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1.
J Environ Sci (China) ; 150: 582-593, 2025 Apr.
Artículo en Inglés | MEDLINE | ID: mdl-39306431

RESUMEN

Coal power plants annually generate quantities of byproducts that release environmentally hazardous heavy metals like Cd and Pb. Understanding the behavior and spatiotemporal impacts on soils of these releases is crucial for pollution control. This study investigated the concentrations and isotope ratios of Cd/Pb in combustion byproducts, depositions and soils collected from a coal-fired power plant or its surrounding area. The pulverized fuel ash (PFA) and desulfurized gypsum (DG) exhibited heavier Cd isotopes with Δ114Cd values of 0.304‰ and 0.269‰, respectively, while bottom ash (BA) showed lighter Cd isotopes (Δ114CdBA-coal = -0.078‰), compared to feed coal. We proposed a two-stage condensation process that governs the distribution of Cd/Pb, including accumulation on PFA and DG within electrostatic precipitators and desulfurization unit, as well as condensation onto fine particles upon release from the stack. Emissions from combustion and large-scale transport make a significant contribution to deposition, while the dispersion of Cd/Pb in deposition is primarily influenced by the prevailing wind patterns. However, the distribution of Cd/Pb in soils not only exhibit predominant wind control but is also potentially influenced by the resuspension of long-term storage byproducts. The power plant significantly contributes to soil in the NW-N-NE directions, even at a considerable distance (66%-79%), demonstrating its pervasive impact on remote regions along these orientations. Additionally, based on the vertical behavior in the profile, we have identified that Cd tends to migrate downward through leaching, while variations in Pb respond to the historical progression of dust removal.


Asunto(s)
Cadmio , Carbón Mineral , Monitoreo del Ambiente , Centrales Eléctricas , Contaminantes del Suelo , Suelo , Cadmio/análisis , Contaminantes del Suelo/análisis , Suelo/química , Plomo/análisis
2.
Affect Sci ; 5(3): 222-231, 2024 Sep.
Artículo en Inglés | MEDLINE | ID: mdl-39391335

RESUMEN

When learning about stimuli comprised of multiple cues, humans and other animals tend to form stronger cue-outcome associations for more salient cues than for less salient cues. This phenomenon, termed overshadowing, has typically been demonstrated between cues that vary in salience because of differences in physical intensity. In this study, we investigated whether differences in the emotional valence of cues in a compound stimulus similarly led to differences in the strength of cue-outcome learning. Using a probabilistic categorisation task in which stimuli were compounds consisting of pairs of emotional or non-emotional cue images, we found consistent evidence for emotional overshadowing across both an initial exploratory study (N = 50) and a confirmatory preregistered replication study (N = 200). Specifically, both pleasant and unpleasant cue images tended to overshadow neutral cue images, but pleasant and unpleasant cue images did not overshadow one another. Moreover, across stimuli, the magnitude of differences in learning between cues was proportional to differences in their absolute emotional valence, suggesting that attentional capture by both positively and negatively valenced emotions drives overshadowing. These findings have implications for understanding associative learning in natural environments, where stimuli are frequently imbued with emotional valence prior to learning. Supplementary Information: The online version contains supplementary material available at 10.1007/s42761-024-00270-0.

3.
J Cell Mol Med ; 28(20): e70177, 2024 Oct.
Artículo en Inglés | MEDLINE | ID: mdl-39470579

RESUMEN

Glioblastoma (GBM) is a highly aggressive and treatment-resistant malignancy that poses a significant challenge in modern medicine. Despite advances in surgical resection, radiotherapy and chemotherapy, complete eradication of GBM remains elusive due to its diffuse invasion into the brain parenchyma and propensity for recurrence. The tumour microenvironment (TME), particularly macrophages, has emerged as a critical player in GBM progression, invasion and metastasis. In the immune microenvironment of glioma, MS4A6A exhibits unique expression characteristics in macrophages. This study aimed to investigate the potential role of MS4A6A, a gene associated with aging and neurodegenerative diseases, in GBM and its potential as a prognostic biomarker and therapeutic target.


Asunto(s)
Neoplasias Encefálicas , Glioblastoma , Análisis de la Célula Individual , Microambiente Tumoral , Humanos , Glioblastoma/genética , Glioblastoma/terapia , Glioblastoma/patología , Glioblastoma/metabolismo , Microambiente Tumoral/genética , Pronóstico , Análisis de la Célula Individual/métodos , Neoplasias Encefálicas/genética , Neoplasias Encefálicas/terapia , Neoplasias Encefálicas/patología , Neoplasias Encefálicas/metabolismo , Biomarcadores de Tumor/genética , Biomarcadores de Tumor/metabolismo , Regulación Neoplásica de la Expresión Génica , Macrófagos/metabolismo , Macrófagos/inmunología , Multiómica
4.
Anal Chem ; 96(44): 17546-17551, 2024 Nov 05.
Artículo en Inglés | MEDLINE | ID: mdl-39431979

RESUMEN

The standard addition method (SAM) is widely used to measure the isotopic compositions of natural samples, particularly those with a complex matrix. However, traditional SAM has limitations for isotope systems with significant variations in isotope composition due to its reliance on approximation in calculation and the requirement for a priori estimates of analyte isotopic compositions and accurate concentrations. To overcome the issues, our work proposes an improved SAM that explicitly calculates isotope ratio R (i.e., XE/YE, 34S/32S for example) instead of approximating R* (mass number of isotope X divided by total mass number of all isotopes of an element) with R in SAM. Additionally, the sample fraction within standard-sample mixture in improved SAM is determined using the isotope compositions of standards, sample-standard mixtures, and the mixtures of both standards, rather than relying on sample concentrations and volumes. Both improvements not only overcome the shortcomings of traditional SAM but also empowered the approach's ability to accurately determine sample concentrations. To validate its effectiveness, we applied the improved SAM to natural samples with substantial sulfur (S) isotope variation (1.94 to 27.19‰) and low S concentration (0.81 to 3.47 µg g-1). The calculated δ34S values and concentrations of these samples are consistent with direct measurements within the error ranges while reducing sample sizes to 20% of those required for direct measurement. Moreover, our method achieves higher accuracy in δ34S values compared with traditional SAM. Both comparisons affirm the reliability and superiority of improved SAM.

5.
Talanta ; 282: 126961, 2024 Sep 28.
Artículo en Inglés | MEDLINE | ID: mdl-39342668

RESUMEN

Developing immunosensing platforms capable of simultaneously detecting multiple cancer markers is crucial for clinical diagnosis and biomedical research. Here, we introduce a novel dual-mode electrochemical biosensing assay platform capable of detecting two gastric cancer biomarkers: pepsinogen I (PG I) and pepsinogen II (PG II). Methylene blue (MB) and Prussian blue (PB) were used as dual signal sources to label PG I and PG II, respectively. The platform integrates an ARM STM32F411 microcontroller and an AD5941 analog front-end, which not only facilitates cyclic voltammetry (CV) and differential pulse voltammetry (DPV) with efficacy comparable to commercial electrochemical workstations but also offers data collection and synchronous analysis capabilities, allowing simultaneous output of PG I and PGR (PG I/PG II) values. Equipped with an interactive screen for operational control and result display, the immunosensing platform provides linear detection ranges for PG I (5 pg/mL-100 ng/mL) and PG II (50 pg/mL-200 ng/mL), enabling rapid detection within 5 min. It demonstrates excellent sensitivity and selectivity when comparing serum samples from healthy individuals and gastric cancer patients. The dual-marker detection platform significantly enhances early diagnosis and screening of gastric cancer, offering substantial improvements over single-marker assays. Furthermore, this platform shows potential for detecting multiple biomarkers in various diseases, highlighting its utility for biomedical applications.

6.
J Hazard Mater ; 480: 135798, 2024 Sep 11.
Artículo en Inglés | MEDLINE | ID: mdl-39278032

RESUMEN

The environmental risk of Cd in soils strongly depends on the mobilization of Cd in soils. However, limited knowledge exists on the redistribution of exogenic Cd inputs in soils, especially across diverse lithological regions. Herein, we aimed to investigate the fate of Cd in soils from two mining areas with contrasting lithologies (siliceous and calcareous) using stable Cd isotopes. The isotope tracing results confirm that mining activities are the main Cd source in both areas. The positive correlation between δ114/110Cd values and goethite/dolomite content indicates the release of heavy Cd isotopes during the dissolution of exogenetic minerals. Additionally, high contents of exchangeable Cd (11 % to 36 %) and Fe oxide-bound Cd (29 % to 42 %) drive plant pumps to transport heavy Cd isotopes from the deeper to upper horizons of the soils from the siliceous area. In the calcareous area, the total organic carbon content is positively correlated with the Cd concentration and δ114/110Cd value, suggesting potential complexation of Cd with organic matter due to the stabilizing effect of carbonate minerals on soil organic matter. This study highlights the different redistributions of exogenous Cd in soils from diverse lithological regions, emphasizing the need to consider regional lithology when developing soil quality standards for Cd.

7.
Child Abuse Negl ; 155: 106961, 2024 Sep.
Artículo en Inglés | MEDLINE | ID: mdl-39096662

RESUMEN

BACKGROUND: Childhood abuse is associated with an increased risk of migraines. However, the literature on this association is limited. OBJECTIVE: To determine the pooled effect size of the association between childhood abuse and migraines. PARTICIPANTS AND SETTING: System review and meta-analysis. METHODS: A systematic literature search for studies published until September 20, 2023, was performed using the Embase, PubMed, and Web of Science databases. Specifically, original articles reporting the statistical effect size (odds ratio) of the association between childhood abuse and migraines were selected. Pooled odds ratios (ORs) and 95 % confidence intervals (CIs) were calculated using random- or fixed-effects models. Publication bias was examined using funnel plots, and sensitivity analysis was used to explore the stability of the pooled results. RESULTS: Twelve studies involving 110,776 participants were included. Individuals with childhood abuse (OR = 1.60, 95 % CI: 1.49, 1.71) were at increased risk of migraine when compared with individuals with no childhood abuse. Of the different types of childhood abuse examined, sexual abuse (OR = 1.71, 95 % CI: 1.43, 2.04), physical abuse (OR = 1.47, 95 % CI: 1.38, 1.56), and emotional abuse (OR = 1.71, 95 % CI: 1.52, 1.93) were associated with an increased risk of migraine. CONCLUSIONS: Childhood abuse increases migraine risk. Multifaceted interventions to curb abuse and related behaviors can effectively reduce migraine risk. However, considering that multiple factors, such as obesity and anxiety, are causatively associated with both childhood abuse and migraines, our findings should be interpreted with caution.


Asunto(s)
Maltrato a los Niños , Trastornos Migrañosos , Humanos , Trastornos Migrañosos/epidemiología , Niño , Maltrato a los Niños/estadística & datos numéricos , Maltrato a los Niños/psicología , Factores de Riesgo , Adultos Sobrevivientes del Maltrato a los Niños/psicología , Adultos Sobrevivientes del Maltrato a los Niños/estadística & datos numéricos
8.
Bioorg Med Chem ; 111: 117843, 2024 Sep 01.
Artículo en Inglés | MEDLINE | ID: mdl-39083980

RESUMEN

This study reported the design and synthesis of novel 1-amido-2-one-4-thio-deoxypyranose as inhibitors of potential drug target TRIP13 for developing new mechanism-based therapeutic agents in the treatment of multiple myeloma (MM). In comparison with the positive control DCZ0415, the most active compounds C16, C18, C20 and C32 exhibited strong anti-proliferative activity against human MM cell lines (ARP-1 and NCI-H929) with IC50 values of 1 âˆ¼ 2 µM. While the surface plasmon resonance (SPR) and ATPase activity assays demonstrated that the representative compound C20 is a potent inhibitor of TRIP13, C20 also showed good antitumor activity in vivo on BALB/c nude mice xenografted with MM tumor cells. An initial structure-activity study showed that the carbonyl group is crucial for anticancer activity. Overall, this study provided novel 1-amido-2-one-4-thio-deoxypyranoses, which are entirely different from previously reported potent inhibitor structures of TRIP13, and thus would aid the development of carbohydrate-based novel agents in MM pharmacotherapy.


Asunto(s)
Antineoplásicos , Proliferación Celular , Diseño de Fármacos , Ratones Endogámicos BALB C , Ratones Desnudos , Mieloma Múltiple , Humanos , Antineoplásicos/farmacología , Antineoplásicos/síntesis química , Antineoplásicos/química , Animales , Mieloma Múltiple/tratamiento farmacológico , Mieloma Múltiple/patología , Mieloma Múltiple/metabolismo , Relación Estructura-Actividad , Ratones , Proliferación Celular/efectos de los fármacos , Línea Celular Tumoral , Ensayos de Selección de Medicamentos Antitumorales , Estructura Molecular , Relación Dosis-Respuesta a Droga , Tanquirasas
9.
Sci Total Environ ; 946: 174134, 2024 Oct 10.
Artículo en Inglés | MEDLINE | ID: mdl-38909792

RESUMEN

Phaeocystis globosa is among the dominant microalgae associated with harmful algal blooms. P. globosa has a polymorphic life cycle and its ecological success has been attributed to algal colony formation, however, few studies have assessed differences in microbial communities and their functional profiles between intra- and extra-colonies during P. globosa blooms. To address this, environmental and metagenomics tools were used to conduct a time-series analysis of the bacterial composition and metabolic characteristics of intra- and extra-colonies during a natural P. globosa bloom. The results show that bacterial composition, biodiversity, and network interactions differed significantly between intra- and extra-colonies. Dominant extra-colonial bacteria were Bacteroidia and Saccharimonadis, while dominant intra-colonial bacteria included Alphaproteobacteria and Gammaproteobacteria. Despite the lower richness and diversity observed in the intra-colonial bacterial community, relative to extra-colonies, the complexity and interconnectedness of the intra-colonial networks were higher. Regarding bacterial function, more functional genes were enriched in substance metabolism (polysaccharides, iron element and dimethylsulfoniopropionate) and signal communication (quorum sensing, indoleacetic acid-IAA) pathways in intra- than in extra-colonies. Conceptual model construction showed that microbial cooperative synthesis of ammonium, vitamin B12, IAA, and siderophores were strongly related to the P. globosa bloom, particularly in the intra-colonial environment. Overall, our data highlight the differences in bacterial structure and functions within and outside the colony during P. globosa blooms. These findings represent fundamental information indicating that phenotypic heterogeneity is a selective strategy that improves microbial population competitiveness and environmental adaptation, benefiting P. globosa bloom formation and persistence.


Asunto(s)
Haptophyta , Floraciones de Algas Nocivas , Microbiota , Haptophyta/crecimiento & desarrollo , Microalgas , Bacterias/clasificación , Biodiversidad
11.
Bioorg Med Chem Lett ; 107: 129776, 2024 Jul 15.
Artículo en Inglés | MEDLINE | ID: mdl-38692523

RESUMEN

Human cytochrome P450 1B1 enzyme (hCYP1B1), a member of hCYP1 subfamily, plays a crucial role in multiple diseases by participating in many metabolic pathways. Although a suite of potent hCYP1B1 inhibitors have been previously reported, most of them also act as aryl hydrocarbon receptor (AhR) agonists that can up-regulate the expression of hCYP1B1 and then counteract their inhibitory potential in living systems. This study aimed to develop novel efficacious hCYP1B1 inhibitors that worked well in living cells but without AhR agonist effects. For these purposes, a series of 1,8-naphthalimide derivatives were designed and synthesized, and their structure-activity relationships (SAR) as hCYP1B1 inhibitors were analyzed. Following three rounds SAR studies, several potent hCYP1B1 inhibitors were discovered, among which compound 3n was selected for further investigations owing to its extremely potent anti-hCYP1B1 activity (IC50 = 0.040 nM) and its blocking AhR transcription activity in living cells. Inhibition kinetic analyses showed that 3n potently inhibited hCYP1B1 via a mix inhibition manner, showing a Ki value of 21.71 pM. Docking simulations suggested that introducing a pyrimidine moiety to the hit compound (1d) facilitated 3n to form two strong interactions with hCYP1B1/heme, viz., the C-Br⋯π halogen bond and the N-Fe coordination bond. Further investigations demonstrated that 3n (5 µM) could significantly reverse the paclitaxel (PTX) resistance in H460/PTX cells, evidenced by the dramatically reduced IC50 values, from 632.6 nM (PTX alone) to 100.8 nM (PTX plus 3n). Collectively, this study devised a highly potent hCYP1B1 inhibitor (3n) without AhR agonist effect, which offered a promising drug candidate for overcoming hCYP1B1-associated drug resistance.


Asunto(s)
Citocromo P-450 CYP1B1 , Diseño de Fármacos , Naftalimidas , Humanos , Relación Estructura-Actividad , Naftalimidas/farmacología , Naftalimidas/química , Naftalimidas/síntesis química , Citocromo P-450 CYP1B1/antagonistas & inhibidores , Citocromo P-450 CYP1B1/metabolismo , Estructura Molecular , Relación Dosis-Respuesta a Droga
12.
Ann Biomed Eng ; 2024 May 05.
Artículo en Inglés | MEDLINE | ID: mdl-38705931

RESUMEN

Advanced glycation end products (AGEs) have garnered significant attention due to their association with chronic diseases and the aging process. The prevalence of geriatric diseases among young individuals has witnessed a notable surge in recent years, potentially attributed to the accelerated pace of modern life. The accumulation of AGEs is primarily attributed to their inherent difficulty in metabolism, which makes them promising biomarkers for chronic disease detection. This review aims to provide a comprehensive overview of the recent advancements and findings in AGE research. The discussion is divided into two main sections: endogenous AGEs (formed within the body) and exogenous AGEs (derived from external sources). Various aspects of AGEs are subsequently summarized, including their production pathways, pathogenic mechanisms, and detection methods. Moreover, this review delves into the future research prospects concerning AGEs. Overall, this comprehensive review underscores the importance of AGEs in the detection of chronic diseases and provides a thorough understanding of their significance. It emphasizes the necessity for further research endeavors to deepen our comprehension of AGEs and their implications for human health.

13.
Cell Mol Biol (Noisy-le-grand) ; 70(3): 142-147, 2024 Mar 31.
Artículo en Inglés | MEDLINE | ID: mdl-38650139

RESUMEN

The diagnostic biomarkers associated with ischemic stroke (IS) that may have clinical utility remain elucidated. Thus, the potential functional lncRNAs in IS were explored. The Gene Expression Omnibus database provided the transcriptome profile of IS for download. WGCNA analysis and integrated bioinformatics were used to find genes that were differentially expressed (DEGs). The Starbase database created the lncRNA-based ceRNA network. In order to investigate the molecular mechanism and involved pathways of DEGs in IS, functional enrichment analysis was carried out. Using qRT-PCR, lncRNAs identified as putative IS biomarkers were confirmed to be expressed in a permanent middle cerebral artery occlusion (MCAO) model. Using the annexin V/PI apoptosis test, the amount of apoptosis in oxygen-glucose deprivation (OGD) cells was measured. A total of 1600 common differentially expressed - protein-coding RNA (DE-pcRNAs) and 26 DE-lncRNAs were identified. The results of enrichment analysis indicate that the cytokine may be regulated by common DE-pcRNAs and are vital in the progress of IS. A lncRNAs-mediated ceRNA network including lncRNAs AU020206, Brip1os, F630028O10Rik and 9530082P21Rik was constructed. The expression of these lncRNAs was significantly increased in MCAO model. Knockdown of lncRNA AU020206 inhibited microglia apoptosis in OGD cell model. We constructed a lncRNAs-mediated ceRNA network and found that lncRNA AU020206 inhibited microglia apoptosis in OGD cell model. These findings provided further evidence for the diagnosis and a novel avenue for targeted therapy of IS.


Asunto(s)
Apoptosis , Accidente Cerebrovascular Isquémico , Microglía , ARN Largo no Codificante , ARN Largo no Codificante/genética , ARN Largo no Codificante/metabolismo , Apoptosis/genética , Apoptosis/efectos de los fármacos , Accidente Cerebrovascular Isquémico/genética , Accidente Cerebrovascular Isquémico/patología , Accidente Cerebrovascular Isquémico/metabolismo , Animales , Microglía/metabolismo , Microglía/efectos de los fármacos , Microglía/patología , Técnicas de Silenciamiento del Gen , Masculino , Redes Reguladoras de Genes , Infarto de la Arteria Cerebral Media/genética , Infarto de la Arteria Cerebral Media/patología , Glucosa/metabolismo , Glucosa/deficiencia , Biología Computacional/métodos , Perfilación de la Expresión Génica , Regulación de la Expresión Génica/efectos de los fármacos , Transcriptoma/genética , Modelos Animales de Enfermedad
14.
Front Pediatr ; 12: 1379689, 2024.
Artículo en Inglés | MEDLINE | ID: mdl-38665377

RESUMEN

Background: The ingestion of jujube pits by children is a rare cause of perianal infection.This article aimed to report two cases of perianal infection in children resulting from the ingestion of jujube pits. Methods: We reviewed the clinical records of perianal infection caused by jujube pits at our hospital. Details of the patients' presentation, imaging studies, complications and treatment were recorded. Results: Both pediatric patients presented with perianal swelling and pain. The caregivers of both patients denied a history of jujube consumption. Magnetic resonance imaging (MRI) indicated the presence of jujube pits, which were subsequently removed during surgery. Postoperatively, both patients recovered well, and follow-up showed no recurrence or the formation of anal fistulas. Conclusion: The ingestion of jujube pits leading to perianal infection is rare and inconspicuous. Early diagnosis and treatment are beneficial in preventing the occurrence of serious complications.

15.
Nat Commun ; 15(1): 2063, 2024 Mar 07.
Artículo en Inglés | MEDLINE | ID: mdl-38453919

RESUMEN

Understanding how organisms have adapted to persist in unpredictable environments is a fundamental goal in biology. Bet hedging, an evolutionary adaptation observed from microbes to humans, facilitates reproduction and population persistence in randomly fluctuating environments. Despite its prevalence, empirical evidence in microalgae, crucial primary producers and carbon sinks, is lacking. Here, we report a bet-hedging strategy in the unicellular microalga Haematococcus pluvialis. We show that isogenic populations reversibly diversify into heterophenotypic mobile and non-mobile cells independently of environmental conditions, likely driven by stochastic gene expression. Mobile cells grow faster but are stress-sensitive, while non-mobile cells prioritise stress resistance over growth. This is due to shifts from growth-promoting activities (cell division, photosynthesis) to resilience-promoting processes (thickened cell wall, cell enlargement, aggregation, accumulation of antioxidant and energy-storing compounds). Our results provide empirical evidence for bet hedging in a microalga, indicating the potential for adaptation to current and future environmental conditions and consequently conservation of ecosystem functions.


Asunto(s)
Ecosistema , Microalgas , Humanos , Evolución Biológica , División Celular , Reproducción
16.
Water Res ; 254: 121401, 2024 May 01.
Artículo en Inglés | MEDLINE | ID: mdl-38447378

RESUMEN

Although being viewed as a promising technology for reclamation of carbon and phosphorus from excess sludge, anaerobic fermentation (AF) grapples with issues such as a low yield of volatile fatty acids (VFAs) and high phosphorus recovery costs. In this study, we synthesized Fe3O4@MOF-808 (FeM) with abundant defects and employed it to simultaneously enhance VFAs and phosphorus recovery during sludge anaerobic fermentation. Through pre-oxidization of sludge catalyzed by FeM-induced peroxydisulfate, the soluble organic matter increased by 2.54 times, thus providing ample substrate for VFAs production. Subsequent AF revealed a remarkable 732.73 % increase in VFAs and a 1592.95 % increase in phosphate. Factors contributing to the high VFAs yield include the non-biological catalysis of unsaturated Zr active sites in defective FeM, enhancing protein hydrolysis, and the inhibition of methanogenesis due to electron competition arising from the transformation between Fe(III) and Fe(II) under Zr influence. Remarkably, FeM exhibited an adsorption capacity of up to 92.64 % for dissolved phosphate through ligand exchange and electrostatic attractions. Furthermore, FeM demonstrated magnetic separation capability from the fermentation broth, coupled with excellent stability and reusability in both catalysis and adsorption processes.


Asunto(s)
Fósforo , Aguas del Alcantarillado , Fermentación , Aguas del Alcantarillado/química , Anaerobiosis , Carbono , Compuestos Férricos , Ácidos Grasos Volátiles/metabolismo , Fosfatos , Concentración de Iones de Hidrógeno
18.
Sci Adv ; 9(50): eadj2170, 2023 Dec 15.
Artículo en Inglés | MEDLINE | ID: mdl-38100586

RESUMEN

Moderately siderophile (e.g., Ni) and highly siderophile elements (HSEs) in the bulk silicate Earth (BSE) are believed to be partly or near-completely delivered by late accretion after the depletion caused by metallic core formation. However, the extent and rate of remixing of late-accreted materials that equilibrated with Earth's pre-late-veneer mantle have long been debated. Observing evidence of this siderophile element-depleted pre-late-veneer mantle would provide powerful confirmation of this model of early mantle evolution. We find that the mantle source of the ~3.8-billion-year-old (Ga) Narssaq ultramafic cumulates from Southwest Greenland exhibits a subtle 60Ni/58Ni excess of ~0.05 per mil and contains a clear HSE deficiency of ~60% relative to the BSE. The intermediate Ni isotopic composition and HSE abundances of the ~3.8-Ga Narssaq mantle mark a transitional Eoarchean snapshot as the poorly mixed 3.8-Ga mantle containing elements of pre-late-veneer mantle material transitions to modern Earth's mantle.

19.
Cancer Med ; 12(23): 21293-21307, 2023 12.
Artículo en Inglés | MEDLINE | ID: mdl-37986544

RESUMEN

BACKGROUND: Glypican-3 (GPC3) is highly expressed in testicular yolk sac tumor (TYST). GPC3 has been evaluated as a cancer vaccine for some types of tumors, but little is known on the effects of GPC3 peptide-based therapy on TYST. Here, we evaluated the antitumor effect of GPC3144-152 on TYST and its potential mechanisms. METHODS: GPC3144-152 -specific CD8+ T cells were induced by vaccine immunization and examined by ELISPOT. The CD8+ T cells were purified for testing their cytotoxicity in vitro against TYST cells by CCK-8 and TUNEL assays and in vivo against tumor growth. The influence of GPC3144-152 loading and/or cGAS silencing on the tumor growth, apoptosis and cGAS/STING signaling was tested by immunohistochemistry, immunofluorescence, flow cytometry, and Western blot. RESULTS: Vaccination with GPC3144-152 induced tumor-specific CD8+ T cells that secreted high levels of IFN-γ and granzyme B, and had potent cytotoxicity against TYST in a dose-dependent manner. Adoptive transfer of CD8+ T cells and treatment with GPC3144-152 significantly inhibited the growth of TYST tumors, but less effective for cGAS-silenced TYST tumors in vivo. Treatment with GPC3144-152 enhanced the infiltration of CD8+ T cells into the tumor environment and their cytotoxicity against TYST tumors in vivo by up-regulating granzyme B and IFN-ß expression, but down-regulating GPC3 expression in the tumors. Co-culture of CD8+ T cells with TYST in the presence of exogenous GPC3144-152 enhanced peptide-specific CD8+ T-cell cytotoxicity in vitro, accompanied by enhancing cGAS, γH2AX, TBK1, and IRF3 phosphorylation in TYST cells, but less effective in cGAS-silenced TYST cells. CONCLUSIONS: These data indicated that GPC3 peptide-specific CD8+ T cells had potent antitumor activity against TYST tumor, particularly for combined treatment with the peptide, which was partially dependent on the intratumoral cGAS/STNG signaling. GPC3 peptide vaccine may be valuable for the combination treatment of TYST.


Asunto(s)
Tumor del Seno Endodérmico , Neoplasias Testiculares , Masculino , Humanos , Linfocitos T CD8-positivos , Granzimas/metabolismo , Tumor del Seno Endodérmico/metabolismo , Glipicanos/metabolismo , Péptidos/metabolismo , Neoplasias Testiculares/metabolismo , Nucleotidiltransferasas
20.
Pediatrics ; 152(6)2023 Dec 01.
Artículo en Inglés | MEDLINE | ID: mdl-37990579

RESUMEN

Ovotesticular (OT) disorder of sex development (DSD) is a rare condition that affects the development of reproductive organs and manifests in a wide range of phenotypic presentations. The clinical diagnosis of this condition is challenging because of its atypical nature, and the variability of presentation in 46,XX OT-DSD cases makes it a complex issue in medical practice. We report a case of a 13-year-old boy who presented with left scrotal pain. Further exploration revealed a tunica rupture without testicular torsion of the left testis, whereas the histopathological analysis of a nodule excised from the right testis indicated the presence of ovotestis tissues. A second nonemergent surgery preserved the testicular tissues as the ovarian tissue in both gonads was excised. After 22 months of follow-up, the patient's testes produced normal testosterone levels sustained over time without any exogenous supplementation. This case reveals that, in male children who present with an acute scrotal disease as adolescents, the gonads should be retained until the etiology is confirmed, and the possibility of OT-DSD should be considered.


Asunto(s)
Trastornos Ovotesticulares del Desarrollo Sexual , Adolescente , Humanos , Masculino , Trastornos Ovotesticulares del Desarrollo Sexual/diagnóstico , Trastornos Ovotesticulares del Desarrollo Sexual/cirugía , Trastornos Ovotesticulares del Desarrollo Sexual/patología , Escroto/cirugía , Desarrollo Sexual
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