCzPhCN and 2FCzPhCN in solutions are 0.49 eV, 0.63 eV and 0.63 eV, and the corresponding ΔEST values of OCzPhCN, BrCzPhCN FCzPhCN powders are 1.19 eV, 0.74 eV and 0.55 eV. The steric hindrance fluorene units result in smaller and stabilized ΔEST in the solid powder states, and the same situation is opposite in the unimolecular solutions. The maximum external quantum efficiency of organic light-emitting diode based on 10,10'-(4,4'-sulfonylbis (4,1-phenylene)) bis (9,9-dimethyl-9,10-dihydroacridine) hosted by OCzPhCN reaches 12.7 %, and the external quantum efficiency at 100 cd/m2 rolls down to 11 %. OCzPhCN is the best emitters in terms of room temperature phosphorescent emission and host applications.

11.
Aging Cell ; : e14342, 2024 Sep 23.
Artículo en Inglés | MEDLINE | ID: mdl-39312903

RESUMEN

The locus coeruleus (LC)-prefrontal cortex (PFC) circuitry is crucial for cognition, planning, posture and mobility. This study examines the role of norepinephrine (NE) in elucidating the neurobiological basis of age-related cognitive and motor declines. Aged mice exhibited reduced spatial learning, impaired memory, decreased physical endurance, and notable changes in locomotor behavior. The neurochemical foundations of these deficits were investigated through fast-scan cyclic voltammetry to measure NE release in the PFC and LC, both in vivo and in brain slices. Additionally, oxygen levels were monitored as a proxy for PFC neuronal function, and NE levels were analyzed in the extracellular space via microdialysis and total content in the PFC. Aged mice exhibited a frequency-dependent increase in NE release in the PFC upon LC stimulation, suggesting alterations in neural responsiveness due to aging. We also recorded slower NE reuptake rates and increased NE content and neuronal activity, indicated by higher oxygen levels and facilitated neuron activation due to membrane depolarization recorded via whole-cell patch-clamp. To understand the basis for LC-driven NE surges in the PFC with aging, we examined the expression levels of two proteins critical for presynaptic NE release and NE reuptake: the α2a-adrenergic receptor and the NE transporter. Both showed a significant decrease in the PFC with aging. These findings support the concept that aging significantly alters the structural and functional dynamics within the LC-PFC neural circuit, impacting NE modulation and neuronal activity, which may underlie the observed declines in cognitive and motor functions in aging populations.

12.
Heliyon ; 10(17): e37230, 2024 Sep 15.
Artículo en Inglés | MEDLINE | ID: mdl-39286117

RESUMEN

Background: SZ-685C, an anthracycline compound derived from the mangrove endophytic fungus Halorosellinia sp. (No. 1403) collected from the South China Sea, has shown strong anticancer activities. Non-functioning pituitary adenomas (NFPAs) are a type of tumor that can be challenging to manage clinically and have a significant unmet medical need. Our research has found that SZ-685C showed an inhibitory effect on the viability, migration ability, and proliferation ability of a human non-functioning pituitary tumor-derived folliculostellate (PDFS) cell line. Methods: SZ-685C was prepared and purified from the mangrove endophytic fungus No. 1403. PDFS cells were exposed to SZ-685C, and the effect of SZ-685C on PDFS cells was evaluated. RNA sequencing was used to analyze the miRNA expression profile in PDFS cells of the control group and SZ-685C-treated group. Quantitative polymerase chain reaction (qPCR) was performed to verify the expression of selected miR-340-3p. The effects of SZ-685C on PDFS cells after overexpression of miR-340-3p were evaluated. Dual-luciferase reporter assays showed PPP1CB is a direct target of miR-340-3p. Finally, the action pathway of the selected miR-340-3p was predicted and evaluated through bioinformatics analysis. Results: SZ-685C reduced cell viability in PDFS cells, accompanied by inhibition of migration ability and proliferation ability. The IC50 value for 24 h is 9.144 ± 0.991 µM, and for 48 h is 4.635 ± 0.551 µM. SZ-685C increased the protein levels of Beclin 1, the ratio of LC3-II to LC3-I, and LAMP-1, and down-regulated p62. MiRNA sequencing and further validation showed that miR-340-3p significantly decreased in PDFS cells treated with SZ-685C. After overexpression of miR-340-3p, the inhibition of viability, migration ability, proliferation ability, and autophagy-promoting effect of SZ-685C on PDFS cells were weakened. SZ-685C caused a decrease in PPP1CB expression and activation of the ERK pathway in PDFS cells, and this trend was reversed after overexpression of miR-340-3p. Conclusions: SZ-685C downregulates the expression of miR-340-3p in PDFS cells, thereby reducing the expression of PPP1CB and activating the ERK pathway to promote autophagic cell death, leading to inhibition of PDFS cell growth.

13.
Sci Rep ; 14(1): 21422, 2024 Sep 13.
Artículo en Inglés | MEDLINE | ID: mdl-39271715

RESUMEN

A large-scale, high-speed, long-runout landslide occurred in Xinmo Village, Maoxian, Sichuan Province, China, on June 24, 2017. It was characterized by fast sliding speed, rapid volume growth, and large impact area. The dynamic process of such landslides and the influence of erosion on the dynamic process are studied by field investigation, numerical inversion and simulation. The results showed that entrainment erosion was a major factor of landslide volumetric change and a salient feature of the landslide process. An exponential equation relating the erosion rate and the deposition volume was established. Moreover, the study found that a slight change of the erosion rate (1e-4) also had a significant impact on the lateral spreading, longitudinal runout, and vertical erosion. As the erosion rate increased, the lateral spreading, longitudinal runout, and vertical erosion of this type of landslide became more obvious. By using the coefficient of variation method, it was obtained that the erosion rate had a greater influence on the vertical erosion than on the lateral spreading and longitudinal runout. In the study of the velocity of the rock avalanche under different erosion conditions, it was found that the erosion amount and the landslide velocity were not strictly linearly related. This study has important significance for understanding the dynamic process and erosion effect of rock avalanche, and provides useful references and insights for future research in related fields.

14.
Curr Microbiol ; 81(11): 368, 2024 Sep 21.
Artículo en Inglés | MEDLINE | ID: mdl-39305346

RESUMEN

In the present study, using genome mining, Streptomyces sp. JL1001, which possesses a leinamycin-type gene cluster, was identified from 14 strains of Streptomyces originating from the rhizosphere soil of Polygonatum cyrtonema Hua. The complete genome of Streptomyces sp. JL1001 was sequenced and analyzed. The genome of Streptomyces sp. JL1001 consists of a 7,943,495 bp chromosome with a 71.71% G+C content and 7315 protein-coding genes. We also identified 36 biosynthetic gene clusters (BGCs) for secondary metabolites in Streptomyces sp. JL1001. Twenty-seven BGCs had low (< 50%) or moderate (50-80%) similarity to other known secondary metabolite BGCs. In addition, a comparative analysis was conducted between the leinamycin-type gene cluster in Streptomyces sp. JL1001 and the biosynthetic gene clusters of leinamycin and largimycin. This study aims to provide a comprehensive analysis of the genomic features of rhizosphere Streptomyces sp. JL1001. It establishes the foundation for further investigation into experimental trials involving novel bioactive metabolites such as AT-less type I polyketides that have important potential applications in medicine and agriculture.


Asunto(s)
Genoma Bacteriano , Familia de Multigenes , Polygonatum , Rizosfera , Microbiología del Suelo , Streptomyces , Streptomyces/genética , Streptomyces/clasificación , Streptomyces/metabolismo , Streptomyces/aislamiento & purificación , Polygonatum/genética , Polygonatum/microbiología , Composición de Base , Metabolismo Secundario , Filogenia , Genómica
15.
J Colloid Interface Sci ; 678(Pt C): 526-535, 2024 Sep 18.
Artículo en Inglés | MEDLINE | ID: mdl-39305620

RESUMEN

The interfacial interaction of carbon nanotubes (CNTs) significantly enhances the output capability of piezoelectric nanogenerators (PENGs). However, overcoming the limitation of low specific surface area in one-dimensional materials remains a significant challenge. This paper introduces a hydrothermal method for composite MOF (C-M) using CNTs and MOF-5, demonstrating localized co-doping between them. Coaxial electrospun piezoelectric fiber membranes (C-MNF) were then prepared using PVDF/PAN as the matrix. Benefiting from C-M's excellent crystallinity and its synergistic interaction with the polymer matrix, the C-MNF-based PENG showed a 125 % increase in output voltage, reaching âˆ¼25 V, compared to coaxial membranes simply mixing MOF-5 and CNTs. As a result, its short-circuit current was âˆ¼1.8 µA, with a piezoelectric coefficient d33 of âˆ¼400 pC N-1. Consequently, this material exhibits superior piezoelectric output capabilities, paving the way for future functional material fabrication.

16.
Neoplasia ; 57: 101055, 2024 Sep 10.
Artículo en Inglés | MEDLINE | ID: mdl-39260131

RESUMEN

BACKGROUND: Glioblastoma (GBM) poses a significant medical challenge due to its aggressive nature and poor prognosis. Mitochondrial unfolded protein response (UPRmt) and the heat shock factor 1 (HSF1) pathway play crucial roles in GBM pathogenesis. Post-translational modifications, such as SUMOylation, regulate the mechanism of action of HSF1 and may influence the progression of GBM. Understanding the interplay between SUMOylation-modified HSF1 and GBM pathophysiology is essential for developing targeted therapies. METHODS: We conducted a comprehensive investigation using cellular, molecular, and in vivo techniques. Cell culture experiments involved establishing stable cell lines, protein extraction, Western blotting, co-immunoprecipitation, and immunofluorescence analysis. Mass spectrometry was utilized for protein interaction studies. Computational modeling techniques were employed for protein structure analysis. Plasmid construction and lentiviral transfection facilitated the manipulation of HSF1 SUMOylation. In vivo studies employed xenograft models for tumor growth assessment. RESULTS: Our research findings indicate that HSF1 primarily undergoes SUMOylation at the lysine residue K298, enhancing its nuclear translocation, stability, and downstream heat shock protein expression, while having no effect on its trimer conformation. SUMOylated HSF1 promoted the UPRmt pathway, leading to increased GBM cell proliferation, migration, invasion, and reduced apoptosis. In vivo studies have confirmed that SUMOylation of HSF1 enhances its oncogenic effect in promoting tumor growth in GBM xenograft models. CONCLUSION: This study elucidates the significance of SUMOylation modification of HSF1 in driving GBM progression. Targeting SUMOylated HSF1 may offer a novel therapeutic approach for GBM treatment. Further investigation into the specific molecular mechanisms influenced by SUMOylated HSF1 is warranted for the development of effective targeted therapies to improve outcomes for GBM patients.

17.
Neoplasia ; 57: 101049, 2024 Sep 11.
Artículo en Inglés | MEDLINE | ID: mdl-39265220

RESUMEN

Prostate cancer (PCa) currently ranks second in male tumor mortality. Targeting immune checkpoint in tumor as immunotherapy is a new direction for tumor treatment. However, targeting PD-1/PD-L1 and CTLA4 to treat PCa has poor immunotherapeutic efficacy because PCa is known as a cold tumor. Understanding the mechanism of immunosuppression in PCa can promote the use of immunotherapy to treat PCa. ELAVL1 is highly expressed in many tumors, participates in almost all tumor biological activities and is an oncogene. ELAVL1 is also involved in the development and differentiation of T and B lymphocytes. However, the relationship between ELAVL1 and tumor immunity has not yet been reported. In recent years, ELAVL1 has been shown to regulate downstream targets in an m6A -dependent manner. PD-L1 has been shown to have m6A sites in multiple tumors that are regulated by m6A. In this study, ELAVL1 was highly expressed in PCa, and PCa with high ELAVL1 expression is immunosuppressive. Knocking down ELAVL1 reduced PD-L1 expression in PCa. Moreover, PD-L1 was shown to have an m6A site, and its m6A level was upregulated in PCa. ELAVL1 interacts with PD-L1 mRNA and promotes PD-L1 RNA stability via m6A, ultimately inhibiting the infiltration of CD4-positive T cells. In addition, androgen receptor (AR) was shown to be regulated with ELAVL1, and knocking down AR could also affect the expression of PD-L1. Therefore, ELAVL1 can directly or indirectly regulate the expression of PD-L1, thereby affecting the infiltration of CD4-positive T cells in PCa and ultimately leading to immune suppression.

18.
Int J Biol Macromol ; : 135958, 2024 Sep 23.
Artículo en Inglés | MEDLINE | ID: mdl-39322156

RESUMEN

C-type lectin (CTL) plays a vital role in parasite adhesion, invading host's cells and immune escape. The objective of this research was to explore whether recombinant T. spiralis CTL (rTsCTL) binding with syndecan-1 damages intestine epithelial integrity and mediates T. spiralis intrusion in mice. The results showed that rTsCTL interacted with syndecan-1 and activated STAT3 pathway in gut epithelium, decreased tight junctions (TJs) expressions and damaged gut epithelium integrity, promoted T. spiralis intrusion, and increased expression level of inflammatory cytokine and mucin. The syndecan-1 inhibitor (ß-xyloside) and STAT3 phosphorylation inhibitor (Stattic) significantly suppressed syndecan-1 expression and STAT3 pathway activation, reduced the expression levels of TJs, pro-inflammatory cytokines (TNF-α and IL-1ß), Muc2 and Muc5a, and declined intestinal permeability in T. spiralis-infected mice. These results revealed that the inhibitors suppressed T. spiralis invasion and development in gut mucosa, decreased intestinal adult burdens and relieved gut inflammation. These findings further testified that the in vivo binding of TsCTL with syndecan-1 destroyed enteral mucosal epithelial integrity and promoted T. spiralis intrusion of gut mucosa via activating STAT3 pathway and decreasing TJs expression. TsCTL could be deemed as a promising vaccine target to interrupt T. spiralis infection.

19.
Animals (Basel) ; 14(18)2024 Sep 23.
Artículo en Inglés | MEDLINE | ID: mdl-39335332

RESUMEN

Growth performance is an important economic trait of broilers but the related serum metabolomics remains unclear. In this study, we utilized non-targeted metabolomics using ultra-high-performance liquid phase tandem mass spectrometry (UHPLC-MS/MS) to establish metabolite profiling in the serum of Chinese Wumeng black-bone chickens. The biomarker metabolites in serum associated with growth performance of chickens were identified by comparing the serum metabolome differences between chickens that significantly differed in their weights at 160 days of age when fed identical diets. A total of 766 metabolites were identified including 13 differential metabolite classes such as lipids and lipid-like molecules, organic acids and their derivatives, and organoheterocyclic compounds. The results of difference analysis using a partial least squares discriminant analysis (PLS-DA) model indicated that the low-body-weight group could be differentiated based on inflammatory markers including prostaglandin a2, kynurenic acid and fatty acid esters of hydroxy fatty acids (FAHFA), and inflammation-related metabolic pathways including tryptophan and arachidonic acid metabolism. In contrast, the sera of high-body-weight chickens were enriched for riboflavin and 2-isopropylmalic acid and for metabolic pathways including riboflavin metabolism, acetyl group transfer into mitochondria, and the tricarboxylic acid (TCA) cycle. These results provide new insights into the practical application of improving the growth performance of local chickens.

20.
Genes (Basel) ; 15(9)2024 Sep 08.
Artículo en Inglés | MEDLINE | ID: mdl-39336770

RESUMEN

Fertilization significantly affects the growth and development of wheat. However, the precise mechanisms underlying gene regulation during flowering in response to fertilization deficiency remain elusive. In this study, fertilization (F) and non-fertilization (CK) ) treatments were set up to reveal examine the effect of fertilization on the photosynthetic capacity of winter wheat during the flowering period through physiological, biochemical, and transcriptome analyses. Upon analyzing analysing their yield, leaf photosynthetic system exchange parameters during flowering, antioxidant enzyme activity, and endogenous hormone parameters, we found that the F treatment resulted in higher net photosynthetic rates during flowering periods than the CK treatment. The superoxide dismutase (SOD) (83.92%), peroxidase (POD) (150.75%), and catalase (CAT) (22.74%) activities of leaves in treated with F during the flowering period were notably elevated compared to those of CK-treated leaves. Abscisic acid (ABA) (1.86%) and gibberellin acid (GA3) (33.69%) levels were reduced, whereas Auxin auxin (IAA) (98.27%) content was increasedwas increased under F treatment compared to those the results under the CK treatment. The chlorophyll a (32.53%), chlorophyll b (56%), total chlorophyll (37.96%), and carotenoid contents (29.80%) under F treatment were also increased compared to CK., exceeded exceeding those obtained under the CK treatment. Furthermore, transcriptional differences between the F and CK conditions were analyzed, and key genes were screened and validated by using q-PCR. Transcriptome analysis identified 2281 differentially expressed genes (DEGs), with enriched pathways related to photosynthesis and light harvesting. DEGs were subjected to cluster simulation, which revealed that 53 DEGS, both up- and down-regulated, responded to the F treatment. qRT-PCR-based validation confirmed the differential expression of genes associated with carbohydrate transport and metabolism, lipid transport, and signal transduction. This study revealed distinctive transcriptional patterns and crucial gene regulation networks in wheat during flowering under fertilization, providing transcriptomic guidance for the precise regulation of wheat breeding.


Asunto(s)
Flores , Regulación de la Expresión Génica de las Plantas , Fotosíntesis , Hojas de la Planta , Triticum , Triticum/genética , Triticum/crecimiento & desarrollo , Triticum/metabolismo , Fotosíntesis/genética , Hojas de la Planta/genética , Hojas de la Planta/crecimiento & desarrollo , Hojas de la Planta/metabolismo , Flores/genética , Flores/crecimiento & desarrollo , Perfilación de la Expresión Génica/métodos , Ácido Abscísico/metabolismo , Transcriptoma , Reguladores del Crecimiento de las Plantas/metabolismo , Proteínas de Plantas/genética , Proteínas de Plantas/metabolismo , Clorofila/metabolismo , Giberelinas/metabolismo , Fertilizantes , Ácidos Indolacéticos/metabolismo
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