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1.
Nature ; 606(7916): 909-916, 2022 06.
Artículo en Inglés | MEDLINE | ID: mdl-35768591

RESUMEN

Thermal insulation under extreme conditions requires materials that can withstand complex thermomechanical stress and retain excellent thermal insulation properties at temperatures exceeding 1,000 degrees Celsius1-3. Ceramic aerogels are attractive thermal insulating materials; however, at very high temperatures, they often show considerably increased thermal conductivity and limited thermomechanical stability that can lead to catastrophic failure4-6. Here we report a multiscale design of hypocrystalline zircon nanofibrous aerogels with a zig-zag architecture that leads to exceptional thermomechanical stability and ultralow thermal conductivity at high temperatures. The aerogels show a near-zero Poisson's ratio (3.3 × 10-4) and a near-zero thermal expansion coefficient (1.2 × 10-7 per degree Celsius), which ensures excellent structural flexibility and thermomechanical properties. They show high thermal stability with ultralow strength degradation (less than 1 per cent) after sharp thermal shocks, and a high working temperature (up to 1,300 degrees Celsius). By deliberately entrapping residue carbon species in the constituent hypocrystalline zircon fibres, we substantially reduce the thermal radiation heat transfer and achieve one of the lowest high-temperature thermal conductivities among ceramic aerogels so far-104 milliwatts per metre per kelvin at 1,000 degrees Celsius. The combined thermomechanical and thermal insulating properties offer an attractive material system for robust thermal insulation under extreme conditions.

2.
Plant Cell ; 36(10): 4143-4167, 2024 Oct 03.
Artículo en Inglés | MEDLINE | ID: mdl-38963884

RESUMEN

As an essential intrinsic component of photosystem II (PSII) in all oxygenic photosynthetic organisms, heme-bridged heterodimer cytochrome b559 (Cyt b559) plays critical roles in the protection and assembly of PSII. However, the underlying mechanisms of Cyt b559 assembly are largely unclear. Here, we characterized the Arabidopsis (Arabidopsis thaliana) rph1 (resistance to Phytophthora1) mutant, which was previously shown to be susceptible to the oomycete pathogen Phytophthora brassicae. Loss of RPH1 leads to a drastic reduction in PSII accumulation, which can be primarily attributed to the defective formation of Cyt b559. Spectroscopic analyses showed that the heme level in PSII supercomplexes isolated from rph1 is significantly reduced, suggesting that RPH1 facilitates proper heme assembly in Cyt b559. Due to the loss of RPH1-mediated processes, a covalently bound PsbE-PsbF heterodimer is formed during the biogenesis of PSII. In addition, rph1 is highly photosensitive and accumulates elevated levels of reactive oxygen species under photoinhibitory-light conditions. RPH1 is a conserved intrinsic thylakoid protein present in green algae and terrestrial plants, but absent in Synechocystis, and it directly interacts with the subunits of Cyt b559. Thus, our data demonstrate that RPH1 represents a chloroplast acquisition specifically promoting the efficient assembly of Cyt b559, probably by mediating proper heme insertion into the apo-Cyt b559 during the initial phase of PSII biogenesis.


Asunto(s)
Proteínas de Arabidopsis , Arabidopsis , Grupo Citocromo b , Complejo de Proteína del Fotosistema II , Phytophthora , Arabidopsis/genética , Arabidopsis/metabolismo , Complejo de Proteína del Fotosistema II/metabolismo , Complejo de Proteína del Fotosistema II/genética , Proteínas de Arabidopsis/metabolismo , Proteínas de Arabidopsis/genética , Grupo Citocromo b/metabolismo , Grupo Citocromo b/genética , Enfermedades de las Plantas/microbiología , Especies Reactivas de Oxígeno/metabolismo , Hemo/metabolismo , Mutación/genética , Tilacoides/metabolismo
3.
Nucleic Acids Res ; 2024 Oct 17.
Artículo en Inglés | MEDLINE | ID: mdl-39417483

RESUMEN

Spatial omics technologies have enabled the creation of intricate spatial maps that capture molecular features and tissue morphology, providing valuable insights into the spatial associations and functional organization of tissues. Accurate annotation of spot or domain types is essential for downstream spatial omics analyses, but this remains challenging. Therefore, this study aimed to develop a manually curated spatial omics database (SpatialRef, https://bio.liclab.net/spatialref/), to provide comprehensive and high-quality spatial omics data with known spot labels across multiple species. The current version of SpatialRef aggregates >9 million manually annotated spots across 17 Human, Mouse and Drosophila tissue types through extensive review and strict quality control, covering multiple spatial sequencing technologies and >400 spot/domain types from original studies. Furthermore, SpatialRef supports various spatial omics analyses about known spot types, including differentially expressed genes, spatially variable genes, Gene Ontology (GO)/KEGG annotation, spatial communication and spatial trajectories. With a user-friendly interface, SpatialRef facilitates querying, browsing and visualizing, thereby aiding in elucidating the functional relevance of spatial domains within the tissue and uncovering potential biological effects.

4.
Plant J ; 2024 Oct 14.
Artículo en Inglés | MEDLINE | ID: mdl-39401077

RESUMEN

Polyamines act as protective compounds directly protecting plants from stress-related damage, while also acting as signaling molecules to participate in serious abiotic stresses. However, the molecular mechanisms underlying these effects are poorly understood. Here, we utilized metabolome genome-wide association study to investigate the polyamine content of wild and cultivated tomato accessions, and we discovered a new gene cluster that drove polyamine content during tomato domestication. The gene cluster contains two polyphenol oxidases (SlPPOE and SlPPOF), two BAHD acyltransferases (SlAT4 and SlAT5), a coumaroyl-CoA ligase (Sl4CL6), and a polyamine uptake transporter (SlPUT3). SlPUT3 mediates polyamine uptake and transport, while the five other genes are involved in polyamine modification. Further salt tolerance assays demonstrated that SlPPOE, SlPPOF, and SlAT5 overexpression lines showed greater phenolamide accumulation and salt tolerance as compared with wild-type (WT). Meanwhile, the exogenous application of Spm to SlPUT3-OE lines displayed salt tolerance compared with WT, while having the opposite effect in slput3 lines, confirms that the polyamine and phenolamide can play a protective role by alleviating cell damage. SlPUT3 interacted with SlPIP2;4, a H2O2 transport protein, to maintain H2O2 homeostasis. Polyamine-derived H2O2 linked Spm to stress responses, suggesting that Spm signaling activates stress response pathways. Collectively, our finding reveals that the H2O2-polyamine-phenolamide module coordinately enhanced tomato salt stress tolerance and provide a foundation for tomato stress-resistance breeding.

5.
EMBO Rep ; 24(7): e56458, 2023 Jul 05.
Artículo en Inglés | MEDLINE | ID: mdl-37249035

RESUMEN

DNA topoisomerase IIα (TOP2A) plays a vital role in replication and cell division by catalytically altering DNA topology. It is a prominent target for anticancer drugs, but clinical efficacy is often compromised due to chemoresistance. In this study, we investigate the role of TOP2A O-GlcNAcylation in breast cancer cells and patient tumor tissues. Our results demonstrate that elevated TOP2A, especially its O-GlcNAcylation, promotes breast cancer malignant progression and resistance to adriamycin (Adm). O-GlcNAcylation at Ser1469 enhances TOP2A chromatin DNA binding and catalytic activity, leading to resistance to Adm in breast cancer cells and xenograft models. Mechanistically, O-GlcNAcylation-modulated interactions between TOP2A and cell cycle regulators influence downstream gene expression and contribute to breast cancer drug resistance. These results reveal a previously unrecognized mechanistic role for TOP2A O-GlcNAcylation in breast cancer chemotherapy resistance and provide support for targeting TOP2A O-GlcNAcylation in cancer therapy.


Asunto(s)
Antineoplásicos , Neoplasias de la Mama , Femenino , Humanos , Antineoplásicos/farmacología , Antineoplásicos/uso terapéutico , Neoplasias de la Mama/tratamiento farmacológico , Neoplasias de la Mama/genética , Neoplasias de la Mama/metabolismo , Doxorrubicina/farmacología , Resistencia a Antineoplásicos
6.
Cell Mol Life Sci ; 81(1): 122, 2024 Mar 08.
Artículo en Inglés | MEDLINE | ID: mdl-38456997

RESUMEN

Doxorubicin-induced cardiotoxicity (DIC), which is a cardiovascular complication, has become the foremost determinant of decreased quality of life and mortality among survivors of malignant tumors, in addition to recurrence and metastasis. The limited ability to accurately predict the occurrence and severity of doxorubicin-induced injury has greatly hindered the prevention of DIC, but reducing the dose to mitigate side effects may compromise the effective treatment of primary malignancies. This has posed a longstanding clinical challenge for oncologists and cardiologists. Ferroptosis in cardiomyocytes has been shown to be a pivotal mechanism underlying cardiac dysfunction in DIC. Ferroptosis is influenced by multiple factors. The innate immune response, as exemplified by neutrophil extracellular traps (NETs), may play a significant role in the regulation of ferroptosis. Therefore, the objective of this study was to investigate the involvement of NETs in doxorubicin-induced cardiomyocyte ferroptosis and elucidate their regulatory role. This study confirmed the presence of NETs in DIC in vivo. Furthermore, we demonstrated that depleting neutrophils effectively reduced the occurrence of doxorubicin-induced ferroptosis and myocardial injury in DIC. Additionally, our findings showed the pivotal role of high mobility group box 1 (HMGB1) as a critical molecule implicated in DIC and emphasized its involvement in the modulation of ferroptosis subsequent to NETs inhibition. Mechanistically, we obtained preliminary evidence suggesting that doxorubicin-induced NETs could modulate yes-associated protein (YAP) activity by releasing HMGB1, which subsequently bound to toll like receptor 4 (TLR4) on the cardiomyocyte membrane, thereby influencing cardiomyocyte ferroptosis in vitro. Our findings suggest that doxorubicin-induced NETs modulate cardiomyocyte ferroptosis via the HMGB1/TLR4/YAP axis, thereby contributing to myocardial injury. This study offers a novel approach for preventing and alleviating DIC by targeting alterations in the immune microenvironment.


Asunto(s)
Trampas Extracelulares , Ferroptosis , Proteína HMGB1 , Cardiopatías , Humanos , Miocitos Cardíacos/metabolismo , Trampas Extracelulares/metabolismo , Proteína HMGB1/metabolismo , Receptor Toll-Like 4/metabolismo , Cardiotoxicidad/metabolismo , Calidad de Vida , Cardiopatías/metabolismo , Doxorrubicina/efectos adversos
7.
Nano Lett ; 2024 Oct 07.
Artículo en Inglés | MEDLINE | ID: mdl-39373902

RESUMEN

Using an alternating electric field is a versatile way to control particle assembly. Programming DNA-AuNP assembly via an electric field remains a significant challenge despite the negative charge of DNA. In DNA-AuNP assembly, a critical percolation state is delicately constructed, where the DNA bond is loosely connected and sensitive to electric fields. In this state, an FCC crystal structure can be successfully constructed by applying a high-frequency electric field to assemble DNA-AuNPs without altering the temperature, which is favorable for temperature-sensitive systems. In addition, the regulation of electric fields can be adjusted through parameters such as the frequency and voltage, which offers more precise control than temperature regulation does. The frequency and voltage can be used to precisely tune the phase structure of DNA-AuNPs from dissolved to disordered or FCC. These findings broaden the potential of DNA-based crystal engineering, revealing new opportunities in electronic nanocomposites and devices.

8.
J Biol Chem ; 299(8): 105010, 2023 08.
Artículo en Inglés | MEDLINE | ID: mdl-37414148

RESUMEN

The obligately anaerobic sulfite-reducing bacterium Bilophila wadsworthia is a common human pathobiont inhabiting the distal intestinal tract. It has a unique ability to utilize a diverse range of food- and host-derived sulfonates to generate sulfite as a terminal electron acceptor (TEA) for anaerobic respiration, converting the sulfonate sulfur to H2S, implicated in inflammatory conditions and colon cancer. The biochemical pathways involved in the metabolism of the C2 sulfonates isethionate and taurine by B. wadsworthia were recently reported. However, its mechanism for metabolizing sulfoacetate, another prevalent C2 sulfonate, remained unknown. Here, we report bioinformatics investigations and in vitro biochemical assays that uncover the molecular basis for the utilization of sulfoacetate as a source of TEA (STEA) for B. wadsworthia, involving conversion to sulfoacetyl-CoA by an ADP-forming sulfoacetate-CoA ligase (SauCD), and stepwise reduction to isethionate by NAD(P)H-dependent enzymes sulfoacetaldehyde dehydrogenase (SauS) and sulfoacetaldehyde reductase (TauF). Isethionate is then cleaved by the O2-sensitive isethionate sulfolyase (IseG), releasing sulfite for dissimilatory reduction to H2S. Sulfoacetate in different environments originates from anthropogenic sources such as detergents, and natural sources such as bacterial metabolism of the highly abundant organosulfonates sulfoquinovose and taurine. Identification of enzymes for anaerobic degradation of this relatively inert and electron-deficient C2 sulfonate provides further insights into sulfur recycling in the anaerobic biosphere, including the human gut microbiome.


Asunto(s)
Bilophila , Humanos , Alcanosulfonatos/metabolismo , Bilophila/metabolismo , Sulfitos/metabolismo , Azufre/metabolismo , Taurina/metabolismo , Microbioma Gastrointestinal
9.
Biochem Biophys Res Commun ; 726: 150274, 2024 09 24.
Artículo en Inglés | MEDLINE | ID: mdl-38924882

RESUMEN

Alzheimer's disease (AD) is a complex neurodegenerative condition with growing evidence implicating the gut microbiota in its pathogenesis. This study aimed to investigate the effects of NMN synbiotics, a combination of ß-nicotinamide mononucleotide (NMN), Lactobacillus plantarum, and lactulose, on the gut microbiota composition and metabolic profiles in APP/PS1 transgenic mice. Results demonstrated that NMN synbiotics led to a notable restructuring of the gut microbiota, with a decreased Firmicutes/Bacteroidetes ratio in the AD mice, suggesting a potential amelioration of gut dysbiosis. Alpha diversity indices indicated a reduction in microbial diversity following NMN synbiotics supplementation, while beta diversity analyses revealed a shift towards a more balanced microbial community structure. Functional predictions based on the 16S rRNA data highlighted alterations in metabolic pathways, particularly those related to amino acid and energy metabolism, which are crucial for neuronal health. The metabolomic analysis uncovered a significant impact of NMN synbiotics on the gut metabolome, with normalization of metabolic composition in AD mice. Differential metabolite functions were enriched in pathways associated with neurotransmitter synthesis and energy metabolism, pointing to the potential therapeutic effects of NMN synbiotics in modulating the gut-brain axis and synaptic function in AD. Immunohistochemical staining observed a significant reduction of amyloid plaques formed by Aß deposition in the brain of AD mice after NMN synbiotics intervention. The findings underscore the potential of using synbiotics to ameliorate the neurodegenerative processes associated with Alzheimer's disease, opening new avenues for therapeutic interventions.


Asunto(s)
Enfermedad de Alzheimer , Precursor de Proteína beta-Amiloide , Modelos Animales de Enfermedad , Microbioma Gastrointestinal , Ratones Transgénicos , Simbióticos , Animales , Enfermedad de Alzheimer/metabolismo , Enfermedad de Alzheimer/dietoterapia , Enfermedad de Alzheimer/terapia , Enfermedad de Alzheimer/microbiología , Simbióticos/administración & dosificación , Ratones , Precursor de Proteína beta-Amiloide/metabolismo , Precursor de Proteína beta-Amiloide/genética , Presenilina-1/metabolismo , Presenilina-1/genética , Mononucleótido de Nicotinamida/metabolismo , Masculino , Disbiosis/metabolismo , Disbiosis/microbiología , Disbiosis/dietoterapia , Disbiosis/terapia
10.
Plant Biotechnol J ; 22(1): 200-215, 2024 Jan.
Artículo en Inglés | MEDLINE | ID: mdl-37752705

RESUMEN

Grain size is one of the important traits in wheat breeding programs aimed at improving yield, and cytokinins, mainly involved in cell division, have a positive impact on grain size. Here, we identified a novel wheat gene TaMADS-GS encoding type I MADS-box transcription factor, which regulates the cytokinins signalling pathway during early stages of grain development to modulate grain size and weight in wheat. TaMADS-GS is exclusively expressed in grains at early stage of seed development and its knockout leads to delayed endosperm cellularization, smaller grain size and lower grain weight. TaMADS-GS protein interacts with the Polycomb Repressive Complex 2 (PRC2) and leads to repression of genes encoding cytokinin oxidase/dehydrogenases (CKXs) stimulating cytokinins inactivation by mediating accumulation of the histone H3 trimethylation at lysine 27 (H3K27me3). Through the screening of a large wheat germplasm collection, an elite allele of the TaMADS-GS exhibits higher ability to repress expression of genes inactivating cytokinins and a positive correlation with grain size and weight, thus representing a novel marker for breeding programs in wheat. Overall, these findings support the relevance of TaMADS-GS as a key regulator of wheat grain size and weight.


Asunto(s)
Endospermo , Factores de Transcripción , Factores de Transcripción/genética , Endospermo/metabolismo , Triticum/metabolismo , Fitomejoramiento , Grano Comestible , Citocininas/metabolismo , Regulación de la Expresión Génica de las Plantas/genética
11.
PLoS Pathog ; 18(7): e1010660, 2022 07.
Artículo en Inglés | MEDLINE | ID: mdl-35816513

RESUMEN

Coxiella burnetii is the etiological agent of the zoonotic disease Q fever, which is featured by its ability to replicate in acid vacuoles resembling the lysosomal network. One key virulence determinant of C. burnetii is the Dot/Icm system that transfers more than 150 effector proteins into host cells. These effectors function to construct the lysosome-like compartment permissive for bacterial replication, but the functions of most of these effectors remain elusive. In this study, we used an affinity tag purification mass spectrometry (AP-MS) approach to generate a C. burnetii-human protein-protein interaction (PPI) map involving 53 C. burnetii effectors and 3480 host proteins. This PPI map revealed that the C. burnetii effector CBU0425 (designated CirB) interacts with most subunits of the 20S core proteasome. We found that ectopically expressed CirB inhibits hydrolytic activity of the proteasome. In addition, overexpression of CirB in C. burnetii caused dramatic inhibition of proteasome activity in host cells, while knocking down CirB expression alleviated such inhibitory effects. Moreover, we showed that a region of CirB that spans residues 91-120 binds to the proteasome subunit PSMB5 (beta 5). Finally, PSMB5 knockdown promotes C. burnetii virulence, highlighting the importance of proteasome activity modulation during the course of C. burnetii infection.


Asunto(s)
Coxiella burnetii , Fiebre Q , Proteínas Bacterianas/genética , Proteínas Bacterianas/metabolismo , Interacciones Huésped-Patógeno , Humanos , Complejo de la Endopetidasa Proteasomal/genética , Complejo de la Endopetidasa Proteasomal/metabolismo , Mapas de Interacción de Proteínas , Fiebre Q/metabolismo , Vacuolas/metabolismo
12.
Opt Express ; 32(1): 104-112, 2024 Jan 01.
Artículo en Inglés | MEDLINE | ID: mdl-38175041

RESUMEN

In this study, we present an ultralow noise single-frequency fiber laser operating at 1550 nm, utilizing a traveling-wave ring cavity configuration. The frequency noise of the laser approaches the thermal noise limit, achieving a white noise level of 0.025 Hz2/Hz, resulting in an instantaneous linewidth of 0.08 Hz. After amplification, the output power reaches 4.94 W while maintaining the same low white noise level as the laser oscillator. The integration linewidths of the laser oscillator and amplifier are 221 Hz and 665 Hz, respectively, with both exhibiting relative intensity noises that approach the quantum shot noise limit. To the best of our knowledge, this work shows the lowest frequency noise combined with relatively high power for this type of ring cavity fiber laser.

13.
Langmuir ; 40(33): 17630-17637, 2024 Aug 20.
Artículo en Inglés | MEDLINE | ID: mdl-39105727

RESUMEN

Shape transformation of polymer particles is generally a nonequilibrium dynamics process. Controlling the shape transformation of polymers is increasingly attractive and challenging for scientists due to their extensive use in drug delivery and cancer therapy. Herein, we investigated the UV-triggered shape transformation pathway of polymeric vesicles assembled from Polystyrene-block-poly(4-vinylpyridine) and 4-hydroxyazobenzene (PS-b-P4VP(Azo-OH)) and the direct assembly pathway of UV-irradiated PS-b-P4VP(Azo-OH) homogeneous solution. In the shape transformation process, well-assembled vesicles can be transformed into toroid, cylindrical, rod-like, and spherical micelles. In the direct assembly pathway, rod-like and spherical micelles can be obtained. Interestingly, the toroid micelles can be obtained only from the UV-triggered shape transformation pathway. Contrasting the two pathways reveals the pathway dependence of PS-b-P4VP(Azo-OH) assembly, suggesting that the final assembly morphology is determined by the initial state and dynamic process. The speed of UV-triggered shape transformation and the final morphology of assemblies can be tuned easily by adjusting the UV illuminance, time, and content of Azo-OH addition. Moreover, the light-responsive polymeric vesicles can be used as drug carriers and have the potential to release drugs precisely.

14.
Arch Virol ; 169(2): 38, 2024 Feb 01.
Artículo en Inglés | MEDLINE | ID: mdl-38300296

RESUMEN

Here, a novel mycovirus, Botryosphaeria dothidea narnavirus 5 (BdNV5), was discovered in the plant-pathogenic fungus Botryosphaeria dothidea strain ZM210167-1. The BdNV5 genome sequence is 2,397 nucleotides (nt) in length and contains a putative open reading frame (ORF) encoding an RNA-dependent RNA polymerase (RdRp) with a molecular mass of 72.77 kDa. A BLASTp search using the RdRp amino acid (aa) sequence showed that it was most similar to the RdRp of Botryosphaeria dothidea narnavirus 4 (42.35%). In a phylogenetic tree based on RdRp aa sequences, BdNV5 clustered with members of the family Narnaviridae. BdNV5 is thus a novel member of the family Narnaviridae infecting the phytopathogenic fungus B. dothidea.


Asunto(s)
Ascomicetos , Virus ARN , Filogenia , Ascomicetos/genética , Secuencia de Aminoácidos , Virus ARN/genética , ARN Polimerasa Dependiente del ARN/genética
15.
Exp Brain Res ; 2024 Sep 25.
Artículo en Inglés | MEDLINE | ID: mdl-39320438

RESUMEN

People with similar levels of autistic traits are reported to exhibit better interactions than those with larger differences in autistic traits. However, whether this "similarity effect" exists at the neural level remains unclear. To address this gap, the present study employed functional near-infrared spectroscopy (fNIRS) hyperscanning technology to assess inter-brain synchronization (IBS) during naturalistic conversations among dyads with three types of autistic trait combinations (20 high-high, 22 high-low, and 18 low-low dyads). The results revealed that the high-high dyads exhibited significantly lower IBS in the right temporoparietal junction (rTPJ) region compared to the low-low dyads, with no significant differences observed between the high-low group and the other two groups. Moreover, though dyadic differences in conversation satisfaction were positively correlated with dyadic autistic trait differences, IBS only showed a significant negative correlation with the dyadic average autistic trait scores and no significant correlation with the dyadic difference scores of autistic traits. These findings suggest that dyads with high autistic traits may have shared feelings about conversations, but cannot produce IBS through successful mutual prediction and understanding.

16.
Cell Mol Biol (Noisy-le-grand) ; 70(2): 44-50, 2024 Feb 29.
Artículo en Inglés | MEDLINE | ID: mdl-38430041

RESUMEN

Molecular pathology and clinical characteristics play a crucial role in guiding treatment selection and predicting the prognosis of diffuse large B-cell lymphoma (DLBCL). The programmed cell death protein 1 (PD-1) and its ligand (PD-L1), have emerged as pivotal regulators of immune checkpoints in cancer. The objectives of this study are to investigate the correlation between the expression levels of PD-1 and soluble PD-L1 (sPD-L1) in the peripheral blood of DLBCL patients, analyze their clinicopathological characteristics, and identify the optimal beneficiary group for PD-1/PD-L1 blockade. Peripheral blood samples were collected from 36 DLBCL patients before their initial treatment at Shandong Cancer Hospital between December 2018 and July 2019. The expression levels of PD-1 and sPD-L1 were measured using flow cytometry and enzyme-linked immunosorbent assay (ELISA), respectively. The clinicopathological characteristics, including age, sex, Ann Arbor stage, International Prognostic Index (IPI) score, response to treatment, etc., were recorded for each patient. The surface expression of PD-1 on peripheral blood T cells was significantly higher in DLBCL patients compared to healthy controls. There was a significant association between elevated PD-1 expression levels and the advanced Ann Arbor stage (P=0.0153) as well as the B group (P=0.0184). Higher sPD-L1 levels were associated with the GCB subtype according to Hans's classification (P=0.0435). The expression levels of PD-1 and sPD-L1 in the peripheral blood of DLBCL patients are significantly correlated with advanced disease stage, B group, and GCB subtype according to Hans's classification. This suggests that the PD-1/PD-L1 axis play a critical role in specific subgroups of DLBCL. Targeting this axis could serve as a potential therapeutic strategy to enhance the clinical outcomes of DLBCL patients. Further studies are necessary to explore the prognostic implications of PD-1 and sPD-L1 expression levels in DLBCL patients.


Asunto(s)
Antígeno B7-H1 , Linfoma de Células B Grandes Difuso , Humanos , Antígeno B7-H1/genética , Receptor de Muerte Celular Programada 1/genética , Linfoma de Células B Grandes Difuso/genética , Ensayo de Inmunoadsorción Enzimática , Citometría de Flujo
17.
J Biochem Mol Toxicol ; 38(10): e23851, 2024 Oct.
Artículo en Inglés | MEDLINE | ID: mdl-39267350

RESUMEN

Doxorubicin (Dox) is frequently employed as a chemotherapy agent for breast cancer. As the chemotherapy moves forward, breast cancer cells tend to develop resistance to Dox, besides that, Dox are also easy to cause cardiotoxicity related to cumulative dose. Therefore, how to potentiate the chemosensitivity of breast cancer cells to Dox while attenuating its cardiotoxicity has become a research hotspot. Tanshinone IIA (Tan IIA) is known for its anticancer activity as well as for its cardioprotective effects. In view of the aforementioned facts, we assessed whether Tan IIA possesses synergism and attenuation effect on Dox for breast cancer chemotherapy. Our studies in vitro indicated that, Tan IIA could potentiate the effect of Dox on breast cancer cells proliferation inhibition and apoptosis promotion by inhibiting ERK1/2 pathway, but interestingly, Tan IIA attenuated the cytotoxicity of Dox to myocardial cells by activating ERK1/2 pathway. Additionally, our studies in vivo also suggested that Tan IIA potentiated the chemotherapeutic effect of Dox against breast cancer while attenuating Dox-induced myocardial injury. Given that Tan IIA had a synergism and attenuation effect on Dox, we believed that Tan IIA can be used as an ideal drug in combination with Dox for breast cancer therapy.


Asunto(s)
Abietanos , Neoplasias de la Mama , Cardiotoxicidad , Doxorrubicina , Sistema de Señalización de MAP Quinasas , Doxorrubicina/efectos adversos , Doxorrubicina/farmacología , Abietanos/farmacología , Femenino , Humanos , Neoplasias de la Mama/tratamiento farmacológico , Neoplasias de la Mama/metabolismo , Neoplasias de la Mama/patología , Sistema de Señalización de MAP Quinasas/efectos de los fármacos , Animales , Cardiotoxicidad/tratamiento farmacológico , Cardiotoxicidad/prevención & control , Cardiotoxicidad/etiología , Sinergismo Farmacológico , Células MCF-7 , Ratones , Apoptosis/efectos de los fármacos , Línea Celular Tumoral , Proteína Quinasa 1 Activada por Mitógenos/metabolismo , Proteína Quinasa 3 Activada por Mitógenos/metabolismo
18.
Genomics ; 115(3): 110621, 2023 05.
Artículo en Inglés | MEDLINE | ID: mdl-37068643

RESUMEN

BACKGROUND: The prognosis of CCA is extremely poor, making it one of the most lethal cancers. Therefore, there is a need to elucidate the pathogenic mechanisms of CCA. In this study, we aimed at identifying lncRNA-related prognostic signatures for CCA through bioinformatics analysis and further validated their functions in CCA tumorigenesis and progression. METHODS: The RNA-seq data of CCA were downloaded from public databases. Differentially expressed lncRNAs (DElncRNAs) were screened. Then, candidate OS- and DFS-related DElncRNAs were selected through Kaplan-Meier survival analysis. Furthermore, LASSO regression was performed to establish the OS and DFS signatures, respectively. Multivariate COX models and nomograms for overall survival (OS) and disease-free survival (DFS) were established based on OS/DFS signature and clinical data. Hub lncRNAs were identified and enrichment analyses were performed to explore their potential functions. Finally, in vitro and in vivo models were used to validate the effects of the hub lncRNAs in CCA tumorigenesis and progression. RESULTS: A total of 925 DElncRNAs were selected, of which six candidate OS-related lncRNAs and 15 candidate DFS-related lncRNAs were identified. The OS and DFS signatures were then established using four lncRNAs, respectively. We found that the OS signature and vascular invasion were independent risk factors for the OS of CCA, while the DFS signature, vascular invasion, and CA19-9 were independent risk factors for the DFS of CCA. Then, nomograms were established to achieve personalized CCA recurrence and death prediction. Furthermore, our study uncovered that MIR4435-2HG and GAPLINC might play crucial roles in CCA progression and be selected as hub lncRNAs. GO and KEGG enrichment analyses revealed that the two hub lncRNAs were closely related to CCA tumorigenesis. Finally, we demonstrated that MIR4435-2HG and GAPLINC can stimulate CCA proliferation and migration in vitro and in vivo. CONCLUSIONS: The established OS and DFS signatures are independent risk factors for OS and DFS of CCA patients, respectively. MIR4435-2HG and GAPLINC were identified as hub lncRNAs. In vitro and in vivo models revealed that MIR4435-2HG and GAPLINC can prompt CCA progression, which might be novel prognostic biomarkers and therapeutic targets for CCA.


Asunto(s)
Neoplasias de los Conductos Biliares , Colangiocarcinoma , ARN Largo no Codificante , Humanos , Pronóstico , Colangiocarcinoma/genética , Conductos Biliares Intrahepáticos , Carcinogénesis , Regulación Neoplásica de la Expresión Génica
19.
Nano Lett ; 23(20): 9547-9554, 2023 Oct 25.
Artículo en Inglés | MEDLINE | ID: mdl-37816225

RESUMEN

Exploring ultrafast carrier dynamics is crucial for the materials' fundamental properties and device design. In this work, we employ time- and energy-resolved photoemission electron microscopy with tunable pump wavelengths from visible to near-infrared to reveal the ultrafast carrier dynamics of the elemental semiconductor tellurium. We find that two discrete sub-bands around the Γ point of the conduction band are involved in excited-state electron ultrafast relaxation and reveal that hot electrons first go through ultrafast intra sub-band cooling on a time scale of about 0.3 ps and then transfer from the higher sub-band to the lower one on a time scale of approximately 1 ps. Additionally, theoretical calculations reveal that the lower one has flat-band characteristics, possessing a large density of states and a long electron lifetime. Our work demonstrates that TR- and ER-PEEM with broad tunable pump wavelengths are powerful techniques in revealing the details of ultrafast carrier dynamics in time and energy domains.

20.
J Environ Manage ; 370: 122323, 2024 Sep 07.
Artículo en Inglés | MEDLINE | ID: mdl-39244922

RESUMEN

The increasing chemical pollution of the drinking water is widely concerned. Large number of organic contaminants cannot be removed by conventional water treatment technology due to their low concentration, and long-term exposure may pose significant risks to human health. Which organic contaminants in drinking water should be given more attention has been a topic of great concern in recent years. To identify the organic contaminants that need attention, this research proposes an improved health risk screening method to quantitatively analyze the risks of accumulation, persistence, toxicity, and antibiotic resistance. Compared with conventional method, 26 compounds were added to the improved screening list, including 9 DBPs (e.g., NDMA), 3 antibiotics (e.g., oxytetracycline), PFNA and other compounds. Overall, antibiotics and plasticizers rose in the risk rankings. From the perspective of the proportion of total risk value, a single risk plays a decisive role (more than 99%) in the ranking. This change suggests that antibiotic resistance and the accumulation of organic matter are as important as their toxic risks to humans. 58 compounds were recommended for the priority control organic contaminants list in drinking water. This list provides the necessary information for authoritative regulations to monitor, control, assess, and manage the risks of environmentally relevant compounds in drinking water in China.

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