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1.
Biophys J ; 2024 Sep 20.
Artículo en Inglés | MEDLINE | ID: mdl-39306670

RESUMEN

α-Synuclein (α-syn) is an abundant presynaptic neuronal protein whose aggregation is strongly associated with Parkinson's disease. It has been proposed that lipid membranes significantly affect the α-syn's aggregation process. Extensive studies have been conducted to understand the interactions between α-syn and lipid membranes and have demonstrated that the N-terminus plays a critical role. However, the dynamics of the interactions and the conformational transitions of the N-terminus of α-syn at the atomistic scale details are still highly desired. In this study, we performed extensive enhanced sampling molecular dynamics simulations to quantify the folding and interactions of wild-type (WT) and N-terminally acetylated (AC) α-syn when interacting with lipid structures. We found that N-terminal acetylation significantly increases the helicity of the first few residues in solution or when interacting with lipid membranes. The observations in simulations showed that the binding of α-syn with lipid membranes mainly follows the induced-fit model, where the disordered α-syn binds with the lipid membrane through the electrostatic interactions and hydrophobic contacts with the packing defects; after stable insertion, the N-terminal acetylation promotes the helical folding of the N-terminus to enhance the anchoring, thus increasing the binding affinity. We have shown the critical role of the first N-terminal residue methionine for recognition and anchoring to the negatively charged membrane. Although N-terminal acetylation neutralizes the positive charge of Met1 that may affect the electrostatic interactions of α-syn with membranes, the increase in helicity of the N-terminus should compensate for the binding affinity. This study provides detailed insight into the folding dynamics of α-syn's N-terminus with or without acetylation in solution and upon interaction with lipids, which clarifies how the N-terminal acetylation regulates the affinity of α-syn binding to lipid membranes. It also shows how packing defects and electrostatic effects co-regulate the N-terminus of α-syn folding and its interaction with membranes.

2.
Food Chem ; 463(Pt 1): 141104, 2024 Sep 03.
Artículo en Inglés | MEDLINE | ID: mdl-39241426

RESUMEN

The study constructed a model of temperature fluctuation (TF, -20 °C âˆ¼ -10 °C) during frozen status to build a link between the tilapia fillets muscle of ice crystal morphology, moisture distribution, protein oxidation index and the edible quality. When TF treatment more than 3 times, the brightness, color and hardness of frozen tilapia fillets decreased significantly, and the cooking loss and thawing loss increased significantly. The free and unconjugated water in frozen fish fillets exceeded 97 % and did not change much after 9 times TF. The K and TVB-N values were within the safety standards (K < 60 %, TVB-N < 30 mg N/100 g). The ice crystals in the tissues were significantly increased. Protein carbonyls and Ca2+-ATPase were significantly reduced, and secondary structures were irregular. Network correlation analysis showed that ice crystal morphology was significantly correlated with the color, texture and protein oxidation index of frozen tilapia fillets. The results would provide theoretical approach for the transportation and sales of tilapia industrial enterprises.

3.
Nat Commun ; 15(1): 7700, 2024 Sep 04.
Artículo en Inglés | MEDLINE | ID: mdl-39227599

RESUMEN

Despite the pivotal role of stannum doping in achieving ultrahigh piezoelectric performance in barium titanate-based ceramics, the fundamental mechanisms underlying this enhancement remain elusive. Here, we introduce a single variable nonstoichiometric stannum strategy in lead-free barium titanate-based ceramics with giant piezoelectricity, revealing that stannum doping contributes intrinsically and extrinsically to enhance piezoelectricity. Density functional theory calculations elucidate the intrinsic enhancement of polarization arising from lattice distortion and increased space for titanium-oxygen bonds induced by optimal stannum doping, which is corroborated by Rayleigh analysis. A phase transition from ferroelectric multiphase coexistence to paraelectric phase is observed, alongside a rapid miniaturized and eventually disappeared domains with increasing stannum doping. This evolution in phase structure and domain configuration induces a nearly vanishing polarization anisotropy and low domain wall energy, facilitating easy polarization rotation and domain wall motion, thereby significantly contributing to the extrinsic piezoelectric response. Consequently, the origins of ultrahigh performance can be attributed to the synergistic effect of stannum-induced intrinsic and extrinsic contributions in barium titanate-based ceramics. This study provides fundamental insights into the role of doping elements and offers guidance for the design of high-performance piezoelectrics.

4.
Int J Nanomedicine ; 19: 9291-9304, 2024.
Artículo en Inglés | MEDLINE | ID: mdl-39282573

RESUMEN

Introduction: The potential toxic effects of wastewater discharges containing silver nanoparticles (AgNPs) and their release into aquatic ecosystems on aquatic organisms are becoming a major concern for environmental and human health. However, the potential risks of AgNPs to aquatic organisms, especially for cardiac development by Focal adhesion pathway, are still poorly understood. Methods: The cardiac development of various concentrations of AgNPs in zebrafish were examined using stereoscopic microscope. The expression levels of cardiac development-related genes were analyzed by qRT-PCR and Whole-mount in situ hybridization (WISH). In addition, Illumina high-throughput global transcriptome analysis was performed to explore the potential signaling pathway involved in the treatment of zebrafish embryos by AgNPs after 72 h. Results: We systematically investigated the cardiac developing toxicity of AgNPs on the embryos of zebrafish. The results demonstrated that 2 or 4 mg/L AgNPs exposure induces cardiac developmental malformations, such as the appearance of pericardial edema phenotype. In addition, after 72 h of exposure, the mRNA levels of cardiac development-related genes, such as myh7, myh6, tpm1, nppa, tbx5, tbx20, myl7 and cmlc1, were significantly lower in AgNPs-treated zebrafish embryos than in control zebrafish embryos. Moreover, RNA sequencing, KEGG (Kyoto Encyclopedia of Genes) and Genomes and GSEA (gene set enrichment analysis) of the DEGs (differentially expressed genes) between the AgNPs-exposed and control groups indicated that the downregulated DEGs were mainly enriched in focal adhesion pathways. Further investigations demonstrated that the mRNA levels of focal adhesion pathway-related genes, such as igf1ra, shc3, grb2b, ptk2aa, akt1, itga4, parvaa, akt3b and vcla, were significantly decreased after AgNPs treatment in zebrafish. Conclusion: Thus, our findings illustrated that AgNPs could impair cardiac development by regulating the focal adhesion pathway in zebrafish.


Asunto(s)
Adhesiones Focales , Corazón , Nanopartículas del Metal , Plata , Pez Cebra , Animales , Pez Cebra/embriología , Nanopartículas del Metal/toxicidad , Nanopartículas del Metal/química , Corazón/efectos de los fármacos , Corazón/embriología , Plata/toxicidad , Plata/química , Adhesiones Focales/efectos de los fármacos , Embrión no Mamífero/efectos de los fármacos , Transducción de Señal/efectos de los fármacos , Regulación del Desarrollo de la Expresión Génica/efectos de los fármacos , Proteínas de Pez Cebra/genética , Proteínas de Pez Cebra/metabolismo
5.
Int J Cancer ; 2024 Sep 15.
Artículo en Inglés | MEDLINE | ID: mdl-39279141

RESUMEN

The association between the American Heart Association (AHA) Life's Essential 8 (LE8) and the risk of pancreatic cancer (PC) remains unclear. Our goal was to assess the relationships between LE8, genetic susceptibility, and PC risk. This cohort consisted of 234,102 participants from the UK Biobank. The components of LE8 include diet, nicotine exposure, sleep, physical activity, blood glucose, body mass index, blood lipids, and blood pressure. LE8 is classified into three categories: low cardiovascular health (CVH), moderate CVH, and high CVH. Measurements were made using Cox proportional risk models to estimate impact of associations between LE8, genetic susceptibility, and incidence of PC in participants. Compared to participants with low LE8 scores, those with moderate and high LE8 scores had a 53% (HR, 0.47; 95% CI, 0.39-0.57) and 70% (HR, 0.30; 95% CI, 0.22-0.41) lower risk of developing PC, respectively. Interestingly, among individuals with high genetic risk, high LE8 scores were associated with greater benefits (HR, 0.24; 95% CI, 0.15-0.40), whereas the protective effect was weaker among those with low genetic risk (HR, 0.40; 95% CI, 0.21-0.75). Participants with a high LE8 score and a low polygenic risk score (PRS) had the lowest risk of PC (HR, 0.19; 95% CI: 0.11-0.33). Furthermore, we observed a significant additive interaction between LE8 and PRS. A higher LE8 score is associated with a lower risk of PC, especially for participants with a high PRS. These findings have important implications for participants most genetically predisposed to PC and for targeted strategies for PC prevention.

6.
Nat Commun ; 15(1): 7892, 2024 Sep 10.
Artículo en Inglés | MEDLINE | ID: mdl-39256391

RESUMEN

Coherent optics has profoundly impacted diverse applications ranging from communications, LiDAR to quantum computations. However, developing coherent systems in integrated photonics comes at great expense in hardware integration and energy efficiency. Here we demonstrate a high-coherence parallelization strategy for advanced integrated coherent systems at minimal cost. By using a self-injection locked microcomb to injection lock distributed feedback lasers, we achieve a record high on-chip gain of 60 dB with no degradation in coherence. This strategy enables highly coherent channels with linewidths down to 10 Hz and power over 20 dBm. The overall electrical-to-optical efficiency reaches 19%, comparable to that of advanced semiconductor lasers. This method supports a silicon photonic communication link with an unprecedented data rate beyond 60 Tbit/s and reduces phase-related DSP consumption by 99.99999% compared to traditional III-V laser pump schemes. This work paves the way for realizing scalable, high-performance coherent integrated photonic systems, potentially benefiting numerous applications.

7.
Bioact Mater ; 41: 108-126, 2024 Nov.
Artículo en Inglés | MEDLINE | ID: mdl-39108335

RESUMEN

Inspired by tug-of-war, a game-changing bone-tendon fixation paradigm was developed. Specifically, injectable citrate-based bioactive self-expansive and planar-fixing screw (iCSP-Scr) consisting of reactive isocyanate (NCO) terminalized citrate-based polyurethane, proanthocyanidin modified hydroxyapatite (HAp) and water (with/without porogen) was developed and administrated in the bone-tendon gap. Instead of the "point to point" tendon fixation by traditional interface screws, along with the moisture-induced crosslinking and expansion of iCSP-Scr within the confined space of the irregularly shaped bone-tendon gap, the tendon graft was evenly squeezed into the bone tunnel in a "surface to surface" manner to realize strong and stable bone-tendon fixation via physical expansion, mechanical interlocking and chemical bonding (between -NCO and the -NH2, -SH groups on bone matrix). The optimized iCSP-Scr exhibited rapid crosslinking, moderate expansion rate, high porosity after crosslinking, as well as tunable elasticity and toughness. The iCSP-Scr possessed favorable biodegradability, biocompatibility, and osteoinductivity derived from citrate, PC and HAp, it was able to promote osteogenesis and new bone growth inward of bone tunnel thus further enhanced the bone/iCSP-Scr mechanical interlock, ultimately leading to stronger tendon fixation (pull-out force 106.15 ± 23.15 N) comparing to titanium screws (93.76 ± 17.89 N) after 14 weeks' ACL reconstruction in a rabbit model. The iCSP-Scr not only can be used as a self-expansive screw facilitating bone-tendon healing, but also can be expanded into other osteogenic application scenarios.

8.
Artículo en Inglés | MEDLINE | ID: mdl-39183099

RESUMEN

BACKGROUND: FLT3-ITD AML is associated with an increased risk of relapse, leading many patients to receive an allogeneic hematopoietic stem cell transplantation (alloHCT) after induction. Unfortunately, relapse rate after alloHCT remains high and strategies are needed to improve outcomes. MATERIALS AND METHODS: We performed a retrospective analysis of adult patients with FLT3-ITD AML who received alloHCT from 6/1/2016 to 12/31/2020 and received gilteritinib (GILT) or sorafenib (SORA)as post-transplant maintenance, outside of a clinical trial. RESULTS: A total of 55 patients were treated with either GILT (n = 27) or SORA (n = 29) for post-HCT maintenance. One patient was treated with SORA after first alloHCT and GILT after second alloHCT. Patient characteristics were comparable between groups. FLT3 inhibitors were utilized in pre-alloHCT therapy in all but 1 patient. The median duration of time that patients remained on GILT was 385 days (range, 10-804) and on SORA 315 days (range, 3-1777). 1-year PFS and relapse incidence were similar between GILT and SORA; PFS was 66% versus 76% (P = .4) and relapse incidence was 19% versus 24% (P = .6), respectively.Both groups had high incidence of Grade 3-4 hematological toxicity, including neutropenia (45% GILT and 34% SORA) and thrombocytopenia (30% GILT and 52% SORA). Only 44% and 14% patients who received GILT and SORA did not discontinue maintenance, respectively. CONCLUSION: Our results revealed comparable PFS and a similar toxicity profile when SORA and GILT are used as post- HCT maintenance therapy.

9.
Mar Biotechnol (NY) ; 2024 Aug 05.
Artículo en Inglés | MEDLINE | ID: mdl-39098943

RESUMEN

Golden cuttlefish play a significant role in the food web of the East and Yellow Seas and are a valuable fishery resource in Chinese coastal waters. Samples of golden cuttlefish were obtained from the northern East China Sea between September 2021 and March 2022, and stable isotope methods were utilized in this study to examine the variations in the forage ecology of golden cuttlefish. Our findings reveal dynamic shifts in carbon and nitrogen stable isotopes (δ13C and δ15N), highlighting intricate foraging strategies tailored to growth and environmental changes. A notable trend emerges: an initial growth-linked rise in δ13C and δ15N enrichment, followed by seasonal fluctuations mirroring seasonal food availability. The ontogenetic niche evolution displays striking habitat shifts and trophic level escalation in small mantle length stages, transitioning to niche overlap and subtle trophic shifts later on. Sex-specific differences emerge, with females occupying higher trophic levels than males in most samples. This comprehensive study underscores the complexity and adaptability of golden cuttlefish feeding ecology, inviting further inquiry into their intricate relationships within the marine ecosystem.

10.
PNAS Nexus ; 3(8): pgae285, 2024 Aug.
Artículo en Inglés | MEDLINE | ID: mdl-39108301

RESUMEN

Secondary lymphoid organs (SLOs), including tonsils (TS), lymph nodes (LN), and Peyer's Patches, exhibit complementary immune functions. However, little is known about the spatial organization of immune cells and extracellular matrix (ECM) in the SLOs. Traditional imaging is limited to a few markers, confining our understanding of the differences between the SLOs. Herein, imaging mass cytometry addressed this gap by simultaneously profiling 25-plex proteins in SLO tissues at subcellular resolution. The antibody panel targeted immune, stromal, chemokine, epigenetic, and functional markers. For robust cell identification, a computational workflow SpatialVizPheno was developed to spatially phenotype 999,970 cells using two approaches, including manual gating and semi-supervised gating, iterative clustering, and annotation. LN exhibited the highest density of B cells while the intestinal tissues contained the highest proportion of regulatory and follicular helper T cells. SpatialVizPheno identified the most prevalent interaction between follicular dendritic cells and stromal cells (SCs), plasmablasts/plasma cells, and the SCs across the lymphoid tissues. Collagen-enriched regions were associated with the spatial orientation of B cell follicles in both TS and LN tissues, but not in intestinal lymphoid tissues. Such spatial differences of immunophenotypes and ECM in different SLO tissues can be used to quantify the relationship between cellular organization and ultimate immune responses.

11.
Water Res ; 265: 122302, 2024 Nov 01.
Artículo en Inglés | MEDLINE | ID: mdl-39178591

RESUMEN

Enriching microorganisms using a 0.22-µm pore size is a general pretreatment procedure in river microbiome research. However, it remains unclear the extent to which this method loses microbiome information. Here, we conducted a comparative metagenomics-based study on microbiomes with sizes over 0.22 µm (large-sized) and between 0.22 µm and 0.1 µm (small-sized) in a subtropical river. Although the absolute concentration of small-sized microbiome was about two orders of magnitude lower than that of large-sized microbiome, sequencing only large-sized microbiome resulted in a significant loss of microbiome diversity. Specifically, the microbial community was different between two sizes, and 347 genera were only detected in small-sized microbiome. Small-sized microbiome had much more diverse viral community than large-sized fraction. The viruses had abundant ecological functions and were hosted by 825 species of 169 families, including pathogen-related families. Small-sized microbiome had distinct antimicrobial resistance risks from large-sized microbiome, showing an enrichment of eight antibiotic resistance gene (ARG) types as well as the detection of 140 unique ARG subtypes and five enriched risk rank I ARGs. Draft genomes of five major resistant pathogens having diverse ecological and pollutant-degrading functions were only assembled in small-sized microbiome. These findings provide novel insights into river ecosystems, and highlight the overlooked small-sized microbiome in the environment.


Asunto(s)
Ecosistema , Microbiota , Ríos , Ríos/microbiología , Metagenómica , Bacterias/genética
12.
Toxics ; 12(7)2024 Jul 06.
Artículo en Inglés | MEDLINE | ID: mdl-39058148

RESUMEN

In this study, the concentrations of trace elements (TEs) in Uroteuthis edulis caught from the East China Sea were determined. There were significant differences between TE concentrations in different body parts. Cu, Zn, and Cd were the most concentrated in the digestive glands and the concentrations of Cr and Co were highest in the gills. No significant differences in concentrations were shown between these tissues. In the four tissues analyzed, the mantle recorded the highest proportion of elemental load, while the digestive glands and gills had the lowest proportions. After maturity, TEs in the mantle showed no significant differences. In the digestive gland, the concentrations of all elements, except Zn, were significantly increased. The gonads illustrated apparent increases in the concentrations of Cr, Cu, and As. In the gills, the concentrations of Co and As were markedly increased.

13.
Bull Environ Contam Toxicol ; 113(2): 19, 2024 Jul 30.
Artículo en Inglés | MEDLINE | ID: mdl-39080019

RESUMEN

Environmental concentrations of antimicrobials can inhibit Cyanobacteria, but little is known about their effects on Cyanobacteria-blooming freshwater ecosystem. Here, a 21 days' outdoor freshwater mesocosm experiment was established to study effects of single and combined tetracycline, triclocarban and zinc at environmental concentrations on microbial community, microbial function and antimicrobial resistance using amplicon- and metagenomic-based methods. Results showed that three chemicals reshaped the microbial community with magnified effects by chemical combinations. Relative abundance of Cyanobacteria was decreased in all chemical groups, especially from 74.5 to 0.9% in combination of three chemicals. Microbial community networks were more simplified after exposure. Proteobacteria and Bacteroidetes predominated in Cyanobacteria-degraded ecosystems, and their relative abundances were significantly correlated with antibiotic resistome, suggesting that they might host antibiotic resistance genes. Notably, relative abundance (copy per 16 S rRNA gene) of total antibiotic resistome reached five to nine folds higher than the initial abundance in chemical-combined groups. The affected antibiotic resistance genes referred to a wide range of antibiotic classes. However, weak effects were detected on biocide/metal resistance and microbial virulence. Three chemicals posed complicated effects on microbial function, some of which had consistent variations across the groups, while some varied greatly in chemical groups. The findings highlight sensitivity of Cyanobacteria-blooming ecosystem to antimicrobials.


Asunto(s)
Carbanilidas , Cianobacterias , Ecosistema , Agua Dulce , Contaminantes Químicos del Agua , Zinc , Cianobacterias/efectos de los fármacos , Cianobacterias/genética , Zinc/toxicidad , Carbanilidas/toxicidad , Agua Dulce/microbiología , Contaminantes Químicos del Agua/toxicidad , Antibacterianos/toxicidad , Antibacterianos/farmacología , Tetraciclina/farmacología , Tetraciclina/toxicidad , Microbiota/efectos de los fármacos
14.
Environ Pollut ; 357: 124482, 2024 Sep 15.
Artículo en Inglés | MEDLINE | ID: mdl-38960118

RESUMEN

Pharmaceutical plant sites play a significant role in the dissemination of antibiotic resistance genes (ARGs) into the environment. It is imperative to comprehensively monitor of ARGs across various environmental media at these sites. This study focused on three pharmaceutical plants, two located in North China and one in South China. Through metagenomic approaches, we examined the composition, mobility potential, and bacterial hosts of ARGs in diverse media such as process water, groundwater, topsoil, soil cores, and pharmaceutical fermentation residues across diverse environmental matrices, including topsoil, soil cores, process water, groundwater, and pharmaceutical fermentation residues. We identified a wide array of ARGs, comprising 21 types and 740 subtypes, with process water exhibiting the highest abundance and diversity. Treatment processes varied in their efficacy in eliminating ARGs, and the clinically relevant ARGs should also be considered when evaluating wastewater treatment plant efficiency. Geographical distinctions in groundwater ARG distribution between northern and southern regions were observed. Soil samples from the three sites showed minimal impact from pharmaceutical activity, with vancomycin-resistance genes being the most prevalent. High levels of ARGs in pharmaceutical fermentation residues underscore the necessity for improved waste management practices. Metagenomic assembly revealed that plasmid-mediated ARGs were more abundant than chromosome-mediated ARGs. Metagenome-assembled genomes (MAGs) analysis identified 166 MAGs, with 62 harboring multiple ARGs. Certain bacteria tended to carry specific types of ARGs, revealing distinct host-resistance associations. This study enhances our understanding of ARG dissemination across different environmental media within pharmaceutical plants and underscores the importance of implementing strict regulations for effluent and residue discharge to control ARG spread.


Asunto(s)
Bacterias , Farmacorresistencia Microbiana , Metagenómica , China , Bacterias/genética , Bacterias/efectos de los fármacos , Farmacorresistencia Microbiana/genética , Microbiología del Suelo , Monitoreo del Ambiente , Farmacorresistencia Bacteriana/genética , Genes Bacterianos , Antibacterianos/farmacología , Agua Subterránea/microbiología , Agua Subterránea/química , Metagenoma
15.
Open Life Sci ; 19(1): 20220923, 2024.
Artículo en Inglés | MEDLINE | ID: mdl-39071492

RESUMEN

The aim of this study is to assess the impact of serum magnesium (Mg) levels on prognostic outcomes in patients with non-small cell lung cancer (NSCLC) undergoing treatment with epidermal growth factor receptor tyrosine kinase inhibitors (EGFR-TKI). A cohort comprising 91 patients with NSCLC with epidermal growth factor receptor mutations received EGFR-TKI therapy. Assessments of liver and kidney function and electrolyte levels were conducted before treatment initiation and after completing two cycles of EGFR-TKI therapy. Data on variables such as age, gender, presence of distant metastasis, smoking history, other therapeutic interventions, and the specific TKI used were collected for analysis. Cox regression analysis revealed that patients with higher Mg levels prior to EGFR-TKI therapy had significantly longer progression-free survival (PFS) and overall survival (OS). Elevated Mg levels remained predictive of PFS and OS after two cycles of EGFR-TKI therapy. Multiple regression analysis confirmed these findings. Additionally, it was observed that smokers might represent a unique population, demonstrating a correlation between OS and Mg levels. Our findings indicate that serum Mg level is a prognostic factor in patients with NSCLC undergoing EGFR-TKI therapy. This may provide new insights into the underlying mechanisms of EGFR-TKI therapy related to electrolyte balance.

16.
Biology (Basel) ; 13(7)2024 Jul 10.
Artículo en Inglés | MEDLINE | ID: mdl-39056708

RESUMEN

The Argentine hake (Merluccius hubbsi) is a vital fishery species in the Southwest Atlantic, recognized for its substantial economic importance. Previous studies have identified Anisakidae larvae as common parasites of M. hubbsi. However, the nutritional relationships between these parasites and their host remain poorly understood. This study employs stable isotope techniques to investigate the specific nutritional relationships between Anisakidae larvae and different tissues of M. hubbsi. The findings reveal notable differences in δ13C and δ15N compositions between the parasites and their host. The lower δ13C values in parasites compared to host tissues indicate the utilization of different carbon sources. The δ15N values of the parasites partially overlap with those of the host's stomach, indicating that the parasites primarily derive nutrients from the host's stomach. Nutritional niche indicators show that parasites have a broad carbon range (CR) and nitrogen range (NR), suggesting a high diversity in nutritional sources. The trophic discrimination factor (ΔTDF), which represents the difference in stable isotope values between host tissues and parasites, was analyzed for both δ13C and δ15N. The ΔTDFδ13C between the host liver and the parasites showed the greatest variation, indicating a strong dependence of the parasites on the liver's carbon sources. In contrast, variations in ΔTDFδ15N between host tissues and parasites were minimal. Analyzing ΔTDF across different stages of gonadal maturity in the host fish indicates that, as the gonads of the host fish mature, ΔTDFδ13C between host tissues and parasites significantly decreases (p < 0.01). The Kruskal-Wallis test showed significant differences in ΔTDFδ13C values among different parasite infection levels in muscle, liver, and stomach tissues, while no significant differences were found for ΔTDFδ15N values. These findings offer valuable insights into the nutritional relationships between parasites and hosts, aiding in a better understanding of the growth conditions and habitats of M. hubbsi.

17.
Aging (Albany NY) ; 16(12): 10636-10656, 2024 06 25.
Artículo en Inglés | MEDLINE | ID: mdl-38925650

RESUMEN

CD8+ T cells play pivotal roles in combating intracellular pathogens and eliminating malignant cells in cancer. However, the prognostic role of CD8+ T cells in ovarian carcinoma is insufficiently exploited. Herein, through univariate Cox regression along with least absolute shrinkage and selection operator (LASSO) regression analyses, we developed a novel prognostic model based on CD8+ T cell markers identified by single-cell sequencing (scRNA-seq) analyses. Patient grouping by the median risk score reveals an excellent prognostic efficacy of this model in both training and validation cohorts. Of note, patients classified as low-risk group exhibit a dramatically improved prognosis. In addition, higher enrichment level of immune-related pathways and increased infiltration level of multiple immune cells are found in patients with lower risk score. Importantly, low-risk patients also exhibited higher response rate to immunotherapies. Summarily, this developed CD8+ T cell-associated prognostic model serves as an excellent predictor for clinical outcomes and aids in guiding therapeutic strategy choices for ovarian cancer patients.


Asunto(s)
Linfocitos T CD8-positivos , Neoplasias Ováricas , Análisis de la Célula Individual , Humanos , Femenino , Linfocitos T CD8-positivos/inmunología , Neoplasias Ováricas/genética , Neoplasias Ováricas/inmunología , Neoplasias Ováricas/mortalidad , Análisis de la Célula Individual/métodos , Pronóstico , RNA-Seq , Biomarcadores de Tumor/genética , Análisis de Secuencia de ARN
18.
ChemSusChem ; : e202400829, 2024 Jun 17.
Artículo en Inglés | MEDLINE | ID: mdl-38884174

RESUMEN

Ferrocene (Fc) and Fc derivatives have gained popularity in recent years due to their unique structure and characteristics. Among Fc's diverse performances, photothermal conversion, as a primary source of energy conversion, has sparked substantial study attention. This Review summaries Fc and Fc derivatives with photothermal characteristics, as well as their applications developed recently. First, methods for the synthesis of Fc-based materials are systematically discussed. Then, the photothermal conversion mechanism based on nonradiative relaxation is summarized. Furthermore, the most recent advances in Fc-based materials in photothermal applications are described, including photothermal degradation, photothermal antibacterial, photothermal therapies, photothermal catalysis, solar-driven water production, and photothermal CO2 separation. Finally, a summary and insights on the photothermal application of Fc-based materials are provided. This paper seeks to provide researchers with a better knowledge of photothermal behavior while also highlighting the potential of Fc and its derivatives in photothermal fields.

19.
Theranostics ; 14(8): 3104-3126, 2024.
Artículo en Inglés | MEDLINE | ID: mdl-38855191

RESUMEN

Background: The stem or progenitor antecedents confer developmental plasticity and unique cell identities to cancer cells via genetic and epigenetic programs. A comprehensive characterization and mapping of the cell-of-origin of breast cancer using novel technologies to unveil novel subtype-specific therapeutic targets is still absent. Methods: We integrated 195,144 high-quality cells from normal breast tissues and 406,501 high-quality cells from primary breast cancer samples to create a large-scale single-cell atlas of human normal and cancerous breasts. Potential heterogeneous origin of malignant cells was explored by contrasting cancer cells against reference normal epithelial cells. Multi-omics analyses and both in vitro and in vivo experiments were performed to screen and validate potential subtype-specific treatment targets. Novel biomarkers of identified immune and stromal cell subpopulations were validated by immunohistochemistry in our cohort. Results: Tumor stratification based on cancer cell-of-origin patterns correlated with clinical outcomes, genomic aberrations and diverse microenvironment constitutions. We found that the luminal progenitor (LP) subtype was robustly associated with poor prognosis, genomic instability and dysfunctional immune microenvironment. However, the LP subtype patients were sensitive to neoadjuvant chemotherapy (NAC), PARP inhibitors (PARPi) and immunotherapy. The LP subtype-specific target PLK1 was investigated by both in vitro and in vivo experiments. Besides, large-scale single-cell profiling of breast cancer inspired us to identify a range of clinically relevant immune and stromal cell subpopulations, including subsets of innate lymphoid cells (ILCs), macrophages and endothelial cells. Conclusion: The present single-cell study revealed the cellular repertoire and cell-of-origin patterns of breast cancer. Combining single-cell and bulk transcriptome data, we elucidated the evolution mimicry from normal to malignant subtypes and expounded the LP subtype with vital clinical implications. Novel immune and stromal cell subpopulations of breast cancer identified in our study could be potential therapeutic targets. Taken together, Our findings lay the foundation for the precise prognostic and therapeutic stratification of breast cancer.


Asunto(s)
Neoplasias de la Mama , Análisis de la Célula Individual , Microambiente Tumoral , Humanos , Análisis de la Célula Individual/métodos , Femenino , Neoplasias de la Mama/patología , Neoplasias de la Mama/genética , Neoplasias de la Mama/inmunología , Microambiente Tumoral/inmunología , Animales , Ratones , Biomarcadores de Tumor/genética , Biomarcadores de Tumor/metabolismo , Línea Celular Tumoral , Pronóstico
20.
J Environ Manage ; 365: 121618, 2024 Aug.
Artículo en Inglés | MEDLINE | ID: mdl-38943747

RESUMEN

Transboundary lakes are shared by multiple administrative regions. The key to balance the development and protection of transboundary lakes is to properly measure the value of water resources. Most of previous studies on the measurement of lake water resources value have not fully considered the ecosystem service function. This paper proposes a new concept "composite water value" to measure the value of transboundary lakes by integrating the external runoff value and the internal runoff value of water resources. The study constructs a composite water value measurement system for transboundary lakes, further analyzes its influencing factors,and applies the system to the case of Nansi Lake, a representative transboundary lake in eastern China. The results show that: (1) The composite water value of lakes is influenced by various factors, including industrial structure, water withdrawal, and water use methods, which impact the external runoff water value; meanwhile, the composite water quality and fluctuations in lake level are closely associated with the internal runoff water value. From 2008 to 2021, the average annual composite water value of Nansi Lake was 39.628 billion yuan, exhibiting a "rising-falling-fluctuating rising" trend due to pollution control policies, reduced precipitation, and enhanced water-saving technologies successively. (2) From a long-term perspective, it is necessary to focus on the internal runoff water use value of lakes. The internal runoff water value of Nansi Lake has been over 75% of the composite water value, and flood storage and water conservation are important manifestations of its ecosystem service value. (3) The external runoff water value of lake is closely related to the internal runoff water value, and relevant departments need to consider the balance between the water withdrawal of multiple cities along the lake and the retained water volume of the lake to achieve the maximum benefit of composite water value.


Asunto(s)
Lagos , Calidad del Agua , China , Ecosistema , Conservación de los Recursos Naturales , Recursos Hídricos , Monitoreo del Ambiente
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